Genitourinary Cancer

In a field of poor outcomes, few standards of care, and small populations of patients scattered across the world, investigators studying rare genitourinary (GU) cancers are gaining ground through international collaboration and novel trial design.

Fundamental clinical questions in the area remain unanswered, including the value of conventional treatments, such as chemotherapy and surgery, vs. emerging immunotherapy combinations.

Managing patients with rare GU cancers presents a variety of challenges, as does conducting research in the field, according to Philippe E. Spiess, MD, MS, FACS, assistant chief of surgical services and senior member in the department of GU oncology at Moffitt Cancer Center, Tampa.

“Unfortunately, there are limited resources for patients – from an education, from a patient advocacy, and ultimately also from a research standpoint,” Dr. Spiess said in an interview, noting difficulties in attaining funding and reaching meaningful endpoints.

The Global Society of Rare Genitourinary Tumors

Last year Dr. Spiess teamed up with Andrea Necchi, MD, of the department of medical oncology at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, to found the Global Society of Rare Genitourinary Tumors (GSRGT), the first organization of its kind.

“We’ve formally established a society and gotten some of the world leaders [in the field] … to work with us in developing educational tools and patient advocacy efforts to really promote and improve the care of patients impacted with rare cancers,” Dr. Spiess said.

He went on to highlight the truly global makeup of GSRGT, which includes members from leading centers in North America, South America, Europe, and India, and described it as a “grass-roots” organization that he and Dr. Necchi privately funded without financial backing from pharmaceutical companies.

The first GSRGT summit took place in 2020; it focused on penile and testis cancers and was attended by more than 350 participants. The second summit, planned for March 2022, in a virtual format, will focus on rare kidney cancers and upper tract cancers.

“We’ll definitely be having a lot of important conversations about important unmet needs, and some of the important clinical trials that patients and clinicians should be aware of,” Dr. Spiess said.

Dr. Spiess is currently involved in the International Penile Advanced Cancer Trial(InPACT), which is aiming to enroll 200 patients with squamous cell carcinoma of the penis. The randomized study will compare outcomes across patients treated with standard surgery alone, neoadjuvant chemotherapy plus surgery, and neoadjuvant chemoradiotherapy plus surgery.

“I think this is going to be a landmark study because it’s going to give really baseline high-quality data on the effectiveness of these therapies,” Dr. Spiess said.

Results are expected in 2024.

Basket trials open doors for patients in need

Other investigators are testing immunotherapy combinations in patients with rare GU tumors via nonrandomized basket trials, which widen inclusion criteria and improve local availability.

According to Bradley McGregor, MD, clinical director of the Lank Center for GU Oncology at the Dana-Farber Cancer Institute in Boston, early results from these trials are promising, both in terms of therapeutic efficacy and the approach itself.

“Patients [with rare GU tumors] would come to us saying, ‘Well, what can we do? What trial?’,” Dr. McGregor said. “But really, there was no trial to get them on.”Basket trials are therefore needed, he said, as they accelerate progress in the field and help meet patient needs.

“For some of these relatively rare diseases … there is no standard of care,” Dr. McGregor said. “And low incidence makes it challenging to conduct a dedicated clinical trial. Those patients are left with minimal therapeutic options. … We look to provide care for that unmet need.”Andrea B. Apolo, MD, described similar experiences as head of the bladder cancer section of the GU malignancies branch of the National Cancer Institute (NCI), Bethesda, Md.

“I’ve been at the NCI for the past 10 years and I’ve gotten a lot of referrals for rare tumors,” Dr. Apolo said. “[These patients] have tried all available standard of care options, and therefore are often looking for clinical trials and new drugs – any kind of therapy that may be effective for their disease.”This call for help, along with a growing scientific curiosity, motivated Dr. Apolo to design trials that would include patients who had nowhere else to go.

“I became very interested in … understanding more about the mechanism of tumorigenesis and understanding rare tumors, biologically, within the lab,” she said, “but also clinically, in terms of finding more effective therapies.”

Both Dr. McGregor and Dr. Apolo are currently conducting basket trials for patients with rare GU tumors. While Dr. McGregor is testing a combination of PD-1 inhibitor nivolumab and CTLA-4 inhibitor ipilimumab, Dr. Apolo is exploring the benefit of cabozantinib, a targeted therapy, given with either nivolumab or nivolumab plus ipilimumab.

When asked about these trials, Dr. Spiess said that “basket trials are important because they may give us an understanding of some potentially useful therapies or combinations;” however, he also pointed out their limitations, noting that they may inaccurately characterize the efficacy of given therapies over a broad array of disease entities even if they are of similar histology. As an example, he noted “very different” genomic profiles across squamous cell carcinomas of the pelvis depending on exact anatomical location, suggesting that these differences may affect responses to therapy, citing a recent study in European Urology that he conducted with Dr. Necchi.¹

“[Basket trials] are probably not going to be the be-all-end-all,” Dr. Spiess said. “It really requires a global initiative to do these types of studies, which the Global Society of Rare Genitourinary Tumors will allow.”

Exploring immunotherapy combinations

Despite the potential limitations, recent basket trials involving immunotherapy regimens have been associated with overall response rates, in some subgroups, that exceed 35%.^2,3

In comparison with previous trials, many of which had response rates in the single digits, or no responses at all, these results are, in Dr. McGregor’s words, “very thought provoking.”Most rare GU malignancies fall into one of four categories: bladder cancer variant histology (BCVH), adrenal tumors, penile squamous cell carcinoma (PSCC), and chemotherapy-refractory germ cell tumors (CRGCT). Among these, BCVH has the strongest evidence supporting clinical use of immunotherapy, based on U.S. approval for urothelial histology, according to Dr. McGregor.⁴Data supporting immunotherapy for the remaining disease subtypes are scarce. Although pembrolizumab is approved for patients with solid tumors that exhibit microsatellite instability (MSI), MSI is uncommon among patients with rare GU cancers; estimated incidence rates are less than 10%.⁴

“As such, clinical trials to address this unmet need are imperative,” Dr. McGregor wrote in a recent review article.⁴

According to Dr. McGregor, programmed death ligand 1 (PD-L1) expression in rare GU tumors may be relatively common in some disease subtypes, such as PSCC, which has a PD-L1 expression rate of up to 60%.⁴

But rare GU tumor trials involving a single checkpoint inhibitor have produced limited results, if any.

The largest trial for adrenocortical carcinoma (ACC), for example, which included 50 patients, showed that avelumab resulted in an objective response rate (ORR) of just 6%.⁵

Pembrolizumab was slightly more effective for ACC, based on a trial involving 39 patients, which returned an ORR of 23%, and another trial involving 15 patients that had a 15% ORR.^6,7

Two other trials, which tested single-agent pembrolizumab or durvalumab in patients with CRGCT, resulted in no responses at all, whereas a trial testing pembrolizumab alone for penile squamous cell carcinoma was terminated in 2020, citing poor accrual.^8,9 Still, the durvalumab trial for CRGCT, led by Dr. Necchi, did offer a glimpse at what might be possible with a combination of immunotherapies. Although no responses were observed among 11 patients who received durvalumab alone, an efficacy signal was observed in a second cohort of 11 patients who were given durvalumab in combination with the CTLA-4 inhibitor tremilimumab.⁹

Out of those 11 patients, 1 had a partial response, and another achieved stable disease.

In light of these findings, and more that have been published since then, the clinical trial landscape for rare GU tumors is shifting toward a combination immunotherapy approach, according to Dr. McGregor.⁴

Nivolumab and ipilimumab

Dr. McGregor is leading a phase II trial (NCT03333616) testing a combination of nivolumab and ipilimumab in patients with a variety of advanced rare GU malignancies, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, CRGCT, PSCC, and prostate cancer of variant histology (PCVH).

“When trials are designed, these patients are often forgotten,” Dr. McGregor noted. “We said, let’s do a trial for all rare GU tumors and just sort of assess and look for a signal, and, hopefully, find a signal that we can then take to the next level.”

Along with appropriate disease phenotype, trial eligibility depended upon an ECOG performance status of 0-2 and no prior exposure to checkpoint inhibitors. Treatment-naive patients were allowed. All participants received nivolumab 3 mg/kg and ipilimumab 1 mg/kg IV every 3 weeks for four doses, followed by maintenance nivolumab at a dose of 480 mg every 4 weeks.

Most recent results, published in Cancer, included data from 55 patients, including 19 with BUTCVH, 18 with adrenal tumors, and 18 with other tumors.³ After a median follow-up of 9.9 months, 28 patients (51%) received all four doses of the regimen, 25 of whom received maintenance therapy with a median of four cycles.

Overall, nine patients (16%) responded to therapy, six of whom (67%) maintained their response for at least 9 months. Two responses were complete, and seven were partial. Median progression-free survival was 2.8 months.

Twenty-two patients (39%) had grade 3 or higher treatment-related adverse events, approximately one-quarter (23%) needed high-dose steroids, and a slightly greater proportion (27%) discontinued the regimen because of adverse events. Three patients exhibited grade 5 toxicity, and one patient death was treatment related. A closer look at the efficacy data suggested that one disease subgroup benefited much more than the others. The overall response rate among 19 patients with BUTCVH was 37%, compared with 6% in the other two cohorts.

“A response rate of 37% compares quite favorably to anything we’ve seen to date,” Dr. McGregor said. “It’s remarkable that [this response] was seen across histologies – we saw this in urachal, we saw this in adenocarcinoma – we really saw this across the board. This is very, very, very intriguing data.”

The phase II trial is ongoing at multiple centers across the country, including the Dana-Farber/Harvard Cancer Center, Boston, the University of Texas MD Anderson Cancer Center, Houston, the Moores Cancer Center at University of California Health, San Diego, the Ohio State University Comprehensive Cancer Center, Columbus, and the Winship Cancer Institute of Emory University, Atlanta.

“We accrued this trial in just under 18 months,” Dr. McGregor said. “I think this shows that with a well-designed trial, we can actually study these diseases and improve outcomes in these patients.” According to Dr. McGregor, the current findings deserve further investigation, potentially including expansion of the BUTCVH cohort. Recruitment is ongoing for a fourth cohort involving patients with tumors that exhibit neuroendocrine differentiation.

Cabozantinib and nivolumab with or without ipilimumab

Dr. Apolo is leading a similar basket trial (NCT02496208) that is testing cabozantinib plus nivolumab with or without ipilimumab.

“What we’re doing is using immunotherapy and a targeted therapy that work in standard urothelial carcinoma and renal cell carcinoma,” Dr. Apolo said. “But really, we don’t know the activity in these rare GU tumors. … There’s still so much we don’t understand about what the driving mutations are, and how we can best target them.”

Most recent data, published in Journal of Clinical Oncology, include 122 patients with metastatic GU tumors, including urothelial carcinoma, clear cell renal cell carcinoma, bladder adenocarcinoma, and other rare GU cancers.²

Among these patients, 54 were in the phase I dose-finding cohort (eight escalating doses) and 64 were in the dose-expansion cohorts.

After a median follow-up of 40.4 months, 64 patients received the dual combination, whereas 56 received the triplet regimen. The ORR for 108 evaluable patients was 38%, including 12 complete responses (11.1%) and 29 partial responses (26.9%). The largest disease cohort, for urothelial carcinoma, included 33 patients and was associated with an ORR of 42.4%, with a complete response rate of 21.2%. Objective response rate was highest for squamous bladder cancer (85.7%; n = 7), followed by clear cell renal carcinoma (62.5%; n = 16), renal medullary cancer (50%; n = 2), penile cancer (44.4%; n = 9), small cell bladder cancer (33.1%; n = 3), bladder adenocarcinoma (20%; n = 15), and prostate cancer (11.1%; n = 9). No responses were seen in six patients with germ cell tumors.

Adding ipilimumab appeared to have a minimal impact on toxicity. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 84% of patients in the dual combination group, compared with 80% receiving the triplet regimen. Most common AEs were hypophosphatemia (16-25%), lipase elevation (20%), fatigue (18-20%), ALT elevation (5-14%), AST elevation (9-11%), diarrhea (9-11%), and thromboembolic event (4-11%). One patient taking the triplet regimen had grade 5 pneumonitis.

These positive phase I results have paved the way for the phase II ICONIC trial (NCT03866382), a national study available through the Alliance Cooperative Group. The trial is currently recruiting, with an estimated enrollment of 224 patients with rare GU tumors.

The ICONIC trial is just one of several studies that Dr. Apolo is conducting for patients with rare GU cancer. “I have several bladder cancer trials where I’m accepting rare GU tumors to enroll,” she said, noting that efficacy signals in these exploratory cohorts may be pursued with expansion studies like ICONIC.

This inclusive strategy is uncovering promising new treatments for some rare GU malignancies, but the rarest of the rare tumor types remain challenging to study, Dr. Apolo said, because very small sample sizes can preclude significant data. “Although we do have the referral base at the NCI, we still get a small number of a lot of rare tumors,” Dr. Apolo said. “What I end up having, a lot of time, are small subsets of rare tumors – I’ll have 4 of one kind, 10 of another.” This situation means that sometimes, time and resources must be focused where they are needed most.

“Sometimes I actually have to decide which are the more common rare tumors so I can study them in a larger cohort,” Dr. Apolo said. “It can have more clinical impact within the community of that rare tumor.” Dr. Apolo described the inherent conflict involved in this decision, but also, its ultimate necessity.

“It’s what you don’t want to do, but you end up doing,” she said. “Because you want to be inclusive and include the rare, rare tumor, but sometimes you just can’t get enough numbers to see if there’s actually a difference [in efficacy]. If it doesn’t work in one patient, does that mean it doesn’t work at all? You need more numbers to really test the efficacy of therapy.”

From clinical trials to clinical practice

To accrue the number of patients needed for practice-altering findings, both Dr. McGregor and Dr. Apolo emphasized the importance of institutional support and collaborative trial designs.

“The FDA is a great ally,” Dr. McGregor said. “They’re acutely aware of the challenges facing patients with rare malignancies – not just GU malignancies. They’re continuing to evaluate the best way to move these drugs forward for those patients. … They’re constantly working with investigators, with industry, looking at data and trying to determine at what threshold these will be practice-changing studies.”

Dr. McGregor suggested that larger trials could shift national guideline recommendations toward combination immunotherapies for patients with rare GU tumors, which would lead to inclusion in compendia, and from there, broader clinical usage.

“At end of the day, luckily, we’re not dealing with drugs that aren’t available,” Dr. McGregor said. “These are drugs that are readily available, approved by the FDA in other settings.”

Dr. Apolo also described strong support from the NCI.

“The NCI really encourages the conduction and enrollment of these rare GU tumor trials, because they understand that the NCI is a really good place to study these rare tumors,” she said. “We have unique resources that make it feasible to conduct some of these trials.”

Dr. Apolo also praised the Alliance Cooperative Group for helping expand patient access to rare GU tumor trials.

“[The Alliance Cooperative Group] makes trials available at community centers across the country,” Dr. Apolo said. “Patients don’t have to travel to the NCI, and they can get the same therapies.”

Still, Dr. Apolo recommended that, when possible, clinicians refer patients with newly diagnosed, rare GU tumors to centers that see a higher number of such cases.

“It’s hard to keep up with all the different treatments that are available right now for different cancers,” Dr. Apolo said. “And sometimes for the rare tumors, there may be great opportunities within a clinical trial that a cancer center may have available that may not be available locally in the community.”

For patients who would like to learn more about rare bladder cancers, Dr. Apolo recommended a visit to the Bladder Cancer Advocacy Network (BCAN) website (bcan.org).

“I’m a big fan of these patient-centered advocacy networks,” Dr. Apolo said. “I like BCAN a lot. It’s a patient-run organization for patients with bladder cancer. With them, I have done a couple of webinars for rare bladder tumors that Ive had some patients tell me are very helpful. They’re a terrific organization that really provides not only emotional support but also educational support for patients that have a diagnosis of bladder cancer and now, rare bladder tumors.” Dr. Spiess offered similar advice for clinicians managing patients with rare GU tumors. He emphasized the key role played by patient advocacy groups, and recommended referral to institutions specializing in specific GU tumor types. For example, he recommended that patients with penile cancer be treated at Moffitt (Tampa) or MD Anderson (Houston), as these centers have the greatest relevant experience. Dr. McGregor disclosed relationships with Bayer, Astellas, Nektar, and others. Dr. Apolo and Dr. Spiess disclosed no conflicts of interest.
 

References

1.Necchi A et al. Eur Urol. 2021 June;79:S929-30.

2.Apolo AB et al. J Clin Oncol. 2021;39(6_suppl):3.

3.McGregor BA et al. Cancer. 2021 Mar 15;127(6):840-9.

4.McGregor BA and Sonpavde GP. Eur Urol Focus. 2020;6(1):14-16.5.Le Tourneau C et al. J Immunother Cancer. 2018 Oct 22;6(1):111.6.Naing A et al. J Immunother Cancer. 2020;8(1).

7.Raj N et al. J Clin Oncol. 2020;38(1):71-80.

8.Adra N et al. Ann Oncol. 2018;29(1):209-14.

9.Necchi A et al. Eur Urol. 2019;75(1):201-3.

In a field of poor outcomes, few standards of care, and small populations of patients scattered across the world, investigators studying rare genitourinary (GU) cancers are gaining ground through international collaboration and novel trial design.

Fundamental clinical questions in the area remain unanswered, including the value of conventional treatments, such as chemotherapy and surgery, vs. emerging immunotherapy combinations.

Managing patients with rare GU cancers presents a variety of challenges, as does conducting research in the field, according to Philippe E. Spiess, MD, MS, FACS, assistant chief of surgical services and senior member in the department of GU oncology at Moffitt Cancer Center, Tampa.

“Unfortunately, there are limited resources for patients – from an education, from a patient advocacy, and ultimately also from a research standpoint,” Dr. Spiess said in an interview, noting difficulties in attaining funding and reaching meaningful endpoints.

The Global Society of Rare Genitourinary Tumors

Last year Dr. Spiess teamed up with Andrea Necchi, MD, of the department of medical oncology at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, to found the Global Society of Rare Genitourinary Tumors (GSRGT), the first organization of its kind.

“We’ve formally established a society and gotten some of the world leaders [in the field] … to work with us in developing educational tools and patient advocacy efforts to really promote and improve the care of patients impacted with rare cancers,” Dr. Spiess said.

He went on to highlight the truly global makeup of GSRGT, which includes members from leading centers in North America, South America, Europe, and India, and described it as a “grass-roots” organization that he and Dr. Necchi privately funded without financial backing from pharmaceutical companies.

The first GSRGT summit took place in 2020; it focused on penile and testis cancers and was attended by more than 350 participants. The second summit, planned for March 2022, in a virtual format, will focus on rare kidney cancers and upper tract cancers.

“We’ll definitely be having a lot of important conversations about important unmet needs, and some of the important clinical trials that patients and clinicians should be aware of,” Dr. Spiess said.

Dr. Spiess is currently involved in the International Penile Advanced Cancer Trial(InPACT), which is aiming to enroll 200 patients with squamous cell carcinoma of the penis. The randomized study will compare outcomes across patients treated with standard surgery alone, neoadjuvant chemotherapy plus surgery, and neoadjuvant chemoradiotherapy plus surgery.

“I think this is going to be a landmark study because it’s going to give really baseline high-quality data on the effectiveness of these therapies,” Dr. Spiess said.

Results are expected in 2024.

Basket trials open doors for patients in need

Other investigators are testing immunotherapy combinations in patients with rare GU tumors via nonrandomized basket trials, which widen inclusion criteria and improve local availability.

According to Bradley McGregor, MD, clinical director of the Lank Center for GU Oncology at the Dana-Farber Cancer Institute in Boston, early results from these trials are promising, both in terms of therapeutic efficacy and the approach itself.

“Patients [with rare GU tumors] would come to us saying, ‘Well, what can we do? What trial?’,” Dr. McGregor said. “But really, there was no trial to get them on.”Basket trials are therefore needed, he said, as they accelerate progress in the field and help meet patient needs.

“For some of these relatively rare diseases … there is no standard of care,” Dr. McGregor said. “And low incidence makes it challenging to conduct a dedicated clinical trial. Those patients are left with minimal therapeutic options. … We look to provide care for that unmet need.”Andrea B. Apolo, MD, described similar experiences as head of the bladder cancer section of the GU malignancies branch of the National Cancer Institute (NCI), Bethesda, Md.

“I’ve been at the NCI for the past 10 years and I’ve gotten a lot of referrals for rare tumors,” Dr. Apolo said. “[These patients] have tried all available standard of care options, and therefore are often looking for clinical trials and new drugs – any kind of therapy that may be effective for their disease.”This call for help, along with a growing scientific curiosity, motivated Dr. Apolo to design trials that would include patients who had nowhere else to go.

“I became very interested in … understanding more about the mechanism of tumorigenesis and understanding rare tumors, biologically, within the lab,” she said, “but also clinically, in terms of finding more effective therapies.”

Both Dr. McGregor and Dr. Apolo are currently conducting basket trials for patients with rare GU tumors. While Dr. McGregor is testing a combination of PD-1 inhibitor nivolumab and CTLA-4 inhibitor ipilimumab, Dr. Apolo is exploring the benefit of cabozantinib, a targeted therapy, given with either nivolumab or nivolumab plus ipilimumab.

When asked about these trials, Dr. Spiess said that “basket trials are important because they may give us an understanding of some potentially useful therapies or combinations;” however, he also pointed out their limitations, noting that they may inaccurately characterize the efficacy of given therapies over a broad array of disease entities even if they are of similar histology. As an example, he noted “very different” genomic profiles across squamous cell carcinomas of the pelvis depending on exact anatomical location, suggesting that these differences may affect responses to therapy, citing a recent study in European Urology that he conducted with Dr. Necchi.¹

“[Basket trials] are probably not going to be the be-all-end-all,” Dr. Spiess said. “It really requires a global initiative to do these types of studies, which the Global Society of Rare Genitourinary Tumors will allow.”

Exploring immunotherapy combinations

Despite the potential limitations, recent basket trials involving immunotherapy regimens have been associated with overall response rates, in some subgroups, that exceed 35%.^2,3

In comparison with previous trials, many of which had response rates in the single digits, or no responses at all, these results are, in Dr. McGregor’s words, “very thought provoking.”Most rare GU malignancies fall into one of four categories: bladder cancer variant histology (BCVH), adrenal tumors, penile squamous cell carcinoma (PSCC), and chemotherapy-refractory germ cell tumors (CRGCT). Among these, BCVH has the strongest evidence supporting clinical use of immunotherapy, based on U.S. approval for urothelial histology, according to Dr. McGregor.⁴Data supporting immunotherapy for the remaining disease subtypes are scarce. Although pembrolizumab is approved for patients with solid tumors that exhibit microsatellite instability (MSI), MSI is uncommon among patients with rare GU cancers; estimated incidence rates are less than 10%.⁴

“As such, clinical trials to address this unmet need are imperative,” Dr. McGregor wrote in a recent review article.⁴

According to Dr. McGregor, programmed death ligand 1 (PD-L1) expression in rare GU tumors may be relatively common in some disease subtypes, such as PSCC, which has a PD-L1 expression rate of up to 60%.⁴

But rare GU tumor trials involving a single checkpoint inhibitor have produced limited results, if any.

The largest trial for adrenocortical carcinoma (ACC), for example, which included 50 patients, showed that avelumab resulted in an objective response rate (ORR) of just 6%.⁵

Pembrolizumab was slightly more effective for ACC, based on a trial involving 39 patients, which returned an ORR of 23%, and another trial involving 15 patients that had a 15% ORR.^6,7

Two other trials, which tested single-agent pembrolizumab or durvalumab in patients with CRGCT, resulted in no responses at all, whereas a trial testing pembrolizumab alone for penile squamous cell carcinoma was terminated in 2020, citing poor accrual.^8,9 Still, the durvalumab trial for CRGCT, led by Dr. Necchi, did offer a glimpse at what might be possible with a combination of immunotherapies. Although no responses were observed among 11 patients who received durvalumab alone, an efficacy signal was observed in a second cohort of 11 patients who were given durvalumab in combination with the CTLA-4 inhibitor tremilimumab.⁹

Out of those 11 patients, 1 had a partial response, and another achieved stable disease.

In light of these findings, and more that have been published since then, the clinical trial landscape for rare GU tumors is shifting toward a combination immunotherapy approach, according to Dr. McGregor.⁴

Nivolumab and ipilimumab

Dr. McGregor is leading a phase II trial (NCT03333616) testing a combination of nivolumab and ipilimumab in patients with a variety of advanced rare GU malignancies, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, CRGCT, PSCC, and prostate cancer of variant histology (PCVH).

“When trials are designed, these patients are often forgotten,” Dr. McGregor noted. “We said, let’s do a trial for all rare GU tumors and just sort of assess and look for a signal, and, hopefully, find a signal that we can then take to the next level.”

Along with appropriate disease phenotype, trial eligibility depended upon an ECOG performance status of 0-2 and no prior exposure to checkpoint inhibitors. Treatment-naive patients were allowed. All participants received nivolumab 3 mg/kg and ipilimumab 1 mg/kg IV every 3 weeks for four doses, followed by maintenance nivolumab at a dose of 480 mg every 4 weeks.

Most recent results, published in Cancer, included data from 55 patients, including 19 with BUTCVH, 18 with adrenal tumors, and 18 with other tumors.³ After a median follow-up of 9.9 months, 28 patients (51%) received all four doses of the regimen, 25 of whom received maintenance therapy with a median of four cycles.

Overall, nine patients (16%) responded to therapy, six of whom (67%) maintained their response for at least 9 months. Two responses were complete, and seven were partial. Median progression-free survival was 2.8 months.

Twenty-two patients (39%) had grade 3 or higher treatment-related adverse events, approximately one-quarter (23%) needed high-dose steroids, and a slightly greater proportion (27%) discontinued the regimen because of adverse events. Three patients exhibited grade 5 toxicity, and one patient death was treatment related. A closer look at the efficacy data suggested that one disease subgroup benefited much more than the others. The overall response rate among 19 patients with BUTCVH was 37%, compared with 6% in the other two cohorts.

“A response rate of 37% compares quite favorably to anything we’ve seen to date,” Dr. McGregor said. “It’s remarkable that [this response] was seen across histologies – we saw this in urachal, we saw this in adenocarcinoma – we really saw this across the board. This is very, very, very intriguing data.”

The phase II trial is ongoing at multiple centers across the country, including the Dana-Farber/Harvard Cancer Center, Boston, the University of Texas MD Anderson Cancer Center, Houston, the Moores Cancer Center at University of California Health, San Diego, the Ohio State University Comprehensive Cancer Center, Columbus, and the Winship Cancer Institute of Emory University, Atlanta.

“We accrued this trial in just under 18 months,” Dr. McGregor said. “I think this shows that with a well-designed trial, we can actually study these diseases and improve outcomes in these patients.” According to Dr. McGregor, the current findings deserve further investigation, potentially including expansion of the BUTCVH cohort. Recruitment is ongoing for a fourth cohort involving patients with tumors that exhibit neuroendocrine differentiation.

Cabozantinib and nivolumab with or without ipilimumab

Dr. Apolo is leading a similar basket trial (NCT02496208) that is testing cabozantinib plus nivolumab with or without ipilimumab.

“What we’re doing is using immunotherapy and a targeted therapy that work in standard urothelial carcinoma and renal cell carcinoma,” Dr. Apolo said. “But really, we don’t know the activity in these rare GU tumors. … There’s still so much we don’t understand about what the driving mutations are, and how we can best target them.”

Most recent data, published in Journal of Clinical Oncology, include 122 patients with metastatic GU tumors, including urothelial carcinoma, clear cell renal cell carcinoma, bladder adenocarcinoma, and other rare GU cancers.²

Among these patients, 54 were in the phase I dose-finding cohort (eight escalating doses) and 64 were in the dose-expansion cohorts.

After a median follow-up of 40.4 months, 64 patients received the dual combination, whereas 56 received the triplet regimen. The ORR for 108 evaluable patients was 38%, including 12 complete responses (11.1%) and 29 partial responses (26.9%). The largest disease cohort, for urothelial carcinoma, included 33 patients and was associated with an ORR of 42.4%, with a complete response rate of 21.2%. Objective response rate was highest for squamous bladder cancer (85.7%; n = 7), followed by clear cell renal carcinoma (62.5%; n = 16), renal medullary cancer (50%; n = 2), penile cancer (44.4%; n = 9), small cell bladder cancer (33.1%; n = 3), bladder adenocarcinoma (20%; n = 15), and prostate cancer (11.1%; n = 9). No responses were seen in six patients with germ cell tumors.

Adding ipilimumab appeared to have a minimal impact on toxicity. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 84% of patients in the dual combination group, compared with 80% receiving the triplet regimen. Most common AEs were hypophosphatemia (16-25%), lipase elevation (20%), fatigue (18-20%), ALT elevation (5-14%), AST elevation (9-11%), diarrhea (9-11%), and thromboembolic event (4-11%). One patient taking the triplet regimen had grade 5 pneumonitis.

These positive phase I results have paved the way for the phase II ICONIC trial (NCT03866382), a national study available through the Alliance Cooperative Group. The trial is currently recruiting, with an estimated enrollment of 224 patients with rare GU tumors.

The ICONIC trial is just one of several studies that Dr. Apolo is conducting for patients with rare GU cancer. “I have several bladder cancer trials where I’m accepting rare GU tumors to enroll,” she said, noting that efficacy signals in these exploratory cohorts may be pursued with expansion studies like ICONIC.

This inclusive strategy is uncovering promising new treatments for some rare GU malignancies, but the rarest of the rare tumor types remain challenging to study, Dr. Apolo said, because very small sample sizes can preclude significant data. “Although we do have the referral base at the NCI, we still get a small number of a lot of rare tumors,” Dr. Apolo said. “What I end up having, a lot of time, are small subsets of rare tumors – I’ll have 4 of one kind, 10 of another.” This situation means that sometimes, time and resources must be focused where they are needed most.

“Sometimes I actually have to decide which are the more common rare tumors so I can study them in a larger cohort,” Dr. Apolo said. “It can have more clinical impact within the community of that rare tumor.” Dr. Apolo described the inherent conflict involved in this decision, but also, its ultimate necessity.

“It’s what you don’t want to do, but you end up doing,” she said. “Because you want to be inclusive and include the rare, rare tumor, but sometimes you just can’t get enough numbers to see if there’s actually a difference [in efficacy]. If it doesn’t work in one patient, does that mean it doesn’t work at all? You need more numbers to really test the efficacy of therapy.”

From clinical trials to clinical practice

To accrue the number of patients needed for practice-altering findings, both Dr. McGregor and Dr. Apolo emphasized the importance of institutional support and collaborative trial designs.

“The FDA is a great ally,” Dr. McGregor said. “They’re acutely aware of the challenges facing patients with rare malignancies – not just GU malignancies. They’re continuing to evaluate the best way to move these drugs forward for those patients. … They’re constantly working with investigators, with industry, looking at data and trying to determine at what threshold these will be practice-changing studies.”

Dr. McGregor suggested that larger trials could shift national guideline recommendations toward combination immunotherapies for patients with rare GU tumors, which would lead to inclusion in compendia, and from there, broader clinical usage.

“At end of the day, luckily, we’re not dealing with drugs that aren’t available,” Dr. McGregor said. “These are drugs that are readily available, approved by the FDA in other settings.”

Dr. Apolo also described strong support from the NCI.

“The NCI really encourages the conduction and enrollment of these rare GU tumor trials, because they understand that the NCI is a really good place to study these rare tumors,” she said. “We have unique resources that make it feasible to conduct some of these trials.”

Dr. Apolo also praised the Alliance Cooperative Group for helping expand patient access to rare GU tumor trials.

“[The Alliance Cooperative Group] makes trials available at community centers across the country,” Dr. Apolo said. “Patients don’t have to travel to the NCI, and they can get the same therapies.”

Still, Dr. Apolo recommended that, when possible, clinicians refer patients with newly diagnosed, rare GU tumors to centers that see a higher number of such cases.

“It’s hard to keep up with all the different treatments that are available right now for different cancers,” Dr. Apolo said. “And sometimes for the rare tumors, there may be great opportunities within a clinical trial that a cancer center may have available that may not be available locally in the community.”

For patients who would like to learn more about rare bladder cancers, Dr. Apolo recommended a visit to the Bladder Cancer Advocacy Network (BCAN) website (bcan.org).

“I’m a big fan of these patient-centered advocacy networks,” Dr. Apolo said. “I like BCAN a lot. It’s a patient-run organization for patients with bladder cancer. With them, I have done a couple of webinars for rare bladder tumors that Ive had some patients tell me are very helpful. They’re a terrific organization that really provides not only emotional support but also educational support for patients that have a diagnosis of bladder cancer and now, rare bladder tumors.” Dr. Spiess offered similar advice for clinicians managing patients with rare GU tumors. He emphasized the key role played by patient advocacy groups, and recommended referral to institutions specializing in specific GU tumor types. For example, he recommended that patients with penile cancer be treated at Moffitt (Tampa) or MD Anderson (Houston), as these centers have the greatest relevant experience. Dr. McGregor disclosed relationships with Bayer, Astellas, Nektar, and others. Dr. Apolo and Dr. Spiess disclosed no conflicts of interest.
 

References

1.Necchi A et al. Eur Urol. 2021 June;79:S929-30.

2.Apolo AB et al. J Clin Oncol. 2021;39(6_suppl):3.

3.McGregor BA et al. Cancer. 2021 Mar 15;127(6):840-9.

4.McGregor BA and Sonpavde GP. Eur Urol Focus. 2020;6(1):14-16.5.Le Tourneau C et al. J Immunother Cancer. 2018 Oct 22;6(1):111.6.Naing A et al. J Immunother Cancer. 2020;8(1).

7.Raj N et al. J Clin Oncol. 2020;38(1):71-80.

8.Adra N et al. Ann Oncol. 2018;29(1):209-14.

9.Necchi A et al. Eur Urol. 2019;75(1):201-3.

In a field of poor outcomes, few standards of care, and small populations of patients scattered across the world, investigators studying rare genitourinary (GU) cancers are gaining ground through international collaboration and novel trial design.

Fundamental clinical questions in the area remain unanswered, including the value of conventional treatments, such as chemotherapy and surgery, vs. emerging immunotherapy combinations.

Managing patients with rare GU cancers presents a variety of challenges, as does conducting research in the field, according to Philippe E. Spiess, MD, MS, FACS, assistant chief of surgical services and senior member in the department of GU oncology at Moffitt Cancer Center, Tampa.

“Unfortunately, there are limited resources for patients – from an education, from a patient advocacy, and ultimately also from a research standpoint,” Dr. Spiess said in an interview, noting difficulties in attaining funding and reaching meaningful endpoints.

The Global Society of Rare Genitourinary Tumors

Last year Dr. Spiess teamed up with Andrea Necchi, MD, of the department of medical oncology at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, to found the Global Society of Rare Genitourinary Tumors (GSRGT), the first organization of its kind.

“We’ve formally established a society and gotten some of the world leaders [in the field] … to work with us in developing educational tools and patient advocacy efforts to really promote and improve the care of patients impacted with rare cancers,” Dr. Spiess said.

He went on to highlight the truly global makeup of GSRGT, which includes members from leading centers in North America, South America, Europe, and India, and described it as a “grass-roots” organization that he and Dr. Necchi privately funded without financial backing from pharmaceutical companies.

The first GSRGT summit took place in 2020; it focused on penile and testis cancers and was attended by more than 350 participants. The second summit, planned for March 2022, in a virtual format, will focus on rare kidney cancers and upper tract cancers.

“We’ll definitely be having a lot of important conversations about important unmet needs, and some of the important clinical trials that patients and clinicians should be aware of,” Dr. Spiess said.

Dr. Spiess is currently involved in the International Penile Advanced Cancer Trial(InPACT), which is aiming to enroll 200 patients with squamous cell carcinoma of the penis. The randomized study will compare outcomes across patients treated with standard surgery alone, neoadjuvant chemotherapy plus surgery, and neoadjuvant chemoradiotherapy plus surgery.

“I think this is going to be a landmark study because it’s going to give really baseline high-quality data on the effectiveness of these therapies,” Dr. Spiess said.

Results are expected in 2024.

Basket trials open doors for patients in need

Other investigators are testing immunotherapy combinations in patients with rare GU tumors via nonrandomized basket trials, which widen inclusion criteria and improve local availability.

According to Bradley McGregor, MD, clinical director of the Lank Center for GU Oncology at the Dana-Farber Cancer Institute in Boston, early results from these trials are promising, both in terms of therapeutic efficacy and the approach itself.

“Patients [with rare GU tumors] would come to us saying, ‘Well, what can we do? What trial?’,” Dr. McGregor said. “But really, there was no trial to get them on.”Basket trials are therefore needed, he said, as they accelerate progress in the field and help meet patient needs.

“For some of these relatively rare diseases … there is no standard of care,” Dr. McGregor said. “And low incidence makes it challenging to conduct a dedicated clinical trial. Those patients are left with minimal therapeutic options. … We look to provide care for that unmet need.”Andrea B. Apolo, MD, described similar experiences as head of the bladder cancer section of the GU malignancies branch of the National Cancer Institute (NCI), Bethesda, Md.

“I’ve been at the NCI for the past 10 years and I’ve gotten a lot of referrals for rare tumors,” Dr. Apolo said. “[These patients] have tried all available standard of care options, and therefore are often looking for clinical trials and new drugs – any kind of therapy that may be effective for their disease.”This call for help, along with a growing scientific curiosity, motivated Dr. Apolo to design trials that would include patients who had nowhere else to go.

“I became very interested in … understanding more about the mechanism of tumorigenesis and understanding rare tumors, biologically, within the lab,” she said, “but also clinically, in terms of finding more effective therapies.”

Both Dr. McGregor and Dr. Apolo are currently conducting basket trials for patients with rare GU tumors. While Dr. McGregor is testing a combination of PD-1 inhibitor nivolumab and CTLA-4 inhibitor ipilimumab, Dr. Apolo is exploring the benefit of cabozantinib, a targeted therapy, given with either nivolumab or nivolumab plus ipilimumab.

When asked about these trials, Dr. Spiess said that “basket trials are important because they may give us an understanding of some potentially useful therapies or combinations;” however, he also pointed out their limitations, noting that they may inaccurately characterize the efficacy of given therapies over a broad array of disease entities even if they are of similar histology. As an example, he noted “very different” genomic profiles across squamous cell carcinomas of the pelvis depending on exact anatomical location, suggesting that these differences may affect responses to therapy, citing a recent study in European Urology that he conducted with Dr. Necchi.¹

“[Basket trials] are probably not going to be the be-all-end-all,” Dr. Spiess said. “It really requires a global initiative to do these types of studies, which the Global Society of Rare Genitourinary Tumors will allow.”

Exploring immunotherapy combinations

Despite the potential limitations, recent basket trials involving immunotherapy regimens have been associated with overall response rates, in some subgroups, that exceed 35%.^2,3

In comparison with previous trials, many of which had response rates in the single digits, or no responses at all, these results are, in Dr. McGregor’s words, “very thought provoking.”Most rare GU malignancies fall into one of four categories: bladder cancer variant histology (BCVH), adrenal tumors, penile squamous cell carcinoma (PSCC), and chemotherapy-refractory germ cell tumors (CRGCT). Among these, BCVH has the strongest evidence supporting clinical use of immunotherapy, based on U.S. approval for urothelial histology, according to Dr. McGregor.⁴Data supporting immunotherapy for the remaining disease subtypes are scarce. Although pembrolizumab is approved for patients with solid tumors that exhibit microsatellite instability (MSI), MSI is uncommon among patients with rare GU cancers; estimated incidence rates are less than 10%.⁴

“As such, clinical trials to address this unmet need are imperative,” Dr. McGregor wrote in a recent review article.⁴

According to Dr. McGregor, programmed death ligand 1 (PD-L1) expression in rare GU tumors may be relatively common in some disease subtypes, such as PSCC, which has a PD-L1 expression rate of up to 60%.⁴

But rare GU tumor trials involving a single checkpoint inhibitor have produced limited results, if any.

The largest trial for adrenocortical carcinoma (ACC), for example, which included 50 patients, showed that avelumab resulted in an objective response rate (ORR) of just 6%.⁵

Pembrolizumab was slightly more effective for ACC, based on a trial involving 39 patients, which returned an ORR of 23%, and another trial involving 15 patients that had a 15% ORR.^6,7

Two other trials, which tested single-agent pembrolizumab or durvalumab in patients with CRGCT, resulted in no responses at all, whereas a trial testing pembrolizumab alone for penile squamous cell carcinoma was terminated in 2020, citing poor accrual.^8,9 Still, the durvalumab trial for CRGCT, led by Dr. Necchi, did offer a glimpse at what might be possible with a combination of immunotherapies. Although no responses were observed among 11 patients who received durvalumab alone, an efficacy signal was observed in a second cohort of 11 patients who were given durvalumab in combination with the CTLA-4 inhibitor tremilimumab.⁹

Out of those 11 patients, 1 had a partial response, and another achieved stable disease.

In light of these findings, and more that have been published since then, the clinical trial landscape for rare GU tumors is shifting toward a combination immunotherapy approach, according to Dr. McGregor.⁴

Nivolumab and ipilimumab

Dr. McGregor is leading a phase II trial (NCT03333616) testing a combination of nivolumab and ipilimumab in patients with a variety of advanced rare GU malignancies, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, CRGCT, PSCC, and prostate cancer of variant histology (PCVH).

“When trials are designed, these patients are often forgotten,” Dr. McGregor noted. “We said, let’s do a trial for all rare GU tumors and just sort of assess and look for a signal, and, hopefully, find a signal that we can then take to the next level.”

Along with appropriate disease phenotype, trial eligibility depended upon an ECOG performance status of 0-2 and no prior exposure to checkpoint inhibitors. Treatment-naive patients were allowed. All participants received nivolumab 3 mg/kg and ipilimumab 1 mg/kg IV every 3 weeks for four doses, followed by maintenance nivolumab at a dose of 480 mg every 4 weeks.

Most recent results, published in Cancer, included data from 55 patients, including 19 with BUTCVH, 18 with adrenal tumors, and 18 with other tumors.³ After a median follow-up of 9.9 months, 28 patients (51%) received all four doses of the regimen, 25 of whom received maintenance therapy with a median of four cycles.

Overall, nine patients (16%) responded to therapy, six of whom (67%) maintained their response for at least 9 months. Two responses were complete, and seven were partial. Median progression-free survival was 2.8 months.

Twenty-two patients (39%) had grade 3 or higher treatment-related adverse events, approximately one-quarter (23%) needed high-dose steroids, and a slightly greater proportion (27%) discontinued the regimen because of adverse events. Three patients exhibited grade 5 toxicity, and one patient death was treatment related. A closer look at the efficacy data suggested that one disease subgroup benefited much more than the others. The overall response rate among 19 patients with BUTCVH was 37%, compared with 6% in the other two cohorts.

“A response rate of 37% compares quite favorably to anything we’ve seen to date,” Dr. McGregor said. “It’s remarkable that [this response] was seen across histologies – we saw this in urachal, we saw this in adenocarcinoma – we really saw this across the board. This is very, very, very intriguing data.”

The phase II trial is ongoing at multiple centers across the country, including the Dana-Farber/Harvard Cancer Center, Boston, the University of Texas MD Anderson Cancer Center, Houston, the Moores Cancer Center at University of California Health, San Diego, the Ohio State University Comprehensive Cancer Center, Columbus, and the Winship Cancer Institute of Emory University, Atlanta.

“We accrued this trial in just under 18 months,” Dr. McGregor said. “I think this shows that with a well-designed trial, we can actually study these diseases and improve outcomes in these patients.” According to Dr. McGregor, the current findings deserve further investigation, potentially including expansion of the BUTCVH cohort. Recruitment is ongoing for a fourth cohort involving patients with tumors that exhibit neuroendocrine differentiation.

Cabozantinib and nivolumab with or without ipilimumab

Dr. Apolo is leading a similar basket trial (NCT02496208) that is testing cabozantinib plus nivolumab with or without ipilimumab.

“What we’re doing is using immunotherapy and a targeted therapy that work in standard urothelial carcinoma and renal cell carcinoma,” Dr. Apolo said. “But really, we don’t know the activity in these rare GU tumors. … There’s still so much we don’t understand about what the driving mutations are, and how we can best target them.”

Most recent data, published in Journal of Clinical Oncology, include 122 patients with metastatic GU tumors, including urothelial carcinoma, clear cell renal cell carcinoma, bladder adenocarcinoma, and other rare GU cancers.²

Among these patients, 54 were in the phase I dose-finding cohort (eight escalating doses) and 64 were in the dose-expansion cohorts.

After a median follow-up of 40.4 months, 64 patients received the dual combination, whereas 56 received the triplet regimen. The ORR for 108 evaluable patients was 38%, including 12 complete responses (11.1%) and 29 partial responses (26.9%). The largest disease cohort, for urothelial carcinoma, included 33 patients and was associated with an ORR of 42.4%, with a complete response rate of 21.2%. Objective response rate was highest for squamous bladder cancer (85.7%; n = 7), followed by clear cell renal carcinoma (62.5%; n = 16), renal medullary cancer (50%; n = 2), penile cancer (44.4%; n = 9), small cell bladder cancer (33.1%; n = 3), bladder adenocarcinoma (20%; n = 15), and prostate cancer (11.1%; n = 9). No responses were seen in six patients with germ cell tumors.

Adding ipilimumab appeared to have a minimal impact on toxicity. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 84% of patients in the dual combination group, compared with 80% receiving the triplet regimen. Most common AEs were hypophosphatemia (16-25%), lipase elevation (20%), fatigue (18-20%), ALT elevation (5-14%), AST elevation (9-11%), diarrhea (9-11%), and thromboembolic event (4-11%). One patient taking the triplet regimen had grade 5 pneumonitis.

These positive phase I results have paved the way for the phase II ICONIC trial (NCT03866382), a national study available through the Alliance Cooperative Group. The trial is currently recruiting, with an estimated enrollment of 224 patients with rare GU tumors.

The ICONIC trial is just one of several studies that Dr. Apolo is conducting for patients with rare GU cancer. “I have several bladder cancer trials where I’m accepting rare GU tumors to enroll,” she said, noting that efficacy signals in these exploratory cohorts may be pursued with expansion studies like ICONIC.

This inclusive strategy is uncovering promising new treatments for some rare GU malignancies, but the rarest of the rare tumor types remain challenging to study, Dr. Apolo said, because very small sample sizes can preclude significant data. “Although we do have the referral base at the NCI, we still get a small number of a lot of rare tumors,” Dr. Apolo said. “What I end up having, a lot of time, are small subsets of rare tumors – I’ll have 4 of one kind, 10 of another.” This situation means that sometimes, time and resources must be focused where they are needed most.

“Sometimes I actually have to decide which are the more common rare tumors so I can study them in a larger cohort,” Dr. Apolo said. “It can have more clinical impact within the community of that rare tumor.” Dr. Apolo described the inherent conflict involved in this decision, but also, its ultimate necessity.

“It’s what you don’t want to do, but you end up doing,” she said. “Because you want to be inclusive and include the rare, rare tumor, but sometimes you just can’t get enough numbers to see if there’s actually a difference [in efficacy]. If it doesn’t work in one patient, does that mean it doesn’t work at all? You need more numbers to really test the efficacy of therapy.”

From clinical trials to clinical practice

To accrue the number of patients needed for practice-altering findings, both Dr. McGregor and Dr. Apolo emphasized the importance of institutional support and collaborative trial designs.

“The FDA is a great ally,” Dr. McGregor said. “They’re acutely aware of the challenges facing patients with rare malignancies – not just GU malignancies. They’re continuing to evaluate the best way to move these drugs forward for those patients. … They’re constantly working with investigators, with industry, looking at data and trying to determine at what threshold these will be practice-changing studies.”

Dr. McGregor suggested that larger trials could shift national guideline recommendations toward combination immunotherapies for patients with rare GU tumors, which would lead to inclusion in compendia, and from there, broader clinical usage.

“At end of the day, luckily, we’re not dealing with drugs that aren’t available,” Dr. McGregor said. “These are drugs that are readily available, approved by the FDA in other settings.”

Dr. Apolo also described strong support from the NCI.

“The NCI really encourages the conduction and enrollment of these rare GU tumor trials, because they understand that the NCI is a really good place to study these rare tumors,” she said. “We have unique resources that make it feasible to conduct some of these trials.”

Dr. Apolo also praised the Alliance Cooperative Group for helping expand patient access to rare GU tumor trials.

“[The Alliance Cooperative Group] makes trials available at community centers across the country,” Dr. Apolo said. “Patients don’t have to travel to the NCI, and they can get the same therapies.”

Still, Dr. Apolo recommended that, when possible, clinicians refer patients with newly diagnosed, rare GU tumors to centers that see a higher number of such cases.

“It’s hard to keep up with all the different treatments that are available right now for different cancers,” Dr. Apolo said. “And sometimes for the rare tumors, there may be great opportunities within a clinical trial that a cancer center may have available that may not be available locally in the community.”

For patients who would like to learn more about rare bladder cancers, Dr. Apolo recommended a visit to the Bladder Cancer Advocacy Network (BCAN) website (bcan.org).

“I’m a big fan of these patient-centered advocacy networks,” Dr. Apolo said. “I like BCAN a lot. It’s a patient-run organization for patients with bladder cancer. With them, I have done a couple of webinars for rare bladder tumors that Ive had some patients tell me are very helpful. They’re a terrific organization that really provides not only emotional support but also educational support for patients that have a diagnosis of bladder cancer and now, rare bladder tumors.” Dr. Spiess offered similar advice for clinicians managing patients with rare GU tumors. He emphasized the key role played by patient advocacy groups, and recommended referral to institutions specializing in specific GU tumor types. For example, he recommended that patients with penile cancer be treated at Moffitt (Tampa) or MD Anderson (Houston), as these centers have the greatest relevant experience. Dr. McGregor disclosed relationships with Bayer, Astellas, Nektar, and others. Dr. Apolo and Dr. Spiess disclosed no conflicts of interest.
 

References

1.Necchi A et al. Eur Urol. 2021 June;79:S929-30.

2.Apolo AB et al. J Clin Oncol. 2021;39(6_suppl):3.

3.McGregor BA et al. Cancer. 2021 Mar 15;127(6):840-9.

4.McGregor BA and Sonpavde GP. Eur Urol Focus. 2020;6(1):14-16.5.Le Tourneau C et al. J Immunother Cancer. 2018 Oct 22;6(1):111.6.Naing A et al. J Immunother Cancer. 2020;8(1).

7.Raj N et al. J Clin Oncol. 2020;38(1):71-80.

8.Adra N et al. Ann Oncol. 2018;29(1):209-14.

9.Necchi A et al. Eur Urol. 2019;75(1):201-3.

I write a lot about watershed moments in my career, things that proved to be moments of tremendous growth, as a person and as a doctor.

One of these occurred early in my career when I met a new patient with ovarian cancer. When I walked into the exam room, I made eye contact with the woman who was accompanied by a man. I assumed they were married, so I went to her first. I introduced myself, stating that I was here to talk about how best to treat her cancer. She stopped me quickly. “Doctor, I am not the patient,” she said. “He is.”

It was the first time I had cared for a transgender man with ovarian cancer. I recall how awkward the following moments were – for all of us. It was the first time I realized that cancer does not have a gender. Men can get breast cancer. Trans women can get prostate cancer. Trans men can get ovarian cancer.

But even many years later, we are not much further along in how prepared we are as a medical community to care for LGBTQ persons. Lesbian, gay, bisexual, transgender, and queer people are not part of the normal medical school curriculum. For most medical students, LGBTQ health is still approached as an aside – perhaps during an infectious disease clerkship, while learning about STDs and HIV. Students do not learn how to approach the male couple seeking to become parents, STD risk reduction for gays and lesbians, or the trans man with ovarian cancer.

But they should, particularly in light of a 2015 study evaluating bias among U.S. medical students. The analysis found that about 45% of medical students exhibited explicit bias against LGBTQ individuals and 8 in 10 held an implicit bias. Fewer than 20% showed no evidence of bias. This lack of preparedness to treat LGBTQ individuals against a backdrop of bias in the medical community often leads patients to mistrust medicine.

To gain perspective outside of oncology, I spoke to Michelle Forcier (she/they), MD, MPH, assistant dean of admissions and professor of pediatrics at Brown University, Providence, R.I. Dr. Forcier agreed that “LGBTQ/rainbow health has been harmfully treated by the system, by both intention and by ignorance.”

“I have had patients who report that EMTs have tried to look under their clothes to determine their gender and transgender patients who have asked point blank to show a provider the results of gender reassignment surgery, not because it was relevant to the issue at hand, but purely out of curiosity,” Dr. Forcier continued. “Then there are the patients who are addressed by the name on their legal record rather than the name that reflects their actual lived experience and identity. These experiences foster this anticipation that is pervasive in this community, that something will be said or done that doesn’t fit who they are, and that ultimately will out them as ‘other.’ ”

I have also felt this sense of being “other” – something I thought I would be immune to as a physician. I have been asked on multiple occasions what my wife does for a living. Moments like this are always awkward. I’m either forced to come out of the closet yet again, or answer vaguely, as if I should be ashamed of my sexuality.

So, how can we move toward equity? Dr. Forcier explained how she lays the groundwork early. “I love pediatrics because kids know when you are being authentic,” she said. “I say who I am, I use she/they pronouns. I also teach by example. If there are more than just my patient in a room, I say, ‘Let’s go around the room and introduce ourselves’ so all have a chance to tell me who they are and how they have come together. If it’s not clear to me, sometimes I prod: ‘How are you here to support [the patient]?’ ”

The point, according to Dr. Forcier: Don’t make assumptions about relationships when you walk into a room with more than one person. Don’t even make assumptions about who the patient is.

But bringing up gender and sexuality can be awkward. Even I sometimes have a hard time. In oncology, patients are there to talk about their cancer and what can be done about it.

“I think it’s really about how it’s framed,” Dr. Forcier said. “In pediatrics, I might start by prefacing it with ‘I am going to ask you some personal questions, and it might seem invasive, but it’s important for your health care. How do you see yourself in the world? What gender identity fits you the best? Who are you attracted to?’ And then I shut up. Doctors need to learn how to stop and wait, provide the space to answer.”

I can see why understanding our patients more deeply is important. We treat people with cancer, not cancer people. As such, understanding someone more fully includes being cognizant of how they identify.

“I am continuously inspired by my LGBTQ patients who have fought to realize who they are and become their truer selves,” Dr. Forcier said. “They know who they are, and they know what they need. They have learned to demand it, to demand that their rights be respected – both civil and human rights.”

As we look toward a future in medicine where diversity, equity, and inclusion have gained prominence and urgency, I think there is reason to be hopeful. In oncology, one institutional study published in 2017 found that, although only about a third of practicing clinicians surveyed were comfortable treating LGBTQ patients, 92% of them acknowledged our unique needs, 78% wanted more education on how to appropriately care for our community, and 64% wanted to be listed as an LGBTQ-friendly provider.

“As an optimist, I believe that those struggling with homophobia/transphobia are open to doing things better,” Dr. Forcier said. “After all, we all strive to be better doctors. Whether explicit or implicit bias is at play, turning moments where colleagues are being inappropriate and showing them an alternative, more inclusive way to handle things is one mechanism to educate, rather than to shame. The bottom line is simple: You don’t have to be perfect. You just have to try.”

Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute and director of medical oncology at Rhode Island Hospital, both in Providence. He is also a professor of medicine at Brown University. His research interests are in novel treatments of women’s cancers and issues related to survivorship, particularly as they relate to sexual health after cancer for both men and women.

A version of this article first appeared on Medscape.com.

I write a lot about watershed moments in my career, things that proved to be moments of tremendous growth, as a person and as a doctor.

One of these occurred early in my career when I met a new patient with ovarian cancer. When I walked into the exam room, I made eye contact with the woman who was accompanied by a man. I assumed they were married, so I went to her first. I introduced myself, stating that I was here to talk about how best to treat her cancer. She stopped me quickly. “Doctor, I am not the patient,” she said. “He is.”

It was the first time I had cared for a transgender man with ovarian cancer. I recall how awkward the following moments were – for all of us. It was the first time I realized that cancer does not have a gender. Men can get breast cancer. Trans women can get prostate cancer. Trans men can get ovarian cancer.

But even many years later, we are not much further along in how prepared we are as a medical community to care for LGBTQ persons. Lesbian, gay, bisexual, transgender, and queer people are not part of the normal medical school curriculum. For most medical students, LGBTQ health is still approached as an aside – perhaps during an infectious disease clerkship, while learning about STDs and HIV. Students do not learn how to approach the male couple seeking to become parents, STD risk reduction for gays and lesbians, or the trans man with ovarian cancer.

But they should, particularly in light of a 2015 study evaluating bias among U.S. medical students. The analysis found that about 45% of medical students exhibited explicit bias against LGBTQ individuals and 8 in 10 held an implicit bias. Fewer than 20% showed no evidence of bias. This lack of preparedness to treat LGBTQ individuals against a backdrop of bias in the medical community often leads patients to mistrust medicine.

To gain perspective outside of oncology, I spoke to Michelle Forcier (she/they), MD, MPH, assistant dean of admissions and professor of pediatrics at Brown University, Providence, R.I. Dr. Forcier agreed that “LGBTQ/rainbow health has been harmfully treated by the system, by both intention and by ignorance.”

“I have had patients who report that EMTs have tried to look under their clothes to determine their gender and transgender patients who have asked point blank to show a provider the results of gender reassignment surgery, not because it was relevant to the issue at hand, but purely out of curiosity,” Dr. Forcier continued. “Then there are the patients who are addressed by the name on their legal record rather than the name that reflects their actual lived experience and identity. These experiences foster this anticipation that is pervasive in this community, that something will be said or done that doesn’t fit who they are, and that ultimately will out them as ‘other.’ ”

I have also felt this sense of being “other” – something I thought I would be immune to as a physician. I have been asked on multiple occasions what my wife does for a living. Moments like this are always awkward. I’m either forced to come out of the closet yet again, or answer vaguely, as if I should be ashamed of my sexuality.

So, how can we move toward equity? Dr. Forcier explained how she lays the groundwork early. “I love pediatrics because kids know when you are being authentic,” she said. “I say who I am, I use she/they pronouns. I also teach by example. If there are more than just my patient in a room, I say, ‘Let’s go around the room and introduce ourselves’ so all have a chance to tell me who they are and how they have come together. If it’s not clear to me, sometimes I prod: ‘How are you here to support [the patient]?’ ”

The point, according to Dr. Forcier: Don’t make assumptions about relationships when you walk into a room with more than one person. Don’t even make assumptions about who the patient is.

But bringing up gender and sexuality can be awkward. Even I sometimes have a hard time. In oncology, patients are there to talk about their cancer and what can be done about it.

“I think it’s really about how it’s framed,” Dr. Forcier said. “In pediatrics, I might start by prefacing it with ‘I am going to ask you some personal questions, and it might seem invasive, but it’s important for your health care. How do you see yourself in the world? What gender identity fits you the best? Who are you attracted to?’ And then I shut up. Doctors need to learn how to stop and wait, provide the space to answer.”

I can see why understanding our patients more deeply is important. We treat people with cancer, not cancer people. As such, understanding someone more fully includes being cognizant of how they identify.

“I am continuously inspired by my LGBTQ patients who have fought to realize who they are and become their truer selves,” Dr. Forcier said. “They know who they are, and they know what they need. They have learned to demand it, to demand that their rights be respected – both civil and human rights.”

As we look toward a future in medicine where diversity, equity, and inclusion have gained prominence and urgency, I think there is reason to be hopeful. In oncology, one institutional study published in 2017 found that, although only about a third of practicing clinicians surveyed were comfortable treating LGBTQ patients, 92% of them acknowledged our unique needs, 78% wanted more education on how to appropriately care for our community, and 64% wanted to be listed as an LGBTQ-friendly provider.

“As an optimist, I believe that those struggling with homophobia/transphobia are open to doing things better,” Dr. Forcier said. “After all, we all strive to be better doctors. Whether explicit or implicit bias is at play, turning moments where colleagues are being inappropriate and showing them an alternative, more inclusive way to handle things is one mechanism to educate, rather than to shame. The bottom line is simple: You don’t have to be perfect. You just have to try.”

Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute and director of medical oncology at Rhode Island Hospital, both in Providence. He is also a professor of medicine at Brown University. His research interests are in novel treatments of women’s cancers and issues related to survivorship, particularly as they relate to sexual health after cancer for both men and women.

A version of this article first appeared on Medscape.com.

I write a lot about watershed moments in my career, things that proved to be moments of tremendous growth, as a person and as a doctor.

One of these occurred early in my career when I met a new patient with ovarian cancer. When I walked into the exam room, I made eye contact with the woman who was accompanied by a man. I assumed they were married, so I went to her first. I introduced myself, stating that I was here to talk about how best to treat her cancer. She stopped me quickly. “Doctor, I am not the patient,” she said. “He is.”

It was the first time I had cared for a transgender man with ovarian cancer. I recall how awkward the following moments were – for all of us. It was the first time I realized that cancer does not have a gender. Men can get breast cancer. Trans women can get prostate cancer. Trans men can get ovarian cancer.

But even many years later, we are not much further along in how prepared we are as a medical community to care for LGBTQ persons. Lesbian, gay, bisexual, transgender, and queer people are not part of the normal medical school curriculum. For most medical students, LGBTQ health is still approached as an aside – perhaps during an infectious disease clerkship, while learning about STDs and HIV. Students do not learn how to approach the male couple seeking to become parents, STD risk reduction for gays and lesbians, or the trans man with ovarian cancer.

But they should, particularly in light of a 2015 study evaluating bias among U.S. medical students. The analysis found that about 45% of medical students exhibited explicit bias against LGBTQ individuals and 8 in 10 held an implicit bias. Fewer than 20% showed no evidence of bias. This lack of preparedness to treat LGBTQ individuals against a backdrop of bias in the medical community often leads patients to mistrust medicine.

To gain perspective outside of oncology, I spoke to Michelle Forcier (she/they), MD, MPH, assistant dean of admissions and professor of pediatrics at Brown University, Providence, R.I. Dr. Forcier agreed that “LGBTQ/rainbow health has been harmfully treated by the system, by both intention and by ignorance.”

“I have had patients who report that EMTs have tried to look under their clothes to determine their gender and transgender patients who have asked point blank to show a provider the results of gender reassignment surgery, not because it was relevant to the issue at hand, but purely out of curiosity,” Dr. Forcier continued. “Then there are the patients who are addressed by the name on their legal record rather than the name that reflects their actual lived experience and identity. These experiences foster this anticipation that is pervasive in this community, that something will be said or done that doesn’t fit who they are, and that ultimately will out them as ‘other.’ ”

I have also felt this sense of being “other” – something I thought I would be immune to as a physician. I have been asked on multiple occasions what my wife does for a living. Moments like this are always awkward. I’m either forced to come out of the closet yet again, or answer vaguely, as if I should be ashamed of my sexuality.

So, how can we move toward equity? Dr. Forcier explained how she lays the groundwork early. “I love pediatrics because kids know when you are being authentic,” she said. “I say who I am, I use she/they pronouns. I also teach by example. If there are more than just my patient in a room, I say, ‘Let’s go around the room and introduce ourselves’ so all have a chance to tell me who they are and how they have come together. If it’s not clear to me, sometimes I prod: ‘How are you here to support [the patient]?’ ”

The point, according to Dr. Forcier: Don’t make assumptions about relationships when you walk into a room with more than one person. Don’t even make assumptions about who the patient is.

But bringing up gender and sexuality can be awkward. Even I sometimes have a hard time. In oncology, patients are there to talk about their cancer and what can be done about it.

“I think it’s really about how it’s framed,” Dr. Forcier said. “In pediatrics, I might start by prefacing it with ‘I am going to ask you some personal questions, and it might seem invasive, but it’s important for your health care. How do you see yourself in the world? What gender identity fits you the best? Who are you attracted to?’ And then I shut up. Doctors need to learn how to stop and wait, provide the space to answer.”

I can see why understanding our patients more deeply is important. We treat people with cancer, not cancer people. As such, understanding someone more fully includes being cognizant of how they identify.

“I am continuously inspired by my LGBTQ patients who have fought to realize who they are and become their truer selves,” Dr. Forcier said. “They know who they are, and they know what they need. They have learned to demand it, to demand that their rights be respected – both civil and human rights.”

As we look toward a future in medicine where diversity, equity, and inclusion have gained prominence and urgency, I think there is reason to be hopeful. In oncology, one institutional study published in 2017 found that, although only about a third of practicing clinicians surveyed were comfortable treating LGBTQ patients, 92% of them acknowledged our unique needs, 78% wanted more education on how to appropriately care for our community, and 64% wanted to be listed as an LGBTQ-friendly provider.

“As an optimist, I believe that those struggling with homophobia/transphobia are open to doing things better,” Dr. Forcier said. “After all, we all strive to be better doctors. Whether explicit or implicit bias is at play, turning moments where colleagues are being inappropriate and showing them an alternative, more inclusive way to handle things is one mechanism to educate, rather than to shame. The bottom line is simple: You don’t have to be perfect. You just have to try.”

Dr. Dizon is the director of women’s cancers at Lifespan Cancer Institute and director of medical oncology at Rhode Island Hospital, both in Providence. He is also a professor of medicine at Brown University. His research interests are in novel treatments of women’s cancers and issues related to survivorship, particularly as they relate to sexual health after cancer for both men and women.

A version of this article first appeared on Medscape.com.

After making a controversial change in September to a long-standing recommendation about the use of active surveillance in men with prostate cancer, the National Comprehensive Cancer Network (NCCN) has reversed course and reinstated its original advice, with a slight tweak.

The influential cancer organization, which is best known for its guidelines, now recommends that “most” men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option. This advice aligns closely with the group’s initial recommendation, published over a decade ago.

But controversy erupted in late September when the NCCN suddenly changed its tune on active surveillance, recommending that men with low-risk disease be managed with either active surveillance, radiation therapy, or surgery, with equal weight given to all three.

The new advice angered physicians who support the concept of active surveillance, which aims to avoid or delay treatment — and potentially life-changing side effects — until signs of disease progression.

The NCCN listened to the complaints.

On Nov. 30, the group largely reverted back to the original recommendation. In updated guidelines, active surveillance returned to its place as the sole “preferred” management option, but for “most” men with low-risk disease, not all.

In an email sent to this news organization, Edward Schaeffer, MD, PhD, chair of the prostate cancer treatment panel, said that “the NCCN Prostate Cancer Panel recently convened” and “extensively revised the Principles of Active Surveillance and Observation.”

Dr. Schaeffer, who is from the Lurie Comprehensive Cancer Center of Northwestern University in Chicago, cited the heterogeneity across the low-risk disease group. Factors associated with an increased probability of near-term grade reclassification from low risk to higher risk include high PSA density, a high number of positive cores (≥ 3), high genomic risk (from tissue-based molecular tumor analysis), and/or a known BRCA2 germline mutation, he added.

Urologists cheered the NCCN’s reversal on Twitter.

“Big news! NCCN guidelines updated again — active surveillance is ‘preferred for most patients’ with low risk prostate cancer and life expectancy >=10 years,” tweeted Stacy Loeb of NYU Langone in New York City.

“Very exciting if true,” tweeted Matthew Cooperberg, MD, of University of California San Francisco, who was one of the most vocal critics of the NCCN’s change in September, calling that move a “step backward” that would likely lead to overtreatment.

A version of this article first appeared on Medscape.com.

After making a controversial change in September to a long-standing recommendation about the use of active surveillance in men with prostate cancer, the National Comprehensive Cancer Network (NCCN) has reversed course and reinstated its original advice, with a slight tweak.

The influential cancer organization, which is best known for its guidelines, now recommends that “most” men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option. This advice aligns closely with the group’s initial recommendation, published over a decade ago.

But controversy erupted in late September when the NCCN suddenly changed its tune on active surveillance, recommending that men with low-risk disease be managed with either active surveillance, radiation therapy, or surgery, with equal weight given to all three.

The new advice angered physicians who support the concept of active surveillance, which aims to avoid or delay treatment — and potentially life-changing side effects — until signs of disease progression.

The NCCN listened to the complaints.

On Nov. 30, the group largely reverted back to the original recommendation. In updated guidelines, active surveillance returned to its place as the sole “preferred” management option, but for “most” men with low-risk disease, not all.

In an email sent to this news organization, Edward Schaeffer, MD, PhD, chair of the prostate cancer treatment panel, said that “the NCCN Prostate Cancer Panel recently convened” and “extensively revised the Principles of Active Surveillance and Observation.”

Dr. Schaeffer, who is from the Lurie Comprehensive Cancer Center of Northwestern University in Chicago, cited the heterogeneity across the low-risk disease group. Factors associated with an increased probability of near-term grade reclassification from low risk to higher risk include high PSA density, a high number of positive cores (≥ 3), high genomic risk (from tissue-based molecular tumor analysis), and/or a known BRCA2 germline mutation, he added.

Urologists cheered the NCCN’s reversal on Twitter.

“Big news! NCCN guidelines updated again — active surveillance is ‘preferred for most patients’ with low risk prostate cancer and life expectancy >=10 years,” tweeted Stacy Loeb of NYU Langone in New York City.

“Very exciting if true,” tweeted Matthew Cooperberg, MD, of University of California San Francisco, who was one of the most vocal critics of the NCCN’s change in September, calling that move a “step backward” that would likely lead to overtreatment.

A version of this article first appeared on Medscape.com.

After making a controversial change in September to a long-standing recommendation about the use of active surveillance in men with prostate cancer, the National Comprehensive Cancer Network (NCCN) has reversed course and reinstated its original advice, with a slight tweak.

The influential cancer organization, which is best known for its guidelines, now recommends that “most” men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option. This advice aligns closely with the group’s initial recommendation, published over a decade ago.

But controversy erupted in late September when the NCCN suddenly changed its tune on active surveillance, recommending that men with low-risk disease be managed with either active surveillance, radiation therapy, or surgery, with equal weight given to all three.

The new advice angered physicians who support the concept of active surveillance, which aims to avoid or delay treatment — and potentially life-changing side effects — until signs of disease progression.

The NCCN listened to the complaints.

On Nov. 30, the group largely reverted back to the original recommendation. In updated guidelines, active surveillance returned to its place as the sole “preferred” management option, but for “most” men with low-risk disease, not all.

In an email sent to this news organization, Edward Schaeffer, MD, PhD, chair of the prostate cancer treatment panel, said that “the NCCN Prostate Cancer Panel recently convened” and “extensively revised the Principles of Active Surveillance and Observation.”

Dr. Schaeffer, who is from the Lurie Comprehensive Cancer Center of Northwestern University in Chicago, cited the heterogeneity across the low-risk disease group. Factors associated with an increased probability of near-term grade reclassification from low risk to higher risk include high PSA density, a high number of positive cores (≥ 3), high genomic risk (from tissue-based molecular tumor analysis), and/or a known BRCA2 germline mutation, he added.

Urologists cheered the NCCN’s reversal on Twitter.

“Big news! NCCN guidelines updated again — active surveillance is ‘preferred for most patients’ with low risk prostate cancer and life expectancy >=10 years,” tweeted Stacy Loeb of NYU Langone in New York City.

“Very exciting if true,” tweeted Matthew Cooperberg, MD, of University of California San Francisco, who was one of the most vocal critics of the NCCN’s change in September, calling that move a “step backward” that would likely lead to overtreatment.

A version of this article first appeared on Medscape.com.

For over a decade, the influential National Comprehensive Cancer Network (NCCN) has been recommending that men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option.

But the NCCN has now reversed this long-standing recommendation in the latest revision of its prostate cancer guideline.

The organization now recommends that low-risk disease be managed with either active surveillance or radiation therapy or surgery, with equal weight given to all three of these initial options.

The change is seen by some as a retreat to the past and was harshly criticized by many experts on Twitter. The complaints were voiced in unusually blunt and strong language for physicians.

“This is a terrible step back that impacts every urologist,” commented John Griffith, MD, of Hartford Healthcare, who practices in New Britain, Conn.

Dr. Griffith explained that he prints out the NCCN guidance with “every patient newly diagnosed” and that the preferred designation is a “huge help” in reassuring them about not treating low-risk disease initially.

In a Twitter thread, Benjamin Davies, MD, of the University of Pittsburgh, facetiously wondered if a time warp was at play: “To suggest for a millisecond that active surveillance isn’t the preferred method for low-risk men is bizarre thinking ... Is this 1980?”

“I’m baffled,” said Brian Chapin, MD, of MD Anderson Cancer Center, Houston, in another Twitter thread.

“This is ludicrous,” said Andrew Vickers, PhD, of Memorial Sloan Kettering Cancer Center in New York City in a tweet.

Alexander Kutikov, MD, of Fox Chase Cancer Center in Philadelphia, commented on Twitter that the change “seems off the rails…a bit stunned by this.”

Matthew Cooperberg, MD, of the University of California San Francisco, and Minhaj Siddiqui, MD, of the University of Maryland in Baltimore both called the move a “step backward.”

Many others also expressed disappointment in the NCCN, whose guidelines are hugely influential because of the role they play clinically as well as with payors and the legal system.

“A huge setback & frankly a disgrace for @NCCN and its processes,” commented Fox Chase’s Dr. Kutikov.

Stacy Loeb, MD, of NYU Langone Health in New York City, suggested the new guidance may stunt use of active surveillance in the United States. She tweeted: “The updated NCCN guideline certainly won’t help the lagging and heterogenous uptake of active surveillance in the U.S. We should be carefully expanding the pool for active surveillance, not narrowing it.”

The purpose of active surveillance is to avoid adverse events from treatment, which can be life-changing as they include incontinence and erectile dysfunction.

The rationale is that many men with low-risk prostate cancer may not need treatment for their disease, as the disease may be slow-growing and may never threaten their life. With active surveillance, men are instead monitored with blood tests, scans, and biopsies to watch for worsening disease, and treated only when there are signs of disease progression.

This active surveillance approach has grown in acceptance among American patients since 2010.

The concern now is that the change in guidance from the NCCN will lead to a reduction in active surveillance, and an increase in initial treatment with surgery and radiotherapy for low-risk disease, which is considered by many to be “overtreatment’ of this disease and may not be medically necessary.  

For example, UCSF’s Dr. Cooperberg said he feared that the changed guidance “will be used by urologists and radiation oncologists to justify overtreatment of low-risk disease.”

Dr. Kutikov agreed but described that possibility differently, citing the risk of lawsuits. He observed that without the NCCN’s “medico-legal buffer” of active surveillance as the preferred initial treatment, there are “further incentives” for overtreatment.

The new NCCN guidance also conflicts with the American Urological Association’s guidelines and dissolves what was once a mostly united front from the two major organizations on active surveillance and low-risk disease.

The AUA Guideline reads: “Clinicians should recommend active surveillance as the preferable care option for most low-risk localized prostate cancer patients (Moderate Recommendation; Evidence Level: Grade B)
 

Patients protest change in wording

Not surprisingly, the revised NCCN guidance was criticized by multiple patient advocacy groups, including Active Surveillance Patients International (ASPI), which wrote a letter to the NCCN protesting the change.

In that letter, the ASPI writes that active surveillance is now chosen as the initial approach for low-risk prostate cancer in about 90% of cases in some European nations, and in about 50% of cases in the United States. It also warns that eliminating the word “preferred” from the NCCN guidelines represents a retreat, and “will have repercussions far beyond what we may first conceive.” 

“Active surveillance should be the preferred choice to preserve quality of life for men with low-risk cancer,” the advocacy group states. “The PIVOT trials indicate for low-risk disease there is basically no advantage to intervention. Why would one risk the side effects if they knew that?”
 

Why now?

The NCCN’s move to alter its low-risk prostate cancer guidance is especially striking because, 11 years ago, the NCCN broke new ground in recommending active surveillance as the sole initial treatment option for low-risk men. (It was also the first guidelines group to recommend the same for very low-risk men.)

So why the change now? This news organization requested, but did not receive,  comment from the NCCN and its chair of the prostate cancer panel, Edward Schaeffer, MD, of Northwestern University in Chicago.  

However, on Twitter, Dr. Schaeffer hinted at what had turned the tables for the NCCN panel – the risk that, over time, some men with low-risk disease who are on active surveillance are reclassified on biopsy as having a higher risk.

He highlighted a 2020 study on that very subject from the University of California, San Francisco, published in the Journal of Urology. Those authors concluded that: “Given the heterogeneity of the disease, some tumors characterized as low risk may merit early treatment while others may be followed much less intensely over some time interval.”

Dr. Schaeffer tweeted: “I think this nicely sums up the low-risk space ...”

Experts reacting to Dr. Schaeffer’s tweet were not swayed.

Looking at additional measures such as genomic scores and PSA density, as advocated by Dr. Schaeffer via the posted 2020 study, is good for assessing individual risk, “but still, active surveillance is the preferred option for low risk,” said MD Anderson’s Dr. Chapin.

UCSF’s Dr. Cooperberg, who was a co-author on that 2020 Journal of Urology paper,  commented that the university’s urology department had “spent the past quarter century arguing active surveillance is ‘preferred’ for almost all low risk [disease]!”

“Many on active surveillance need treatment someday, but that does not justify immediate overtreatment,” he concluded.

A version of this article first appeared on Medscape.com.

For over a decade, the influential National Comprehensive Cancer Network (NCCN) has been recommending that men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option.

But the NCCN has now reversed this long-standing recommendation in the latest revision of its prostate cancer guideline.

The organization now recommends that low-risk disease be managed with either active surveillance or radiation therapy or surgery, with equal weight given to all three of these initial options.

The change is seen by some as a retreat to the past and was harshly criticized by many experts on Twitter. The complaints were voiced in unusually blunt and strong language for physicians.

“This is a terrible step back that impacts every urologist,” commented John Griffith, MD, of Hartford Healthcare, who practices in New Britain, Conn.

Dr. Griffith explained that he prints out the NCCN guidance with “every patient newly diagnosed” and that the preferred designation is a “huge help” in reassuring them about not treating low-risk disease initially.

In a Twitter thread, Benjamin Davies, MD, of the University of Pittsburgh, facetiously wondered if a time warp was at play: “To suggest for a millisecond that active surveillance isn’t the preferred method for low-risk men is bizarre thinking ... Is this 1980?”

“I’m baffled,” said Brian Chapin, MD, of MD Anderson Cancer Center, Houston, in another Twitter thread.

“This is ludicrous,” said Andrew Vickers, PhD, of Memorial Sloan Kettering Cancer Center in New York City in a tweet.

Alexander Kutikov, MD, of Fox Chase Cancer Center in Philadelphia, commented on Twitter that the change “seems off the rails…a bit stunned by this.”

Matthew Cooperberg, MD, of the University of California San Francisco, and Minhaj Siddiqui, MD, of the University of Maryland in Baltimore both called the move a “step backward.”

Many others also expressed disappointment in the NCCN, whose guidelines are hugely influential because of the role they play clinically as well as with payors and the legal system.

“A huge setback & frankly a disgrace for @NCCN and its processes,” commented Fox Chase’s Dr. Kutikov.

Stacy Loeb, MD, of NYU Langone Health in New York City, suggested the new guidance may stunt use of active surveillance in the United States. She tweeted: “The updated NCCN guideline certainly won’t help the lagging and heterogenous uptake of active surveillance in the U.S. We should be carefully expanding the pool for active surveillance, not narrowing it.”

The purpose of active surveillance is to avoid adverse events from treatment, which can be life-changing as they include incontinence and erectile dysfunction.

The rationale is that many men with low-risk prostate cancer may not need treatment for their disease, as the disease may be slow-growing and may never threaten their life. With active surveillance, men are instead monitored with blood tests, scans, and biopsies to watch for worsening disease, and treated only when there are signs of disease progression.

This active surveillance approach has grown in acceptance among American patients since 2010.

The concern now is that the change in guidance from the NCCN will lead to a reduction in active surveillance, and an increase in initial treatment with surgery and radiotherapy for low-risk disease, which is considered by many to be “overtreatment’ of this disease and may not be medically necessary.  

For example, UCSF’s Dr. Cooperberg said he feared that the changed guidance “will be used by urologists and radiation oncologists to justify overtreatment of low-risk disease.”

Dr. Kutikov agreed but described that possibility differently, citing the risk of lawsuits. He observed that without the NCCN’s “medico-legal buffer” of active surveillance as the preferred initial treatment, there are “further incentives” for overtreatment.

The new NCCN guidance also conflicts with the American Urological Association’s guidelines and dissolves what was once a mostly united front from the two major organizations on active surveillance and low-risk disease.

The AUA Guideline reads: “Clinicians should recommend active surveillance as the preferable care option for most low-risk localized prostate cancer patients (Moderate Recommendation; Evidence Level: Grade B)
 

Patients protest change in wording

Not surprisingly, the revised NCCN guidance was criticized by multiple patient advocacy groups, including Active Surveillance Patients International (ASPI), which wrote a letter to the NCCN protesting the change.

In that letter, the ASPI writes that active surveillance is now chosen as the initial approach for low-risk prostate cancer in about 90% of cases in some European nations, and in about 50% of cases in the United States. It also warns that eliminating the word “preferred” from the NCCN guidelines represents a retreat, and “will have repercussions far beyond what we may first conceive.” 

“Active surveillance should be the preferred choice to preserve quality of life for men with low-risk cancer,” the advocacy group states. “The PIVOT trials indicate for low-risk disease there is basically no advantage to intervention. Why would one risk the side effects if they knew that?”
 

Why now?

The NCCN’s move to alter its low-risk prostate cancer guidance is especially striking because, 11 years ago, the NCCN broke new ground in recommending active surveillance as the sole initial treatment option for low-risk men. (It was also the first guidelines group to recommend the same for very low-risk men.)

So why the change now? This news organization requested, but did not receive,  comment from the NCCN and its chair of the prostate cancer panel, Edward Schaeffer, MD, of Northwestern University in Chicago.  

However, on Twitter, Dr. Schaeffer hinted at what had turned the tables for the NCCN panel – the risk that, over time, some men with low-risk disease who are on active surveillance are reclassified on biopsy as having a higher risk.

He highlighted a 2020 study on that very subject from the University of California, San Francisco, published in the Journal of Urology. Those authors concluded that: “Given the heterogeneity of the disease, some tumors characterized as low risk may merit early treatment while others may be followed much less intensely over some time interval.”

Dr. Schaeffer tweeted: “I think this nicely sums up the low-risk space ...”

Experts reacting to Dr. Schaeffer’s tweet were not swayed.

Looking at additional measures such as genomic scores and PSA density, as advocated by Dr. Schaeffer via the posted 2020 study, is good for assessing individual risk, “but still, active surveillance is the preferred option for low risk,” said MD Anderson’s Dr. Chapin.

UCSF’s Dr. Cooperberg, who was a co-author on that 2020 Journal of Urology paper,  commented that the university’s urology department had “spent the past quarter century arguing active surveillance is ‘preferred’ for almost all low risk [disease]!”

“Many on active surveillance need treatment someday, but that does not justify immediate overtreatment,” he concluded.

A version of this article first appeared on Medscape.com.

For over a decade, the influential National Comprehensive Cancer Network (NCCN) has been recommending that men with low-risk prostate cancer be offered active surveillance as the lone “preferred” initial treatment option.

But the NCCN has now reversed this long-standing recommendation in the latest revision of its prostate cancer guideline.

The organization now recommends that low-risk disease be managed with either active surveillance or radiation therapy or surgery, with equal weight given to all three of these initial options.

The change is seen by some as a retreat to the past and was harshly criticized by many experts on Twitter. The complaints were voiced in unusually blunt and strong language for physicians.

“This is a terrible step back that impacts every urologist,” commented John Griffith, MD, of Hartford Healthcare, who practices in New Britain, Conn.

Dr. Griffith explained that he prints out the NCCN guidance with “every patient newly diagnosed” and that the preferred designation is a “huge help” in reassuring them about not treating low-risk disease initially.

In a Twitter thread, Benjamin Davies, MD, of the University of Pittsburgh, facetiously wondered if a time warp was at play: “To suggest for a millisecond that active surveillance isn’t the preferred method for low-risk men is bizarre thinking ... Is this 1980?”

“I’m baffled,” said Brian Chapin, MD, of MD Anderson Cancer Center, Houston, in another Twitter thread.

“This is ludicrous,” said Andrew Vickers, PhD, of Memorial Sloan Kettering Cancer Center in New York City in a tweet.

Alexander Kutikov, MD, of Fox Chase Cancer Center in Philadelphia, commented on Twitter that the change “seems off the rails…a bit stunned by this.”

Matthew Cooperberg, MD, of the University of California San Francisco, and Minhaj Siddiqui, MD, of the University of Maryland in Baltimore both called the move a “step backward.”

Many others also expressed disappointment in the NCCN, whose guidelines are hugely influential because of the role they play clinically as well as with payors and the legal system.

“A huge setback & frankly a disgrace for @NCCN and its processes,” commented Fox Chase’s Dr. Kutikov.

Stacy Loeb, MD, of NYU Langone Health in New York City, suggested the new guidance may stunt use of active surveillance in the United States. She tweeted: “The updated NCCN guideline certainly won’t help the lagging and heterogenous uptake of active surveillance in the U.S. We should be carefully expanding the pool for active surveillance, not narrowing it.”

The purpose of active surveillance is to avoid adverse events from treatment, which can be life-changing as they include incontinence and erectile dysfunction.

The rationale is that many men with low-risk prostate cancer may not need treatment for their disease, as the disease may be slow-growing and may never threaten their life. With active surveillance, men are instead monitored with blood tests, scans, and biopsies to watch for worsening disease, and treated only when there are signs of disease progression.

This active surveillance approach has grown in acceptance among American patients since 2010.

The concern now is that the change in guidance from the NCCN will lead to a reduction in active surveillance, and an increase in initial treatment with surgery and radiotherapy for low-risk disease, which is considered by many to be “overtreatment’ of this disease and may not be medically necessary.  

For example, UCSF’s Dr. Cooperberg said he feared that the changed guidance “will be used by urologists and radiation oncologists to justify overtreatment of low-risk disease.”

Dr. Kutikov agreed but described that possibility differently, citing the risk of lawsuits. He observed that without the NCCN’s “medico-legal buffer” of active surveillance as the preferred initial treatment, there are “further incentives” for overtreatment.

The new NCCN guidance also conflicts with the American Urological Association’s guidelines and dissolves what was once a mostly united front from the two major organizations on active surveillance and low-risk disease.

The AUA Guideline reads: “Clinicians should recommend active surveillance as the preferable care option for most low-risk localized prostate cancer patients (Moderate Recommendation; Evidence Level: Grade B)
 

Patients protest change in wording

Not surprisingly, the revised NCCN guidance was criticized by multiple patient advocacy groups, including Active Surveillance Patients International (ASPI), which wrote a letter to the NCCN protesting the change.

In that letter, the ASPI writes that active surveillance is now chosen as the initial approach for low-risk prostate cancer in about 90% of cases in some European nations, and in about 50% of cases in the United States. It also warns that eliminating the word “preferred” from the NCCN guidelines represents a retreat, and “will have repercussions far beyond what we may first conceive.” 

“Active surveillance should be the preferred choice to preserve quality of life for men with low-risk cancer,” the advocacy group states. “The PIVOT trials indicate for low-risk disease there is basically no advantage to intervention. Why would one risk the side effects if they knew that?”
 

Why now?

The NCCN’s move to alter its low-risk prostate cancer guidance is especially striking because, 11 years ago, the NCCN broke new ground in recommending active surveillance as the sole initial treatment option for low-risk men. (It was also the first guidelines group to recommend the same for very low-risk men.)

So why the change now? This news organization requested, but did not receive,  comment from the NCCN and its chair of the prostate cancer panel, Edward Schaeffer, MD, of Northwestern University in Chicago.  

However, on Twitter, Dr. Schaeffer hinted at what had turned the tables for the NCCN panel – the risk that, over time, some men with low-risk disease who are on active surveillance are reclassified on biopsy as having a higher risk.

He highlighted a 2020 study on that very subject from the University of California, San Francisco, published in the Journal of Urology. Those authors concluded that: “Given the heterogeneity of the disease, some tumors characterized as low risk may merit early treatment while others may be followed much less intensely over some time interval.”

Dr. Schaeffer tweeted: “I think this nicely sums up the low-risk space ...”

Experts reacting to Dr. Schaeffer’s tweet were not swayed.

Looking at additional measures such as genomic scores and PSA density, as advocated by Dr. Schaeffer via the posted 2020 study, is good for assessing individual risk, “but still, active surveillance is the preferred option for low risk,” said MD Anderson’s Dr. Chapin.

UCSF’s Dr. Cooperberg, who was a co-author on that 2020 Journal of Urology paper,  commented that the university’s urology department had “spent the past quarter century arguing active surveillance is ‘preferred’ for almost all low risk [disease]!”

“Many on active surveillance need treatment someday, but that does not justify immediate overtreatment,” he concluded.

A version of this article first appeared on Medscape.com.

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that increased Gleason pattern 4 tumor burden is associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of the University of East Anglia, Norwich, England. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease.”

The study by Dr. Clark and colleagues was published online on Nov. 3, 2021, in Life.

Tests using the traditional blood-based biomarker for prostate cancer – prostate-specific antigen (PSA) – have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Dr. Clark and colleagues explained. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Dr. Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors wrote.

The researchers also examined radical-prostatectomy specimens from nine men – three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumors showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Dr. Clark said in an interview. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told this news organization. Dr. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Dr. Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit – the men do not have to come to a hospital to provide a urine sample,” Dr. Clark said.

The study did not receive commercial funding. Dr. Clark and two coauthors have filed a patent application related to their research.
 

A version of this article first appeared on Medscape.com.

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that increased Gleason pattern 4 tumor burden is associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of the University of East Anglia, Norwich, England. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease.”

The study by Dr. Clark and colleagues was published online on Nov. 3, 2021, in Life.

Tests using the traditional blood-based biomarker for prostate cancer – prostate-specific antigen (PSA) – have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Dr. Clark and colleagues explained. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Dr. Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors wrote.

The researchers also examined radical-prostatectomy specimens from nine men – three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumors showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Dr. Clark said in an interview. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told this news organization. Dr. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Dr. Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit – the men do not have to come to a hospital to provide a urine sample,” Dr. Clark said.

The study did not receive commercial funding. Dr. Clark and two coauthors have filed a patent application related to their research.
 

A version of this article first appeared on Medscape.com.

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that increased Gleason pattern 4 tumor burden is associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of the University of East Anglia, Norwich, England. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease.”

The study by Dr. Clark and colleagues was published online on Nov. 3, 2021, in Life.

Tests using the traditional blood-based biomarker for prostate cancer – prostate-specific antigen (PSA) – have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Dr. Clark and colleagues explained. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Dr. Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors wrote.

The researchers also examined radical-prostatectomy specimens from nine men – three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumors showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Dr. Clark said in an interview. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told this news organization. Dr. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Dr. Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit – the men do not have to come to a hospital to provide a urine sample,” Dr. Clark said.

The study did not receive commercial funding. Dr. Clark and two coauthors have filed a patent application related to their research.
 

A version of this article first appeared on Medscape.com.

Men who carry certain pathogenic variants in mismatch repair genes that characterize Lynch syndrome may have a higher risk of prostate cancer, shows a new study. However, for men who carry MSH2 and MSH6 variants, the risk of contracting cancer rises significantly.

Called IMPACT, the study, which was published online in The Lancet Oncology, is an international, prospective study of 828 men aged between 40 and 69 years who were prostate cancer free, but they carried germline pathogenic variants in one of the mismatch repair genes MLH1, MSH2, or MSH6.

The researchers, who were led by Rosalind A. Eeles, PhD, a specialist in oncogenetics with the Institute of Cancer Research, London, found that after one screening “a higher incidence of prostate cancer was detected in men with MSH2 and MHS6 pathogenic variants, compared with age-matched noncarrier controls.”

She and her team also found that MSH2 carriers “were diagnosed at a nonsignificantly younger age and had more clinically significant disease at diagnosis, compared with noncarriers. These data add evidence that prostate screening in this higher-risk context has potential to detect tumors that are highly likely to need treatment.”

The findings suggest that targeted prostate-specific antigen (PSA) screening in men with mismatch repair gene pathogenic variants is justifiable. “Testing for mismatch repair variants will likely become routine practice at diagnosis over the coming years,” the authors wrote.

Lynch syndrome can increase the risk of prostate cancer by 2-10 times, yet there is no international consensus for screening. The 2019 National Comprehensive Cancer Network guidelines recommend considering tumor testing for deficient mismatch repair in men with regional or metastatic prostate cancer. The NCCN also recommends germline testing for all newly diagnosed men with high-risk, very-high-risk, regional, or metastatic prostate cancer.

Currently, the PSA test is the most commonly used test, however, it is not recommended as a routine screening tool because of the negative consequences of overdetection. The American Cancer Society and European Association of Urology recommend PSA screening for men with a strong family history of prostate cancer. The EAU also supports annual PSA screening for men with BRCA2 variants.

“From a treatment perspective, knowledge of mismatch repair pathogenic variant status is increasingly important because of the evidence that mismatch repair-deficient prostate tumors can be sensitive to immune checkpoint inhibitors,” the investigators wrote.

NCCN guidelines support the use of the progressive death–1 inhibitor pembrolizumab (Keytruda, Merck) in these patients, among others.

Although immune checkpoint inhibitors are predominantly used to treat metastatic disease, “this field is rapidly evolving and we will likely see these treatments move earlier in the treatment pathway,” the authors predicted.
 

The findings in detail

The IMPACT study was established in 2005 to assess targeted PSA screening in men with BRCA1 or BRCA2 pathogenic variants. It was extended in 2012 to include men from families with MLH1, MSH2, and MSH6 pathogenic variants.

In this new report, within the first round of screening, 6% of the cohort had a PSA concentration higher than 3.0 ng/mL and the overall incidence of prostate cancer was 1.9%, the investigators noted.

MSH2 carriers were diagnosed at 58 years old on average, compared with 66 years old for the control group. MSH2-positive men had more clinically significant disease, compared with noncarriers. The incidence of prostate cancer was higher at 4.3% in MSH2 carriers than in controls at 0.5%. In MSH6 carriers, the incidence of prostate cancer was 3.0%, compared with 0% for controls.

Only 4% of men underwent a biopsy and only one cancer was found among the MSH2 noncarriers while no cancers were found in MLH1 carriers, MLH1 noncarriers, or MSH6 noncarriers.

The overall positive predictive value of using a PSA threshold of 3.0 ng/mL was 51.4%; separated by genetic status, the PPV in MSH2 carriers was higher at 72.2% and in MSH6 carriers, the PPV was 80%, the researchers noted.

Limitations of the study include the fact that the number of cancers detected in the study was relatively small, thus requiring further data from subsequent screening rounds.

One study coauthor disclosed a potential conflict of interest by holding a PSA test patent.

Men who carry certain pathogenic variants in mismatch repair genes that characterize Lynch syndrome may have a higher risk of prostate cancer, shows a new study. However, for men who carry MSH2 and MSH6 variants, the risk of contracting cancer rises significantly.

Called IMPACT, the study, which was published online in The Lancet Oncology, is an international, prospective study of 828 men aged between 40 and 69 years who were prostate cancer free, but they carried germline pathogenic variants in one of the mismatch repair genes MLH1, MSH2, or MSH6.

The researchers, who were led by Rosalind A. Eeles, PhD, a specialist in oncogenetics with the Institute of Cancer Research, London, found that after one screening “a higher incidence of prostate cancer was detected in men with MSH2 and MHS6 pathogenic variants, compared with age-matched noncarrier controls.”

She and her team also found that MSH2 carriers “were diagnosed at a nonsignificantly younger age and had more clinically significant disease at diagnosis, compared with noncarriers. These data add evidence that prostate screening in this higher-risk context has potential to detect tumors that are highly likely to need treatment.”

The findings suggest that targeted prostate-specific antigen (PSA) screening in men with mismatch repair gene pathogenic variants is justifiable. “Testing for mismatch repair variants will likely become routine practice at diagnosis over the coming years,” the authors wrote.

Lynch syndrome can increase the risk of prostate cancer by 2-10 times, yet there is no international consensus for screening. The 2019 National Comprehensive Cancer Network guidelines recommend considering tumor testing for deficient mismatch repair in men with regional or metastatic prostate cancer. The NCCN also recommends germline testing for all newly diagnosed men with high-risk, very-high-risk, regional, or metastatic prostate cancer.

Currently, the PSA test is the most commonly used test, however, it is not recommended as a routine screening tool because of the negative consequences of overdetection. The American Cancer Society and European Association of Urology recommend PSA screening for men with a strong family history of prostate cancer. The EAU also supports annual PSA screening for men with BRCA2 variants.

“From a treatment perspective, knowledge of mismatch repair pathogenic variant status is increasingly important because of the evidence that mismatch repair-deficient prostate tumors can be sensitive to immune checkpoint inhibitors,” the investigators wrote.

NCCN guidelines support the use of the progressive death–1 inhibitor pembrolizumab (Keytruda, Merck) in these patients, among others.

Although immune checkpoint inhibitors are predominantly used to treat metastatic disease, “this field is rapidly evolving and we will likely see these treatments move earlier in the treatment pathway,” the authors predicted.
 

The findings in detail

The IMPACT study was established in 2005 to assess targeted PSA screening in men with BRCA1 or BRCA2 pathogenic variants. It was extended in 2012 to include men from families with MLH1, MSH2, and MSH6 pathogenic variants.

In this new report, within the first round of screening, 6% of the cohort had a PSA concentration higher than 3.0 ng/mL and the overall incidence of prostate cancer was 1.9%, the investigators noted.

MSH2 carriers were diagnosed at 58 years old on average, compared with 66 years old for the control group. MSH2-positive men had more clinically significant disease, compared with noncarriers. The incidence of prostate cancer was higher at 4.3% in MSH2 carriers than in controls at 0.5%. In MSH6 carriers, the incidence of prostate cancer was 3.0%, compared with 0% for controls.

Only 4% of men underwent a biopsy and only one cancer was found among the MSH2 noncarriers while no cancers were found in MLH1 carriers, MLH1 noncarriers, or MSH6 noncarriers.

The overall positive predictive value of using a PSA threshold of 3.0 ng/mL was 51.4%; separated by genetic status, the PPV in MSH2 carriers was higher at 72.2% and in MSH6 carriers, the PPV was 80%, the researchers noted.

Limitations of the study include the fact that the number of cancers detected in the study was relatively small, thus requiring further data from subsequent screening rounds.

One study coauthor disclosed a potential conflict of interest by holding a PSA test patent.

Men who carry certain pathogenic variants in mismatch repair genes that characterize Lynch syndrome may have a higher risk of prostate cancer, shows a new study. However, for men who carry MSH2 and MSH6 variants, the risk of contracting cancer rises significantly.

Called IMPACT, the study, which was published online in The Lancet Oncology, is an international, prospective study of 828 men aged between 40 and 69 years who were prostate cancer free, but they carried germline pathogenic variants in one of the mismatch repair genes MLH1, MSH2, or MSH6.

The researchers, who were led by Rosalind A. Eeles, PhD, a specialist in oncogenetics with the Institute of Cancer Research, London, found that after one screening “a higher incidence of prostate cancer was detected in men with MSH2 and MHS6 pathogenic variants, compared with age-matched noncarrier controls.”

She and her team also found that MSH2 carriers “were diagnosed at a nonsignificantly younger age and had more clinically significant disease at diagnosis, compared with noncarriers. These data add evidence that prostate screening in this higher-risk context has potential to detect tumors that are highly likely to need treatment.”

The findings suggest that targeted prostate-specific antigen (PSA) screening in men with mismatch repair gene pathogenic variants is justifiable. “Testing for mismatch repair variants will likely become routine practice at diagnosis over the coming years,” the authors wrote.

Lynch syndrome can increase the risk of prostate cancer by 2-10 times, yet there is no international consensus for screening. The 2019 National Comprehensive Cancer Network guidelines recommend considering tumor testing for deficient mismatch repair in men with regional or metastatic prostate cancer. The NCCN also recommends germline testing for all newly diagnosed men with high-risk, very-high-risk, regional, or metastatic prostate cancer.

Currently, the PSA test is the most commonly used test, however, it is not recommended as a routine screening tool because of the negative consequences of overdetection. The American Cancer Society and European Association of Urology recommend PSA screening for men with a strong family history of prostate cancer. The EAU also supports annual PSA screening for men with BRCA2 variants.

“From a treatment perspective, knowledge of mismatch repair pathogenic variant status is increasingly important because of the evidence that mismatch repair-deficient prostate tumors can be sensitive to immune checkpoint inhibitors,” the investigators wrote.

NCCN guidelines support the use of the progressive death–1 inhibitor pembrolizumab (Keytruda, Merck) in these patients, among others.

Although immune checkpoint inhibitors are predominantly used to treat metastatic disease, “this field is rapidly evolving and we will likely see these treatments move earlier in the treatment pathway,” the authors predicted.
 

The findings in detail

The IMPACT study was established in 2005 to assess targeted PSA screening in men with BRCA1 or BRCA2 pathogenic variants. It was extended in 2012 to include men from families with MLH1, MSH2, and MSH6 pathogenic variants.

In this new report, within the first round of screening, 6% of the cohort had a PSA concentration higher than 3.0 ng/mL and the overall incidence of prostate cancer was 1.9%, the investigators noted.

MSH2 carriers were diagnosed at 58 years old on average, compared with 66 years old for the control group. MSH2-positive men had more clinically significant disease, compared with noncarriers. The incidence of prostate cancer was higher at 4.3% in MSH2 carriers than in controls at 0.5%. In MSH6 carriers, the incidence of prostate cancer was 3.0%, compared with 0% for controls.

Only 4% of men underwent a biopsy and only one cancer was found among the MSH2 noncarriers while no cancers were found in MLH1 carriers, MLH1 noncarriers, or MSH6 noncarriers.

The overall positive predictive value of using a PSA threshold of 3.0 ng/mL was 51.4%; separated by genetic status, the PPV in MSH2 carriers was higher at 72.2% and in MSH6 carriers, the PPV was 80%, the researchers noted.

Limitations of the study include the fact that the number of cancers detected in the study was relatively small, thus requiring further data from subsequent screening rounds.

One study coauthor disclosed a potential conflict of interest by holding a PSA test patent.

A new systematic review and meta-analysis finds that unvaccinated cancer patients who contracted COVID-19 last year, were more than two times more likely – than people without cancer – to develop a case of COVID-19 so severe it required hospitalization in an intensive care unit.

“Our study provides the most precise measure to date of the effect of COVID-19 in cancer patients,” wrote researchers who were led by Paolo Boffetta, MD, MPH, a specialist in population science with the Stony Brook Cancer Center in New York.

Dr. Boffetta and colleagues also found that patients with hematologic neoplasms had a higher mortality rate from COVID-19 comparable to that of all cancers combined.

Cancer patients have long been considered to be among those patients who are at high risk of developing COVID-19, and if they contract the disease, they are at high risk of having poor outcomes. Other high-risk patients include those with hypertension, diabetes, chronic kidney disease, or COPD, or the elderly. But how high the risk of developing severe COVID-19 disease is for cancer patients hasn’t yet been documented on a wide scale.

The study, which was made available as a preprint on medRxiv on Oct. 23, is based on an analysis of COVID-19 cases that were documented in 35 reviews, meta-analyses, case reports, and studies indexed in PubMed from authors in North America, Europe, and Asia.

In this study, the pooled odds ratio for mortality for all patients with any cancer was 2.32 (95% confidence interval, 1.82-2.94; 24 studies). For ICU admission, the odds ratio was 2.39 (95% CI, 1.90-3.02; I2 0.0%; 5 studies). And, for disease severity or hospitalization, it was 2.08 (95% CI, 1.60-2.72; I2 92.1%; 15 studies). The pooled mortality odds ratio for hematologic neoplasms was 2.14 (95% CI, 1.87-2.44; I2 20.8%; 8 studies).

Their findings, which have not yet been peer reviewed, confirmed the results of a similar analysis from China published as a preprint in May 2020. The analysis included 181,323 patients (23,736 cancer patients) from 26 studies reported an odds ratio of 2.54 (95% CI, 1.47-4.42). “Cancer patients with COVID-19 have an increased likelihood of death compared to non-cancer COVID-19 patients,” Venkatesulu et al. wrote. And a systematic review and meta-analysis of five studies of 2,619 patients published in October 2020 in Medicine also found a significantly higher risk of death from COVID-19 among cancer patients (odds ratio, 2.63; 95% confidence interval, 1.14-6.06; P = .023; I2 = 26.4%).

Fakih et al., writing in the journal Hematology/Oncology and Stem Cell Therapy conducted a meta-analysis early last year finding a threefold increase for admission to the intensive care unit, an almost fourfold increase for a severe SARS-CoV-2 infection, and a fivefold increase for being intubated.

The three studies show that mortality rates were higher early in the pandemic “when diagnosis and treatment for SARS-CoV-2 might have been delayed, resulting in higher death rate,” Boffetta et al. wrote, adding that their analysis showed only a twofold increase most likely because it was a year-long analysis.

“Future studies will be able to better analyze this association for the different subtypes of cancer. Furthermore, they will eventually be able to evaluate whether the difference among vaccinated population is reduced,” Boffetta et al. wrote.

The authors noted several limitations for the study, including the fact that many of the studies included in the analysis did not include sex, age, comorbidities, and therapy. Nor were the authors able to analyze specific cancers other than hematologic neoplasms.

The authors declared no conflicts of interest.

A new systematic review and meta-analysis finds that unvaccinated cancer patients who contracted COVID-19 last year, were more than two times more likely – than people without cancer – to develop a case of COVID-19 so severe it required hospitalization in an intensive care unit.

“Our study provides the most precise measure to date of the effect of COVID-19 in cancer patients,” wrote researchers who were led by Paolo Boffetta, MD, MPH, a specialist in population science with the Stony Brook Cancer Center in New York.

Dr. Boffetta and colleagues also found that patients with hematologic neoplasms had a higher mortality rate from COVID-19 comparable to that of all cancers combined.

Cancer patients have long been considered to be among those patients who are at high risk of developing COVID-19, and if they contract the disease, they are at high risk of having poor outcomes. Other high-risk patients include those with hypertension, diabetes, chronic kidney disease, or COPD, or the elderly. But how high the risk of developing severe COVID-19 disease is for cancer patients hasn’t yet been documented on a wide scale.

The study, which was made available as a preprint on medRxiv on Oct. 23, is based on an analysis of COVID-19 cases that were documented in 35 reviews, meta-analyses, case reports, and studies indexed in PubMed from authors in North America, Europe, and Asia.

In this study, the pooled odds ratio for mortality for all patients with any cancer was 2.32 (95% confidence interval, 1.82-2.94; 24 studies). For ICU admission, the odds ratio was 2.39 (95% CI, 1.90-3.02; I2 0.0%; 5 studies). And, for disease severity or hospitalization, it was 2.08 (95% CI, 1.60-2.72; I2 92.1%; 15 studies). The pooled mortality odds ratio for hematologic neoplasms was 2.14 (95% CI, 1.87-2.44; I2 20.8%; 8 studies).

Their findings, which have not yet been peer reviewed, confirmed the results of a similar analysis from China published as a preprint in May 2020. The analysis included 181,323 patients (23,736 cancer patients) from 26 studies reported an odds ratio of 2.54 (95% CI, 1.47-4.42). “Cancer patients with COVID-19 have an increased likelihood of death compared to non-cancer COVID-19 patients,” Venkatesulu et al. wrote. And a systematic review and meta-analysis of five studies of 2,619 patients published in October 2020 in Medicine also found a significantly higher risk of death from COVID-19 among cancer patients (odds ratio, 2.63; 95% confidence interval, 1.14-6.06; P = .023; I2 = 26.4%).

Fakih et al., writing in the journal Hematology/Oncology and Stem Cell Therapy conducted a meta-analysis early last year finding a threefold increase for admission to the intensive care unit, an almost fourfold increase for a severe SARS-CoV-2 infection, and a fivefold increase for being intubated.

The three studies show that mortality rates were higher early in the pandemic “when diagnosis and treatment for SARS-CoV-2 might have been delayed, resulting in higher death rate,” Boffetta et al. wrote, adding that their analysis showed only a twofold increase most likely because it was a year-long analysis.

“Future studies will be able to better analyze this association for the different subtypes of cancer. Furthermore, they will eventually be able to evaluate whether the difference among vaccinated population is reduced,” Boffetta et al. wrote.

The authors noted several limitations for the study, including the fact that many of the studies included in the analysis did not include sex, age, comorbidities, and therapy. Nor were the authors able to analyze specific cancers other than hematologic neoplasms.

The authors declared no conflicts of interest.

A new systematic review and meta-analysis finds that unvaccinated cancer patients who contracted COVID-19 last year, were more than two times more likely – than people without cancer – to develop a case of COVID-19 so severe it required hospitalization in an intensive care unit.

“Our study provides the most precise measure to date of the effect of COVID-19 in cancer patients,” wrote researchers who were led by Paolo Boffetta, MD, MPH, a specialist in population science with the Stony Brook Cancer Center in New York.

Dr. Boffetta and colleagues also found that patients with hematologic neoplasms had a higher mortality rate from COVID-19 comparable to that of all cancers combined.

Cancer patients have long been considered to be among those patients who are at high risk of developing COVID-19, and if they contract the disease, they are at high risk of having poor outcomes. Other high-risk patients include those with hypertension, diabetes, chronic kidney disease, or COPD, or the elderly. But how high the risk of developing severe COVID-19 disease is for cancer patients hasn’t yet been documented on a wide scale.

The study, which was made available as a preprint on medRxiv on Oct. 23, is based on an analysis of COVID-19 cases that were documented in 35 reviews, meta-analyses, case reports, and studies indexed in PubMed from authors in North America, Europe, and Asia.

In this study, the pooled odds ratio for mortality for all patients with any cancer was 2.32 (95% confidence interval, 1.82-2.94; 24 studies). For ICU admission, the odds ratio was 2.39 (95% CI, 1.90-3.02; I2 0.0%; 5 studies). And, for disease severity or hospitalization, it was 2.08 (95% CI, 1.60-2.72; I2 92.1%; 15 studies). The pooled mortality odds ratio for hematologic neoplasms was 2.14 (95% CI, 1.87-2.44; I2 20.8%; 8 studies).

Their findings, which have not yet been peer reviewed, confirmed the results of a similar analysis from China published as a preprint in May 2020. The analysis included 181,323 patients (23,736 cancer patients) from 26 studies reported an odds ratio of 2.54 (95% CI, 1.47-4.42). “Cancer patients with COVID-19 have an increased likelihood of death compared to non-cancer COVID-19 patients,” Venkatesulu et al. wrote. And a systematic review and meta-analysis of five studies of 2,619 patients published in October 2020 in Medicine also found a significantly higher risk of death from COVID-19 among cancer patients (odds ratio, 2.63; 95% confidence interval, 1.14-6.06; P = .023; I2 = 26.4%).

Fakih et al., writing in the journal Hematology/Oncology and Stem Cell Therapy conducted a meta-analysis early last year finding a threefold increase for admission to the intensive care unit, an almost fourfold increase for a severe SARS-CoV-2 infection, and a fivefold increase for being intubated.

The three studies show that mortality rates were higher early in the pandemic “when diagnosis and treatment for SARS-CoV-2 might have been delayed, resulting in higher death rate,” Boffetta et al. wrote, adding that their analysis showed only a twofold increase most likely because it was a year-long analysis.

“Future studies will be able to better analyze this association for the different subtypes of cancer. Furthermore, they will eventually be able to evaluate whether the difference among vaccinated population is reduced,” Boffetta et al. wrote.

The authors noted several limitations for the study, including the fact that many of the studies included in the analysis did not include sex, age, comorbidities, and therapy. Nor were the authors able to analyze specific cancers other than hematologic neoplasms.

The authors declared no conflicts of interest.

Breast cancer screening using urine samples based on the volatile organic compounds (VOCs) sensed by a trained dog is feasible, according to a preliminary study published in the journal Biology June 10.

“The extrapolation of our results to widespread implementation is still uncertain,” wrote Shoko Kure, MD, PhD, of Nippon Medical School in Tokyo, and colleagues. “However, even if few dogs could be trained to detect breast cancer, the result may open the door to a robust and inexpensive way to detect breast cancer.” They added that “dog cancer detection is entirely noninvasive, safe and easy for both patients and everyone.” 

Early detection of breast cancer, which is the leading cause of death globally, is essential for more efficient treatment. While mammography can detect asymptomatic breast cancer and reduce mortality, it has a poor compliance, is less sensitive in dense breast tissue, detects nonmalignant lesions, and has not been shown to reduce mortality in women younger than 40. VOCs are emitted in the breath, blood, and urine, with different volatile patterns correlated with a variety of diseases including cancers, which dogs can be trained to detect. Breast cancer screening by dog sniffing of the VOCs in urine samples has not been attempted.

Dogs have been used as medical detectives for several cancers and conditions. A study published in 2018 showed that trained dogs who were able to differentiate the specific odor from the metabolic waste of breast cancer in vitro could identify that of colorectal cancer, and vice versa. More recently, research showed that trained dogs could detect advanced prostate cancer in urine samples with high specificity and sensitivity. In this double-blinded pilot study, two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. The canine olfaction system was 71% sensitive and as much as 76% specific at detecting Gleason 9 cancer. Along with cancer, trained dogs have been shown to identify people with COVID-19, even those who were asymptomatic. In this study, dogs who sniffed swab samples of armpit sweat could identify which samples came from patients infected with COVID-19 with up to 100% accuracy, while ruling out infection with up to 99% accuracy.

The double-blind study by Dr. Kure aimed to assess the potential of VOCs in urine samples for breast cancer screening by using a single trained sniffer dog – in this case a 9-year-old female Labrador retriever. Urine samples from 40 patients with primary breast cancer and 142 patients with non-breast malignant diseases were included along with samples from 18 healthy volunteers. In 40 times out of 40 runs of the double-blind test, the dog correctly identified urine samples of patients with breast cancer, with 100% sensitivity and 100% specificity.

“The dog in this test successfully differentiated breast cancer from non-breast malignancies and healthy controls,” the authors wrote. “This is the first, preliminary study indicating the feasibility of developing a new breast cancer screening method using urine samples based on VOCs.”

While the authors noted that the study was limited as it relied on one trained dog, they suggested that this method has potential in low-income countries where access to mammography is inadequate.

“Some well-trained sniffing dogs traveling around medically underserved [countries] all over the world could save many lives. Even when a healthy control was indicated by a trained dog, there would be a suspicion of undiagnosed/early-stage cancer, and the person would be advised to undergo medical screening,” the authors wrote.

The authors declared no conflicts of interest.

Breast cancer screening using urine samples based on the volatile organic compounds (VOCs) sensed by a trained dog is feasible, according to a preliminary study published in the journal Biology June 10.

“The extrapolation of our results to widespread implementation is still uncertain,” wrote Shoko Kure, MD, PhD, of Nippon Medical School in Tokyo, and colleagues. “However, even if few dogs could be trained to detect breast cancer, the result may open the door to a robust and inexpensive way to detect breast cancer.” They added that “dog cancer detection is entirely noninvasive, safe and easy for both patients and everyone.” 

Early detection of breast cancer, which is the leading cause of death globally, is essential for more efficient treatment. While mammography can detect asymptomatic breast cancer and reduce mortality, it has a poor compliance, is less sensitive in dense breast tissue, detects nonmalignant lesions, and has not been shown to reduce mortality in women younger than 40. VOCs are emitted in the breath, blood, and urine, with different volatile patterns correlated with a variety of diseases including cancers, which dogs can be trained to detect. Breast cancer screening by dog sniffing of the VOCs in urine samples has not been attempted.

Dogs have been used as medical detectives for several cancers and conditions. A study published in 2018 showed that trained dogs who were able to differentiate the specific odor from the metabolic waste of breast cancer in vitro could identify that of colorectal cancer, and vice versa. More recently, research showed that trained dogs could detect advanced prostate cancer in urine samples with high specificity and sensitivity. In this double-blinded pilot study, two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. The canine olfaction system was 71% sensitive and as much as 76% specific at detecting Gleason 9 cancer. Along with cancer, trained dogs have been shown to identify people with COVID-19, even those who were asymptomatic. In this study, dogs who sniffed swab samples of armpit sweat could identify which samples came from patients infected with COVID-19 with up to 100% accuracy, while ruling out infection with up to 99% accuracy.

The double-blind study by Dr. Kure aimed to assess the potential of VOCs in urine samples for breast cancer screening by using a single trained sniffer dog – in this case a 9-year-old female Labrador retriever. Urine samples from 40 patients with primary breast cancer and 142 patients with non-breast malignant diseases were included along with samples from 18 healthy volunteers. In 40 times out of 40 runs of the double-blind test, the dog correctly identified urine samples of patients with breast cancer, with 100% sensitivity and 100% specificity.

“The dog in this test successfully differentiated breast cancer from non-breast malignancies and healthy controls,” the authors wrote. “This is the first, preliminary study indicating the feasibility of developing a new breast cancer screening method using urine samples based on VOCs.”

While the authors noted that the study was limited as it relied on one trained dog, they suggested that this method has potential in low-income countries where access to mammography is inadequate.

“Some well-trained sniffing dogs traveling around medically underserved [countries] all over the world could save many lives. Even when a healthy control was indicated by a trained dog, there would be a suspicion of undiagnosed/early-stage cancer, and the person would be advised to undergo medical screening,” the authors wrote.

The authors declared no conflicts of interest.

Breast cancer screening using urine samples based on the volatile organic compounds (VOCs) sensed by a trained dog is feasible, according to a preliminary study published in the journal Biology June 10.

“The extrapolation of our results to widespread implementation is still uncertain,” wrote Shoko Kure, MD, PhD, of Nippon Medical School in Tokyo, and colleagues. “However, even if few dogs could be trained to detect breast cancer, the result may open the door to a robust and inexpensive way to detect breast cancer.” They added that “dog cancer detection is entirely noninvasive, safe and easy for both patients and everyone.” 

Early detection of breast cancer, which is the leading cause of death globally, is essential for more efficient treatment. While mammography can detect asymptomatic breast cancer and reduce mortality, it has a poor compliance, is less sensitive in dense breast tissue, detects nonmalignant lesions, and has not been shown to reduce mortality in women younger than 40. VOCs are emitted in the breath, blood, and urine, with different volatile patterns correlated with a variety of diseases including cancers, which dogs can be trained to detect. Breast cancer screening by dog sniffing of the VOCs in urine samples has not been attempted.

Dogs have been used as medical detectives for several cancers and conditions. A study published in 2018 showed that trained dogs who were able to differentiate the specific odor from the metabolic waste of breast cancer in vitro could identify that of colorectal cancer, and vice versa. More recently, research showed that trained dogs could detect advanced prostate cancer in urine samples with high specificity and sensitivity. In this double-blinded pilot study, two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. The canine olfaction system was 71% sensitive and as much as 76% specific at detecting Gleason 9 cancer. Along with cancer, trained dogs have been shown to identify people with COVID-19, even those who were asymptomatic. In this study, dogs who sniffed swab samples of armpit sweat could identify which samples came from patients infected with COVID-19 with up to 100% accuracy, while ruling out infection with up to 99% accuracy.

The double-blind study by Dr. Kure aimed to assess the potential of VOCs in urine samples for breast cancer screening by using a single trained sniffer dog – in this case a 9-year-old female Labrador retriever. Urine samples from 40 patients with primary breast cancer and 142 patients with non-breast malignant diseases were included along with samples from 18 healthy volunteers. In 40 times out of 40 runs of the double-blind test, the dog correctly identified urine samples of patients with breast cancer, with 100% sensitivity and 100% specificity.

“The dog in this test successfully differentiated breast cancer from non-breast malignancies and healthy controls,” the authors wrote. “This is the first, preliminary study indicating the feasibility of developing a new breast cancer screening method using urine samples based on VOCs.”

While the authors noted that the study was limited as it relied on one trained dog, they suggested that this method has potential in low-income countries where access to mammography is inadequate.

“Some well-trained sniffing dogs traveling around medically underserved [countries] all over the world could save many lives. Even when a healthy control was indicated by a trained dog, there would be a suspicion of undiagnosed/early-stage cancer, and the person would be advised to undergo medical screening,” the authors wrote.

The authors declared no conflicts of interest.

In patients with metastatic urothelial carcinoma, immunotherapy, antibody drug conjugates and targeted agents are being added to the potential treatment options for this incurable condition, which has a limited life expectancy. This is according to a review of the recent therapeutic advances and ongoing clinical trials in metastatic urothelial carcinoma.

“Survival in the metastatic setting is 12-15 months with cisplatin-based combination chemotherapy, but only 3-6 months if left untreated,” wrote Srikala S. Sridhar, MD, of the University of Toronto, and colleagues. Their report is in Therapeutic Advances in Medical Oncology. “More recently, with the advent of immunotherapy, antibody-drug conjugates, and targeted agents, the treatment landscape has changed significantly, with overall survival now approaching two years.”

Both the incidence and mortality from bladder cancer have risen over the past few decades. Around 5% of patients are metastatic at presentation, but nearly half of patients with muscle-invasive bladder cancer will eventually relapse and develop metastatic disease.

For first-line treatment in metastatic urothelial carcinoma, cisplatin-based chemotherapy remains the preferred option with response rates up to 72%, but durability is an issue with most patients experiencing disease progression. In patients with locally advanced or metastatic disease, who are not eligible for cisplatin-based chemotherapy and whose tumors express PD-L1, or patients who are not eligible for any platinum-based regimen regardless of PD-L1 status, the immune checkpoint inhibitors atezolizumab and pembrolizumab have received accelerated Food and Drug administration approval. More recently, pembrolizumab gained full FDA approval for use in patients not eligible to receive platinum-based chemotherapy.

While phase 3 studies are evaluating chemotherapy combined with atezolizumab or pembrolizumab, the results have not been promising. Moreover, the decreased survival observed in the immunotherapy-alone arms of these trials led the FDA to issue a warning that single agent immunotherapy should be used only in patients who are not eligible for cisplatin-based therapy and have PD-L1 expression, or in those not eligible for any platinum-based regimens regardless of PD-L1 expression.

“More intensive treatment in metastatic urothelial carcinoma is not always better,” the authors wrote. “Some of the reasons for this could be that chemotherapy and immunotherapy are targeting a similar population of cells, or that chemotherapy and immunotherapy are antagonistic on some level.”

Maintenance strategies are considered standard of care for other advanced solid tumors. In patients with bladder cancer without disease progression after a first line platinum-based chemotherapy, maintenance avelumab, an anti PD-L1, has shown an overall survival of 21.4 months versus 14.3 months with best supportive care, a finding that the authors described as “practice changing.” Meanwhile, a separate trial showed increased progression-free survival with maintenance pembrolizumab, but no increased overall survival.

For second-line treatment, immunotherapy is currently the standard of care in patients with disease progression during or after platinum-based chemotherapy. While the efficiency of five anti PD-1 and PD-L1 antibodies has been reported in the second-line setting, pembrolizumab is the only immune checkpoint inhibitor to receive full FDA approval. Atezolizumab, nivolumab, avelumab, and durvalumab have received accelerated approval.

“In urothelial carcinomas, PD-1 appears to have an advantage over anti PD-L1 in the second-line setting, but in the maintenance setting, it seems to be the opposite,” the authors wrote.

Erdafitinib is the only fibroblast growth factor receptor (FGFR) inhibitor approved for locally advanced or metastatic urothelial carcinoma, progressing on platinum-based chemotherapy. The oral potent tyrosine kinase inhibitor of FGFR 1-4 is approved for use only in patients with susceptible FGFR3 gene mutations or FGFR2/3 gene fusions. Despite being approved for second-line treatment, erdafitinib is used mainly in third-line treatment after progression on immunotherapy. 

The antibody drug conjugates sacituzumab govitecan and enfortumab vedotin, which have gained accelerated FDA approval, provide other options for patients with metastatic urothelial carcinoma resistant to chemotherapy and checkpoint inhibitors. As these antibody drug conjugates have different mechanisms of action and toxicity profiles, they could be used in the same patient throughout the disease course, but further research is needed. Meanwhile, many chemotherapy options, including docetaxel, gemcitabine, ifosfamide, and pemetrexed, have been tested in metastatic urothelial carcinoma with some response after platinum-based treatment.

“A number of studies evaluating promising therapeutic strategies are still ongoing and will hopefully provide information for some important unanswered questions and further guide treatment sequencing in advanced urothelial carcinoma,” the authors wrote.

They declared that there are no conflicts of interest.

In patients with metastatic urothelial carcinoma, immunotherapy, antibody drug conjugates and targeted agents are being added to the potential treatment options for this incurable condition, which has a limited life expectancy. This is according to a review of the recent therapeutic advances and ongoing clinical trials in metastatic urothelial carcinoma.

“Survival in the metastatic setting is 12-15 months with cisplatin-based combination chemotherapy, but only 3-6 months if left untreated,” wrote Srikala S. Sridhar, MD, of the University of Toronto, and colleagues. Their report is in Therapeutic Advances in Medical Oncology. “More recently, with the advent of immunotherapy, antibody-drug conjugates, and targeted agents, the treatment landscape has changed significantly, with overall survival now approaching two years.”

Both the incidence and mortality from bladder cancer have risen over the past few decades. Around 5% of patients are metastatic at presentation, but nearly half of patients with muscle-invasive bladder cancer will eventually relapse and develop metastatic disease.

For first-line treatment in metastatic urothelial carcinoma, cisplatin-based chemotherapy remains the preferred option with response rates up to 72%, but durability is an issue with most patients experiencing disease progression. In patients with locally advanced or metastatic disease, who are not eligible for cisplatin-based chemotherapy and whose tumors express PD-L1, or patients who are not eligible for any platinum-based regimen regardless of PD-L1 status, the immune checkpoint inhibitors atezolizumab and pembrolizumab have received accelerated Food and Drug administration approval. More recently, pembrolizumab gained full FDA approval for use in patients not eligible to receive platinum-based chemotherapy.

While phase 3 studies are evaluating chemotherapy combined with atezolizumab or pembrolizumab, the results have not been promising. Moreover, the decreased survival observed in the immunotherapy-alone arms of these trials led the FDA to issue a warning that single agent immunotherapy should be used only in patients who are not eligible for cisplatin-based therapy and have PD-L1 expression, or in those not eligible for any platinum-based regimens regardless of PD-L1 expression.

“More intensive treatment in metastatic urothelial carcinoma is not always better,” the authors wrote. “Some of the reasons for this could be that chemotherapy and immunotherapy are targeting a similar population of cells, or that chemotherapy and immunotherapy are antagonistic on some level.”

Maintenance strategies are considered standard of care for other advanced solid tumors. In patients with bladder cancer without disease progression after a first line platinum-based chemotherapy, maintenance avelumab, an anti PD-L1, has shown an overall survival of 21.4 months versus 14.3 months with best supportive care, a finding that the authors described as “practice changing.” Meanwhile, a separate trial showed increased progression-free survival with maintenance pembrolizumab, but no increased overall survival.

For second-line treatment, immunotherapy is currently the standard of care in patients with disease progression during or after platinum-based chemotherapy. While the efficiency of five anti PD-1 and PD-L1 antibodies has been reported in the second-line setting, pembrolizumab is the only immune checkpoint inhibitor to receive full FDA approval. Atezolizumab, nivolumab, avelumab, and durvalumab have received accelerated approval.

“In urothelial carcinomas, PD-1 appears to have an advantage over anti PD-L1 in the second-line setting, but in the maintenance setting, it seems to be the opposite,” the authors wrote.

Erdafitinib is the only fibroblast growth factor receptor (FGFR) inhibitor approved for locally advanced or metastatic urothelial carcinoma, progressing on platinum-based chemotherapy. The oral potent tyrosine kinase inhibitor of FGFR 1-4 is approved for use only in patients with susceptible FGFR3 gene mutations or FGFR2/3 gene fusions. Despite being approved for second-line treatment, erdafitinib is used mainly in third-line treatment after progression on immunotherapy. 

The antibody drug conjugates sacituzumab govitecan and enfortumab vedotin, which have gained accelerated FDA approval, provide other options for patients with metastatic urothelial carcinoma resistant to chemotherapy and checkpoint inhibitors. As these antibody drug conjugates have different mechanisms of action and toxicity profiles, they could be used in the same patient throughout the disease course, but further research is needed. Meanwhile, many chemotherapy options, including docetaxel, gemcitabine, ifosfamide, and pemetrexed, have been tested in metastatic urothelial carcinoma with some response after platinum-based treatment.

“A number of studies evaluating promising therapeutic strategies are still ongoing and will hopefully provide information for some important unanswered questions and further guide treatment sequencing in advanced urothelial carcinoma,” the authors wrote.

They declared that there are no conflicts of interest.

In patients with metastatic urothelial carcinoma, immunotherapy, antibody drug conjugates and targeted agents are being added to the potential treatment options for this incurable condition, which has a limited life expectancy. This is according to a review of the recent therapeutic advances and ongoing clinical trials in metastatic urothelial carcinoma.

“Survival in the metastatic setting is 12-15 months with cisplatin-based combination chemotherapy, but only 3-6 months if left untreated,” wrote Srikala S. Sridhar, MD, of the University of Toronto, and colleagues. Their report is in Therapeutic Advances in Medical Oncology. “More recently, with the advent of immunotherapy, antibody-drug conjugates, and targeted agents, the treatment landscape has changed significantly, with overall survival now approaching two years.”

Both the incidence and mortality from bladder cancer have risen over the past few decades. Around 5% of patients are metastatic at presentation, but nearly half of patients with muscle-invasive bladder cancer will eventually relapse and develop metastatic disease.

For first-line treatment in metastatic urothelial carcinoma, cisplatin-based chemotherapy remains the preferred option with response rates up to 72%, but durability is an issue with most patients experiencing disease progression. In patients with locally advanced or metastatic disease, who are not eligible for cisplatin-based chemotherapy and whose tumors express PD-L1, or patients who are not eligible for any platinum-based regimen regardless of PD-L1 status, the immune checkpoint inhibitors atezolizumab and pembrolizumab have received accelerated Food and Drug administration approval. More recently, pembrolizumab gained full FDA approval for use in patients not eligible to receive platinum-based chemotherapy.

While phase 3 studies are evaluating chemotherapy combined with atezolizumab or pembrolizumab, the results have not been promising. Moreover, the decreased survival observed in the immunotherapy-alone arms of these trials led the FDA to issue a warning that single agent immunotherapy should be used only in patients who are not eligible for cisplatin-based therapy and have PD-L1 expression, or in those not eligible for any platinum-based regimens regardless of PD-L1 expression.

“More intensive treatment in metastatic urothelial carcinoma is not always better,” the authors wrote. “Some of the reasons for this could be that chemotherapy and immunotherapy are targeting a similar population of cells, or that chemotherapy and immunotherapy are antagonistic on some level.”

Maintenance strategies are considered standard of care for other advanced solid tumors. In patients with bladder cancer without disease progression after a first line platinum-based chemotherapy, maintenance avelumab, an anti PD-L1, has shown an overall survival of 21.4 months versus 14.3 months with best supportive care, a finding that the authors described as “practice changing.” Meanwhile, a separate trial showed increased progression-free survival with maintenance pembrolizumab, but no increased overall survival.

For second-line treatment, immunotherapy is currently the standard of care in patients with disease progression during or after platinum-based chemotherapy. While the efficiency of five anti PD-1 and PD-L1 antibodies has been reported in the second-line setting, pembrolizumab is the only immune checkpoint inhibitor to receive full FDA approval. Atezolizumab, nivolumab, avelumab, and durvalumab have received accelerated approval.

“In urothelial carcinomas, PD-1 appears to have an advantage over anti PD-L1 in the second-line setting, but in the maintenance setting, it seems to be the opposite,” the authors wrote.

Erdafitinib is the only fibroblast growth factor receptor (FGFR) inhibitor approved for locally advanced or metastatic urothelial carcinoma, progressing on platinum-based chemotherapy. The oral potent tyrosine kinase inhibitor of FGFR 1-4 is approved for use only in patients with susceptible FGFR3 gene mutations or FGFR2/3 gene fusions. Despite being approved for second-line treatment, erdafitinib is used mainly in third-line treatment after progression on immunotherapy. 

The antibody drug conjugates sacituzumab govitecan and enfortumab vedotin, which have gained accelerated FDA approval, provide other options for patients with metastatic urothelial carcinoma resistant to chemotherapy and checkpoint inhibitors. As these antibody drug conjugates have different mechanisms of action and toxicity profiles, they could be used in the same patient throughout the disease course, but further research is needed. Meanwhile, many chemotherapy options, including docetaxel, gemcitabine, ifosfamide, and pemetrexed, have been tested in metastatic urothelial carcinoma with some response after platinum-based treatment.

“A number of studies evaluating promising therapeutic strategies are still ongoing and will hopefully provide information for some important unanswered questions and further guide treatment sequencing in advanced urothelial carcinoma,” the authors wrote.

They declared that there are no conflicts of interest.

The number of same-day discharges has grown with the increase in robotic-assisted surgeries and advances in imaging and pressures to reduce hospital costs. COVID-19 has, perhaps temporarily, increased the same-day surgery numbers as surgeries have been restricted and hospital beds are needed for COVID-19 patients.

Urologist Ronney Abaza, MD, a robotic surgery specialist in Dublin, Ohio, and colleagues, reviewed robotic surgeries at their hospital during COVID-19 restrictions on surgery in Ohio between March 17 and June 5, 2020, and compared them with robotic procedures before COVID-19 and after restrictions were lifted. They published their results in Urology.

Since 2016, the hospital has offered the option of same-day discharge (SDD) to all robotic urologic surgery patients, regardless of procedure or patient-specific factors.

Among patients who had surgery during COVID-19 restrictions, 98% (87/89 patients) opted for SDD versus 52% in the group having surgery before the restrictions (P < .00001). After the COVID-19 surgery restrictions were lifted, the higher rate of SDD remained at 98%.

“There were no differences in 30-day complications or readmissions between SDD and overnight patients,” the authors write.
 

The right patient, the right motivation for successful surgery

Brian Lane, MD, PhD, a urologic oncologist with Spectrum Health in Grand Rapids, Michigan, told this news organization that, for nephrectomies, uptake of same-day discharge will continue to be slow.

“You have to have the right patient, the right patient motivation, and the surgery has to go smoothly,” he said. “If you start sending everyone home the same day, you will certainly see readmissions,” he said.

Dr. Lane is part of the Michigan Urologic Surgery Improvement Collaborative and he said the group recently looked at same-day discharge outcomes after robotic prostatectomies with SDD as compared with 1-2 nights in the hospital.

The work has not yet been published but, “There was a slight signal that there were increased readmissions with same-day discharge vs. 0-1 day,” he said.

A paper on outcomes of same-day discharge in total knee arthroplasty in the Journal of Bone & Joint Surgery found a higher risk of perioperative complications “including component failure, surgical site infection, knee stiffness, and deep vein thrombosis.” Researchers compared outcomes between 4,391 patients who underwent outpatient TKA and 128,951 patients who underwent inpatient TKA.

But for other many surgeries, same-day discharge numbers are increasing without worsening outcomes.

A paper in the Journal of Robotic Surgery found that same-day discharge following robotic-assisted endometrial cancer staging is “safe and feasible.”

Stephen Bradley, MD, MPH, with the Minneapolis Heart Institute in Minneapolis, and colleagues write in the Journal of the American College of Cardiology: Cardiovascular Interventions that they found a large increase in the use of same-day discharge after elective percutaneous coronary intervention (PCI) was not associated with worse 30-day mortality rates or readmission.

In that study, 114,461 patients were discharged the same day they underwent PCI. The proportion of patients who had a same-day discharge increased from 4.5% in 2009 to 28.6% in the fourth quarter of 2017.

Risk-adjusted 30-day mortality did not change in that time, while risk-adjusted rehospitalization decreased over time and more quickly when patients had same-day discharge.

Deepak L. Bhatt, MD, MPH, and Jonathan G. Sung, MBCHB, both of Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, wrote in an accompanying article that, “Advances in the devices and techniques of PCI have improved the safety and efficacy of the procedure. In selected patients, same-day discharge has become possible, and overnight in-hospital observation can be avoided. By reducing unnecessary hospital stays, both patients and hospitals could benefit.”

Evan Garden, a medical student at Icahn School of Medicine at Mount Sinai in New York, presented findings at the American Urological Association 2021 annual meeting that show patients selected for same-day discharge after partial or radical nephrectomy did not have increased rates of postoperative complications or readmissions in the immediate postoperative period, compared with standard discharge of 1-3 days.
 

Case studies in nephrectomy

While several case studies have looked at the feasibility and safety of performing partial and radical nephrectomy with same-day discharge in select cases, “this topic has not been addressed on a national level,” Mr. Garden said.

Few patients who have partial or radical nephrectomies have same-day discharges. The researchers found that fewer than 1% of patients who have either procedure in the sample studied were discharged the same day.

Researchers used the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, a nationally representative deidentified database that prospectively tracks patient characteristics and 30-day perioperative outcomes for major inpatient and outpatient surgical procedures at more than 700 hospitals.

They extracted all minimally invasive partial and radical nephrectomies from 2012 to 2019 and refined the cohort to 28,140 patients who were theoretically eligible for same-day discharge: Of those, 237 (0.8%) had SSD, and 27,903 (99.2%) had a standard-length discharge (SLD).

The team found that there were no differences in 30-day complications or readmissions between same-day discharge (Clavien-Dindo [CD] I/II, 4.22%; CD III, 0%; CD IV, 1.27%; readmission, 4.64%); and SLD (CD I/II, 4.11%; CD III, 0.95%; CD IV, 0.79%; readmission, 3.90%; all P > .05).

Controlling for demographic and clinical variables, SDD was not associated with greater risk of 30-day complications or readmissions (CD I/II: odds ratio, 1.08; 95% confidence interval, 0.57-2.048; P = .813; CD IV: OR 1.699; 95% CI, 0.537-5.375; P = .367; readmission: OR, 1.254; 95% CI, 0.681-2.31; P = .467).

Mr. Garden and coauthors report no relevant financial relationships.

Dr. Lane reports no relevant financial relationships.

The number of same-day discharges has grown with the increase in robotic-assisted surgeries and advances in imaging and pressures to reduce hospital costs. COVID-19 has, perhaps temporarily, increased the same-day surgery numbers as surgeries have been restricted and hospital beds are needed for COVID-19 patients.

Urologist Ronney Abaza, MD, a robotic surgery specialist in Dublin, Ohio, and colleagues, reviewed robotic surgeries at their hospital during COVID-19 restrictions on surgery in Ohio between March 17 and June 5, 2020, and compared them with robotic procedures before COVID-19 and after restrictions were lifted. They published their results in Urology.

Since 2016, the hospital has offered the option of same-day discharge (SDD) to all robotic urologic surgery patients, regardless of procedure or patient-specific factors.

Among patients who had surgery during COVID-19 restrictions, 98% (87/89 patients) opted for SDD versus 52% in the group having surgery before the restrictions (P < .00001). After the COVID-19 surgery restrictions were lifted, the higher rate of SDD remained at 98%.

“There were no differences in 30-day complications or readmissions between SDD and overnight patients,” the authors write.
 

The right patient, the right motivation for successful surgery

Brian Lane, MD, PhD, a urologic oncologist with Spectrum Health in Grand Rapids, Michigan, told this news organization that, for nephrectomies, uptake of same-day discharge will continue to be slow.

“You have to have the right patient, the right patient motivation, and the surgery has to go smoothly,” he said. “If you start sending everyone home the same day, you will certainly see readmissions,” he said.

Dr. Lane is part of the Michigan Urologic Surgery Improvement Collaborative and he said the group recently looked at same-day discharge outcomes after robotic prostatectomies with SDD as compared with 1-2 nights in the hospital.

The work has not yet been published but, “There was a slight signal that there were increased readmissions with same-day discharge vs. 0-1 day,” he said.

A paper on outcomes of same-day discharge in total knee arthroplasty in the Journal of Bone & Joint Surgery found a higher risk of perioperative complications “including component failure, surgical site infection, knee stiffness, and deep vein thrombosis.” Researchers compared outcomes between 4,391 patients who underwent outpatient TKA and 128,951 patients who underwent inpatient TKA.

But for other many surgeries, same-day discharge numbers are increasing without worsening outcomes.

A paper in the Journal of Robotic Surgery found that same-day discharge following robotic-assisted endometrial cancer staging is “safe and feasible.”

Stephen Bradley, MD, MPH, with the Minneapolis Heart Institute in Minneapolis, and colleagues write in the Journal of the American College of Cardiology: Cardiovascular Interventions that they found a large increase in the use of same-day discharge after elective percutaneous coronary intervention (PCI) was not associated with worse 30-day mortality rates or readmission.

In that study, 114,461 patients were discharged the same day they underwent PCI. The proportion of patients who had a same-day discharge increased from 4.5% in 2009 to 28.6% in the fourth quarter of 2017.

Risk-adjusted 30-day mortality did not change in that time, while risk-adjusted rehospitalization decreased over time and more quickly when patients had same-day discharge.

Deepak L. Bhatt, MD, MPH, and Jonathan G. Sung, MBCHB, both of Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, wrote in an accompanying article that, “Advances in the devices and techniques of PCI have improved the safety and efficacy of the procedure. In selected patients, same-day discharge has become possible, and overnight in-hospital observation can be avoided. By reducing unnecessary hospital stays, both patients and hospitals could benefit.”

Evan Garden, a medical student at Icahn School of Medicine at Mount Sinai in New York, presented findings at the American Urological Association 2021 annual meeting that show patients selected for same-day discharge after partial or radical nephrectomy did not have increased rates of postoperative complications or readmissions in the immediate postoperative period, compared with standard discharge of 1-3 days.
 

Case studies in nephrectomy

While several case studies have looked at the feasibility and safety of performing partial and radical nephrectomy with same-day discharge in select cases, “this topic has not been addressed on a national level,” Mr. Garden said.

Few patients who have partial or radical nephrectomies have same-day discharges. The researchers found that fewer than 1% of patients who have either procedure in the sample studied were discharged the same day.

Researchers used the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, a nationally representative deidentified database that prospectively tracks patient characteristics and 30-day perioperative outcomes for major inpatient and outpatient surgical procedures at more than 700 hospitals.

They extracted all minimally invasive partial and radical nephrectomies from 2012 to 2019 and refined the cohort to 28,140 patients who were theoretically eligible for same-day discharge: Of those, 237 (0.8%) had SSD, and 27,903 (99.2%) had a standard-length discharge (SLD).

The team found that there were no differences in 30-day complications or readmissions between same-day discharge (Clavien-Dindo [CD] I/II, 4.22%; CD III, 0%; CD IV, 1.27%; readmission, 4.64%); and SLD (CD I/II, 4.11%; CD III, 0.95%; CD IV, 0.79%; readmission, 3.90%; all P > .05).

Controlling for demographic and clinical variables, SDD was not associated with greater risk of 30-day complications or readmissions (CD I/II: odds ratio, 1.08; 95% confidence interval, 0.57-2.048; P = .813; CD IV: OR 1.699; 95% CI, 0.537-5.375; P = .367; readmission: OR, 1.254; 95% CI, 0.681-2.31; P = .467).

Mr. Garden and coauthors report no relevant financial relationships.

Dr. Lane reports no relevant financial relationships.

The number of same-day discharges has grown with the increase in robotic-assisted surgeries and advances in imaging and pressures to reduce hospital costs. COVID-19 has, perhaps temporarily, increased the same-day surgery numbers as surgeries have been restricted and hospital beds are needed for COVID-19 patients.

Urologist Ronney Abaza, MD, a robotic surgery specialist in Dublin, Ohio, and colleagues, reviewed robotic surgeries at their hospital during COVID-19 restrictions on surgery in Ohio between March 17 and June 5, 2020, and compared them with robotic procedures before COVID-19 and after restrictions were lifted. They published their results in Urology.

Since 2016, the hospital has offered the option of same-day discharge (SDD) to all robotic urologic surgery patients, regardless of procedure or patient-specific factors.

Among patients who had surgery during COVID-19 restrictions, 98% (87/89 patients) opted for SDD versus 52% in the group having surgery before the restrictions (P < .00001). After the COVID-19 surgery restrictions were lifted, the higher rate of SDD remained at 98%.

“There were no differences in 30-day complications or readmissions between SDD and overnight patients,” the authors write.
 

The right patient, the right motivation for successful surgery

Brian Lane, MD, PhD, a urologic oncologist with Spectrum Health in Grand Rapids, Michigan, told this news organization that, for nephrectomies, uptake of same-day discharge will continue to be slow.

“You have to have the right patient, the right patient motivation, and the surgery has to go smoothly,” he said. “If you start sending everyone home the same day, you will certainly see readmissions,” he said.

Dr. Lane is part of the Michigan Urologic Surgery Improvement Collaborative and he said the group recently looked at same-day discharge outcomes after robotic prostatectomies with SDD as compared with 1-2 nights in the hospital.

The work has not yet been published but, “There was a slight signal that there were increased readmissions with same-day discharge vs. 0-1 day,” he said.

A paper on outcomes of same-day discharge in total knee arthroplasty in the Journal of Bone & Joint Surgery found a higher risk of perioperative complications “including component failure, surgical site infection, knee stiffness, and deep vein thrombosis.” Researchers compared outcomes between 4,391 patients who underwent outpatient TKA and 128,951 patients who underwent inpatient TKA.

But for other many surgeries, same-day discharge numbers are increasing without worsening outcomes.

A paper in the Journal of Robotic Surgery found that same-day discharge following robotic-assisted endometrial cancer staging is “safe and feasible.”

Stephen Bradley, MD, MPH, with the Minneapolis Heart Institute in Minneapolis, and colleagues write in the Journal of the American College of Cardiology: Cardiovascular Interventions that they found a large increase in the use of same-day discharge after elective percutaneous coronary intervention (PCI) was not associated with worse 30-day mortality rates or readmission.

In that study, 114,461 patients were discharged the same day they underwent PCI. The proportion of patients who had a same-day discharge increased from 4.5% in 2009 to 28.6% in the fourth quarter of 2017.

Risk-adjusted 30-day mortality did not change in that time, while risk-adjusted rehospitalization decreased over time and more quickly when patients had same-day discharge.

Deepak L. Bhatt, MD, MPH, and Jonathan G. Sung, MBCHB, both of Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, wrote in an accompanying article that, “Advances in the devices and techniques of PCI have improved the safety and efficacy of the procedure. In selected patients, same-day discharge has become possible, and overnight in-hospital observation can be avoided. By reducing unnecessary hospital stays, both patients and hospitals could benefit.”

Evan Garden, a medical student at Icahn School of Medicine at Mount Sinai in New York, presented findings at the American Urological Association 2021 annual meeting that show patients selected for same-day discharge after partial or radical nephrectomy did not have increased rates of postoperative complications or readmissions in the immediate postoperative period, compared with standard discharge of 1-3 days.
 

Case studies in nephrectomy

While several case studies have looked at the feasibility and safety of performing partial and radical nephrectomy with same-day discharge in select cases, “this topic has not been addressed on a national level,” Mr. Garden said.

Few patients who have partial or radical nephrectomies have same-day discharges. The researchers found that fewer than 1% of patients who have either procedure in the sample studied were discharged the same day.

Researchers used the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, a nationally representative deidentified database that prospectively tracks patient characteristics and 30-day perioperative outcomes for major inpatient and outpatient surgical procedures at more than 700 hospitals.

They extracted all minimally invasive partial and radical nephrectomies from 2012 to 2019 and refined the cohort to 28,140 patients who were theoretically eligible for same-day discharge: Of those, 237 (0.8%) had SSD, and 27,903 (99.2%) had a standard-length discharge (SLD).

The team found that there were no differences in 30-day complications or readmissions between same-day discharge (Clavien-Dindo [CD] I/II, 4.22%; CD III, 0%; CD IV, 1.27%; readmission, 4.64%); and SLD (CD I/II, 4.11%; CD III, 0.95%; CD IV, 0.79%; readmission, 3.90%; all P > .05).

Controlling for demographic and clinical variables, SDD was not associated with greater risk of 30-day complications or readmissions (CD I/II: odds ratio, 1.08; 95% confidence interval, 0.57-2.048; P = .813; CD IV: OR 1.699; 95% CI, 0.537-5.375; P = .367; readmission: OR, 1.254; 95% CI, 0.681-2.31; P = .467).

Mr. Garden and coauthors report no relevant financial relationships.

Dr. Lane reports no relevant financial relationships.