Gynecologic Cancer

Older adults are more susceptible to adverse drug reactions because of changes in physiology, clearance, and reserves. Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.^1-3

Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
 

Geriatric assessment and chemotherapy-related toxic effects

A cluster randomized trial¹ at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.

The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.

The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
 

Geriatric assessment in community oncology practices

A recent study by Supriya G. Mohile, MD, and colleagues² is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.

The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
 

Geriatric assessment and oncologist-patient communication

A secondary analysis³ of data from Dr. Mohile and colleagues² evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.

In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.

Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.

References

1. Li D et al. JAMA Oncol. 2021;7:e214158.

2. Mohile SG et al. Lancet. 2021;398:1894-1904.

3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.

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

Older adults are more susceptible to adverse drug reactions because of changes in physiology, clearance, and reserves. Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.^1-3

Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
 

Geriatric assessment and chemotherapy-related toxic effects

A cluster randomized trial¹ at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.

The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.

The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
 

Geriatric assessment in community oncology practices

A recent study by Supriya G. Mohile, MD, and colleagues² is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.

The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
 

Geriatric assessment and oncologist-patient communication

A secondary analysis³ of data from Dr. Mohile and colleagues² evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.

In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.

Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.

References

1. Li D et al. JAMA Oncol. 2021;7:e214158.

2. Mohile SG et al. Lancet. 2021;398:1894-1904.

3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.

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

Older adults are more susceptible to adverse drug reactions because of changes in physiology, clearance, and reserves. Age-related changes that potentiate adverse drug reactions include alterations in absorption, distribution, metabolism, and excretion. As such, older patients often require adjustments in medications to optimize safety and use. Medication adjustment is especially important for older patients on complex medication regimens for multiple conditions, such as those undergoing cancer treatment. Three recent high-quality randomized trials evaluated the use of geriatric assessment (GA) in older adults with cancer.^1-3

Interdisciplinary GA can identify aging-related conditions associated with poor outcomes in older patients with cancer (e.g., toxic effects of chemotherapy) and provide recommendations aimed at improving health outcomes. The results of these trials suggest that interdisciplinary GA can improve care outcomes and oncologists’ communication for older adults with cancer, and should be considered an emerging standard of care.
 

Geriatric assessment and chemotherapy-related toxic effects

A cluster randomized trial¹ at City of Hope National Medical Center conducted between August 2015 and February 2019 enrolled 613 participants and randomly assigned them to receive a GA-guided intervention or usual standard of care in a 2-to-1 ratio. Participants were eligible for the study if they were aged ≥65 years; had a diagnosis of solid malignant neoplasm of any stage; were starting a new chemotherapy regimen; and were fluent in English, Spanish, or Chinese.

The intervention included a GA at baseline followed by assessments focused on six common areas: sleep problems, problems with eating and feeding, incontinence, confusion, evidence of falls, and skin breakdown. An interdisciplinary team (oncologist, nurse practitioner, pharmacist, physical therapist, occupational therapist, social worker, and nutritionist) performed the assessment and developed a plan of care. Interventions were multifactorial and could include referral to specialists; recommendations for medication changes; symptom management; nutritional intervention with diet recommendations and supplementation; and interventions targeting social, spiritual, and functional well-being. Follow-up by a nurse practitioner continued until completion of chemotherapy or 6 months after starting chemotherapy, whichever was earlier.

The primary outcome was grade 3 or higher chemotherapy-related toxic effects using National Cancer Institute criteria, and secondary outcomes were advance directive completion, emergency room visits and unplanned hospitalizations, and survival up to 12 months. Results showed a 10% absolute reduction in the incidence of grade 3 or higher toxic effects (P = .02), with a number needed to treat of 10. Advance directive completion also increased by 15%, but no differences were observed for other outcomes. This study offers high-quality evidence that a GA-based intervention can reduce toxic effects of chemotherapy regimens for older adults with cancer.
 

Geriatric assessment in community oncology practices

A recent study by Supriya G. Mohile, MD, and colleagues² is the first nationwide multicenter clinical trial to demonstrate the effects of GA and GA-guided management. This study was conducted in 40 oncology practices from the University of Rochester National Cancer Institute Community Oncology Research Program network. Centers were randomly assigned to intervention or usual care (362 patients treated by 68 oncologists in the intervention group and 371 patients treated by 91 oncologists in the usual-care group). Eligibility criteria were age ≥70 years; impairment in at least one GA domain other than polypharmacy; incurable advanced solid tumor or lymphoma with a plan to start new cancer treatment with a high risk for toxic effects within 4 weeks; and English language fluency. Both study groups underwent a baseline GA that assessed patients’ physical performance, functional status, comorbidity, cognition, nutrition, social support, polypharmacy, and psychological status. For the intervention group, a summary and management recommendations were provided to the treating oncologists.

The primary outcome was grade 3 or higher toxic effects within 3 months of starting a new regimen; secondary outcomes included treatment intensity and survival and GA outcomes within 3 months. A smaller proportion of patients in the intervention group experienced toxicity (51% vs. 71%), with an absolute risk reduction of 20%. Patients in the intervention group also had fewer falls and a greater reduction in medications used; there were no other differences in secondary outcomes. This study offers very strong and generalizable evidence that incorporating GA in the care of older adults with cancer at risk for toxicity can reduce toxicity as well as improve other outcomes, such as falls and polypharmacy.
 

Geriatric assessment and oncologist-patient communication

A secondary analysis³ of data from Dr. Mohile and colleagues² evaluated the effect of GA-guided recommendations on oncologist-patient communication regarding comorbidities. Patients (n = 541) included in this analysis were 76.6 years of age on average and had 3.2 (standard deviation, 1.9) comorbid conditions. All patients underwent GA, but only oncologists in the intervention arm received GA-based recommendations. Clinical encounters between oncologist and patient immediately following the GA were audio recorded and analyzed to examine communication between oncologists and participants as it relates to chronic comorbid conditions.

In the intervention arm, more discussions regarding comorbidities took place, and more participants’ concerns about comorbidities were acknowledged. More importantly, participants in the intervention group were 2.4 times more likely to have their concerns about comorbidities addressed through referral or education, compared with the usual-care group (P = .004). Moreover, 41% of oncologists in the intervention arm modified dosage or cancer treatment schedule because of concern about tolerability or comorbidities. This study demonstrates beneficial effects of GA in increasing communication and perhaps consideration of comorbidities of older adults when planning cancer treatment.

Dr. Hung is professor of geriatrics and palliative care at Mount Sinai Hospital, New York. He disclosed no relevant conflicts of interest.

References

1. Li D et al. JAMA Oncol. 2021;7:e214158.

2. Mohile SG et al. Lancet. 2021;398:1894-1904.

3. Kleckner AS et al. JCO Oncol Pract. 2022;18:e9-19.

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

Despite the challenges of an ongoing COVID-19 pandemic, researchers in 2021 delivered practice-changing studies in gynecologic oncology. In this cancer Update, we highlight 4 studies that shed light on the surgical and systemic therapies that may improve outcomes for patients with cancers of the ovary, endometrium, and cervix. We review DESKTOP III, a trial that investigated the role of cytoreductive surgery in patients with recurrent ovarian cancer, and SENTOR, a study that evaluated the performance of sentinel lymph node biopsy in patients with high-grade endometrial cancers. Additionally, we examine 2 studies of systemic therapy that reveal the growing role of targeted therapies and immuno-oncology in the treatment of gynecologic malignancies.

A new era for patients with BRCA mutation–associated ovarian cancer

Banerjee S, Moore KN, Colombo N, et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021;22:1721-1731.

Ovarian cancer remains the most lethal gynecologic malignancy due to the frequency of advanced-stage diagnosis and frequent relapse after primary therapy. But for ovarian cancer patients with inherited mutations of the BRCA1 or BRCA2 genes, poly(ADP-ribose) polymerase (PARP) inhibitors, a class of oral anticancer medicines that target DNA repair, have ushered in a new era in which the possibility of long-term remission, and even cure, is more likely than at any other time.

Olaparib trial details

The SOLO1 study was a double-blind, placebo-controlled, phase 3 trial that investigated the role of PARP inhibitor maintenance therapy with olaparib in patients with pathologic BRCA1 or BRCA2 mutations who responded to platinum-based chemotherapy administered for a newly diagnosed, advanced-stage ovarian cancer.¹ The study enrolled 391 patients, with 260 randomly assigned to receive olaparib for 24 months and 131 patients randomly assigned to receive placebo tablets. Most patients in the study had a mutation in the BRCA1 gene (72%), 27% had a BRCA2 mutation, and 1% had mutations in both genes.

The primary analysis of SOLO1 was published in 2018 and was based on a median follow-up of 3.4 years.¹ That study showed that olaparib maintenance therapy resulted in a large progression-free survival benefit and led to its approval by the US Food and Drug Administration (FDA) as a maintenance therapy for patients with BRCA-mutated advanced ovarian cancer who responded to first-line platinum-based chemotherapy.

In 2021, Banerjee and colleagues updated the progression-free survival results for the SOLO1 trial after 5 years of follow-up.² In this study, the patients randomly assigned to olaparib maintenance therapy had a persistent and statistically significant progression-free survival benefit, with the median progression-free survival reaching 56 months among the olaparib group compared with 13.8 months in the placebo group (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.25–0.43).² Olaparib maintenance therapy resulted in more clinically significant adverse events, including anemia and neutropenia. Serious adverse events occurred in 55 (21%) of the olaparib-treated patients and 17 (13%) of the placebo-treated patients, but no treatment-related adverse events were fatal.

Continue to: Cytoreductive surgery for recurrent ovarian cancer improves survival in well-selected patients...

Cytoreductive surgery for recurrent ovarian cancer improves survival in well-selected patients

Harter P, Sehouli J, Vergote I, et al; DESKTOP III Investigators. Randomized trial of cytoreductive surgery for relapsed ovarian cancer. N Engl J Med. 2021;385:2123- 2131.

In the DESKTOP III trial, Harter and colleagues contribute results to the ongoing discourse surrounding treatment options for patients with recurrent, platinum-sensitive ovarian cancer.³ Systemic therapies continue to be the mainstay of treatment in this setting; however, several groups have attempted to evaluate the role of secondary cytoreductive surgery in this setting.^4,5

Specific inclusion criteria employed

The DESKTOP III investigators randomly assigned 407 patients with platinum-sensitive recurrent ovarian cancer to secondary cytoreductive surgery followed by platinum-based chemotherapy (n = 206) or platinum-based chemotherapy alone (n = 201).³ An essential aspect of the study’s design was the use of specific inclusion criteria known to identify patients with a high likelihood of complete resection at the time of secondary cytoreduction.^6,7 Patients were eligible only if they had at least a 6-month remission following platinum-based chemotherapy, had a complete resection at their previous surgery, had no restriction on physical activity, and had ascites of no more than 500 mL.

Surgery group had superior overall and progression-free survival

After a median follow-up of approximately 70 months, patients randomly assigned to surgery had superior overall survival (53.7 months) compared with those assigned to chemotherapy alone (46.0 months; HR, 0.75; 95% CI, 0.59–0.96).³ Progression-free survival also was improved among patients who underwent surgery (median 18.4 vs 12.7 months; HR, 0.66; 95% CI, 0.54–0.82). Subgroup analyses did not identify any subset of patients who did not benefit from surgery. Whether a complete resection was achieved at secondary cytoreduction was highly prognostic: Patients who had a complete resection had a median overall survival of 61.9 months compared with 27.7 months in patients with residual disease. There were no deaths within 90 days of surgery.

Continue to: Immunotherapy enters first-line treatment regimen for advanced cervical cancer...

Immunotherapy enters first-line treatment regimen for advanced cervical cancer

Colombo N, Dubot C, Lorusso D, et al; KEYNOTE-826 Investigators. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021;385:1856-1867.

Persistent, recurrent, and metastatic cervical cancer carries a very poor prognosis: Most patients progress less than a year after starting treatment, and fewer than half survive for 2 years. First-line treatment in this setting has been platinum-based chemotherapy, often given with bevacizumab, a humanized monoclonal antibody that inhibits tumor growth by blocking angiogenesis.⁸ Pembrolizumab, an immune checkpoint inhibitor, targets cancer cells by blocking their ability to evade the immune system, and it is FDA approved and widely administered to patients with advanced cervical cancer who progress after first-line treatment.⁹

Addition of pembrolizumab extended survival

In the KEYNOTE-826 trial, Colombo and colleagues investigated the efficacy of incorporating an immune checkpoint inhibitor into the first-line treatment regimen for patients with persistent, recurrent, and metastatic cervical cancer.¹⁰ Researchers in this double-blinded, phase 3, randomized controlled trial assigned 617 patients to receive pembrolizumab or placebo concurrently with the investigator’s choice platinum-based chemotherapy. Bevacizumab was administered at the discretion of the treating oncologist.

The proportion of patients who survived at least 2 years following randomization was significantly higher among those assigned to pembrolizumab compared with placebo (53% vs 42%; HR, 0.67, 95% CI, 0.54–0.84).¹⁰ Similarly, median progression-free survival was superior among patients who received pembrolizumab compared with those who received placebo (10.4 months vs 8.2 months; HR, 0.65; 95% CI, 0.53–0.79). The role of bevacizumab in conjunction with pembrolizumab and platinum-based chemotherapy was not elucidated in this study because bevacizumab administration was not randomly assigned.

Anemia and neutropenia were the most common adverse events and were more frequent in the pembrolizumab group, but there were no new safety concerns related to concurrent use of pembrolizumab with cytotoxic chemotherapy and bevacizumab. Importantly, subgroup analysis results suggested that pembrolizumab was effective only in patients whose tumors expressed PD-L1 (programmed death ligand 1), a biomarker of pembrolizumab sensitivity in cervical cancer.

Continue to: Endometrial cancer surgical staging...

Endometrial cancer surgical staging: Is sentinel lymph node biopsy a viable option for high-risk histologies?

Cusimano MC, Vicus D, Pulman K, et al. Assessment of sentinel lymph node biopsy vs lymphadenectomy for intermediate- and high-grade endometrial cancer staging. JAMA Surg. 2021;156:157-164.

The use of intraoperative sentinel lymph node mapping and biopsy to identify lymph node metastases among patients undergoing surgical staging for endometrial cancer has become increasingly common. Lymph node status is an important prognostic factor, and it guides adjuvant treatment decisions in endometrial cancer. However, traditional pelvic and para-aortic lymphadenectomy is associated with increased risk of lower-extremity lymphedema, postoperative complications, and intraoperative injury.

Sentinel lymph node biopsy seeks to identify lymph node metastases while minimizing surgical morbidity by identifying and excising only lymph nodes that directly receive lymphatic drainage from the uterus. The combination of a fluorescent dye (indocyanine green) and near infrared cameras have led to the broad adoption of sentinel lymph node biopsy in endometrial cancer staging surgery. This practice is supported by prospective studies that demonstrate the high diagnostic accuracy of this approach.^11,12 However, because most patients included in prior studies had low-grade endometrial cancer, the utility of sentinel lymph node biopsy in cases of high-grade histology has been less clear.

Sentinel lymph node biopsy vs lymphadenectomy for staging

In the SENTOR trial, Cusimano and colleagues examined the diagnostic accuracy of sentinel lymph node mapping and biopsy, using indocyanine green, in patients with intermediate- or high-grade early-stage endometrial cancer.¹³

All eligible patients (N = 156) underwent traditional or robot-assisted laparoscopic hysterectomy with sentinel lymph node biopsy. Subsequently, patients with grade 2 endometrioid carcinoma underwent bilateral pelvic lymphadenectomy, and those with high-grade histology (grade 3 endometrioid, serous, carcinosarcoma, clear cell, undifferentiated or dedifferentiated, and mixed high grade) underwent bilateral pelvic and para-aortic lymphadenectomy. The investigators evaluated the diagnostic characteristics of sentinel lymph node biopsy, treating complete lymphadenectomy as the gold standard.

Of the 156 patients enrolled, the median age was 65.5 and median body mass index was 27.5; 126 patients (81%) had high-grade histology. The sentinel lymph node biopsy had a sensitivity of 96% (95% CI, 81%–100%), identifying 26 of the 27 patients with nodal metastases. The false-negative rate was 4% (95% CI, 0%–9%) and the negative predictive value was 99% (95% CI, 96%–100%). Intraoperative adverse events occurred in 5 patients (3%), but none occurred during the sentinel lymph node biopsy. ●

Despite the challenges of an ongoing COVID-19 pandemic, researchers in 2021 delivered practice-changing studies in gynecologic oncology. In this cancer Update, we highlight 4 studies that shed light on the surgical and systemic therapies that may improve outcomes for patients with cancers of the ovary, endometrium, and cervix. We review DESKTOP III, a trial that investigated the role of cytoreductive surgery in patients with recurrent ovarian cancer, and SENTOR, a study that evaluated the performance of sentinel lymph node biopsy in patients with high-grade endometrial cancers. Additionally, we examine 2 studies of systemic therapy that reveal the growing role of targeted therapies and immuno-oncology in the treatment of gynecologic malignancies.

A new era for patients with BRCA mutation–associated ovarian cancer

Banerjee S, Moore KN, Colombo N, et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021;22:1721-1731.

Ovarian cancer remains the most lethal gynecologic malignancy due to the frequency of advanced-stage diagnosis and frequent relapse after primary therapy. But for ovarian cancer patients with inherited mutations of the BRCA1 or BRCA2 genes, poly(ADP-ribose) polymerase (PARP) inhibitors, a class of oral anticancer medicines that target DNA repair, have ushered in a new era in which the possibility of long-term remission, and even cure, is more likely than at any other time.

Olaparib trial details

The SOLO1 study was a double-blind, placebo-controlled, phase 3 trial that investigated the role of PARP inhibitor maintenance therapy with olaparib in patients with pathologic BRCA1 or BRCA2 mutations who responded to platinum-based chemotherapy administered for a newly diagnosed, advanced-stage ovarian cancer.¹ The study enrolled 391 patients, with 260 randomly assigned to receive olaparib for 24 months and 131 patients randomly assigned to receive placebo tablets. Most patients in the study had a mutation in the BRCA1 gene (72%), 27% had a BRCA2 mutation, and 1% had mutations in both genes.

The primary analysis of SOLO1 was published in 2018 and was based on a median follow-up of 3.4 years.¹ That study showed that olaparib maintenance therapy resulted in a large progression-free survival benefit and led to its approval by the US Food and Drug Administration (FDA) as a maintenance therapy for patients with BRCA-mutated advanced ovarian cancer who responded to first-line platinum-based chemotherapy.

In 2021, Banerjee and colleagues updated the progression-free survival results for the SOLO1 trial after 5 years of follow-up.² In this study, the patients randomly assigned to olaparib maintenance therapy had a persistent and statistically significant progression-free survival benefit, with the median progression-free survival reaching 56 months among the olaparib group compared with 13.8 months in the placebo group (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.25–0.43).² Olaparib maintenance therapy resulted in more clinically significant adverse events, including anemia and neutropenia. Serious adverse events occurred in 55 (21%) of the olaparib-treated patients and 17 (13%) of the placebo-treated patients, but no treatment-related adverse events were fatal.

Continue to: Cytoreductive surgery for recurrent ovarian cancer improves survival in well-selected patients...

Cytoreductive surgery for recurrent ovarian cancer improves survival in well-selected patients

Harter P, Sehouli J, Vergote I, et al; DESKTOP III Investigators. Randomized trial of cytoreductive surgery for relapsed ovarian cancer. N Engl J Med. 2021;385:2123- 2131.

In the DESKTOP III trial, Harter and colleagues contribute results to the ongoing discourse surrounding treatment options for patients with recurrent, platinum-sensitive ovarian cancer.³ Systemic therapies continue to be the mainstay of treatment in this setting; however, several groups have attempted to evaluate the role of secondary cytoreductive surgery in this setting.^4,5

Specific inclusion criteria employed

The DESKTOP III investigators randomly assigned 407 patients with platinum-sensitive recurrent ovarian cancer to secondary cytoreductive surgery followed by platinum-based chemotherapy (n = 206) or platinum-based chemotherapy alone (n = 201).³ An essential aspect of the study’s design was the use of specific inclusion criteria known to identify patients with a high likelihood of complete resection at the time of secondary cytoreduction.^6,7 Patients were eligible only if they had at least a 6-month remission following platinum-based chemotherapy, had a complete resection at their previous surgery, had no restriction on physical activity, and had ascites of no more than 500 mL.

Surgery group had superior overall and progression-free survival

After a median follow-up of approximately 70 months, patients randomly assigned to surgery had superior overall survival (53.7 months) compared with those assigned to chemotherapy alone (46.0 months; HR, 0.75; 95% CI, 0.59–0.96).³ Progression-free survival also was improved among patients who underwent surgery (median 18.4 vs 12.7 months; HR, 0.66; 95% CI, 0.54–0.82). Subgroup analyses did not identify any subset of patients who did not benefit from surgery. Whether a complete resection was achieved at secondary cytoreduction was highly prognostic: Patients who had a complete resection had a median overall survival of 61.9 months compared with 27.7 months in patients with residual disease. There were no deaths within 90 days of surgery.

Continue to: Immunotherapy enters first-line treatment regimen for advanced cervical cancer...

Immunotherapy enters first-line treatment regimen for advanced cervical cancer

Colombo N, Dubot C, Lorusso D, et al; KEYNOTE-826 Investigators. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021;385:1856-1867.

Persistent, recurrent, and metastatic cervical cancer carries a very poor prognosis: Most patients progress less than a year after starting treatment, and fewer than half survive for 2 years. First-line treatment in this setting has been platinum-based chemotherapy, often given with bevacizumab, a humanized monoclonal antibody that inhibits tumor growth by blocking angiogenesis.⁸ Pembrolizumab, an immune checkpoint inhibitor, targets cancer cells by blocking their ability to evade the immune system, and it is FDA approved and widely administered to patients with advanced cervical cancer who progress after first-line treatment.⁹

Addition of pembrolizumab extended survival

In the KEYNOTE-826 trial, Colombo and colleagues investigated the efficacy of incorporating an immune checkpoint inhibitor into the first-line treatment regimen for patients with persistent, recurrent, and metastatic cervical cancer.¹⁰ Researchers in this double-blinded, phase 3, randomized controlled trial assigned 617 patients to receive pembrolizumab or placebo concurrently with the investigator’s choice platinum-based chemotherapy. Bevacizumab was administered at the discretion of the treating oncologist.

The proportion of patients who survived at least 2 years following randomization was significantly higher among those assigned to pembrolizumab compared with placebo (53% vs 42%; HR, 0.67, 95% CI, 0.54–0.84).¹⁰ Similarly, median progression-free survival was superior among patients who received pembrolizumab compared with those who received placebo (10.4 months vs 8.2 months; HR, 0.65; 95% CI, 0.53–0.79). The role of bevacizumab in conjunction with pembrolizumab and platinum-based chemotherapy was not elucidated in this study because bevacizumab administration was not randomly assigned.

Anemia and neutropenia were the most common adverse events and were more frequent in the pembrolizumab group, but there were no new safety concerns related to concurrent use of pembrolizumab with cytotoxic chemotherapy and bevacizumab. Importantly, subgroup analysis results suggested that pembrolizumab was effective only in patients whose tumors expressed PD-L1 (programmed death ligand 1), a biomarker of pembrolizumab sensitivity in cervical cancer.

Continue to: Endometrial cancer surgical staging...

Endometrial cancer surgical staging: Is sentinel lymph node biopsy a viable option for high-risk histologies?

Cusimano MC, Vicus D, Pulman K, et al. Assessment of sentinel lymph node biopsy vs lymphadenectomy for intermediate- and high-grade endometrial cancer staging. JAMA Surg. 2021;156:157-164.

The use of intraoperative sentinel lymph node mapping and biopsy to identify lymph node metastases among patients undergoing surgical staging for endometrial cancer has become increasingly common. Lymph node status is an important prognostic factor, and it guides adjuvant treatment decisions in endometrial cancer. However, traditional pelvic and para-aortic lymphadenectomy is associated with increased risk of lower-extremity lymphedema, postoperative complications, and intraoperative injury.

Sentinel lymph node biopsy seeks to identify lymph node metastases while minimizing surgical morbidity by identifying and excising only lymph nodes that directly receive lymphatic drainage from the uterus. The combination of a fluorescent dye (indocyanine green) and near infrared cameras have led to the broad adoption of sentinel lymph node biopsy in endometrial cancer staging surgery. This practice is supported by prospective studies that demonstrate the high diagnostic accuracy of this approach.^11,12 However, because most patients included in prior studies had low-grade endometrial cancer, the utility of sentinel lymph node biopsy in cases of high-grade histology has been less clear.

Sentinel lymph node biopsy vs lymphadenectomy for staging

In the SENTOR trial, Cusimano and colleagues examined the diagnostic accuracy of sentinel lymph node mapping and biopsy, using indocyanine green, in patients with intermediate- or high-grade early-stage endometrial cancer.¹³

All eligible patients (N = 156) underwent traditional or robot-assisted laparoscopic hysterectomy with sentinel lymph node biopsy. Subsequently, patients with grade 2 endometrioid carcinoma underwent bilateral pelvic lymphadenectomy, and those with high-grade histology (grade 3 endometrioid, serous, carcinosarcoma, clear cell, undifferentiated or dedifferentiated, and mixed high grade) underwent bilateral pelvic and para-aortic lymphadenectomy. The investigators evaluated the diagnostic characteristics of sentinel lymph node biopsy, treating complete lymphadenectomy as the gold standard.

Of the 156 patients enrolled, the median age was 65.5 and median body mass index was 27.5; 126 patients (81%) had high-grade histology. The sentinel lymph node biopsy had a sensitivity of 96% (95% CI, 81%–100%), identifying 26 of the 27 patients with nodal metastases. The false-negative rate was 4% (95% CI, 0%–9%) and the negative predictive value was 99% (95% CI, 96%–100%). Intraoperative adverse events occurred in 5 patients (3%), but none occurred during the sentinel lymph node biopsy. ●

Despite the challenges of an ongoing COVID-19 pandemic, researchers in 2021 delivered practice-changing studies in gynecologic oncology. In this cancer Update, we highlight 4 studies that shed light on the surgical and systemic therapies that may improve outcomes for patients with cancers of the ovary, endometrium, and cervix. We review DESKTOP III, a trial that investigated the role of cytoreductive surgery in patients with recurrent ovarian cancer, and SENTOR, a study that evaluated the performance of sentinel lymph node biopsy in patients with high-grade endometrial cancers. Additionally, we examine 2 studies of systemic therapy that reveal the growing role of targeted therapies and immuno-oncology in the treatment of gynecologic malignancies.

A new era for patients with BRCA mutation–associated ovarian cancer

Banerjee S, Moore KN, Colombo N, et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5-year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021;22:1721-1731.

Ovarian cancer remains the most lethal gynecologic malignancy due to the frequency of advanced-stage diagnosis and frequent relapse after primary therapy. But for ovarian cancer patients with inherited mutations of the BRCA1 or BRCA2 genes, poly(ADP-ribose) polymerase (PARP) inhibitors, a class of oral anticancer medicines that target DNA repair, have ushered in a new era in which the possibility of long-term remission, and even cure, is more likely than at any other time.

Olaparib trial details

The SOLO1 study was a double-blind, placebo-controlled, phase 3 trial that investigated the role of PARP inhibitor maintenance therapy with olaparib in patients with pathologic BRCA1 or BRCA2 mutations who responded to platinum-based chemotherapy administered for a newly diagnosed, advanced-stage ovarian cancer.¹ The study enrolled 391 patients, with 260 randomly assigned to receive olaparib for 24 months and 131 patients randomly assigned to receive placebo tablets. Most patients in the study had a mutation in the BRCA1 gene (72%), 27% had a BRCA2 mutation, and 1% had mutations in both genes.

The primary analysis of SOLO1 was published in 2018 and was based on a median follow-up of 3.4 years.¹ That study showed that olaparib maintenance therapy resulted in a large progression-free survival benefit and led to its approval by the US Food and Drug Administration (FDA) as a maintenance therapy for patients with BRCA-mutated advanced ovarian cancer who responded to first-line platinum-based chemotherapy.

In 2021, Banerjee and colleagues updated the progression-free survival results for the SOLO1 trial after 5 years of follow-up.² In this study, the patients randomly assigned to olaparib maintenance therapy had a persistent and statistically significant progression-free survival benefit, with the median progression-free survival reaching 56 months among the olaparib group compared with 13.8 months in the placebo group (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.25–0.43).² Olaparib maintenance therapy resulted in more clinically significant adverse events, including anemia and neutropenia. Serious adverse events occurred in 55 (21%) of the olaparib-treated patients and 17 (13%) of the placebo-treated patients, but no treatment-related adverse events were fatal.

Continue to: Cytoreductive surgery for recurrent ovarian cancer improves survival in well-selected patients...

Cytoreductive surgery for recurrent ovarian cancer improves survival in well-selected patients

Harter P, Sehouli J, Vergote I, et al; DESKTOP III Investigators. Randomized trial of cytoreductive surgery for relapsed ovarian cancer. N Engl J Med. 2021;385:2123- 2131.

In the DESKTOP III trial, Harter and colleagues contribute results to the ongoing discourse surrounding treatment options for patients with recurrent, platinum-sensitive ovarian cancer.³ Systemic therapies continue to be the mainstay of treatment in this setting; however, several groups have attempted to evaluate the role of secondary cytoreductive surgery in this setting.^4,5

Specific inclusion criteria employed

The DESKTOP III investigators randomly assigned 407 patients with platinum-sensitive recurrent ovarian cancer to secondary cytoreductive surgery followed by platinum-based chemotherapy (n = 206) or platinum-based chemotherapy alone (n = 201).³ An essential aspect of the study’s design was the use of specific inclusion criteria known to identify patients with a high likelihood of complete resection at the time of secondary cytoreduction.^6,7 Patients were eligible only if they had at least a 6-month remission following platinum-based chemotherapy, had a complete resection at their previous surgery, had no restriction on physical activity, and had ascites of no more than 500 mL.

Surgery group had superior overall and progression-free survival

After a median follow-up of approximately 70 months, patients randomly assigned to surgery had superior overall survival (53.7 months) compared with those assigned to chemotherapy alone (46.0 months; HR, 0.75; 95% CI, 0.59–0.96).³ Progression-free survival also was improved among patients who underwent surgery (median 18.4 vs 12.7 months; HR, 0.66; 95% CI, 0.54–0.82). Subgroup analyses did not identify any subset of patients who did not benefit from surgery. Whether a complete resection was achieved at secondary cytoreduction was highly prognostic: Patients who had a complete resection had a median overall survival of 61.9 months compared with 27.7 months in patients with residual disease. There were no deaths within 90 days of surgery.

Continue to: Immunotherapy enters first-line treatment regimen for advanced cervical cancer...

Immunotherapy enters first-line treatment regimen for advanced cervical cancer

Colombo N, Dubot C, Lorusso D, et al; KEYNOTE-826 Investigators. Pembrolizumab for persistent, recurrent, or metastatic cervical cancer. N Engl J Med. 2021;385:1856-1867.

Persistent, recurrent, and metastatic cervical cancer carries a very poor prognosis: Most patients progress less than a year after starting treatment, and fewer than half survive for 2 years. First-line treatment in this setting has been platinum-based chemotherapy, often given with bevacizumab, a humanized monoclonal antibody that inhibits tumor growth by blocking angiogenesis.⁸ Pembrolizumab, an immune checkpoint inhibitor, targets cancer cells by blocking their ability to evade the immune system, and it is FDA approved and widely administered to patients with advanced cervical cancer who progress after first-line treatment.⁹

Addition of pembrolizumab extended survival

In the KEYNOTE-826 trial, Colombo and colleagues investigated the efficacy of incorporating an immune checkpoint inhibitor into the first-line treatment regimen for patients with persistent, recurrent, and metastatic cervical cancer.¹⁰ Researchers in this double-blinded, phase 3, randomized controlled trial assigned 617 patients to receive pembrolizumab or placebo concurrently with the investigator’s choice platinum-based chemotherapy. Bevacizumab was administered at the discretion of the treating oncologist.

The proportion of patients who survived at least 2 years following randomization was significantly higher among those assigned to pembrolizumab compared with placebo (53% vs 42%; HR, 0.67, 95% CI, 0.54–0.84).¹⁰ Similarly, median progression-free survival was superior among patients who received pembrolizumab compared with those who received placebo (10.4 months vs 8.2 months; HR, 0.65; 95% CI, 0.53–0.79). The role of bevacizumab in conjunction with pembrolizumab and platinum-based chemotherapy was not elucidated in this study because bevacizumab administration was not randomly assigned.

Anemia and neutropenia were the most common adverse events and were more frequent in the pembrolizumab group, but there were no new safety concerns related to concurrent use of pembrolizumab with cytotoxic chemotherapy and bevacizumab. Importantly, subgroup analysis results suggested that pembrolizumab was effective only in patients whose tumors expressed PD-L1 (programmed death ligand 1), a biomarker of pembrolizumab sensitivity in cervical cancer.

Continue to: Endometrial cancer surgical staging...

Endometrial cancer surgical staging: Is sentinel lymph node biopsy a viable option for high-risk histologies?

Cusimano MC, Vicus D, Pulman K, et al. Assessment of sentinel lymph node biopsy vs lymphadenectomy for intermediate- and high-grade endometrial cancer staging. JAMA Surg. 2021;156:157-164.

The use of intraoperative sentinel lymph node mapping and biopsy to identify lymph node metastases among patients undergoing surgical staging for endometrial cancer has become increasingly common. Lymph node status is an important prognostic factor, and it guides adjuvant treatment decisions in endometrial cancer. However, traditional pelvic and para-aortic lymphadenectomy is associated with increased risk of lower-extremity lymphedema, postoperative complications, and intraoperative injury.

Sentinel lymph node biopsy seeks to identify lymph node metastases while minimizing surgical morbidity by identifying and excising only lymph nodes that directly receive lymphatic drainage from the uterus. The combination of a fluorescent dye (indocyanine green) and near infrared cameras have led to the broad adoption of sentinel lymph node biopsy in endometrial cancer staging surgery. This practice is supported by prospective studies that demonstrate the high diagnostic accuracy of this approach.^11,12 However, because most patients included in prior studies had low-grade endometrial cancer, the utility of sentinel lymph node biopsy in cases of high-grade histology has been less clear.

Sentinel lymph node biopsy vs lymphadenectomy for staging

In the SENTOR trial, Cusimano and colleagues examined the diagnostic accuracy of sentinel lymph node mapping and biopsy, using indocyanine green, in patients with intermediate- or high-grade early-stage endometrial cancer.¹³

All eligible patients (N = 156) underwent traditional or robot-assisted laparoscopic hysterectomy with sentinel lymph node biopsy. Subsequently, patients with grade 2 endometrioid carcinoma underwent bilateral pelvic lymphadenectomy, and those with high-grade histology (grade 3 endometrioid, serous, carcinosarcoma, clear cell, undifferentiated or dedifferentiated, and mixed high grade) underwent bilateral pelvic and para-aortic lymphadenectomy. The investigators evaluated the diagnostic characteristics of sentinel lymph node biopsy, treating complete lymphadenectomy as the gold standard.

Of the 156 patients enrolled, the median age was 65.5 and median body mass index was 27.5; 126 patients (81%) had high-grade histology. The sentinel lymph node biopsy had a sensitivity of 96% (95% CI, 81%–100%), identifying 26 of the 27 patients with nodal metastases. The false-negative rate was 4% (95% CI, 0%–9%) and the negative predictive value was 99% (95% CI, 96%–100%). Intraoperative adverse events occurred in 5 patients (3%), but none occurred during the sentinel lymph node biopsy. ●

The standard management for early-stage endometrial cancer involves surgery with hysterectomy, salpingectomy with or without oophorectomy, and staging lymph node sampling. Surgery serves as both a therapeutic and diagnostic intervention because surgical pathology results are in turn used to predict the likelihood of relapse and guide adjuvant therapy decisions. However, in some cases, surgical intervention is not feasible or desired, particularly if fertility preservation is a goal. Fortunately, there are nonsurgical options that are associated with favorable outcomes to offer these patients.

Endometrial cancer is associated with obesity attributable to causative mechanisms that promote endometrial hyperplasia, cellular proliferation, and heightened hormonal and growth factor signaling. Not only does obesity drive the development of endometrial cancer, but it also complicates the treatment of the disease. For example, endometrial cancer staging surgery is less successfully completed through a minimally invasive route as body mass index increases, primarily because of limitations in surgical exposure.¹ In fact, obesity can prevent surgery from being offered through any route. In addition to body habitus, determination of inoperability is also significantly influenced by the presence of coronary artery disease, hypertension, and diabetes.² Given that these comorbidities are more commonly experienced by women who are overweight, obesity creates a perfect storm of causative and complicating factors for optimal treatment.

While surgeons may determine the candidacy of patients for hysterectomy, patients themselves also drive this decision-making, particularly in the case of young patients who desire fertility preservation. Approximately 10% of patients with endometrial cancer are premenopausal, a number that is increasing over time. These women may have experienced infertility prior to their diagnosis, yet still strongly desire the attempt to conceive, particularly if they have suffered from anovulatory menstrual cycles or polycystic ovarian disease. Women with Lynch syndrome are at a higher risk for developing their cancer in premenopausal years. Therefore, it is critical that gynecologic oncologists consider nonsurgical remedies for these women and understand their potential for success.

Certain criteria should be met for women undergoing nonsurgical management of endometrial cancer, particularly if chosen electively for fertility preservation. Diagnosis should be obtained with a curettage specimen (rather than a pipelle) to optimize the accuracy of establishing tumor grade and to “debulk” the endometrial tissue. Pretreatment imaging is necessary to rule out distant metastatic disease. MRI is particularly helpful in approximating the depth of myometrial invasion of the malignancy and is recommended for patients desiring fertility preservation. Patients who have an endometrial cancer that is deeply invasive into the myometrium are poor candidates for fertility preservation and have a higher risk for metastatic disease, particularly to lymph nodes, and treatment decisions (such as surgery, or, if inoperable, radiation which treats nodal basins) should be considered for these women.

Hormonal therapy has long been identified as a highly effective systemic therapy for endometrial cancers, particularly those that are low grade and express estrogen and progesterone receptors. Progesterone can be administered orally in preparations such as megestrol or medroxyprogesterone or “locally” with levonorgestrel-releasing intrauterine devices. Oral preparations are straightforward, typically low-cost agents. Likelihood of success is 50%-75%. However, the systemic side effects of these agents, which include increased venous thromboembolism risk and appetite stimulation, are particularly problematic in this population. Therefore, many providers prefer to place progestin-releasing intrauterine devices to “bypass” these side effects, avoid issues with adherence to dosing, and provide some preventative endometrial coverage after resolution of the cancer. Recent trials have observed elimination of endometrial cancer on repeat sampling in 67%-76% of cases.^3-5 This strategy may be more successful when it is paired with the addition of GnRH agonists.⁴

When hormonal therapy is chosen for primary endometrial cancer treatment, it is typically monitored for efficacy with repeat endometrial samplings, most commonly with pipelle biopsies to avoid displacement of an intrauterine device, though repeat D&C may be more effective in achieving a complete pathologic response to treatment. Most providers recommend resampling the endometrium at 3-month intervals until resolution of the malignancy has been documented, and thereafter if any new bleeding events develop. For women who have demonstrated resolution of carcinoma on repeat sampling, data are lacking to guide decision-making regarding resumption of conception efforts, ongoing surveillance, and completion hysterectomy after they finish childbearing. If malignancy continues to be identified after 6 months of hormonal therapy, consideration should be made of a more definitive treatment (such as surgery, if feasible, or radiation if not). Continued hormonal therapy can also be considered, as delayed responses remain common even 1 year after starting therapy.⁶ If hormonal therapy is prolonged for persistent disease, repeat MRI is recommended at 6 months to document lack of progression.

Radiation, preferably with both intracavitary and external beam treatment, is the most definitive intervention for inoperable early-stage endometrial cancer. Unfortunately, fertility is not preserved with this approach. However, for patients with high-grade tumors that are less likely to express hormone receptors or respond to hormonal therapies, this may be the only treatment option available. Typical treatment courses include 5 weeks of external beam radiation treatments, focused on treating the pelvis as a whole, including occult metastases not identified on imaging. Optimal therapy also includes placement of intracavitary radiation implants, such as Heymans capsules, to concentrate the dose at the uterine fundus, while minimizing toxicity to the adjacent bladder and bowel structures. While definitive radiation is considered inferior to a primary surgical effort, disease-specific survival can be observed in more than 80% of patients treated this way.⁷

While surgery remains the standard intervention for women with early-stage endometrial cancer, hormonal therapy or radiation remain viable options with high rates of success for women who are not surgical candidates or who desire fertility preservation.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Walker JL et al. J Clin Oncol. 2009;27(32):5331-6.

2. Ertel M et al. Ann Surg Oncol. 2021;28(13):8987-95.

3. Janda M et al. Gynecol Oncol. 2021;161(1):143-51.

4. Novikova OV et al. Gynecol Oncol. 2021;161(1):152-9.

5. Westin SN et al. Am J Obstet Gynecol. 2021;224(2):191.e1-15.

6. Cho A et al. Gynecol Oncol. 2021;160(2):413-17.

7. Dutta SW et al. Brachytherapy. 2017;16(3):526-33.

The standard management for early-stage endometrial cancer involves surgery with hysterectomy, salpingectomy with or without oophorectomy, and staging lymph node sampling. Surgery serves as both a therapeutic and diagnostic intervention because surgical pathology results are in turn used to predict the likelihood of relapse and guide adjuvant therapy decisions. However, in some cases, surgical intervention is not feasible or desired, particularly if fertility preservation is a goal. Fortunately, there are nonsurgical options that are associated with favorable outcomes to offer these patients.

Endometrial cancer is associated with obesity attributable to causative mechanisms that promote endometrial hyperplasia, cellular proliferation, and heightened hormonal and growth factor signaling. Not only does obesity drive the development of endometrial cancer, but it also complicates the treatment of the disease. For example, endometrial cancer staging surgery is less successfully completed through a minimally invasive route as body mass index increases, primarily because of limitations in surgical exposure.¹ In fact, obesity can prevent surgery from being offered through any route. In addition to body habitus, determination of inoperability is also significantly influenced by the presence of coronary artery disease, hypertension, and diabetes.² Given that these comorbidities are more commonly experienced by women who are overweight, obesity creates a perfect storm of causative and complicating factors for optimal treatment.

While surgeons may determine the candidacy of patients for hysterectomy, patients themselves also drive this decision-making, particularly in the case of young patients who desire fertility preservation. Approximately 10% of patients with endometrial cancer are premenopausal, a number that is increasing over time. These women may have experienced infertility prior to their diagnosis, yet still strongly desire the attempt to conceive, particularly if they have suffered from anovulatory menstrual cycles or polycystic ovarian disease. Women with Lynch syndrome are at a higher risk for developing their cancer in premenopausal years. Therefore, it is critical that gynecologic oncologists consider nonsurgical remedies for these women and understand their potential for success.

Certain criteria should be met for women undergoing nonsurgical management of endometrial cancer, particularly if chosen electively for fertility preservation. Diagnosis should be obtained with a curettage specimen (rather than a pipelle) to optimize the accuracy of establishing tumor grade and to “debulk” the endometrial tissue. Pretreatment imaging is necessary to rule out distant metastatic disease. MRI is particularly helpful in approximating the depth of myometrial invasion of the malignancy and is recommended for patients desiring fertility preservation. Patients who have an endometrial cancer that is deeply invasive into the myometrium are poor candidates for fertility preservation and have a higher risk for metastatic disease, particularly to lymph nodes, and treatment decisions (such as surgery, or, if inoperable, radiation which treats nodal basins) should be considered for these women.

Hormonal therapy has long been identified as a highly effective systemic therapy for endometrial cancers, particularly those that are low grade and express estrogen and progesterone receptors. Progesterone can be administered orally in preparations such as megestrol or medroxyprogesterone or “locally” with levonorgestrel-releasing intrauterine devices. Oral preparations are straightforward, typically low-cost agents. Likelihood of success is 50%-75%. However, the systemic side effects of these agents, which include increased venous thromboembolism risk and appetite stimulation, are particularly problematic in this population. Therefore, many providers prefer to place progestin-releasing intrauterine devices to “bypass” these side effects, avoid issues with adherence to dosing, and provide some preventative endometrial coverage after resolution of the cancer. Recent trials have observed elimination of endometrial cancer on repeat sampling in 67%-76% of cases.^3-5 This strategy may be more successful when it is paired with the addition of GnRH agonists.⁴

When hormonal therapy is chosen for primary endometrial cancer treatment, it is typically monitored for efficacy with repeat endometrial samplings, most commonly with pipelle biopsies to avoid displacement of an intrauterine device, though repeat D&C may be more effective in achieving a complete pathologic response to treatment. Most providers recommend resampling the endometrium at 3-month intervals until resolution of the malignancy has been documented, and thereafter if any new bleeding events develop. For women who have demonstrated resolution of carcinoma on repeat sampling, data are lacking to guide decision-making regarding resumption of conception efforts, ongoing surveillance, and completion hysterectomy after they finish childbearing. If malignancy continues to be identified after 6 months of hormonal therapy, consideration should be made of a more definitive treatment (such as surgery, if feasible, or radiation if not). Continued hormonal therapy can also be considered, as delayed responses remain common even 1 year after starting therapy.⁶ If hormonal therapy is prolonged for persistent disease, repeat MRI is recommended at 6 months to document lack of progression.

Radiation, preferably with both intracavitary and external beam treatment, is the most definitive intervention for inoperable early-stage endometrial cancer. Unfortunately, fertility is not preserved with this approach. However, for patients with high-grade tumors that are less likely to express hormone receptors or respond to hormonal therapies, this may be the only treatment option available. Typical treatment courses include 5 weeks of external beam radiation treatments, focused on treating the pelvis as a whole, including occult metastases not identified on imaging. Optimal therapy also includes placement of intracavitary radiation implants, such as Heymans capsules, to concentrate the dose at the uterine fundus, while minimizing toxicity to the adjacent bladder and bowel structures. While definitive radiation is considered inferior to a primary surgical effort, disease-specific survival can be observed in more than 80% of patients treated this way.⁷

While surgery remains the standard intervention for women with early-stage endometrial cancer, hormonal therapy or radiation remain viable options with high rates of success for women who are not surgical candidates or who desire fertility preservation.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Walker JL et al. J Clin Oncol. 2009;27(32):5331-6.

2. Ertel M et al. Ann Surg Oncol. 2021;28(13):8987-95.

3. Janda M et al. Gynecol Oncol. 2021;161(1):143-51.

4. Novikova OV et al. Gynecol Oncol. 2021;161(1):152-9.

5. Westin SN et al. Am J Obstet Gynecol. 2021;224(2):191.e1-15.

6. Cho A et al. Gynecol Oncol. 2021;160(2):413-17.

7. Dutta SW et al. Brachytherapy. 2017;16(3):526-33.

The standard management for early-stage endometrial cancer involves surgery with hysterectomy, salpingectomy with or without oophorectomy, and staging lymph node sampling. Surgery serves as both a therapeutic and diagnostic intervention because surgical pathology results are in turn used to predict the likelihood of relapse and guide adjuvant therapy decisions. However, in some cases, surgical intervention is not feasible or desired, particularly if fertility preservation is a goal. Fortunately, there are nonsurgical options that are associated with favorable outcomes to offer these patients.

Endometrial cancer is associated with obesity attributable to causative mechanisms that promote endometrial hyperplasia, cellular proliferation, and heightened hormonal and growth factor signaling. Not only does obesity drive the development of endometrial cancer, but it also complicates the treatment of the disease. For example, endometrial cancer staging surgery is less successfully completed through a minimally invasive route as body mass index increases, primarily because of limitations in surgical exposure.¹ In fact, obesity can prevent surgery from being offered through any route. In addition to body habitus, determination of inoperability is also significantly influenced by the presence of coronary artery disease, hypertension, and diabetes.² Given that these comorbidities are more commonly experienced by women who are overweight, obesity creates a perfect storm of causative and complicating factors for optimal treatment.

While surgeons may determine the candidacy of patients for hysterectomy, patients themselves also drive this decision-making, particularly in the case of young patients who desire fertility preservation. Approximately 10% of patients with endometrial cancer are premenopausal, a number that is increasing over time. These women may have experienced infertility prior to their diagnosis, yet still strongly desire the attempt to conceive, particularly if they have suffered from anovulatory menstrual cycles or polycystic ovarian disease. Women with Lynch syndrome are at a higher risk for developing their cancer in premenopausal years. Therefore, it is critical that gynecologic oncologists consider nonsurgical remedies for these women and understand their potential for success.

Certain criteria should be met for women undergoing nonsurgical management of endometrial cancer, particularly if chosen electively for fertility preservation. Diagnosis should be obtained with a curettage specimen (rather than a pipelle) to optimize the accuracy of establishing tumor grade and to “debulk” the endometrial tissue. Pretreatment imaging is necessary to rule out distant metastatic disease. MRI is particularly helpful in approximating the depth of myometrial invasion of the malignancy and is recommended for patients desiring fertility preservation. Patients who have an endometrial cancer that is deeply invasive into the myometrium are poor candidates for fertility preservation and have a higher risk for metastatic disease, particularly to lymph nodes, and treatment decisions (such as surgery, or, if inoperable, radiation which treats nodal basins) should be considered for these women.

Hormonal therapy has long been identified as a highly effective systemic therapy for endometrial cancers, particularly those that are low grade and express estrogen and progesterone receptors. Progesterone can be administered orally in preparations such as megestrol or medroxyprogesterone or “locally” with levonorgestrel-releasing intrauterine devices. Oral preparations are straightforward, typically low-cost agents. Likelihood of success is 50%-75%. However, the systemic side effects of these agents, which include increased venous thromboembolism risk and appetite stimulation, are particularly problematic in this population. Therefore, many providers prefer to place progestin-releasing intrauterine devices to “bypass” these side effects, avoid issues with adherence to dosing, and provide some preventative endometrial coverage after resolution of the cancer. Recent trials have observed elimination of endometrial cancer on repeat sampling in 67%-76% of cases.^3-5 This strategy may be more successful when it is paired with the addition of GnRH agonists.⁴

When hormonal therapy is chosen for primary endometrial cancer treatment, it is typically monitored for efficacy with repeat endometrial samplings, most commonly with pipelle biopsies to avoid displacement of an intrauterine device, though repeat D&C may be more effective in achieving a complete pathologic response to treatment. Most providers recommend resampling the endometrium at 3-month intervals until resolution of the malignancy has been documented, and thereafter if any new bleeding events develop. For women who have demonstrated resolution of carcinoma on repeat sampling, data are lacking to guide decision-making regarding resumption of conception efforts, ongoing surveillance, and completion hysterectomy after they finish childbearing. If malignancy continues to be identified after 6 months of hormonal therapy, consideration should be made of a more definitive treatment (such as surgery, if feasible, or radiation if not). Continued hormonal therapy can also be considered, as delayed responses remain common even 1 year after starting therapy.⁶ If hormonal therapy is prolonged for persistent disease, repeat MRI is recommended at 6 months to document lack of progression.

Radiation, preferably with both intracavitary and external beam treatment, is the most definitive intervention for inoperable early-stage endometrial cancer. Unfortunately, fertility is not preserved with this approach. However, for patients with high-grade tumors that are less likely to express hormone receptors or respond to hormonal therapies, this may be the only treatment option available. Typical treatment courses include 5 weeks of external beam radiation treatments, focused on treating the pelvis as a whole, including occult metastases not identified on imaging. Optimal therapy also includes placement of intracavitary radiation implants, such as Heymans capsules, to concentrate the dose at the uterine fundus, while minimizing toxicity to the adjacent bladder and bowel structures. While definitive radiation is considered inferior to a primary surgical effort, disease-specific survival can be observed in more than 80% of patients treated this way.⁷

While surgery remains the standard intervention for women with early-stage endometrial cancer, hormonal therapy or radiation remain viable options with high rates of success for women who are not surgical candidates or who desire fertility preservation.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Walker JL et al. J Clin Oncol. 2009;27(32):5331-6.

2. Ertel M et al. Ann Surg Oncol. 2021;28(13):8987-95.

3. Janda M et al. Gynecol Oncol. 2021;161(1):143-51.

4. Novikova OV et al. Gynecol Oncol. 2021;161(1):152-9.

5. Westin SN et al. Am J Obstet Gynecol. 2021;224(2):191.e1-15.

6. Cho A et al. Gynecol Oncol. 2021;160(2):413-17.

7. Dutta SW et al. Brachytherapy. 2017;16(3):526-33.

Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic, getting opioid prescriptions filled in a timely manner with the clinician’s drug of choice can feel like a Sisyphean task.

A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.

She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.

Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.

Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.

Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic, getting opioid prescriptions filled in a timely manner with the clinician’s drug of choice can feel like a Sisyphean task.

A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.

She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.

Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.

Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.

Pain management is a huge part of how we in palliative care help patients – and most of the time, I think we do it well, but in the regulatory environment of the opioid epidemic, getting opioid prescriptions filled in a timely manner with the clinician’s drug of choice can feel like a Sisyphean task.

A patient – let’s call her Joan – calls me in distress. She is a 62-year-old woman with widespread metastatic breast cancer. Her pain is mainly due to bone metastases, but she also has discomfort due to the cancer’s invasion of the thin membranes that line her lungs and abdomen.

She was started on a combination opioid and acetaminophen tablet about 2 months ago by her oncologist, but is now requiring it around the clock, nearing the ceiling dose for this particular medication.

Given that her pain is escalating, Joan and I discuss starting a long-acting opioid to better manage the peak and trough effect of short-acting opioids, which can make a patient feel that the pain is relieved only for a few hours at a time, with sharp spikes throughout the day that mandate the next dose of short-acting opioid. This tethers the patient to the clock, having to take as many as six or eight doses of medication per day, and can be very disruptive to daily life.

Sarah F. D’Ambruoso, NP, is a palliative care nurse practitioner in Santa Monica, Calif.

Among patients with ovarian cancer who have achieved remission, routine surveillance with virtual appointments, along with tumor marker monitoring and imaging, may offer an alternative to the currently mandated frequent in-person visits.

The suggestion comes from Jacqueline Feinberg, MD, gynecologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York, and colleagues, who conducted a retrospective study of 147 patients who experienced ovarian cancer recurrence within 2 years of their first clinical remission, and found that none of these recurrences were detected by physical examination alone.

About one third of these patients had a recurrence that was first detected by tumor marker, over half by imaging, and the rest by the presentation of new symptoms and biopsies taken during nononcologic surgery.

“This finding suggests that virtual visits, which have quickly gained acceptance during the COVID-19 pandemic, combined with a surveillance protocol for tumor marker testing and imaging, may be sufficient to identify ovarian cancer recurrence,” the team concluded. The study was published in the International Journal of Gynecologic Cancer.

The COVID-19 pandemic has accelerated the use of telemedicine, with new international guidelines recommending minimizing in-person contact, noted the authors.

They wondered how this would work in patients who have achieved remission from ovarian cancer.

At MSKCC, the usual surveillance protocol for the first 2 years after ovarian cancer remission includes an in-person physical examination every 3 months, along with CA-125 testing and imaging of the chest, abdomen, and pelvis. For year 3, the time between surveillance testing is extended to every 3-6 months, for the fourth and fifth year, to every 6 months. Beyond 5 years, physical examination and testing for the protein CA-125 are performed annually, and imaging is optional.

However, there is no strong evidence to support this current surveillance regimen, the authors pointed out. They sought to determine if it was possible to do virtual visits instead, along with tumor marker monitoring and imaging.
 

Evidence for virtual exams

To answer that question, Dr. Feinberg and colleagues conducted a retrospective study that included patients who were initially seen from January 2015 to December 2017, and who had achieved clinical remission and then experienced ovarian cancer recurrence with 2 years of remission.

A total of 147 patients were included in the final analysis. None of these patients had their recurrence detected on routine physical exam, including pelvic exam, as the primary method of detection. More than half of patients (n = 81; 55%) had their recurrence detected on radiographic scan, whereas for 46 patients (31%), it was by tumor marker. Among the remaining patients, 17 (12%) experienced new symptoms and for 3 (2%), it was by biopsy during a nononcologic surgery.

By the time treatment was initiated for recurrence, 111 patients (75%) had multiple positive findings; 48 (33%) had symptoms, 21 (14%) had physical exam findings, 106 (72%) had increases in their tumor markers, and 141 (96%) had changes on their imaging.

In addition, 131 (89%) had baseline increases in CA-125, and of 16 remaining patients, 12 experienced a CA-125 increase during recurrence.

There were 21 patients who had positive physical exam findings following their recurrence, which had already been detected. Within this subset, 19 had concurrent symptoms, and for 6 of them, symptom onset had been the primary method of detection. For the 2 patients without symptoms, recurrence was initially detected by a rise in CA-125 on routine check in one patient, by surveillance imaging in the other.

The authors are now planning a pilot virtual intensive surveillance program, where they will evaluate patient-reported outcomes

The study was funded in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748. Study author Dennis Chi, MD, reports personal fees from Bovie Medical (now Apyx Medical), Verthermia, C Surgeries, and Biom’Up, and is also a former stockholder of Intuitive Surgical and TransEnterix. The other authors disclosed no relevant financial relationships.

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

Among patients with ovarian cancer who have achieved remission, routine surveillance with virtual appointments, along with tumor marker monitoring and imaging, may offer an alternative to the currently mandated frequent in-person visits.

The suggestion comes from Jacqueline Feinberg, MD, gynecologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York, and colleagues, who conducted a retrospective study of 147 patients who experienced ovarian cancer recurrence within 2 years of their first clinical remission, and found that none of these recurrences were detected by physical examination alone.

About one third of these patients had a recurrence that was first detected by tumor marker, over half by imaging, and the rest by the presentation of new symptoms and biopsies taken during nononcologic surgery.

“This finding suggests that virtual visits, which have quickly gained acceptance during the COVID-19 pandemic, combined with a surveillance protocol for tumor marker testing and imaging, may be sufficient to identify ovarian cancer recurrence,” the team concluded. The study was published in the International Journal of Gynecologic Cancer.

The COVID-19 pandemic has accelerated the use of telemedicine, with new international guidelines recommending minimizing in-person contact, noted the authors.

They wondered how this would work in patients who have achieved remission from ovarian cancer.

At MSKCC, the usual surveillance protocol for the first 2 years after ovarian cancer remission includes an in-person physical examination every 3 months, along with CA-125 testing and imaging of the chest, abdomen, and pelvis. For year 3, the time between surveillance testing is extended to every 3-6 months, for the fourth and fifth year, to every 6 months. Beyond 5 years, physical examination and testing for the protein CA-125 are performed annually, and imaging is optional.

However, there is no strong evidence to support this current surveillance regimen, the authors pointed out. They sought to determine if it was possible to do virtual visits instead, along with tumor marker monitoring and imaging.
 

Evidence for virtual exams

To answer that question, Dr. Feinberg and colleagues conducted a retrospective study that included patients who were initially seen from January 2015 to December 2017, and who had achieved clinical remission and then experienced ovarian cancer recurrence with 2 years of remission.

A total of 147 patients were included in the final analysis. None of these patients had their recurrence detected on routine physical exam, including pelvic exam, as the primary method of detection. More than half of patients (n = 81; 55%) had their recurrence detected on radiographic scan, whereas for 46 patients (31%), it was by tumor marker. Among the remaining patients, 17 (12%) experienced new symptoms and for 3 (2%), it was by biopsy during a nononcologic surgery.

By the time treatment was initiated for recurrence, 111 patients (75%) had multiple positive findings; 48 (33%) had symptoms, 21 (14%) had physical exam findings, 106 (72%) had increases in their tumor markers, and 141 (96%) had changes on their imaging.

In addition, 131 (89%) had baseline increases in CA-125, and of 16 remaining patients, 12 experienced a CA-125 increase during recurrence.

There were 21 patients who had positive physical exam findings following their recurrence, which had already been detected. Within this subset, 19 had concurrent symptoms, and for 6 of them, symptom onset had been the primary method of detection. For the 2 patients without symptoms, recurrence was initially detected by a rise in CA-125 on routine check in one patient, by surveillance imaging in the other.

The authors are now planning a pilot virtual intensive surveillance program, where they will evaluate patient-reported outcomes

The study was funded in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748. Study author Dennis Chi, MD, reports personal fees from Bovie Medical (now Apyx Medical), Verthermia, C Surgeries, and Biom’Up, and is also a former stockholder of Intuitive Surgical and TransEnterix. The other authors disclosed no relevant financial relationships.

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

Among patients with ovarian cancer who have achieved remission, routine surveillance with virtual appointments, along with tumor marker monitoring and imaging, may offer an alternative to the currently mandated frequent in-person visits.

The suggestion comes from Jacqueline Feinberg, MD, gynecologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York, and colleagues, who conducted a retrospective study of 147 patients who experienced ovarian cancer recurrence within 2 years of their first clinical remission, and found that none of these recurrences were detected by physical examination alone.

About one third of these patients had a recurrence that was first detected by tumor marker, over half by imaging, and the rest by the presentation of new symptoms and biopsies taken during nononcologic surgery.

“This finding suggests that virtual visits, which have quickly gained acceptance during the COVID-19 pandemic, combined with a surveillance protocol for tumor marker testing and imaging, may be sufficient to identify ovarian cancer recurrence,” the team concluded. The study was published in the International Journal of Gynecologic Cancer.

The COVID-19 pandemic has accelerated the use of telemedicine, with new international guidelines recommending minimizing in-person contact, noted the authors.

They wondered how this would work in patients who have achieved remission from ovarian cancer.

At MSKCC, the usual surveillance protocol for the first 2 years after ovarian cancer remission includes an in-person physical examination every 3 months, along with CA-125 testing and imaging of the chest, abdomen, and pelvis. For year 3, the time between surveillance testing is extended to every 3-6 months, for the fourth and fifth year, to every 6 months. Beyond 5 years, physical examination and testing for the protein CA-125 are performed annually, and imaging is optional.

However, there is no strong evidence to support this current surveillance regimen, the authors pointed out. They sought to determine if it was possible to do virtual visits instead, along with tumor marker monitoring and imaging.
 

Evidence for virtual exams

To answer that question, Dr. Feinberg and colleagues conducted a retrospective study that included patients who were initially seen from January 2015 to December 2017, and who had achieved clinical remission and then experienced ovarian cancer recurrence with 2 years of remission.

A total of 147 patients were included in the final analysis. None of these patients had their recurrence detected on routine physical exam, including pelvic exam, as the primary method of detection. More than half of patients (n = 81; 55%) had their recurrence detected on radiographic scan, whereas for 46 patients (31%), it was by tumor marker. Among the remaining patients, 17 (12%) experienced new symptoms and for 3 (2%), it was by biopsy during a nononcologic surgery.

By the time treatment was initiated for recurrence, 111 patients (75%) had multiple positive findings; 48 (33%) had symptoms, 21 (14%) had physical exam findings, 106 (72%) had increases in their tumor markers, and 141 (96%) had changes on their imaging.

In addition, 131 (89%) had baseline increases in CA-125, and of 16 remaining patients, 12 experienced a CA-125 increase during recurrence.

There were 21 patients who had positive physical exam findings following their recurrence, which had already been detected. Within this subset, 19 had concurrent symptoms, and for 6 of them, symptom onset had been the primary method of detection. For the 2 patients without symptoms, recurrence was initially detected by a rise in CA-125 on routine check in one patient, by surveillance imaging in the other.

The authors are now planning a pilot virtual intensive surveillance program, where they will evaluate patient-reported outcomes

The study was funded in part through the National Institutes of Health/National Cancer Institute Cancer Center Support Grant P30 CA008748. Study author Dennis Chi, MD, reports personal fees from Bovie Medical (now Apyx Medical), Verthermia, C Surgeries, and Biom’Up, and is also a former stockholder of Intuitive Surgical and TransEnterix. The other authors disclosed no relevant financial relationships.

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

Women in the United States are less likely to die of ovarian cancer, but more likely to die of endometrial cancer than they were 3 decades ago, according to a recent research letter published in Obstetrics & Gynecology.

“This convergence is because of a steady reduction in the death rate for ovarian cancer, partly because of advances in treatment, alongside a steep increase in the death rate for endometrial cancer,” Rebecca L. Siegel, MPH, corresponding author and senior scientific director of surveillance research at the American Cancer Society, said in an interview. “Endometrial cancer has not had any major treatment advances in 40 years.”

However, Ms. Siegel and colleagues also found Black women had a twofold higher endometrial cancer–related mortality rate over the same time frame, compared with White women. The disparity in endometrial cancer mortality rates for Black women compared with White women is alarming, the authors said, and might be an underestimate because of a higher rate of hysterectomy among Black women.

The researchers analyzed endometrial and ovarian cancer mortality rates from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program (SEER) with the SEER*Stat software, stratifying the data by whether the person belonged to mutually exclusive racial and ethnic categories of White, Asian or Pacific Islander, Black, or Hispanic. They identified 232,957 women who died from endometrial cancer and 419,085 people who died from ovarian cancer between 1990 and 2019.

Ms. Siegel and colleagues found there was a decrease in ovarian cancer mortality rates between 1990 (9.3 per 100,000 women) and 2019 (6.0 per 100,000 women) (average annual percent change, 22.7%; 95% confidence interval, 23.5%-22.0%). While endometrial cancer mortality decreased between 1990 (4.3 per 100,000 women) and 1997 (4.0 per 100,000 women), it increased between 1997 and 2019 (5.1 per 100,000 women) (average annual percent change, 1.7%; 95% CI, 1.3%-2.1%). When measuring ovarian cancer mortality to endometrial cancer mortality from 1990 (9.3 vs. 4.3 per 100,000), compared with 2019 (6.0 vs. 5.1 per 100,000), there is a significant decline in excess deaths from ovarian cancer.

“Three decades ago, women in the United States were almost twice as likely to die from ovarian cancer as they were to die from endometrial cancer,” Ms. Siegel said in an interview. “Today the difference is only 15% higher, or an excess of less than 1 death per of 100,000 women.”
 

Growing racial disparity in endometrial cancer mortality

While these results persisted for some racial and ethnic subgroups, it did not persist for Black women, who saw an increase in endometrial cancer mortality rate from 7.2 per 100,000 women between 1990 and 1994 to 9.1 per 100,000 women between 2015 and 2019. Compared with White women, there was a significant increase in the mortality rate ratio for uterine cancer for Black women, from 1.83 between 1990 and 1994 (95% CI, 1.77-1.89) to 1.98 between 2015 and 2019 (95% CI, 1.93-2.02) (P < .001).

“Endometrial cancer has one of the largest racial disparities of any cancer. The 5-year relative survival rate for Black women is 63% compared to 84% for White women – a 21% gap in absolute terms. This is largely due to less access to high-quality health care, which is reflected in both later-stage diagnosis and lower survival for every stage of disease,” Ms. Siegel said in an interview. Other factors that contribute include lack of guideline-concordant surgical treatment, and increased risk of aggressive tumor subtypes.

Alex A. Francoeur, MD; and Ritu Salani, MD, MBA, of the department of obstetrics and gynecology at the University of California, Los Angeles, who were not involved in the study, said the research by Ms. Siegel and colleagues “highlights growing disparities in uterine cancer between non-Hispanic Black and non-Hispanic White women.”

“Understanding race as a social, not biological construct, and as a proxy for socioeconomic status, is key to understanding this disparity,” said Dr. Francoeur, a third-year ob.gyn. resident at UCLA Health, and Dr. Salani, an Ob.Gyn. News editorial board member. “For example, many studies cite a more advanced stage at diagnosis as an explanation for racial disparities in endometrial cancer; however, this is a substitute for differences in health care access as well as other socioeconomic factors such as income and education.”

Dr. Francoeur and Dr. Salani also acknowledged other disparities in risk factors may play a role in the differences in endometrial mortality rates such as obesity, which “in non-Hispanic Black women is over 60% greater than non-Hispanic White women.”

In terms of limitations, they noted that SEER’s database is less representative of the population, compared with the United States Cancer Statistics database (36.7% vs. 99%), and that factors such as greater prevalence of hysterectomy may contribute to larger racial disparities.

“Future studies need to examine inequities in treatment by race as well as the importance of health care systems in the stage of diagnosis,” they said.

Ms. Siegel said her team plans to follow the patterns outlined in this analysis and examine factors like cancer subtype, socioeconomic status, and place of residence in the future. “However, health inequalities are rooted in systemic racism, so documentation is necessary but insufficient to effect change, which must occur at the institutional level. A more concerted effort is needed to ensure that every woman receives appropriate treatment, regardless of the color of her skin, and education of providers to reduce racial bias and help increase trust in the health care system should be required.”

The authors reported no relevant financial disclosures. Dr. Francoeur and Dr. Salani reported no relevant financial disclosures.

Women in the United States are less likely to die of ovarian cancer, but more likely to die of endometrial cancer than they were 3 decades ago, according to a recent research letter published in Obstetrics & Gynecology.

“This convergence is because of a steady reduction in the death rate for ovarian cancer, partly because of advances in treatment, alongside a steep increase in the death rate for endometrial cancer,” Rebecca L. Siegel, MPH, corresponding author and senior scientific director of surveillance research at the American Cancer Society, said in an interview. “Endometrial cancer has not had any major treatment advances in 40 years.”

However, Ms. Siegel and colleagues also found Black women had a twofold higher endometrial cancer–related mortality rate over the same time frame, compared with White women. The disparity in endometrial cancer mortality rates for Black women compared with White women is alarming, the authors said, and might be an underestimate because of a higher rate of hysterectomy among Black women.

The researchers analyzed endometrial and ovarian cancer mortality rates from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program (SEER) with the SEER*Stat software, stratifying the data by whether the person belonged to mutually exclusive racial and ethnic categories of White, Asian or Pacific Islander, Black, or Hispanic. They identified 232,957 women who died from endometrial cancer and 419,085 people who died from ovarian cancer between 1990 and 2019.

Ms. Siegel and colleagues found there was a decrease in ovarian cancer mortality rates between 1990 (9.3 per 100,000 women) and 2019 (6.0 per 100,000 women) (average annual percent change, 22.7%; 95% confidence interval, 23.5%-22.0%). While endometrial cancer mortality decreased between 1990 (4.3 per 100,000 women) and 1997 (4.0 per 100,000 women), it increased between 1997 and 2019 (5.1 per 100,000 women) (average annual percent change, 1.7%; 95% CI, 1.3%-2.1%). When measuring ovarian cancer mortality to endometrial cancer mortality from 1990 (9.3 vs. 4.3 per 100,000), compared with 2019 (6.0 vs. 5.1 per 100,000), there is a significant decline in excess deaths from ovarian cancer.

“Three decades ago, women in the United States were almost twice as likely to die from ovarian cancer as they were to die from endometrial cancer,” Ms. Siegel said in an interview. “Today the difference is only 15% higher, or an excess of less than 1 death per of 100,000 women.”
 

Growing racial disparity in endometrial cancer mortality

While these results persisted for some racial and ethnic subgroups, it did not persist for Black women, who saw an increase in endometrial cancer mortality rate from 7.2 per 100,000 women between 1990 and 1994 to 9.1 per 100,000 women between 2015 and 2019. Compared with White women, there was a significant increase in the mortality rate ratio for uterine cancer for Black women, from 1.83 between 1990 and 1994 (95% CI, 1.77-1.89) to 1.98 between 2015 and 2019 (95% CI, 1.93-2.02) (P < .001).

“Endometrial cancer has one of the largest racial disparities of any cancer. The 5-year relative survival rate for Black women is 63% compared to 84% for White women – a 21% gap in absolute terms. This is largely due to less access to high-quality health care, which is reflected in both later-stage diagnosis and lower survival for every stage of disease,” Ms. Siegel said in an interview. Other factors that contribute include lack of guideline-concordant surgical treatment, and increased risk of aggressive tumor subtypes.

Alex A. Francoeur, MD; and Ritu Salani, MD, MBA, of the department of obstetrics and gynecology at the University of California, Los Angeles, who were not involved in the study, said the research by Ms. Siegel and colleagues “highlights growing disparities in uterine cancer between non-Hispanic Black and non-Hispanic White women.”

“Understanding race as a social, not biological construct, and as a proxy for socioeconomic status, is key to understanding this disparity,” said Dr. Francoeur, a third-year ob.gyn. resident at UCLA Health, and Dr. Salani, an Ob.Gyn. News editorial board member. “For example, many studies cite a more advanced stage at diagnosis as an explanation for racial disparities in endometrial cancer; however, this is a substitute for differences in health care access as well as other socioeconomic factors such as income and education.”

Dr. Francoeur and Dr. Salani also acknowledged other disparities in risk factors may play a role in the differences in endometrial mortality rates such as obesity, which “in non-Hispanic Black women is over 60% greater than non-Hispanic White women.”

In terms of limitations, they noted that SEER’s database is less representative of the population, compared with the United States Cancer Statistics database (36.7% vs. 99%), and that factors such as greater prevalence of hysterectomy may contribute to larger racial disparities.

“Future studies need to examine inequities in treatment by race as well as the importance of health care systems in the stage of diagnosis,” they said.

Ms. Siegel said her team plans to follow the patterns outlined in this analysis and examine factors like cancer subtype, socioeconomic status, and place of residence in the future. “However, health inequalities are rooted in systemic racism, so documentation is necessary but insufficient to effect change, which must occur at the institutional level. A more concerted effort is needed to ensure that every woman receives appropriate treatment, regardless of the color of her skin, and education of providers to reduce racial bias and help increase trust in the health care system should be required.”

The authors reported no relevant financial disclosures. Dr. Francoeur and Dr. Salani reported no relevant financial disclosures.

Women in the United States are less likely to die of ovarian cancer, but more likely to die of endometrial cancer than they were 3 decades ago, according to a recent research letter published in Obstetrics & Gynecology.

“This convergence is because of a steady reduction in the death rate for ovarian cancer, partly because of advances in treatment, alongside a steep increase in the death rate for endometrial cancer,” Rebecca L. Siegel, MPH, corresponding author and senior scientific director of surveillance research at the American Cancer Society, said in an interview. “Endometrial cancer has not had any major treatment advances in 40 years.”

However, Ms. Siegel and colleagues also found Black women had a twofold higher endometrial cancer–related mortality rate over the same time frame, compared with White women. The disparity in endometrial cancer mortality rates for Black women compared with White women is alarming, the authors said, and might be an underestimate because of a higher rate of hysterectomy among Black women.

The researchers analyzed endometrial and ovarian cancer mortality rates from the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program (SEER) with the SEER*Stat software, stratifying the data by whether the person belonged to mutually exclusive racial and ethnic categories of White, Asian or Pacific Islander, Black, or Hispanic. They identified 232,957 women who died from endometrial cancer and 419,085 people who died from ovarian cancer between 1990 and 2019.

Ms. Siegel and colleagues found there was a decrease in ovarian cancer mortality rates between 1990 (9.3 per 100,000 women) and 2019 (6.0 per 100,000 women) (average annual percent change, 22.7%; 95% confidence interval, 23.5%-22.0%). While endometrial cancer mortality decreased between 1990 (4.3 per 100,000 women) and 1997 (4.0 per 100,000 women), it increased between 1997 and 2019 (5.1 per 100,000 women) (average annual percent change, 1.7%; 95% CI, 1.3%-2.1%). When measuring ovarian cancer mortality to endometrial cancer mortality from 1990 (9.3 vs. 4.3 per 100,000), compared with 2019 (6.0 vs. 5.1 per 100,000), there is a significant decline in excess deaths from ovarian cancer.

“Three decades ago, women in the United States were almost twice as likely to die from ovarian cancer as they were to die from endometrial cancer,” Ms. Siegel said in an interview. “Today the difference is only 15% higher, or an excess of less than 1 death per of 100,000 women.”
 

Growing racial disparity in endometrial cancer mortality

While these results persisted for some racial and ethnic subgroups, it did not persist for Black women, who saw an increase in endometrial cancer mortality rate from 7.2 per 100,000 women between 1990 and 1994 to 9.1 per 100,000 women between 2015 and 2019. Compared with White women, there was a significant increase in the mortality rate ratio for uterine cancer for Black women, from 1.83 between 1990 and 1994 (95% CI, 1.77-1.89) to 1.98 between 2015 and 2019 (95% CI, 1.93-2.02) (P < .001).

“Endometrial cancer has one of the largest racial disparities of any cancer. The 5-year relative survival rate for Black women is 63% compared to 84% for White women – a 21% gap in absolute terms. This is largely due to less access to high-quality health care, which is reflected in both later-stage diagnosis and lower survival for every stage of disease,” Ms. Siegel said in an interview. Other factors that contribute include lack of guideline-concordant surgical treatment, and increased risk of aggressive tumor subtypes.

Alex A. Francoeur, MD; and Ritu Salani, MD, MBA, of the department of obstetrics and gynecology at the University of California, Los Angeles, who were not involved in the study, said the research by Ms. Siegel and colleagues “highlights growing disparities in uterine cancer between non-Hispanic Black and non-Hispanic White women.”

“Understanding race as a social, not biological construct, and as a proxy for socioeconomic status, is key to understanding this disparity,” said Dr. Francoeur, a third-year ob.gyn. resident at UCLA Health, and Dr. Salani, an Ob.Gyn. News editorial board member. “For example, many studies cite a more advanced stage at diagnosis as an explanation for racial disparities in endometrial cancer; however, this is a substitute for differences in health care access as well as other socioeconomic factors such as income and education.”

Dr. Francoeur and Dr. Salani also acknowledged other disparities in risk factors may play a role in the differences in endometrial mortality rates such as obesity, which “in non-Hispanic Black women is over 60% greater than non-Hispanic White women.”

In terms of limitations, they noted that SEER’s database is less representative of the population, compared with the United States Cancer Statistics database (36.7% vs. 99%), and that factors such as greater prevalence of hysterectomy may contribute to larger racial disparities.

“Future studies need to examine inequities in treatment by race as well as the importance of health care systems in the stage of diagnosis,” they said.

Ms. Siegel said her team plans to follow the patterns outlined in this analysis and examine factors like cancer subtype, socioeconomic status, and place of residence in the future. “However, health inequalities are rooted in systemic racism, so documentation is necessary but insufficient to effect change, which must occur at the institutional level. A more concerted effort is needed to ensure that every woman receives appropriate treatment, regardless of the color of her skin, and education of providers to reduce racial bias and help increase trust in the health care system should be required.”

The authors reported no relevant financial disclosures. Dr. Francoeur and Dr. Salani reported no relevant financial disclosures.

The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.

Early in my career, before I had any notion that years later I would be doing palliative care consults in a cancer center, I heard a senior physician refer to palliative care as “the most misunderstood” medical specialty. I wasn’t sure what she meant at that time, but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.

A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.¹ Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.¹

It’s not giving up

This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.

I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.

“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.

“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.

I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.

“I looked up palliative care on Google and saw the word hospice.”

“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”

She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”

That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.

Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.² As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
 

More than pain management

Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.³

“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”

“Tell me about the patient,” I ask, taking a few steps in their direction.

“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”

“I might be able to help her with the appetite and the mood changes. 
I can at least talk with her and see where she’s at,” I offer.

“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her? 
She doesn’t have any pain.” He sounds skeptical.

“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”

I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.⁴

In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
 

Palliative care is more than medical or nursing care

A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.

We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.

I ask her what else is bothering her.

She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.

We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.

I ask her what conversations with her priest have been like.

At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.⁴ That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
 

“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”

A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.

I say my own small prayer for Ms. Lopez and head home, the day’s work completed.

Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles. 

References

1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.

2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.

3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.

4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.

The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.

Early in my career, before I had any notion that years later I would be doing palliative care consults in a cancer center, I heard a senior physician refer to palliative care as “the most misunderstood” medical specialty. I wasn’t sure what she meant at that time, but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.

A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.¹ Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.¹

It’s not giving up

This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.

I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.

“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.

“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.

I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.

“I looked up palliative care on Google and saw the word hospice.”

“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”

She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”

That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.

Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.² As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
 

More than pain management

Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.³

“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”

“Tell me about the patient,” I ask, taking a few steps in their direction.

“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”

“I might be able to help her with the appetite and the mood changes. 
I can at least talk with her and see where she’s at,” I offer.

“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her? 
She doesn’t have any pain.” He sounds skeptical.

“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”

I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.⁴

In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
 

Palliative care is more than medical or nursing care

A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.

We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.

I ask her what else is bothering her.

She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.

We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.

I ask her what conversations with her priest have been like.

At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.⁴ That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
 

“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”

A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.

I say my own small prayer for Ms. Lopez and head home, the day’s work completed.

Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles. 

References

1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.

2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.

3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.

4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.

The names of health care professionals and patients cited within the dialogue text have been changed to protect their privacy.

Early in my career, before I had any notion that years later I would be doing palliative care consults in a cancer center, I heard a senior physician refer to palliative care as “the most misunderstood” medical specialty. I wasn’t sure what she meant at that time, but over the years I have come to realize that she was right – most people, including many within health care, don’t have a good appreciation of what palliative care is or how it can help patients and health care teams.

A recent national survey about cancer-related health information found that of more than 1,000 surveyed Americans, less than 30% professed any knowledge of palliative care. Of those who had some knowledge of palliative care, around 30% believed palliative care was synonymous with hospice.¹ Another 15% believed that a patient would have to give up cancer-directed treatments to receive palliative care.¹

It’s not giving up

This persistent belief that palliative care is equivalent to hospice, or is tantamount to “giving up,” is one of the most commonly held myths I encounter in everyday practice.

I knock on the exam door and walk in.
A small, trim woman in her late 50s is sitting in a chair, arms folded across her chest, face drawn in.

“Hi,” I start. “I’m Sarah, the palliative care nurse practitioner who works in this clinic. I work closely with Dr. Smith.”
Dr. Smith is the patient’s oncologist.

“I really didn’t want to meet you,” she says in a quiet voice, her eyes large with concern.

I don’t take it personally. Few patients really want to be in the position of needing to meet the palliative care team.

“I looked up palliative care on Google and saw the word hospice.”

“Yeah,” I say. “I hear that a lot. Well, I can reassure you that this isn’t hospice.
In this clinic, our focus is on your cancer symptoms, your treatment side effects, and your quality of life.”

She looks visibly relieved. “Quality of life,” she echoes. “I need more of that.”
“OK,” I say. “So, tell me what you’re struggling with the most right now.”

That’s how many palliative care visits start. I actually prefer if patients haven’t heard of palliative care because it allows me to frame it for them, rather than having to start by addressing a myth or a prior negative experience. Even when patients haven’t had a negative experience with palliative care per se, typically, if they’ve interacted with palliative care in the past, it’s usually because someone they loved died in a hospital setting and it is the memory of that terrible loss that becomes synonymous with their recollection of palliative care.

Many patients I meet have never seen another outpatient palliative care practitioner – and this makes sense – we are still too few and far between. Most established palliative care teams are hospital based and many patients seen in the community do not have easy access to palliative care teams where they receive oncologic care.² As an embedded practitioner, I see patients in the same exam rooms and infusion centers where they receive their cancer therapies, so I’m effectively woven into the fabric of their oncology experience. Just being there in the cancer center allows me to be in the right place at the right time for the right patients and their care teams.
 

More than pain management

Another myth I tend to dispel a lot is that palliative care is just a euphemism for “pain management.” I have seen this less lately, but still occasionally in the chart I’ll see documented in a note, “patient is seeing palliative/pain management,” when a patient is seeing me or one of my colleagues. Unfortunately, when providers have limited or outdated views of what palliative care is or the value it brings to patient-centered cancer care, referrals to palliative care tend to be delayed.³

“I really think Ms. Lopez could benefit from seeing palliative care,” an oncology nurse practitioner says to an oncologist.
I’m standing nearby, about to see another patient in one of the exam rooms in our clinic.
“But I don’t think she’s ready. And besides, she doesn’t have any pain,” he says.
He turns to me quizzically. “What do you think?”

“Tell me about the patient,” I ask, taking a few steps in their direction.

“Well, she’s a 64-year-old woman with metastatic cancer.
She has a really poor appetite and is losing some weight.
Seems a bit down, kind of pessimistic about things.
Her scan showed some new growth, so guess I’m not surprised by that.”

“I might be able to help her with the appetite and the mood changes. 
I can at least talk with her and see where she’s at,” I offer.

“Alright,” he says. “We’ll put the palliative referral in.”
He hesitates. “But are you sure you want to see her? 
She doesn’t have any pain.” He sounds skeptical.

“Yeah, I mean, it sounds like she has symptoms that are bothering her, so I’d be happy to see her. She sounds completely appropriate for palliative care.”

I hear this assumption a lot – that palliative care is somehow equivalent to pain management and that unless a patient’s pain is severe, it’s not worth referring the patient to palliative care. Don’t get me wrong – we do a lot of pain management, but at its heart, palliative care is an interdisciplinary specialty focused on improving or maintaining quality of life for people with serious illness. Because the goal is so broad, care can take many shapes.⁴

In addition to pain, palliative care clinicians commonly treat nausea, shortness of breath, constipation or diarrhea, poor appetite, fatigue, anxiety, depression, and insomnia.
 

Palliative care is more than medical or nursing care

A related misconception about palliative care held by many lay people and health care workers alike is that palliative care is primarily medical or nursing care focused mostly on alleviating physical symptoms such as pain or nausea. This couldn’t be further from the truth.

We’ve been talking for a while.
Ms. Lopez tells me about her struggles to maintain her weight while undergoing chemotherapy. She has low-grade nausea that is impacting her ability and desire to eat more and didn’t think that her weight loss was severe enough to warrant taking medication.
We talk about how she may be able to use antinausea medication sparingly to alleviate nausea while also limiting side effects from the medications—which was a big concern for her.

I ask her what else is bothering her.

She tells me that she has always been a strong Catholic and even when life has gotten tough, her faith was never shaken – until now.
She is struggling to understand why she ended up with metastatic cancer at such a relatively young age—why would God do this to her?
She had plans for retirement that have since evaporated in the face of a foreshortened life.
Why did this happen to her of all people? She was completely healthy until her diagnosis.
Her face is wet with tears.

We talk a little about how a diagnosis like this can change so much of a person’s life and identity. I try to validate her experience. She’s clearly suffering from a sense that her life is not what she expected, and she is struggling to integrate how her future looks at this point.

I ask her what conversations with her priest have been like.

At this point you may be wondering where this conversation is going. Why are we talking about Ms. Lopez’s religion? Palliative care is best delivered through high functioning interdisciplinary teams that can include other supportive people in a patient’s life. We work in concert to try to bring comfort to a patient and their family.⁴ That support network can include nurses, physicians, social workers, and chaplains. In this case, Ms. Lopez had not yet reached out to her priest. She hasn’t had the time or energy to contact her priest given her symptoms.
 

“Can I contact your priest for you?
Maybe he can visit or call and chat with you?”
She nods and wipes tears away.
“That would be really nice,” she says. “I’d love it if he could pray with me.”

A few hours after the visit, I call Ms. Lopez’s priest.
I ask him to reach out to her and about her request for prayer.
He says he’s been thinking about her and that her presence has been missed at weekly Mass. He thanks me for the call and says he’ll call her tomorrow.

I say my own small prayer for Ms. Lopez and head home, the day’s work completed.

Sarah D'Ambruoso was born and raised in Maine. She completed her undergraduate and graduate nursing education at New York University and UCLA, respectively, and currently works as a palliative care nurse practitioner in an oncology clinic in Los Angeles. 

References

1. Cheng BT et al. Patterns of palliative care beliefs among adults in the U.S.: Analysis of a National Cancer Database. J Pain Symptom Manage. 2019 Aug 10. doi: 10.1016/j.jpainsymman.2019.07.030.

2. Finlay E et al. Filling the gap: Creating an outpatient palliative care program in your institution. Am Soc Clin Oncol Educ Book. 2018 May 23. doi: 10.1200/EDBK_200775.

3. Von Roenn JH et al. Barriers and approaches to the successful integration of palliative care and oncology practice. J Natl Compr Canc Netw. 2013 Mar. doi: 10.6004/jnccn.2013.0209.

4. Ferrell BR et al. Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2016.70.1474.

The goal of advanced ovarian cancer surgery is to remove all gross disease, or all visible and palpable disease implants. This became the established standard when improved survival was consistently observed among patients who had undergone complete surgical resection. Traditionally, definitions of no gross residual disease have been left in the hands, and eyes, of the surgeon. However, new technology has emerged which affords surgeons the ability to visualize ovarian cancer deposits that are imperceptible to the naked eye. But will this improve upon the poor cure rates for advanced ovarian cancer?

Many are familiar with the traditional definitions of “optimal” (less than 1 cm–sized deposits at any one location) and “suboptimal” (greater than 1 cm–sized deposits remaining) when referring to surgical cytoreduction of ovarian cancer. This nomenclature was introduced to define, categorize, and prognosticate patient groups after surgery. In recent years we have moved away from these descriptive definitions of ovarian cancer resection, borrowing from surgical oncology measures of surgical outcomes where “R0” defines surgical resection with negative margins, “R1” includes resection with positive microscopic margins (negative for tumor intraoperatively, but positive on microscopic pathology), and “R2” refers to macroscopic residual disease remaining.¹

In ovarian cancer, surgeons have adopted the expression R0 to include patients in whom there is no gross visible or palpable residual disease, a special, favorable subgrouping of the previous “optimal” group. R1 is applied to patients with macroscopic, residual disease that fits within the traditional “optimal” cytoreduction classification (<1 cm in any one location). Obviously, these are significant variations to the traditional surgical oncology definitions, but not without supporting data. For example, patients with no gross residual disease (now defined as “R0”) have been observed to have improved survival, compared with patients who are “optimally” debulked but with R1 (<1 cm) residual disease.² Therefore, this new goal of complete surgical resection has replaced the previous standard of “optimal” cytoreduction in which small macroscopic residual disease was acceptable.

Whether or not a surgery is completed with no gross residual disease is a subjective assessment made by the surgeon, and in practice, highly inaccurate. When a posttrial ad hoc analysis of 1,873 patients with advanced ovarian cancer who had been enrolled in a Gynecologic Oncology Group cooperative trial correlated surgeons’ assessments of “optimal” cytoreduction with objective postoperative radiographic findings (performed, on average, less than 1 month postoperatively) they found that postoperative CT scans identified lesions >1 cm in 40% of cases that had been characterized by surgeons as an “optimal” cytoreduction.³ Most commonly, discrepant lesions were identified in the upper abdominal quadrants and retroperitoneal aortic nodal regions. Therefore, surgeons’ subjective assessment of cytoreduction is prone to error, and given how important the completeness of cytoreduction is for clinical outcomes, there is interest in discovering methods to improve upon surgeons’ ability to discriminate volume of disease.

Pafolacianine (Cytalux, On Target Laboratories) is a novel drug that binds a fluorescent molecule to folic acid targeting the folate alpha receptors which are overexpressed on nonmucinous epithelial ovarian cancer cells compared with adjacent nonmalignant tissues.⁴ The drug is intravenously infused preoperatively and then visualized with companion near-infrared imaging devices during surgery to visualize its fluorescent signal where it is bound to ovarian cancer implants. In a phase 2 study of 178 patients with confirmed or suspected ovarian cancer, pafolacianine was able to detect implants of ovarian cancer in 26.9% of cases where the surgeon’s visual inspection was negative.⁵ Of note, the false-positive rate of this drug was not trivial, at 20%. Based on this efficacy data, the drug has been granted FDA approved for use in ovarian cancer surgery to augment the surgeon’s visualization of cancer. However, important questions remain unanswered by these preliminary data.

Will removal of additional microscopic ovarian cancer implants, only seen by pafolacianine, improve the survival of patients with ovarian cancer, and what effect will the addition of this extra surgery have on their surgical morbidity and risk? The use of pafolacianine to augment ovarian cancer debulking surgeries pivots on the premise that ovarian cancer outcomes are determined by surgical “effort” more than the biology of the disease. Otherwise said: The more we surgically remove, the more we cure. But this seems an old-fashioned notion, increasingly challenged by data. It has been shown that, when ovarian cancer debulking surgeries are necessarily more radical because of extensive disease distribution, prognosis is worse, compared with those patients with less extensive disease distribution.⁶ The effect of surgical effort contributes less than that of predetermined patterns of disease presentation. Additionally, genomic traits are different in tumors that are objectively determined to be not amenable to optimal cytoreduction, compared with resectable tumors.⁷ These data suggest that it is the disease, more than the surgeon, that most influences outcomes.

Additionally, the question of whether surgical removal of microscopic disease improves ovarian cancer survival has already been addressed with negative findings. The LION trial randomized 647 women with advanced ovarian cancer to primary cytoreductive surgery either with or without routine lymphadenectomy of clinically negative nodes.⁸ This study found no survival benefit to resecting clinically negative, microscopically positive nodes. In light of these data, it is difficult to imagine that there would be different results with the resection of microscopic peritoneal disease implants identified by pafolacianine.

While pafolacianine promises to move us closer to a true “R0” (negative margins) resection of ovarian cancer, is this even a feasible goal in a disease that is widely metastatic, particularly in the peritoneal cavity? What do “negative margins” mean in the peritoneal cavity? The sensitivity of pafolacianine in detecting microscopic disease is obviously not so high that it can guarantee patients a complete resection of a disseminated disease, and we still do not know what absolute benefit is derived from moving a little bit further on the continuum of surgical resection.

Perhaps augmentation of debulking is not the only, or best, use of pafolacianine for ovarian cancer surgery. Perhaps it might serve a role in diagnostics or staging of the disease rather than for a therapeutic purpose. In the meantime, we await ongoing clinical trials in this space to better inform clinicians what benefits, or harms, they might expect from the addition of this new drug as we continue to define the “optimal” surgical procedure for advanced ovarian cancer.

Dr. Emma Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest.

References

1. Hermanek P, Wittekind C. Semin Surg Oncol 1994;10:12-20.

2. Elattar A et al. Cochrane Database Syst Rev 2011 Aug 10;2011(8):CD007565.

3. Eskander RN et al. Gynecol Oncol 2018;149:525-30.

4. Randall LM et al. Gynecol Oncol 2019;155:63-8.

5. Food and Drug Administration. FDA approves pafolacianine for identifying malignant ovarian cancer lesions. 2021 Dec 1.

6. Horowitz NS et al. J Clin Oncol 2015;33:937-43.

7. Lee S et al. Cell Rep. 2020;31:107502.

8. Harter P et al. N Engl J Med 2019;380:822-32.

The goal of advanced ovarian cancer surgery is to remove all gross disease, or all visible and palpable disease implants. This became the established standard when improved survival was consistently observed among patients who had undergone complete surgical resection. Traditionally, definitions of no gross residual disease have been left in the hands, and eyes, of the surgeon. However, new technology has emerged which affords surgeons the ability to visualize ovarian cancer deposits that are imperceptible to the naked eye. But will this improve upon the poor cure rates for advanced ovarian cancer?

Many are familiar with the traditional definitions of “optimal” (less than 1 cm–sized deposits at any one location) and “suboptimal” (greater than 1 cm–sized deposits remaining) when referring to surgical cytoreduction of ovarian cancer. This nomenclature was introduced to define, categorize, and prognosticate patient groups after surgery. In recent years we have moved away from these descriptive definitions of ovarian cancer resection, borrowing from surgical oncology measures of surgical outcomes where “R0” defines surgical resection with negative margins, “R1” includes resection with positive microscopic margins (negative for tumor intraoperatively, but positive on microscopic pathology), and “R2” refers to macroscopic residual disease remaining.¹

In ovarian cancer, surgeons have adopted the expression R0 to include patients in whom there is no gross visible or palpable residual disease, a special, favorable subgrouping of the previous “optimal” group. R1 is applied to patients with macroscopic, residual disease that fits within the traditional “optimal” cytoreduction classification (<1 cm in any one location). Obviously, these are significant variations to the traditional surgical oncology definitions, but not without supporting data. For example, patients with no gross residual disease (now defined as “R0”) have been observed to have improved survival, compared with patients who are “optimally” debulked but with R1 (<1 cm) residual disease.² Therefore, this new goal of complete surgical resection has replaced the previous standard of “optimal” cytoreduction in which small macroscopic residual disease was acceptable.

Whether or not a surgery is completed with no gross residual disease is a subjective assessment made by the surgeon, and in practice, highly inaccurate. When a posttrial ad hoc analysis of 1,873 patients with advanced ovarian cancer who had been enrolled in a Gynecologic Oncology Group cooperative trial correlated surgeons’ assessments of “optimal” cytoreduction with objective postoperative radiographic findings (performed, on average, less than 1 month postoperatively) they found that postoperative CT scans identified lesions >1 cm in 40% of cases that had been characterized by surgeons as an “optimal” cytoreduction.³ Most commonly, discrepant lesions were identified in the upper abdominal quadrants and retroperitoneal aortic nodal regions. Therefore, surgeons’ subjective assessment of cytoreduction is prone to error, and given how important the completeness of cytoreduction is for clinical outcomes, there is interest in discovering methods to improve upon surgeons’ ability to discriminate volume of disease.

Pafolacianine (Cytalux, On Target Laboratories) is a novel drug that binds a fluorescent molecule to folic acid targeting the folate alpha receptors which are overexpressed on nonmucinous epithelial ovarian cancer cells compared with adjacent nonmalignant tissues.⁴ The drug is intravenously infused preoperatively and then visualized with companion near-infrared imaging devices during surgery to visualize its fluorescent signal where it is bound to ovarian cancer implants. In a phase 2 study of 178 patients with confirmed or suspected ovarian cancer, pafolacianine was able to detect implants of ovarian cancer in 26.9% of cases where the surgeon’s visual inspection was negative.⁵ Of note, the false-positive rate of this drug was not trivial, at 20%. Based on this efficacy data, the drug has been granted FDA approved for use in ovarian cancer surgery to augment the surgeon’s visualization of cancer. However, important questions remain unanswered by these preliminary data.

Will removal of additional microscopic ovarian cancer implants, only seen by pafolacianine, improve the survival of patients with ovarian cancer, and what effect will the addition of this extra surgery have on their surgical morbidity and risk? The use of pafolacianine to augment ovarian cancer debulking surgeries pivots on the premise that ovarian cancer outcomes are determined by surgical “effort” more than the biology of the disease. Otherwise said: The more we surgically remove, the more we cure. But this seems an old-fashioned notion, increasingly challenged by data. It has been shown that, when ovarian cancer debulking surgeries are necessarily more radical because of extensive disease distribution, prognosis is worse, compared with those patients with less extensive disease distribution.⁶ The effect of surgical effort contributes less than that of predetermined patterns of disease presentation. Additionally, genomic traits are different in tumors that are objectively determined to be not amenable to optimal cytoreduction, compared with resectable tumors.⁷ These data suggest that it is the disease, more than the surgeon, that most influences outcomes.

Additionally, the question of whether surgical removal of microscopic disease improves ovarian cancer survival has already been addressed with negative findings. The LION trial randomized 647 women with advanced ovarian cancer to primary cytoreductive surgery either with or without routine lymphadenectomy of clinically negative nodes.⁸ This study found no survival benefit to resecting clinically negative, microscopically positive nodes. In light of these data, it is difficult to imagine that there would be different results with the resection of microscopic peritoneal disease implants identified by pafolacianine.

While pafolacianine promises to move us closer to a true “R0” (negative margins) resection of ovarian cancer, is this even a feasible goal in a disease that is widely metastatic, particularly in the peritoneal cavity? What do “negative margins” mean in the peritoneal cavity? The sensitivity of pafolacianine in detecting microscopic disease is obviously not so high that it can guarantee patients a complete resection of a disseminated disease, and we still do not know what absolute benefit is derived from moving a little bit further on the continuum of surgical resection.

Perhaps augmentation of debulking is not the only, or best, use of pafolacianine for ovarian cancer surgery. Perhaps it might serve a role in diagnostics or staging of the disease rather than for a therapeutic purpose. In the meantime, we await ongoing clinical trials in this space to better inform clinicians what benefits, or harms, they might expect from the addition of this new drug as we continue to define the “optimal” surgical procedure for advanced ovarian cancer.

Dr. Emma Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest.

References

1. Hermanek P, Wittekind C. Semin Surg Oncol 1994;10:12-20.

2. Elattar A et al. Cochrane Database Syst Rev 2011 Aug 10;2011(8):CD007565.

3. Eskander RN et al. Gynecol Oncol 2018;149:525-30.

4. Randall LM et al. Gynecol Oncol 2019;155:63-8.

5. Food and Drug Administration. FDA approves pafolacianine for identifying malignant ovarian cancer lesions. 2021 Dec 1.

6. Horowitz NS et al. J Clin Oncol 2015;33:937-43.

7. Lee S et al. Cell Rep. 2020;31:107502.

8. Harter P et al. N Engl J Med 2019;380:822-32.

The goal of advanced ovarian cancer surgery is to remove all gross disease, or all visible and palpable disease implants. This became the established standard when improved survival was consistently observed among patients who had undergone complete surgical resection. Traditionally, definitions of no gross residual disease have been left in the hands, and eyes, of the surgeon. However, new technology has emerged which affords surgeons the ability to visualize ovarian cancer deposits that are imperceptible to the naked eye. But will this improve upon the poor cure rates for advanced ovarian cancer?

Many are familiar with the traditional definitions of “optimal” (less than 1 cm–sized deposits at any one location) and “suboptimal” (greater than 1 cm–sized deposits remaining) when referring to surgical cytoreduction of ovarian cancer. This nomenclature was introduced to define, categorize, and prognosticate patient groups after surgery. In recent years we have moved away from these descriptive definitions of ovarian cancer resection, borrowing from surgical oncology measures of surgical outcomes where “R0” defines surgical resection with negative margins, “R1” includes resection with positive microscopic margins (negative for tumor intraoperatively, but positive on microscopic pathology), and “R2” refers to macroscopic residual disease remaining.¹

In ovarian cancer, surgeons have adopted the expression R0 to include patients in whom there is no gross visible or palpable residual disease, a special, favorable subgrouping of the previous “optimal” group. R1 is applied to patients with macroscopic, residual disease that fits within the traditional “optimal” cytoreduction classification (<1 cm in any one location). Obviously, these are significant variations to the traditional surgical oncology definitions, but not without supporting data. For example, patients with no gross residual disease (now defined as “R0”) have been observed to have improved survival, compared with patients who are “optimally” debulked but with R1 (<1 cm) residual disease.² Therefore, this new goal of complete surgical resection has replaced the previous standard of “optimal” cytoreduction in which small macroscopic residual disease was acceptable.

Whether or not a surgery is completed with no gross residual disease is a subjective assessment made by the surgeon, and in practice, highly inaccurate. When a posttrial ad hoc analysis of 1,873 patients with advanced ovarian cancer who had been enrolled in a Gynecologic Oncology Group cooperative trial correlated surgeons’ assessments of “optimal” cytoreduction with objective postoperative radiographic findings (performed, on average, less than 1 month postoperatively) they found that postoperative CT scans identified lesions >1 cm in 40% of cases that had been characterized by surgeons as an “optimal” cytoreduction.³ Most commonly, discrepant lesions were identified in the upper abdominal quadrants and retroperitoneal aortic nodal regions. Therefore, surgeons’ subjective assessment of cytoreduction is prone to error, and given how important the completeness of cytoreduction is for clinical outcomes, there is interest in discovering methods to improve upon surgeons’ ability to discriminate volume of disease.

Pafolacianine (Cytalux, On Target Laboratories) is a novel drug that binds a fluorescent molecule to folic acid targeting the folate alpha receptors which are overexpressed on nonmucinous epithelial ovarian cancer cells compared with adjacent nonmalignant tissues.⁴ The drug is intravenously infused preoperatively and then visualized with companion near-infrared imaging devices during surgery to visualize its fluorescent signal where it is bound to ovarian cancer implants. In a phase 2 study of 178 patients with confirmed or suspected ovarian cancer, pafolacianine was able to detect implants of ovarian cancer in 26.9% of cases where the surgeon’s visual inspection was negative.⁵ Of note, the false-positive rate of this drug was not trivial, at 20%. Based on this efficacy data, the drug has been granted FDA approved for use in ovarian cancer surgery to augment the surgeon’s visualization of cancer. However, important questions remain unanswered by these preliminary data.

Will removal of additional microscopic ovarian cancer implants, only seen by pafolacianine, improve the survival of patients with ovarian cancer, and what effect will the addition of this extra surgery have on their surgical morbidity and risk? The use of pafolacianine to augment ovarian cancer debulking surgeries pivots on the premise that ovarian cancer outcomes are determined by surgical “effort” more than the biology of the disease. Otherwise said: The more we surgically remove, the more we cure. But this seems an old-fashioned notion, increasingly challenged by data. It has been shown that, when ovarian cancer debulking surgeries are necessarily more radical because of extensive disease distribution, prognosis is worse, compared with those patients with less extensive disease distribution.⁶ The effect of surgical effort contributes less than that of predetermined patterns of disease presentation. Additionally, genomic traits are different in tumors that are objectively determined to be not amenable to optimal cytoreduction, compared with resectable tumors.⁷ These data suggest that it is the disease, more than the surgeon, that most influences outcomes.

Additionally, the question of whether surgical removal of microscopic disease improves ovarian cancer survival has already been addressed with negative findings. The LION trial randomized 647 women with advanced ovarian cancer to primary cytoreductive surgery either with or without routine lymphadenectomy of clinically negative nodes.⁸ This study found no survival benefit to resecting clinically negative, microscopically positive nodes. In light of these data, it is difficult to imagine that there would be different results with the resection of microscopic peritoneal disease implants identified by pafolacianine.

While pafolacianine promises to move us closer to a true “R0” (negative margins) resection of ovarian cancer, is this even a feasible goal in a disease that is widely metastatic, particularly in the peritoneal cavity? What do “negative margins” mean in the peritoneal cavity? The sensitivity of pafolacianine in detecting microscopic disease is obviously not so high that it can guarantee patients a complete resection of a disseminated disease, and we still do not know what absolute benefit is derived from moving a little bit further on the continuum of surgical resection.

Perhaps augmentation of debulking is not the only, or best, use of pafolacianine for ovarian cancer surgery. Perhaps it might serve a role in diagnostics or staging of the disease rather than for a therapeutic purpose. In the meantime, we await ongoing clinical trials in this space to better inform clinicians what benefits, or harms, they might expect from the addition of this new drug as we continue to define the “optimal” surgical procedure for advanced ovarian cancer.

Dr. Emma Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest.

References

1. Hermanek P, Wittekind C. Semin Surg Oncol 1994;10:12-20.

2. Elattar A et al. Cochrane Database Syst Rev 2011 Aug 10;2011(8):CD007565.

3. Eskander RN et al. Gynecol Oncol 2018;149:525-30.

4. Randall LM et al. Gynecol Oncol 2019;155:63-8.

5. Food and Drug Administration. FDA approves pafolacianine for identifying malignant ovarian cancer lesions. 2021 Dec 1.

6. Horowitz NS et al. J Clin Oncol 2015;33:937-43.

7. Lee S et al. Cell Rep. 2020;31:107502.

8. Harter P et al. N Engl J Med 2019;380:822-32.

The number of women screened for cervical cancer in the United States declined between 2005 and 2019 with lack of knowledge about the need for screening being cited as the most common reason for not receiving up-to-date screening. These are the results of a population-based, cross-sectional study conducted by the U.S. Preventive Services Task Force and were published online in JAMA Network Open.

“The fact that this reason increased over time across most sociodemographic groups suggests a need for interventions targeting screening awareness for all women,” lead author Ryan Suk, PhD, MS, from the University of Texas Health Science Center, Houston, and colleagues wrote.

Between 2005 and 2019, the researchers evaluated data from 20,557 women (weighted, 113.1 million women) included in the U.S. National Health Interview Survey. The cohort included women aged 21-65 years without previous hysterectomy and included data on sociodemographic factors such as race, ethnicity, sexual orientation, health insurance type, and rurality of residence.

Dr. Suk and colleagues found that the proportion of women without current screening increased from 2005 to 2019 (from 14.4% to 23.0%; P < .001) and that a higher proportion of those women were in the 21- to 29-year age group (weighted, 29.1%), compared with women in the 30- to 65-year age group (weighted, 21.1%; P < .001). Regardless of age, not knowing that screening was indicated was the most common reason cited for not having up-to-date screening.
 

Sociodemographic factors influence on rates and reasons for overdue screening

Based on weighted population estimates, 6.1% of women included were Asian, 17.2% were Hispanic, 13.1% were non-Hispanic Black, 61% were non-Hispanic White, and 2.7% were other races and/or ethnicities.

Dr. Suk and colleagues found that Asian women had the highest rates of overdue screening, compared with non-Hispanic White women, who had the lowest rates (weighted, 31.4% vs. 20.1%, respectively). The authors also found that reasons for overdue screening varied by sociodemographic factors. For example, while both Asian and Hispanic women cited lack of knowledge as a barrier to routine screening, Asian women were more likely to also report lack of recommendation from a health care professional as a barrier while Hispanic women were more likely to also report lack of access as a barrier to timely screening.

Over the 14-year study period, higher rates of overdue screening were also noted among those identifying as LGBTQ+ versus heterosexual (32.0% vs. 22.2%; P < .001), those with no insurance versus private insurance (41.7% vs. 18.1%; P < .001), and those living in rural versus urban areas (26.2% vs. 22.6%; P = .04).

For the study, guideline-concordant, up-to-date screening in 2005 was defined as screening every 3 years for women aged 21-65 years based on USPSTF guidelines and clinical recommendations. For 2019, up-to-date screening was defined as screening every 3 years with a Papanicolaou (Pap smear) test alone for women aged 21-29 years and screening every 3 years with a Pap smear alone or every 5 years with high-risk human papillomavirus testing or cotesting for women aged 30-65 years.

Dr. Suk and colleagues suggested that guideline updates over the study period could have led to uncertainty regarding appropriate timing and recommended screening intervals, which in turn, may have played a role in decreased cancer screening recommendations.

“Studies have suggested that changing guidelines may produce an increase in both overscreening and underscreening but those already at higher risk of cervical cancer may be most susceptible to underscreening,” wrote the authors.

In an interview, Ruchi Garg, MD, from Mid Atlantic Gynecologic Oncology and Pelvic Surgery Associates, Fairfax, Va., commented: “I think it has been hard to keep up with the guidelines changing so frequently. Furthermore it’s not clearly delineated (or at least there seems to be confusion or extrapolation) that the guidelines are just for Pap smear and that it doesn’t translate into a well woman checkup/pelvic exam; [however], if physicians continue to tell the patients to come in every year, then there won’t be so much underscreening since the physicians/providers will be able to keep track of when the Pap smears need to get done.”

Similar to the study authors, Dr. Garg also suggested that community lectures and public health announcements, particularly when guidelines are updated, will be helpful in enhancing patient education and reducing the rate of this preventable cancer.

The study authors and commentator disclosed no relevant financial relationships.

The number of women screened for cervical cancer in the United States declined between 2005 and 2019 with lack of knowledge about the need for screening being cited as the most common reason for not receiving up-to-date screening. These are the results of a population-based, cross-sectional study conducted by the U.S. Preventive Services Task Force and were published online in JAMA Network Open.

“The fact that this reason increased over time across most sociodemographic groups suggests a need for interventions targeting screening awareness for all women,” lead author Ryan Suk, PhD, MS, from the University of Texas Health Science Center, Houston, and colleagues wrote.

Between 2005 and 2019, the researchers evaluated data from 20,557 women (weighted, 113.1 million women) included in the U.S. National Health Interview Survey. The cohort included women aged 21-65 years without previous hysterectomy and included data on sociodemographic factors such as race, ethnicity, sexual orientation, health insurance type, and rurality of residence.

Dr. Suk and colleagues found that the proportion of women without current screening increased from 2005 to 2019 (from 14.4% to 23.0%; P < .001) and that a higher proportion of those women were in the 21- to 29-year age group (weighted, 29.1%), compared with women in the 30- to 65-year age group (weighted, 21.1%; P < .001). Regardless of age, not knowing that screening was indicated was the most common reason cited for not having up-to-date screening.
 

Sociodemographic factors influence on rates and reasons for overdue screening

Based on weighted population estimates, 6.1% of women included were Asian, 17.2% were Hispanic, 13.1% were non-Hispanic Black, 61% were non-Hispanic White, and 2.7% were other races and/or ethnicities.

Dr. Suk and colleagues found that Asian women had the highest rates of overdue screening, compared with non-Hispanic White women, who had the lowest rates (weighted, 31.4% vs. 20.1%, respectively). The authors also found that reasons for overdue screening varied by sociodemographic factors. For example, while both Asian and Hispanic women cited lack of knowledge as a barrier to routine screening, Asian women were more likely to also report lack of recommendation from a health care professional as a barrier while Hispanic women were more likely to also report lack of access as a barrier to timely screening.

Over the 14-year study period, higher rates of overdue screening were also noted among those identifying as LGBTQ+ versus heterosexual (32.0% vs. 22.2%; P < .001), those with no insurance versus private insurance (41.7% vs. 18.1%; P < .001), and those living in rural versus urban areas (26.2% vs. 22.6%; P = .04).

For the study, guideline-concordant, up-to-date screening in 2005 was defined as screening every 3 years for women aged 21-65 years based on USPSTF guidelines and clinical recommendations. For 2019, up-to-date screening was defined as screening every 3 years with a Papanicolaou (Pap smear) test alone for women aged 21-29 years and screening every 3 years with a Pap smear alone or every 5 years with high-risk human papillomavirus testing or cotesting for women aged 30-65 years.

Dr. Suk and colleagues suggested that guideline updates over the study period could have led to uncertainty regarding appropriate timing and recommended screening intervals, which in turn, may have played a role in decreased cancer screening recommendations.

“Studies have suggested that changing guidelines may produce an increase in both overscreening and underscreening but those already at higher risk of cervical cancer may be most susceptible to underscreening,” wrote the authors.

In an interview, Ruchi Garg, MD, from Mid Atlantic Gynecologic Oncology and Pelvic Surgery Associates, Fairfax, Va., commented: “I think it has been hard to keep up with the guidelines changing so frequently. Furthermore it’s not clearly delineated (or at least there seems to be confusion or extrapolation) that the guidelines are just for Pap smear and that it doesn’t translate into a well woman checkup/pelvic exam; [however], if physicians continue to tell the patients to come in every year, then there won’t be so much underscreening since the physicians/providers will be able to keep track of when the Pap smears need to get done.”

Similar to the study authors, Dr. Garg also suggested that community lectures and public health announcements, particularly when guidelines are updated, will be helpful in enhancing patient education and reducing the rate of this preventable cancer.

The study authors and commentator disclosed no relevant financial relationships.

The number of women screened for cervical cancer in the United States declined between 2005 and 2019 with lack of knowledge about the need for screening being cited as the most common reason for not receiving up-to-date screening. These are the results of a population-based, cross-sectional study conducted by the U.S. Preventive Services Task Force and were published online in JAMA Network Open.

“The fact that this reason increased over time across most sociodemographic groups suggests a need for interventions targeting screening awareness for all women,” lead author Ryan Suk, PhD, MS, from the University of Texas Health Science Center, Houston, and colleagues wrote.

Between 2005 and 2019, the researchers evaluated data from 20,557 women (weighted, 113.1 million women) included in the U.S. National Health Interview Survey. The cohort included women aged 21-65 years without previous hysterectomy and included data on sociodemographic factors such as race, ethnicity, sexual orientation, health insurance type, and rurality of residence.

Dr. Suk and colleagues found that the proportion of women without current screening increased from 2005 to 2019 (from 14.4% to 23.0%; P < .001) and that a higher proportion of those women were in the 21- to 29-year age group (weighted, 29.1%), compared with women in the 30- to 65-year age group (weighted, 21.1%; P < .001). Regardless of age, not knowing that screening was indicated was the most common reason cited for not having up-to-date screening.
 

Sociodemographic factors influence on rates and reasons for overdue screening

Based on weighted population estimates, 6.1% of women included were Asian, 17.2% were Hispanic, 13.1% were non-Hispanic Black, 61% were non-Hispanic White, and 2.7% were other races and/or ethnicities.

Dr. Suk and colleagues found that Asian women had the highest rates of overdue screening, compared with non-Hispanic White women, who had the lowest rates (weighted, 31.4% vs. 20.1%, respectively). The authors also found that reasons for overdue screening varied by sociodemographic factors. For example, while both Asian and Hispanic women cited lack of knowledge as a barrier to routine screening, Asian women were more likely to also report lack of recommendation from a health care professional as a barrier while Hispanic women were more likely to also report lack of access as a barrier to timely screening.

Over the 14-year study period, higher rates of overdue screening were also noted among those identifying as LGBTQ+ versus heterosexual (32.0% vs. 22.2%; P < .001), those with no insurance versus private insurance (41.7% vs. 18.1%; P < .001), and those living in rural versus urban areas (26.2% vs. 22.6%; P = .04).

For the study, guideline-concordant, up-to-date screening in 2005 was defined as screening every 3 years for women aged 21-65 years based on USPSTF guidelines and clinical recommendations. For 2019, up-to-date screening was defined as screening every 3 years with a Papanicolaou (Pap smear) test alone for women aged 21-29 years and screening every 3 years with a Pap smear alone or every 5 years with high-risk human papillomavirus testing or cotesting for women aged 30-65 years.

Dr. Suk and colleagues suggested that guideline updates over the study period could have led to uncertainty regarding appropriate timing and recommended screening intervals, which in turn, may have played a role in decreased cancer screening recommendations.

“Studies have suggested that changing guidelines may produce an increase in both overscreening and underscreening but those already at higher risk of cervical cancer may be most susceptible to underscreening,” wrote the authors.

In an interview, Ruchi Garg, MD, from Mid Atlantic Gynecologic Oncology and Pelvic Surgery Associates, Fairfax, Va., commented: “I think it has been hard to keep up with the guidelines changing so frequently. Furthermore it’s not clearly delineated (or at least there seems to be confusion or extrapolation) that the guidelines are just for Pap smear and that it doesn’t translate into a well woman checkup/pelvic exam; [however], if physicians continue to tell the patients to come in every year, then there won’t be so much underscreening since the physicians/providers will be able to keep track of when the Pap smears need to get done.”

Similar to the study authors, Dr. Garg also suggested that community lectures and public health announcements, particularly when guidelines are updated, will be helpful in enhancing patient education and reducing the rate of this preventable cancer.

The study authors and commentator disclosed no relevant financial relationships.

A new study offers fresh insight into early indications of high-risk, early-stage, epithelial ovarian cancer: More than 70% have at least one symptom such as abdominal/pelvic pain or increased girth/fullness, and women with larger tumors have more symptoms.

“Even in early-stage disease, ovarian cancer is not necessarily a silent disease,” said lead author and gynecologic oncologist/surgeon John K. Chan, MD, of Palo Alto Medical Foundation/California Pacific/Sutter Research Institute.

The study appeared online Jan. 6, in the journal Obstetrics & Gynecology.*

According to Dr. Chan, most previous studies of symptoms in ovarian cancer have focused on those with advanced disease since that’s when it’s typically diagnosed. “Given these gaps in knowledge from prior reports, we performed this analysis to evaluate the presentation and characteristic symptoms of early-stage ovarian cancer and to attempt to identify the relationship between these symptoms with respect to clinicopathologic characteristics and prognosis in early-stage disease.”

Dr. Chan and colleagues retrospectively tracked 419 patients who were subjects in a clinical trial of chemotherapy doses. The patients all had high-risk, early-stage epithelial ovarian cancer (stage IA-IB and grade 3, any clear cell, stage IC or II).

Of the patients, 40% presented with one symptom, while 32% had multiple symptoms. The other 28% had no symptoms, and their masses were diagnosed upon discovery during physical examination. “Other investigators have found that nearly 95% of patients with ovarian cancer were symptomatic,” Dr. Chan said. “The lower percentage of symptomatic patients in our study may be because all 419 patients had early-stage disease as opposed to advanced-stage disease.”

The most common symptoms were abdominal or pelvic pain (31%; 95% confidence interval, 27%-36%), fullness or increased abdominal girth (27%; 95% CI, 22%-31%), abnormal vaginal bleeding (13%; 95% CI, 10%-17%), urinary problems (10%; 95% CI, 8%-14%), and gastrointestinal problems (6%; 95% CI, 4%-8%).

There was no statistically significant link between number of symptoms and age (younger than 60 or 60 or older), cancer stage, or histologic subtype. However, patients with the largest tumors (>15 cm) were more likely to have multiple symptoms than those with the smallest tumors (10 cm or smaller): 46% vs. 21% (P < .001).

Also, 79% of those with the largest tumors (>15 cm) had at least one symptom, compared with 65% of those with the smallest tumors (10 cm or smaller, P < .001)

Unlike other studies, this report didn’t find a link between the number of symptoms and mortality. This finding surprised the researchers, Dr. Chan said, as did the lack of connections between symptoms and age, stage, or histologic subtype. “We were expecting that the younger patients may have more symptoms given the association with endometriosis and clear cell cancers,” he said. “We also thought that those who are less symptomatic may have more stage I and low-grade indolent tumors with better survival, but we did not find that.”

The researchers noted limitations such as the lack of standardization in the patient data.

In the big picture, Dr. Chan said, “patients and health care professionals need to have a higher index of suspicion in symptomatic ovarian cancer patients to increase early detection and potentially improve cures. Ovarian cancer does not always kill. In fact, up to 80% of our early-stage disease patients are cured.”

He called for “additional research to evaluate symptom awareness in early-stage cancers and possibly incorporating novel serum biomarkers and wearable monitoring devices. Wearables may be able to assess for frequency or duration of symptoms, which may be an important factor in distinguishing symptoms that are more concerning for ovarian cancer.”

In an adjoining commentary, Barbara A. Goff, MD, chair of obstetrics and gynecology at the University of Washington, Seattle, noted that, while ovarian cancers diagnosed early have a high survival rate, prospective randomized trials of transvaginal ultrasonography and tumor marker screening strategies have failed to reduce mortality. There’s currently no recommended screening test for women at average risk.

There are other challenges, she wrote. For one, “many health care professionals are seemingly unaware of the symptoms typically associated with ovarian cancer, so misdiagnosis remains common.” And “one of the concerns about the symptoms of ovarian cancer is that they can be vague and commonly present in the general population.”

Dr. Goff praised the study, called for more education about the symptoms of ovarian cancer, and wrote that “symptom recognition with appropriate diagnostic testing remains very important in our efforts to improve outcomes.”

The National Institutes of Health funded the study. Several study authors, including Dr. Chan, reported various disclosures.

Correction, 1/31/22: An earlier version of this article misstated the date of publication.

A new study offers fresh insight into early indications of high-risk, early-stage, epithelial ovarian cancer: More than 70% have at least one symptom such as abdominal/pelvic pain or increased girth/fullness, and women with larger tumors have more symptoms.

“Even in early-stage disease, ovarian cancer is not necessarily a silent disease,” said lead author and gynecologic oncologist/surgeon John K. Chan, MD, of Palo Alto Medical Foundation/California Pacific/Sutter Research Institute.

The study appeared online Jan. 6, in the journal Obstetrics & Gynecology.*

According to Dr. Chan, most previous studies of symptoms in ovarian cancer have focused on those with advanced disease since that’s when it’s typically diagnosed. “Given these gaps in knowledge from prior reports, we performed this analysis to evaluate the presentation and characteristic symptoms of early-stage ovarian cancer and to attempt to identify the relationship between these symptoms with respect to clinicopathologic characteristics and prognosis in early-stage disease.”

Dr. Chan and colleagues retrospectively tracked 419 patients who were subjects in a clinical trial of chemotherapy doses. The patients all had high-risk, early-stage epithelial ovarian cancer (stage IA-IB and grade 3, any clear cell, stage IC or II).

Of the patients, 40% presented with one symptom, while 32% had multiple symptoms. The other 28% had no symptoms, and their masses were diagnosed upon discovery during physical examination. “Other investigators have found that nearly 95% of patients with ovarian cancer were symptomatic,” Dr. Chan said. “The lower percentage of symptomatic patients in our study may be because all 419 patients had early-stage disease as opposed to advanced-stage disease.”

The most common symptoms were abdominal or pelvic pain (31%; 95% confidence interval, 27%-36%), fullness or increased abdominal girth (27%; 95% CI, 22%-31%), abnormal vaginal bleeding (13%; 95% CI, 10%-17%), urinary problems (10%; 95% CI, 8%-14%), and gastrointestinal problems (6%; 95% CI, 4%-8%).

There was no statistically significant link between number of symptoms and age (younger than 60 or 60 or older), cancer stage, or histologic subtype. However, patients with the largest tumors (>15 cm) were more likely to have multiple symptoms than those with the smallest tumors (10 cm or smaller): 46% vs. 21% (P < .001).

Also, 79% of those with the largest tumors (>15 cm) had at least one symptom, compared with 65% of those with the smallest tumors (10 cm or smaller, P < .001)

Unlike other studies, this report didn’t find a link between the number of symptoms and mortality. This finding surprised the researchers, Dr. Chan said, as did the lack of connections between symptoms and age, stage, or histologic subtype. “We were expecting that the younger patients may have more symptoms given the association with endometriosis and clear cell cancers,” he said. “We also thought that those who are less symptomatic may have more stage I and low-grade indolent tumors with better survival, but we did not find that.”

The researchers noted limitations such as the lack of standardization in the patient data.

In the big picture, Dr. Chan said, “patients and health care professionals need to have a higher index of suspicion in symptomatic ovarian cancer patients to increase early detection and potentially improve cures. Ovarian cancer does not always kill. In fact, up to 80% of our early-stage disease patients are cured.”

He called for “additional research to evaluate symptom awareness in early-stage cancers and possibly incorporating novel serum biomarkers and wearable monitoring devices. Wearables may be able to assess for frequency or duration of symptoms, which may be an important factor in distinguishing symptoms that are more concerning for ovarian cancer.”

In an adjoining commentary, Barbara A. Goff, MD, chair of obstetrics and gynecology at the University of Washington, Seattle, noted that, while ovarian cancers diagnosed early have a high survival rate, prospective randomized trials of transvaginal ultrasonography and tumor marker screening strategies have failed to reduce mortality. There’s currently no recommended screening test for women at average risk.

There are other challenges, she wrote. For one, “many health care professionals are seemingly unaware of the symptoms typically associated with ovarian cancer, so misdiagnosis remains common.” And “one of the concerns about the symptoms of ovarian cancer is that they can be vague and commonly present in the general population.”

Dr. Goff praised the study, called for more education about the symptoms of ovarian cancer, and wrote that “symptom recognition with appropriate diagnostic testing remains very important in our efforts to improve outcomes.”

The National Institutes of Health funded the study. Several study authors, including Dr. Chan, reported various disclosures.

Correction, 1/31/22: An earlier version of this article misstated the date of publication.

A new study offers fresh insight into early indications of high-risk, early-stage, epithelial ovarian cancer: More than 70% have at least one symptom such as abdominal/pelvic pain or increased girth/fullness, and women with larger tumors have more symptoms.

“Even in early-stage disease, ovarian cancer is not necessarily a silent disease,” said lead author and gynecologic oncologist/surgeon John K. Chan, MD, of Palo Alto Medical Foundation/California Pacific/Sutter Research Institute.

The study appeared online Jan. 6, in the journal Obstetrics & Gynecology.*

According to Dr. Chan, most previous studies of symptoms in ovarian cancer have focused on those with advanced disease since that’s when it’s typically diagnosed. “Given these gaps in knowledge from prior reports, we performed this analysis to evaluate the presentation and characteristic symptoms of early-stage ovarian cancer and to attempt to identify the relationship between these symptoms with respect to clinicopathologic characteristics and prognosis in early-stage disease.”

Dr. Chan and colleagues retrospectively tracked 419 patients who were subjects in a clinical trial of chemotherapy doses. The patients all had high-risk, early-stage epithelial ovarian cancer (stage IA-IB and grade 3, any clear cell, stage IC or II).

Of the patients, 40% presented with one symptom, while 32% had multiple symptoms. The other 28% had no symptoms, and their masses were diagnosed upon discovery during physical examination. “Other investigators have found that nearly 95% of patients with ovarian cancer were symptomatic,” Dr. Chan said. “The lower percentage of symptomatic patients in our study may be because all 419 patients had early-stage disease as opposed to advanced-stage disease.”

The most common symptoms were abdominal or pelvic pain (31%; 95% confidence interval, 27%-36%), fullness or increased abdominal girth (27%; 95% CI, 22%-31%), abnormal vaginal bleeding (13%; 95% CI, 10%-17%), urinary problems (10%; 95% CI, 8%-14%), and gastrointestinal problems (6%; 95% CI, 4%-8%).

There was no statistically significant link between number of symptoms and age (younger than 60 or 60 or older), cancer stage, or histologic subtype. However, patients with the largest tumors (>15 cm) were more likely to have multiple symptoms than those with the smallest tumors (10 cm or smaller): 46% vs. 21% (P < .001).

Also, 79% of those with the largest tumors (>15 cm) had at least one symptom, compared with 65% of those with the smallest tumors (10 cm or smaller, P < .001)

Unlike other studies, this report didn’t find a link between the number of symptoms and mortality. This finding surprised the researchers, Dr. Chan said, as did the lack of connections between symptoms and age, stage, or histologic subtype. “We were expecting that the younger patients may have more symptoms given the association with endometriosis and clear cell cancers,” he said. “We also thought that those who are less symptomatic may have more stage I and low-grade indolent tumors with better survival, but we did not find that.”

The researchers noted limitations such as the lack of standardization in the patient data.

In the big picture, Dr. Chan said, “patients and health care professionals need to have a higher index of suspicion in symptomatic ovarian cancer patients to increase early detection and potentially improve cures. Ovarian cancer does not always kill. In fact, up to 80% of our early-stage disease patients are cured.”

He called for “additional research to evaluate symptom awareness in early-stage cancers and possibly incorporating novel serum biomarkers and wearable monitoring devices. Wearables may be able to assess for frequency or duration of symptoms, which may be an important factor in distinguishing symptoms that are more concerning for ovarian cancer.”

In an adjoining commentary, Barbara A. Goff, MD, chair of obstetrics and gynecology at the University of Washington, Seattle, noted that, while ovarian cancers diagnosed early have a high survival rate, prospective randomized trials of transvaginal ultrasonography and tumor marker screening strategies have failed to reduce mortality. There’s currently no recommended screening test for women at average risk.

There are other challenges, she wrote. For one, “many health care professionals are seemingly unaware of the symptoms typically associated with ovarian cancer, so misdiagnosis remains common.” And “one of the concerns about the symptoms of ovarian cancer is that they can be vague and commonly present in the general population.”

Dr. Goff praised the study, called for more education about the symptoms of ovarian cancer, and wrote that “symptom recognition with appropriate diagnostic testing remains very important in our efforts to improve outcomes.”

The National Institutes of Health funded the study. Several study authors, including Dr. Chan, reported various disclosures.

Correction, 1/31/22: An earlier version of this article misstated the date of publication.