Renal Cell Carcinoma

Plasma glycosaminoglycan (GAG) measurements can accurately distinguish metastatic clear-cell renal cell carcinoma (ccRCC) from healthy samples, and can provide accurate diagnostic and prognostic information that may be of value in managing the disease, according to new findings.

A new GAG score had 93.5% sensitivity and 94.7% specificity (discovery set) for differentiating RCC from healthy samples, and the sensitivity estimate was independently validated. The score remained independent and uncorrelated to tumor stage, grade, size, and histology, or confounders such as age or gender, according to investigators. The report is in European Oncology Urology.

The authors note that in both retrospective and prospective studies of metastatic ccRCC cases, the composition and levels of plasma and urine GAGs are significantly different when compared with healthy specimens, and GAG scores have correlated with patient outcomes including progression free and overall survival in some cohorts. But it remains unclear if the alterations in plasma and urine GAGs are limited to just metastatic cases of ccRCC or if they correlate with other histopathologic characteristics in RCC. It is also unclear if the correlation between GAG scores and prognosis is limited to patients who receive systemic therapy or if it is applicable to those who are surgically treated RCC as well.

“These results expand our knowledge on the diagnostic and prognostic potential of plasma GAGs in RCC, which was so far limited to metastatic ccRCC in our previous studies,” wrote Francesco Gatto, MD, of Chalmers University of Technology, Göteborg, Sweden, and his colleagues. “Plasma GAG alterations appear to originate as a response to the tumor and occur early if not concomitantly with tumor formation, and probably independent of its progression.”

To investigate the sensitivity and specificity of plasma GAGs for detection of early-stage RCC as well as its utility in predicting recurrence and death after RCC surgery, Dr. Gatto and his team conducted a retrospective case-control study that included 175 RCC patients who underwent surgery between May 2011 and February 2014 and 19 healthy controls.

Plasma GAGs were measured in both preoperative and postoperative RCC cases and the control group, and a discovery set was analyzed to update the historical GAG score. The sensitivity of the new GAG score that was developed for detecting RCC versus controls was then validated using the remaining samples.

In the first discovery set, which included 67 participants, the new GAG score distinguished RCC from controls with an area under the receiver operating characteristic curve (AUC) of 0.999. In their validation cohort (n = 108), the new GAG score achieved an AUC of 0.991 (95% CI 0.977-1) and at the prespecified cutoff, the validated sensitivity was 93.5%. Specificity could not be validated because the same control group was used in both sets.

Factors including tumor size, grade, and stage, radical nephrectomy, and positive surgical margins were significantly associated with overall survival as were three of five GAG properties in the new scoring system, although the new GAG score did not reach significance by itself (hazard ratio, 1.25; P = 0.08). When looking at whether the new GAG score changed after surgery, the authors found that it was quite variable across patients, and an increased score was observed for 53% of cases and a decrease for 47% after surgery. This change did not appear correlated with outcomes as shown by the recurrence rate within 2 years of surgery.

SOURCE: Gatto F et al. Eur Urol Oncol. 2018 Jun 13. doi: 10.1016/j.euo.2018.04.015.

Plasma glycosaminoglycan (GAG) measurements can accurately distinguish metastatic clear-cell renal cell carcinoma (ccRCC) from healthy samples, and can provide accurate diagnostic and prognostic information that may be of value in managing the disease, according to new findings.

A new GAG score had 93.5% sensitivity and 94.7% specificity (discovery set) for differentiating RCC from healthy samples, and the sensitivity estimate was independently validated. The score remained independent and uncorrelated to tumor stage, grade, size, and histology, or confounders such as age or gender, according to investigators. The report is in European Oncology Urology.

The authors note that in both retrospective and prospective studies of metastatic ccRCC cases, the composition and levels of plasma and urine GAGs are significantly different when compared with healthy specimens, and GAG scores have correlated with patient outcomes including progression free and overall survival in some cohorts. But it remains unclear if the alterations in plasma and urine GAGs are limited to just metastatic cases of ccRCC or if they correlate with other histopathologic characteristics in RCC. It is also unclear if the correlation between GAG scores and prognosis is limited to patients who receive systemic therapy or if it is applicable to those who are surgically treated RCC as well.

“These results expand our knowledge on the diagnostic and prognostic potential of plasma GAGs in RCC, which was so far limited to metastatic ccRCC in our previous studies,” wrote Francesco Gatto, MD, of Chalmers University of Technology, Göteborg, Sweden, and his colleagues. “Plasma GAG alterations appear to originate as a response to the tumor and occur early if not concomitantly with tumor formation, and probably independent of its progression.”

To investigate the sensitivity and specificity of plasma GAGs for detection of early-stage RCC as well as its utility in predicting recurrence and death after RCC surgery, Dr. Gatto and his team conducted a retrospective case-control study that included 175 RCC patients who underwent surgery between May 2011 and February 2014 and 19 healthy controls.

Plasma GAGs were measured in both preoperative and postoperative RCC cases and the control group, and a discovery set was analyzed to update the historical GAG score. The sensitivity of the new GAG score that was developed for detecting RCC versus controls was then validated using the remaining samples.

In the first discovery set, which included 67 participants, the new GAG score distinguished RCC from controls with an area under the receiver operating characteristic curve (AUC) of 0.999. In their validation cohort (n = 108), the new GAG score achieved an AUC of 0.991 (95% CI 0.977-1) and at the prespecified cutoff, the validated sensitivity was 93.5%. Specificity could not be validated because the same control group was used in both sets.

Factors including tumor size, grade, and stage, radical nephrectomy, and positive surgical margins were significantly associated with overall survival as were three of five GAG properties in the new scoring system, although the new GAG score did not reach significance by itself (hazard ratio, 1.25; P = 0.08). When looking at whether the new GAG score changed after surgery, the authors found that it was quite variable across patients, and an increased score was observed for 53% of cases and a decrease for 47% after surgery. This change did not appear correlated with outcomes as shown by the recurrence rate within 2 years of surgery.

SOURCE: Gatto F et al. Eur Urol Oncol. 2018 Jun 13. doi: 10.1016/j.euo.2018.04.015.

Plasma glycosaminoglycan (GAG) measurements can accurately distinguish metastatic clear-cell renal cell carcinoma (ccRCC) from healthy samples, and can provide accurate diagnostic and prognostic information that may be of value in managing the disease, according to new findings.

A new GAG score had 93.5% sensitivity and 94.7% specificity (discovery set) for differentiating RCC from healthy samples, and the sensitivity estimate was independently validated. The score remained independent and uncorrelated to tumor stage, grade, size, and histology, or confounders such as age or gender, according to investigators. The report is in European Oncology Urology.

The authors note that in both retrospective and prospective studies of metastatic ccRCC cases, the composition and levels of plasma and urine GAGs are significantly different when compared with healthy specimens, and GAG scores have correlated with patient outcomes including progression free and overall survival in some cohorts. But it remains unclear if the alterations in plasma and urine GAGs are limited to just metastatic cases of ccRCC or if they correlate with other histopathologic characteristics in RCC. It is also unclear if the correlation between GAG scores and prognosis is limited to patients who receive systemic therapy or if it is applicable to those who are surgically treated RCC as well.

“These results expand our knowledge on the diagnostic and prognostic potential of plasma GAGs in RCC, which was so far limited to metastatic ccRCC in our previous studies,” wrote Francesco Gatto, MD, of Chalmers University of Technology, Göteborg, Sweden, and his colleagues. “Plasma GAG alterations appear to originate as a response to the tumor and occur early if not concomitantly with tumor formation, and probably independent of its progression.”

To investigate the sensitivity and specificity of plasma GAGs for detection of early-stage RCC as well as its utility in predicting recurrence and death after RCC surgery, Dr. Gatto and his team conducted a retrospective case-control study that included 175 RCC patients who underwent surgery between May 2011 and February 2014 and 19 healthy controls.

Plasma GAGs were measured in both preoperative and postoperative RCC cases and the control group, and a discovery set was analyzed to update the historical GAG score. The sensitivity of the new GAG score that was developed for detecting RCC versus controls was then validated using the remaining samples.

In the first discovery set, which included 67 participants, the new GAG score distinguished RCC from controls with an area under the receiver operating characteristic curve (AUC) of 0.999. In their validation cohort (n = 108), the new GAG score achieved an AUC of 0.991 (95% CI 0.977-1) and at the prespecified cutoff, the validated sensitivity was 93.5%. Specificity could not be validated because the same control group was used in both sets.

Factors including tumor size, grade, and stage, radical nephrectomy, and positive surgical margins were significantly associated with overall survival as were three of five GAG properties in the new scoring system, although the new GAG score did not reach significance by itself (hazard ratio, 1.25; P = 0.08). When looking at whether the new GAG score changed after surgery, the authors found that it was quite variable across patients, and an increased score was observed for 53% of cases and a decrease for 47% after surgery. This change did not appear correlated with outcomes as shown by the recurrence rate within 2 years of surgery.

SOURCE: Gatto F et al. Eur Urol Oncol. 2018 Jun 13. doi: 10.1016/j.euo.2018.04.015.

In patients with clear cell renal cell carcinoma (ccRCC), radiogenomic analysis can reveal associations between specific features on CT imaging and messenger RNA-based tumor subtyping, authors of a preliminary analysis contend.

Among 177 patients with ccRCC for whom CT data and molecular subtyping information were available, well-defined vs. poorly-defined tumor margins were significantly associated with messenger RNA (mRNA) subtype m1 tumors, and a combination of margin definition and other qualitative tumor features was significantly associated with m3 subtype, reported Lan Bowen, MD, and Li Xiaojing, MD, from Huizhou (China) Central People’s Hospital.

“We demonstrated m1-subtype is positively associated with well-defined margin while m3-subtype is positively associated with ill-defined margin, renal vein invasion, and collecting-system invasion. These findings should be further investigated and validated in other cohorts,” they wrote. The report was published in Academic Radiology.

Radiogenomic analysis is a method for identifying associations between imaging features and gene expression profiles to provide information that can be used for clinical decision making.

The investigators used the technique to retrospectively explore associations between ccRCC mRNA-based subtyping and CT features.

They identified data on a total of 177 patients with ccRCC from The Cancer Genome Atlas for whom complete CT imaging, including contrast-enhanced images, and mRNA-based subtyping were available.

CT features studied included calcifications, margin definition, renal vein invasion, collecting-system invasion, multicystic tumors, nodular tumor enhancement, and intratumoral vasculature.

In univariate logistic regression analysis, well-defined tumor margins (vs. poorly-defined margins) were significant associated with m1 subtype (odd ratio [OR] 2.104, P = .041).

Similarly, a combination of well-defined tumor margins (OR 2.104, P = .013), no collecting system invasion (OR 0.421, P = .028), and renal vein invasion (OR 2.164, P = .026) were significantly associated with the m3 subtype.

They were no significant associations between CT imaging features and either the m2 or m4 subtypes, the authors found.

The authors did not report study funding sources or potential conflicts of interest.

SOURCE: Bowen L, Xiaojing L. Acad Radiol. doi: 10.1016/j.acra.2018.05.002.

In patients with clear cell renal cell carcinoma (ccRCC), radiogenomic analysis can reveal associations between specific features on CT imaging and messenger RNA-based tumor subtyping, authors of a preliminary analysis contend.

Among 177 patients with ccRCC for whom CT data and molecular subtyping information were available, well-defined vs. poorly-defined tumor margins were significantly associated with messenger RNA (mRNA) subtype m1 tumors, and a combination of margin definition and other qualitative tumor features was significantly associated with m3 subtype, reported Lan Bowen, MD, and Li Xiaojing, MD, from Huizhou (China) Central People’s Hospital.

“We demonstrated m1-subtype is positively associated with well-defined margin while m3-subtype is positively associated with ill-defined margin, renal vein invasion, and collecting-system invasion. These findings should be further investigated and validated in other cohorts,” they wrote. The report was published in Academic Radiology.

Radiogenomic analysis is a method for identifying associations between imaging features and gene expression profiles to provide information that can be used for clinical decision making.

The investigators used the technique to retrospectively explore associations between ccRCC mRNA-based subtyping and CT features.

They identified data on a total of 177 patients with ccRCC from The Cancer Genome Atlas for whom complete CT imaging, including contrast-enhanced images, and mRNA-based subtyping were available.

CT features studied included calcifications, margin definition, renal vein invasion, collecting-system invasion, multicystic tumors, nodular tumor enhancement, and intratumoral vasculature.

In univariate logistic regression analysis, well-defined tumor margins (vs. poorly-defined margins) were significant associated with m1 subtype (odd ratio [OR] 2.104, P = .041).

Similarly, a combination of well-defined tumor margins (OR 2.104, P = .013), no collecting system invasion (OR 0.421, P = .028), and renal vein invasion (OR 2.164, P = .026) were significantly associated with the m3 subtype.

They were no significant associations between CT imaging features and either the m2 or m4 subtypes, the authors found.

The authors did not report study funding sources or potential conflicts of interest.

SOURCE: Bowen L, Xiaojing L. Acad Radiol. doi: 10.1016/j.acra.2018.05.002.

In patients with clear cell renal cell carcinoma (ccRCC), radiogenomic analysis can reveal associations between specific features on CT imaging and messenger RNA-based tumor subtyping, authors of a preliminary analysis contend.

Among 177 patients with ccRCC for whom CT data and molecular subtyping information were available, well-defined vs. poorly-defined tumor margins were significantly associated with messenger RNA (mRNA) subtype m1 tumors, and a combination of margin definition and other qualitative tumor features was significantly associated with m3 subtype, reported Lan Bowen, MD, and Li Xiaojing, MD, from Huizhou (China) Central People’s Hospital.

“We demonstrated m1-subtype is positively associated with well-defined margin while m3-subtype is positively associated with ill-defined margin, renal vein invasion, and collecting-system invasion. These findings should be further investigated and validated in other cohorts,” they wrote. The report was published in Academic Radiology.

Radiogenomic analysis is a method for identifying associations between imaging features and gene expression profiles to provide information that can be used for clinical decision making.

The investigators used the technique to retrospectively explore associations between ccRCC mRNA-based subtyping and CT features.

They identified data on a total of 177 patients with ccRCC from The Cancer Genome Atlas for whom complete CT imaging, including contrast-enhanced images, and mRNA-based subtyping were available.

CT features studied included calcifications, margin definition, renal vein invasion, collecting-system invasion, multicystic tumors, nodular tumor enhancement, and intratumoral vasculature.

In univariate logistic regression analysis, well-defined tumor margins (vs. poorly-defined margins) were significant associated with m1 subtype (odd ratio [OR] 2.104, P = .041).

Similarly, a combination of well-defined tumor margins (OR 2.104, P = .013), no collecting system invasion (OR 0.421, P = .028), and renal vein invasion (OR 2.164, P = .026) were significantly associated with the m3 subtype.

They were no significant associations between CT imaging features and either the m2 or m4 subtypes, the authors found.

The authors did not report study funding sources or potential conflicts of interest.

SOURCE: Bowen L, Xiaojing L. Acad Radiol. doi: 10.1016/j.acra.2018.05.002.

Clear cell papillary renal cell carcinoma (CCPRCC), a recently identified, rare type of renal tumor, appears to have an indolent course with low risk of either local invasion or distant metastasis, results of a small retrospective study suggest.

Among 25 patients with CCPRCC followed for as long as 119 months, there were no cases of local recurrence or distant metastasis, reported Wei-Jen Chen, MD, of Tapei (Taiwan) Veterans General Hospital, and colleagues.

“Based on our findings, CCPRCC has an indolent behavior even if the patients are immunosuppressed or if they receive less invasive therapy. Microscopically, CCPRCC is considered to be a tumor of low malignant potential, as all tumors in our series were of low nuclear grade,” they wrote in a study published online in the Journal of the Chinese Medical Association.

“Whenever the diagnosis is made in a high grade renal tumor, it should be carefully re-confirmed by either cytogenetic or molecular genetic methods,” the authors reported.

CCPRCC was newly recognized as a distinct renal malignancy in the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. The classification describes CCPRCC as “a renal epithelial neoplasm composed of low-grade clear epithelial cells arranged in tubules and papillae with a predominantly linear nuclear alignment away from the basement membrane.”

Although rare, these tumors account for up to 5% of all resected renal tumors, and arise sporadically in patients with end-stage renal disease (ESRD) and von Hippel-Lindau syndrome, the classification states, adding that “according to current knowledge, these tumors have indolent behavior.”

To see if they could verify that last statement, Dr. Chen and associates collected data on all patients diagnosed at their institution with CCPRCC from January 2008 through September 2016.

They identified a total of 25 patients (11 men and 14 women) with a mean age at diagnosis of 62.8 years. Of this group, three patients with poor general condition underwent cryotherapy after a biopsy-confirmed diagnosis of CCPRCC.

All of the remaining 22 patients underwent surgical resection. Of this group, four had ESRD; three of these patients had received a kidney transplant prior to diagnosis of CCPRCC in the native kidneys, and one had three tumors over both kidneys.

“Three patients had other types of synchronous RCC; one with acquired cystic kidney disease-associated RCC, and the others with ccRCC. All CCPRCCs were localized and low grade (pT1a- pT1b, Fuhrman grade 2), and all of the patients are currently alive with no evidence of disease,” the investigators wrote.

Mean follow-up was 49.7 months (range 12 to 119 months).

One additional patient who was not included in the series was initially diagnosed with CCPRCC with lung metastasis. This patient, who died 3 years and 8 months after cytoreductive nephrectomy, had a clinical course distinct from that of all the other patients, leading the investigators to reexamine his kidney specimen with whole-exome sequencing. The sequencing led to a revision of the diagnosis to clear cell RCC.

The investigators noted that clear cell RCC, papillary RCC, and translocation RCC are three RCC subtypes that should be considered in the differential diagnosis of CCPRCC.

SOURCE: Chen W-J et al. J Chinese Med Assoc. 2018 July 20. doi: 10.1016/j.jcma.2018.04.005.

Clear cell papillary renal cell carcinoma (CCPRCC), a recently identified, rare type of renal tumor, appears to have an indolent course with low risk of either local invasion or distant metastasis, results of a small retrospective study suggest.

Among 25 patients with CCPRCC followed for as long as 119 months, there were no cases of local recurrence or distant metastasis, reported Wei-Jen Chen, MD, of Tapei (Taiwan) Veterans General Hospital, and colleagues.

“Based on our findings, CCPRCC has an indolent behavior even if the patients are immunosuppressed or if they receive less invasive therapy. Microscopically, CCPRCC is considered to be a tumor of low malignant potential, as all tumors in our series were of low nuclear grade,” they wrote in a study published online in the Journal of the Chinese Medical Association.

“Whenever the diagnosis is made in a high grade renal tumor, it should be carefully re-confirmed by either cytogenetic or molecular genetic methods,” the authors reported.

CCPRCC was newly recognized as a distinct renal malignancy in the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. The classification describes CCPRCC as “a renal epithelial neoplasm composed of low-grade clear epithelial cells arranged in tubules and papillae with a predominantly linear nuclear alignment away from the basement membrane.”

Although rare, these tumors account for up to 5% of all resected renal tumors, and arise sporadically in patients with end-stage renal disease (ESRD) and von Hippel-Lindau syndrome, the classification states, adding that “according to current knowledge, these tumors have indolent behavior.”

To see if they could verify that last statement, Dr. Chen and associates collected data on all patients diagnosed at their institution with CCPRCC from January 2008 through September 2016.

They identified a total of 25 patients (11 men and 14 women) with a mean age at diagnosis of 62.8 years. Of this group, three patients with poor general condition underwent cryotherapy after a biopsy-confirmed diagnosis of CCPRCC.

All of the remaining 22 patients underwent surgical resection. Of this group, four had ESRD; three of these patients had received a kidney transplant prior to diagnosis of CCPRCC in the native kidneys, and one had three tumors over both kidneys.

“Three patients had other types of synchronous RCC; one with acquired cystic kidney disease-associated RCC, and the others with ccRCC. All CCPRCCs were localized and low grade (pT1a- pT1b, Fuhrman grade 2), and all of the patients are currently alive with no evidence of disease,” the investigators wrote.

Mean follow-up was 49.7 months (range 12 to 119 months).

One additional patient who was not included in the series was initially diagnosed with CCPRCC with lung metastasis. This patient, who died 3 years and 8 months after cytoreductive nephrectomy, had a clinical course distinct from that of all the other patients, leading the investigators to reexamine his kidney specimen with whole-exome sequencing. The sequencing led to a revision of the diagnosis to clear cell RCC.

The investigators noted that clear cell RCC, papillary RCC, and translocation RCC are three RCC subtypes that should be considered in the differential diagnosis of CCPRCC.

SOURCE: Chen W-J et al. J Chinese Med Assoc. 2018 July 20. doi: 10.1016/j.jcma.2018.04.005.

Clear cell papillary renal cell carcinoma (CCPRCC), a recently identified, rare type of renal tumor, appears to have an indolent course with low risk of either local invasion or distant metastasis, results of a small retrospective study suggest.

Among 25 patients with CCPRCC followed for as long as 119 months, there were no cases of local recurrence or distant metastasis, reported Wei-Jen Chen, MD, of Tapei (Taiwan) Veterans General Hospital, and colleagues.

“Based on our findings, CCPRCC has an indolent behavior even if the patients are immunosuppressed or if they receive less invasive therapy. Microscopically, CCPRCC is considered to be a tumor of low malignant potential, as all tumors in our series were of low nuclear grade,” they wrote in a study published online in the Journal of the Chinese Medical Association.

“Whenever the diagnosis is made in a high grade renal tumor, it should be carefully re-confirmed by either cytogenetic or molecular genetic methods,” the authors reported.

CCPRCC was newly recognized as a distinct renal malignancy in the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. The classification describes CCPRCC as “a renal epithelial neoplasm composed of low-grade clear epithelial cells arranged in tubules and papillae with a predominantly linear nuclear alignment away from the basement membrane.”

Although rare, these tumors account for up to 5% of all resected renal tumors, and arise sporadically in patients with end-stage renal disease (ESRD) and von Hippel-Lindau syndrome, the classification states, adding that “according to current knowledge, these tumors have indolent behavior.”

To see if they could verify that last statement, Dr. Chen and associates collected data on all patients diagnosed at their institution with CCPRCC from January 2008 through September 2016.

They identified a total of 25 patients (11 men and 14 women) with a mean age at diagnosis of 62.8 years. Of this group, three patients with poor general condition underwent cryotherapy after a biopsy-confirmed diagnosis of CCPRCC.

All of the remaining 22 patients underwent surgical resection. Of this group, four had ESRD; three of these patients had received a kidney transplant prior to diagnosis of CCPRCC in the native kidneys, and one had three tumors over both kidneys.

“Three patients had other types of synchronous RCC; one with acquired cystic kidney disease-associated RCC, and the others with ccRCC. All CCPRCCs were localized and low grade (pT1a- pT1b, Fuhrman grade 2), and all of the patients are currently alive with no evidence of disease,” the investigators wrote.

Mean follow-up was 49.7 months (range 12 to 119 months).

One additional patient who was not included in the series was initially diagnosed with CCPRCC with lung metastasis. This patient, who died 3 years and 8 months after cytoreductive nephrectomy, had a clinical course distinct from that of all the other patients, leading the investigators to reexamine his kidney specimen with whole-exome sequencing. The sequencing led to a revision of the diagnosis to clear cell RCC.

The investigators noted that clear cell RCC, papillary RCC, and translocation RCC are three RCC subtypes that should be considered in the differential diagnosis of CCPRCC.

SOURCE: Chen W-J et al. J Chinese Med Assoc. 2018 July 20. doi: 10.1016/j.jcma.2018.04.005.

An analysis of conditional survival outcomes for patients with metastatic renal cell carcinoma (mRCC) has suggested that first-line therapy with a tyrosine kinase inhibitor (TKI) can result in improved survival odds over time.

Patients with mRCC treated with a TKI upfront had gradual increases over time in conditional overall survival estimates when compared with baseline survival predictions, a retrospective review has indicated.

Patients who survived at least 36 months after the start of therapy had an estimated 36-month conditional overall survival (OS) rate that was 7.3% higher than the predicted survival at the initiation of therapy, reported Seong Il Seo, MD, PhD, from Samsung Medical Center in Seoul, North Korea, and his colleagues.

The investigators also found that, while predictors of survival changed over time, previous metastasectomy was a key prognosticator of conditional overall survival throughout 36 months of follow-up, they reported in The Journal of Urology.

“To our knowledge, our data are the first to reveal the beneficial role of metastasectomy on conditional OS probabilities with time since an initial survival estimation, particularly in patients at intermediate and poor risk. [Conditional survival] estimates can be beneficial to counsel patients with mRCC about more practical prognoses and helpful to continuously adjust surveillance planning in these patients,” they wrote.

Conditional survival is an analytical method for providing more accurate estimates of how prognoses change over time when patients with aggressive metastatic disease, such as mRCC, are exposed to therapies such as nephrectomy or TKIs.

The investigators retrospectively reviewed records for 1,131 patients with mRCC in the Korean Renal Cancer Study Group database. They calculated conditional OS using a nomogram that indicated the likelihood that a patient would survive an additional number of years given that he or she had already survived a certain number of years. They also created a multivariate regression model to identify predictors of conditional survival over time.

They found that, at all survival times after the start of TKI therapy (6, 12, 18, 24, and 36 months), conditional overall survival gradually increased when compared with baseline survival estimates.

“While the actual overall survival rate decreased with time, the 36-month conditional overall survival rate was calculated as 7.3% higher in patients who had already survived 36 months compared to baseline estimations at the time of initial tyrosine kinase inhibitor treatment,” they wrote.

In the multivariate model, prognostic factors such as gender, pathologic T stage, and Heng risk classification became nonsignificant over time, but previous metastasectomy remained a significant independent predictor of survival after TKI therapy at all time points except for 18 months.

“This study largely corroborates previous data from the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium), and it provides useful information on prognostication,” commented Adam B. Weiner, MD, of Northwestern University in Chicago, in a brief accompanying editorial.

The study was supported by a National Research Foundation of Korea research grant funded by the Ministry of Science and Information and Communications Technology and by a Korea Health Technology R&D Project grant through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare in South Korea. No conflicts of interest were reported.

SOURCE: Kang M et al. J Urol. 2018 June 22. doi: 10.1016/j.juro.2018.06.030.

 

An analysis of conditional survival outcomes for patients with metastatic renal cell carcinoma (mRCC) has suggested that first-line therapy with a tyrosine kinase inhibitor (TKI) can result in improved survival odds over time.

Patients with mRCC treated with a TKI upfront had gradual increases over time in conditional overall survival estimates when compared with baseline survival predictions, a retrospective review has indicated.

Patients who survived at least 36 months after the start of therapy had an estimated 36-month conditional overall survival (OS) rate that was 7.3% higher than the predicted survival at the initiation of therapy, reported Seong Il Seo, MD, PhD, from Samsung Medical Center in Seoul, North Korea, and his colleagues.

The investigators also found that, while predictors of survival changed over time, previous metastasectomy was a key prognosticator of conditional overall survival throughout 36 months of follow-up, they reported in The Journal of Urology.

“To our knowledge, our data are the first to reveal the beneficial role of metastasectomy on conditional OS probabilities with time since an initial survival estimation, particularly in patients at intermediate and poor risk. [Conditional survival] estimates can be beneficial to counsel patients with mRCC about more practical prognoses and helpful to continuously adjust surveillance planning in these patients,” they wrote.

Conditional survival is an analytical method for providing more accurate estimates of how prognoses change over time when patients with aggressive metastatic disease, such as mRCC, are exposed to therapies such as nephrectomy or TKIs.

The investigators retrospectively reviewed records for 1,131 patients with mRCC in the Korean Renal Cancer Study Group database. They calculated conditional OS using a nomogram that indicated the likelihood that a patient would survive an additional number of years given that he or she had already survived a certain number of years. They also created a multivariate regression model to identify predictors of conditional survival over time.

They found that, at all survival times after the start of TKI therapy (6, 12, 18, 24, and 36 months), conditional overall survival gradually increased when compared with baseline survival estimates.

“While the actual overall survival rate decreased with time, the 36-month conditional overall survival rate was calculated as 7.3% higher in patients who had already survived 36 months compared to baseline estimations at the time of initial tyrosine kinase inhibitor treatment,” they wrote.

In the multivariate model, prognostic factors such as gender, pathologic T stage, and Heng risk classification became nonsignificant over time, but previous metastasectomy remained a significant independent predictor of survival after TKI therapy at all time points except for 18 months.

“This study largely corroborates previous data from the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium), and it provides useful information on prognostication,” commented Adam B. Weiner, MD, of Northwestern University in Chicago, in a brief accompanying editorial.

The study was supported by a National Research Foundation of Korea research grant funded by the Ministry of Science and Information and Communications Technology and by a Korea Health Technology R&D Project grant through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare in South Korea. No conflicts of interest were reported.

SOURCE: Kang M et al. J Urol. 2018 June 22. doi: 10.1016/j.juro.2018.06.030.

 

An analysis of conditional survival outcomes for patients with metastatic renal cell carcinoma (mRCC) has suggested that first-line therapy with a tyrosine kinase inhibitor (TKI) can result in improved survival odds over time.

Patients with mRCC treated with a TKI upfront had gradual increases over time in conditional overall survival estimates when compared with baseline survival predictions, a retrospective review has indicated.

Patients who survived at least 36 months after the start of therapy had an estimated 36-month conditional overall survival (OS) rate that was 7.3% higher than the predicted survival at the initiation of therapy, reported Seong Il Seo, MD, PhD, from Samsung Medical Center in Seoul, North Korea, and his colleagues.

The investigators also found that, while predictors of survival changed over time, previous metastasectomy was a key prognosticator of conditional overall survival throughout 36 months of follow-up, they reported in The Journal of Urology.

“To our knowledge, our data are the first to reveal the beneficial role of metastasectomy on conditional OS probabilities with time since an initial survival estimation, particularly in patients at intermediate and poor risk. [Conditional survival] estimates can be beneficial to counsel patients with mRCC about more practical prognoses and helpful to continuously adjust surveillance planning in these patients,” they wrote.

Conditional survival is an analytical method for providing more accurate estimates of how prognoses change over time when patients with aggressive metastatic disease, such as mRCC, are exposed to therapies such as nephrectomy or TKIs.

The investigators retrospectively reviewed records for 1,131 patients with mRCC in the Korean Renal Cancer Study Group database. They calculated conditional OS using a nomogram that indicated the likelihood that a patient would survive an additional number of years given that he or she had already survived a certain number of years. They also created a multivariate regression model to identify predictors of conditional survival over time.

They found that, at all survival times after the start of TKI therapy (6, 12, 18, 24, and 36 months), conditional overall survival gradually increased when compared with baseline survival estimates.

“While the actual overall survival rate decreased with time, the 36-month conditional overall survival rate was calculated as 7.3% higher in patients who had already survived 36 months compared to baseline estimations at the time of initial tyrosine kinase inhibitor treatment,” they wrote.

In the multivariate model, prognostic factors such as gender, pathologic T stage, and Heng risk classification became nonsignificant over time, but previous metastasectomy remained a significant independent predictor of survival after TKI therapy at all time points except for 18 months.

“This study largely corroborates previous data from the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium), and it provides useful information on prognostication,” commented Adam B. Weiner, MD, of Northwestern University in Chicago, in a brief accompanying editorial.

The study was supported by a National Research Foundation of Korea research grant funded by the Ministry of Science and Information and Communications Technology and by a Korea Health Technology R&D Project grant through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare in South Korea. No conflicts of interest were reported.

SOURCE: Kang M et al. J Urol. 2018 June 22. doi: 10.1016/j.juro.2018.06.030.

 

Gene expression profiling and/or immunohistochemistry can identify occult renal cell carcinoma (RCC) in a subset of patients diagnosed with carcinoma of unknown primary (CUP), suggesting that these patients could benefit from RCC-specific targeted therapy or immunotherapy, investigators contend.

Of 539 patients presenting at a single center with CUP, a 92-gene reverse transcription polymerase chain reaction molecular cancer classifier assay (MCCA) performed on biopsy specimens identified 24 as having RCC. All of the patients had clinical characteristics typical of advanced RCC, but none had suspicious renal lesions on CT scans, reported F. Anthony Greco, MD and John D. Hainsworth, MD, of the Sarah Cannon Cancer Center and Research Institute in Nashville, Tenn.

“Although further experience is necessary, these patients responded to RCC-specific therapy in a manner consistent with advanced RCC. These patients are unlikely to benefit from treatment with empiric chemotherapy. The reliable identification of RCC patients within the heterogeneous CUP population is possible using MCCA, and has potentially important therapeutic implications,” they wrote. The report was published in Clinical Genitourinary Cancer.

They noted that previously the only therapeutic option for patients with CUP suspected of being renal in origin was ineffective systemic chemotherapy, making a specific diagnosis of more academic interest than clinical importance.

“This situation has now changed because of the introduction of several targeted agents and immune checkpoint blockers that improve survival in patients with advanced RCC. It is likely that these new RCC treatments are also more effective than empiric chemotherapy for patients with CUP who have an occult renal primary site. Therefore, recognition of the RCC subset of patients within the CUP population has practical therapeutic importance,” they wrote.

Dr. Greco and Dr. Hainsworth conducted a retrospective review of patients at their center with CUP from 2008 through 2013 who had RCC predicted by MCCA.

A total of 539 patients presented with CUP during the study period, and of this group, 24 (4.4%) had RCC identified by MCCA.

The patients, 18 men and 6 women, with a median age of 61 years, all had abdominal CT scans that failed to show renal lesions suggestive of a primary RCC. Nine of the 24 patients had baseline MCCA performed as part of a prospective phase 2 clinical trial; the other 15 were patients treated at the center who had MCCA performed later in the clinical course, usually during or after first-line empiric chemotherapy.

Sixteen patients had metastases in the retroperitoneum, 10 in the mediastinum, 6 in bone, 5 in the liver, and 5 in lungs and/or pleura.

Pathologic studies using light microscopy showed poorly differentiated carcinomas in eight patients, poorly differentiated adenocarcinomas in nine, and well or moderately differentiated adenocarcinomas in seven patients.

A pathologist identified RCC as the possible primary in only 4 of the 24 patients. Immunohistochemistry tests in these patients were consistent with a diagnosis of RCC. Only 5 of the 24 had focal features suggestive of RCC, including one clear-cell and four papillary histologies.

Sixteen of the 24 patients received first-line treatment for advanced RCC, including sunitinib, temsirolimus, bevacizumab, and/or interleukin 1. Four other patients received RCC-specific therapy following empiric chemotherapy (three patients who received RCC-specific therapies in the first line also received it in the second line).

Among the 16 patients who received first-line RCC-specific therapies there were 3 partial responses (PR), 10 cases of stable disease (SD), 2 of progressive disease (PD), and 1 patient was not evaluable. The median duration of both PR and SD was 8 months.

Of the eight patients who received first-line empiric chemotherapy, one had a PR, two had SD, and five had PD.

For the seven patients who received second-line RCC-specific therapy after either first-line chemotherapy or site-specific therapy, responses included one PR, two SD, two PD, and two not evaluable.

Median survival for all 24 patients was 12 months (range 2 to more than 43 months). Median survival of the 16 patients who received first-line RCC-specific treatment was 14 months (range 2-25 months).

Median survival for all 20 patients who received RCC-specific treatment at some time during their course was 16 months (range, 2 to more than 43 months).

The authors called for further prospective studies of this subset of patients with CUP.

SOURCE: Greco FA, Hainsworth JD. Clin Genitourin Cancer. 2018 Aug;16(4):e893-8.

Gene expression profiling and/or immunohistochemistry can identify occult renal cell carcinoma (RCC) in a subset of patients diagnosed with carcinoma of unknown primary (CUP), suggesting that these patients could benefit from RCC-specific targeted therapy or immunotherapy, investigators contend.

Of 539 patients presenting at a single center with CUP, a 92-gene reverse transcription polymerase chain reaction molecular cancer classifier assay (MCCA) performed on biopsy specimens identified 24 as having RCC. All of the patients had clinical characteristics typical of advanced RCC, but none had suspicious renal lesions on CT scans, reported F. Anthony Greco, MD and John D. Hainsworth, MD, of the Sarah Cannon Cancer Center and Research Institute in Nashville, Tenn.

“Although further experience is necessary, these patients responded to RCC-specific therapy in a manner consistent with advanced RCC. These patients are unlikely to benefit from treatment with empiric chemotherapy. The reliable identification of RCC patients within the heterogeneous CUP population is possible using MCCA, and has potentially important therapeutic implications,” they wrote. The report was published in Clinical Genitourinary Cancer.

They noted that previously the only therapeutic option for patients with CUP suspected of being renal in origin was ineffective systemic chemotherapy, making a specific diagnosis of more academic interest than clinical importance.

“This situation has now changed because of the introduction of several targeted agents and immune checkpoint blockers that improve survival in patients with advanced RCC. It is likely that these new RCC treatments are also more effective than empiric chemotherapy for patients with CUP who have an occult renal primary site. Therefore, recognition of the RCC subset of patients within the CUP population has practical therapeutic importance,” they wrote.

Dr. Greco and Dr. Hainsworth conducted a retrospective review of patients at their center with CUP from 2008 through 2013 who had RCC predicted by MCCA.

A total of 539 patients presented with CUP during the study period, and of this group, 24 (4.4%) had RCC identified by MCCA.

The patients, 18 men and 6 women, with a median age of 61 years, all had abdominal CT scans that failed to show renal lesions suggestive of a primary RCC. Nine of the 24 patients had baseline MCCA performed as part of a prospective phase 2 clinical trial; the other 15 were patients treated at the center who had MCCA performed later in the clinical course, usually during or after first-line empiric chemotherapy.

Sixteen patients had metastases in the retroperitoneum, 10 in the mediastinum, 6 in bone, 5 in the liver, and 5 in lungs and/or pleura.

Pathologic studies using light microscopy showed poorly differentiated carcinomas in eight patients, poorly differentiated adenocarcinomas in nine, and well or moderately differentiated adenocarcinomas in seven patients.

A pathologist identified RCC as the possible primary in only 4 of the 24 patients. Immunohistochemistry tests in these patients were consistent with a diagnosis of RCC. Only 5 of the 24 had focal features suggestive of RCC, including one clear-cell and four papillary histologies.

Sixteen of the 24 patients received first-line treatment for advanced RCC, including sunitinib, temsirolimus, bevacizumab, and/or interleukin 1. Four other patients received RCC-specific therapy following empiric chemotherapy (three patients who received RCC-specific therapies in the first line also received it in the second line).

Among the 16 patients who received first-line RCC-specific therapies there were 3 partial responses (PR), 10 cases of stable disease (SD), 2 of progressive disease (PD), and 1 patient was not evaluable. The median duration of both PR and SD was 8 months.

Of the eight patients who received first-line empiric chemotherapy, one had a PR, two had SD, and five had PD.

For the seven patients who received second-line RCC-specific therapy after either first-line chemotherapy or site-specific therapy, responses included one PR, two SD, two PD, and two not evaluable.

Median survival for all 24 patients was 12 months (range 2 to more than 43 months). Median survival of the 16 patients who received first-line RCC-specific treatment was 14 months (range 2-25 months).

Median survival for all 20 patients who received RCC-specific treatment at some time during their course was 16 months (range, 2 to more than 43 months).

The authors called for further prospective studies of this subset of patients with CUP.

SOURCE: Greco FA, Hainsworth JD. Clin Genitourin Cancer. 2018 Aug;16(4):e893-8.

Gene expression profiling and/or immunohistochemistry can identify occult renal cell carcinoma (RCC) in a subset of patients diagnosed with carcinoma of unknown primary (CUP), suggesting that these patients could benefit from RCC-specific targeted therapy or immunotherapy, investigators contend.

Of 539 patients presenting at a single center with CUP, a 92-gene reverse transcription polymerase chain reaction molecular cancer classifier assay (MCCA) performed on biopsy specimens identified 24 as having RCC. All of the patients had clinical characteristics typical of advanced RCC, but none had suspicious renal lesions on CT scans, reported F. Anthony Greco, MD and John D. Hainsworth, MD, of the Sarah Cannon Cancer Center and Research Institute in Nashville, Tenn.

“Although further experience is necessary, these patients responded to RCC-specific therapy in a manner consistent with advanced RCC. These patients are unlikely to benefit from treatment with empiric chemotherapy. The reliable identification of RCC patients within the heterogeneous CUP population is possible using MCCA, and has potentially important therapeutic implications,” they wrote. The report was published in Clinical Genitourinary Cancer.

They noted that previously the only therapeutic option for patients with CUP suspected of being renal in origin was ineffective systemic chemotherapy, making a specific diagnosis of more academic interest than clinical importance.

“This situation has now changed because of the introduction of several targeted agents and immune checkpoint blockers that improve survival in patients with advanced RCC. It is likely that these new RCC treatments are also more effective than empiric chemotherapy for patients with CUP who have an occult renal primary site. Therefore, recognition of the RCC subset of patients within the CUP population has practical therapeutic importance,” they wrote.

Dr. Greco and Dr. Hainsworth conducted a retrospective review of patients at their center with CUP from 2008 through 2013 who had RCC predicted by MCCA.

A total of 539 patients presented with CUP during the study period, and of this group, 24 (4.4%) had RCC identified by MCCA.

The patients, 18 men and 6 women, with a median age of 61 years, all had abdominal CT scans that failed to show renal lesions suggestive of a primary RCC. Nine of the 24 patients had baseline MCCA performed as part of a prospective phase 2 clinical trial; the other 15 were patients treated at the center who had MCCA performed later in the clinical course, usually during or after first-line empiric chemotherapy.

Sixteen patients had metastases in the retroperitoneum, 10 in the mediastinum, 6 in bone, 5 in the liver, and 5 in lungs and/or pleura.

Pathologic studies using light microscopy showed poorly differentiated carcinomas in eight patients, poorly differentiated adenocarcinomas in nine, and well or moderately differentiated adenocarcinomas in seven patients.

A pathologist identified RCC as the possible primary in only 4 of the 24 patients. Immunohistochemistry tests in these patients were consistent with a diagnosis of RCC. Only 5 of the 24 had focal features suggestive of RCC, including one clear-cell and four papillary histologies.

Sixteen of the 24 patients received first-line treatment for advanced RCC, including sunitinib, temsirolimus, bevacizumab, and/or interleukin 1. Four other patients received RCC-specific therapy following empiric chemotherapy (three patients who received RCC-specific therapies in the first line also received it in the second line).

Among the 16 patients who received first-line RCC-specific therapies there were 3 partial responses (PR), 10 cases of stable disease (SD), 2 of progressive disease (PD), and 1 patient was not evaluable. The median duration of both PR and SD was 8 months.

Of the eight patients who received first-line empiric chemotherapy, one had a PR, two had SD, and five had PD.

For the seven patients who received second-line RCC-specific therapy after either first-line chemotherapy or site-specific therapy, responses included one PR, two SD, two PD, and two not evaluable.

Median survival for all 24 patients was 12 months (range 2 to more than 43 months). Median survival of the 16 patients who received first-line RCC-specific treatment was 14 months (range 2-25 months).

Median survival for all 20 patients who received RCC-specific treatment at some time during their course was 16 months (range, 2 to more than 43 months).

The authors called for further prospective studies of this subset of patients with CUP.

SOURCE: Greco FA, Hainsworth JD. Clin Genitourin Cancer. 2018 Aug;16(4):e893-8.

Germline mutations in patients with advanced renal cell carcinoma may be more common than previously suspected.

In a single-center cohort of 254 patients with advanced renal cell carcinoma (RCC) who received matched tumor-germline DNA sequencing, over a third (35.7%) of patients who had mutations in genes associated with RCC had not met current clinical criteria for testing.

In all, pathogenic germline mutations were identified in 41 patients (16.1%), with 14 patients’ mutations (5.5%) in genes known to be associated with RCC. For the remaining 27 patients (10.5%), the mutations were in non–RCC-associated genes, investigators reported in JAMA Oncology.

Of the non–RCC-associated mutations, CHEK2 was particularly common among patients with clear cell RCC (ccRCC), occurring in eight patients with ccRCC and two with non ccRCC (nccRCC). The overall odds ratio for this mutation among the study cohort was 3.0, compared with the general population (95% confidence interval 1.3-5.8; P = .003). “Although there are currently no RCC-specific screening recommendations for individuals with CHEK2 mutations, there may be incremental screening for other cancers, justifying including this gene on RCC panel tests,” wrote Maria Carlo, MD, and her coauthors.

Germline FH mutations were seen in seven patients, all with nccRCC. This higher rate of hereditary leiomyomatosis and RCC (HLRCC) was higher than previously reported in the literature, and clinical cues to the diagnosis were few among the study patients. Even though clues pointing to HLRCC were seen when tumor samples were submitted for histopathology to the genitourinary specialists at the study site, “it is unclear whether nonspecialist pathologists would be able to draw the same conclusions,” wrote Dr. Carlo and her colleagues.

Renal cell cancer–associated mutations were significantly more common in patients with nccRCC than in the ccRCC group: 9/74 (11.7%) nccRCC patients had an RCC-associated mutation, compared with 3/177 of the ccRCC group (P = .001).

The patient’s course of therapy could be guided by the mutation identified in 10% (eight) of the nccRCC patients, “none of which would have been identified with somatic-only sequencing,” wrote Dr. Carlo and associates. “Our results suggest that germline mutations in cancer-associated genes in patients with advanced RCC may be prevalent, and many of these mutations can be used to guide therapy.”

The 254 patients (median age 56 years, 70.5% male, 83.1% non-Hispanic white) were drawn from 267 patients with American Joint Committee on Cancer (AJCC) stage III or IV RCC participating in clinical trials at Memorial Sloan Kettering Cancer Center, New York, where Dr. Carlo practices as an oncologist. The patients included in the cohort were those who consented to germline sequencing and results disclosure.

To determine which pathogenic variants were identified by the study protocol that would have been missed by current testing standards, the investigators assumed that for those who met guidelines, the multigene test panel would probe for VHL, VH, FLCN, MET, SDHB, SDHD, BAP1, TSC1, TSC2, TP53, and MITF. If another mutation was picked up by the next-generation sequencing used in the study, or if a mutation was found in an individual who otherwise would not have been tested, the finding was considered incremental and attributable to the study protocol.

Implications of the additional mutations picked up by the tumor-germline sequencing approach go beyond the patient, said the researchers, who have seen several of the study participants’ family members receive positive test results for cancer-associated mutations as well. “Relatives who are also found to carry FH mutations should be considered for RCC screening. Early detection may increase the likelihood of cure and survivorship,” wrote Dr. Carlo and her coinvestigators.

Dr. Carlo reported serving as a consultant for Pfizer. Other authors reported multiple associations with pharmaceutical companies. The study was funded by the National Institutes of Health, the J. Randall and Kathleen L. MacDonald Kidney Cancer Research Fund, and the Robert and Kate Niehaus Center for Inherited Cancer Genomics at Memorial Sloan Kettering Cancer Center.

SOURCE: Carlo M et al. JAMA Oncol. 2018 Jul 5. doi: 10.1001/jamaoncol.2018.1986.

Germline mutations in patients with advanced renal cell carcinoma may be more common than previously suspected.

In a single-center cohort of 254 patients with advanced renal cell carcinoma (RCC) who received matched tumor-germline DNA sequencing, over a third (35.7%) of patients who had mutations in genes associated with RCC had not met current clinical criteria for testing.

In all, pathogenic germline mutations were identified in 41 patients (16.1%), with 14 patients’ mutations (5.5%) in genes known to be associated with RCC. For the remaining 27 patients (10.5%), the mutations were in non–RCC-associated genes, investigators reported in JAMA Oncology.

Of the non–RCC-associated mutations, CHEK2 was particularly common among patients with clear cell RCC (ccRCC), occurring in eight patients with ccRCC and two with non ccRCC (nccRCC). The overall odds ratio for this mutation among the study cohort was 3.0, compared with the general population (95% confidence interval 1.3-5.8; P = .003). “Although there are currently no RCC-specific screening recommendations for individuals with CHEK2 mutations, there may be incremental screening for other cancers, justifying including this gene on RCC panel tests,” wrote Maria Carlo, MD, and her coauthors.

Germline FH mutations were seen in seven patients, all with nccRCC. This higher rate of hereditary leiomyomatosis and RCC (HLRCC) was higher than previously reported in the literature, and clinical cues to the diagnosis were few among the study patients. Even though clues pointing to HLRCC were seen when tumor samples were submitted for histopathology to the genitourinary specialists at the study site, “it is unclear whether nonspecialist pathologists would be able to draw the same conclusions,” wrote Dr. Carlo and her colleagues.

Renal cell cancer–associated mutations were significantly more common in patients with nccRCC than in the ccRCC group: 9/74 (11.7%) nccRCC patients had an RCC-associated mutation, compared with 3/177 of the ccRCC group (P = .001).

The patient’s course of therapy could be guided by the mutation identified in 10% (eight) of the nccRCC patients, “none of which would have been identified with somatic-only sequencing,” wrote Dr. Carlo and associates. “Our results suggest that germline mutations in cancer-associated genes in patients with advanced RCC may be prevalent, and many of these mutations can be used to guide therapy.”

The 254 patients (median age 56 years, 70.5% male, 83.1% non-Hispanic white) were drawn from 267 patients with American Joint Committee on Cancer (AJCC) stage III or IV RCC participating in clinical trials at Memorial Sloan Kettering Cancer Center, New York, where Dr. Carlo practices as an oncologist. The patients included in the cohort were those who consented to germline sequencing and results disclosure.

To determine which pathogenic variants were identified by the study protocol that would have been missed by current testing standards, the investigators assumed that for those who met guidelines, the multigene test panel would probe for VHL, VH, FLCN, MET, SDHB, SDHD, BAP1, TSC1, TSC2, TP53, and MITF. If another mutation was picked up by the next-generation sequencing used in the study, or if a mutation was found in an individual who otherwise would not have been tested, the finding was considered incremental and attributable to the study protocol.

Implications of the additional mutations picked up by the tumor-germline sequencing approach go beyond the patient, said the researchers, who have seen several of the study participants’ family members receive positive test results for cancer-associated mutations as well. “Relatives who are also found to carry FH mutations should be considered for RCC screening. Early detection may increase the likelihood of cure and survivorship,” wrote Dr. Carlo and her coinvestigators.

Dr. Carlo reported serving as a consultant for Pfizer. Other authors reported multiple associations with pharmaceutical companies. The study was funded by the National Institutes of Health, the J. Randall and Kathleen L. MacDonald Kidney Cancer Research Fund, and the Robert and Kate Niehaus Center for Inherited Cancer Genomics at Memorial Sloan Kettering Cancer Center.

SOURCE: Carlo M et al. JAMA Oncol. 2018 Jul 5. doi: 10.1001/jamaoncol.2018.1986.

Germline mutations in patients with advanced renal cell carcinoma may be more common than previously suspected.

In a single-center cohort of 254 patients with advanced renal cell carcinoma (RCC) who received matched tumor-germline DNA sequencing, over a third (35.7%) of patients who had mutations in genes associated with RCC had not met current clinical criteria for testing.

In all, pathogenic germline mutations were identified in 41 patients (16.1%), with 14 patients’ mutations (5.5%) in genes known to be associated with RCC. For the remaining 27 patients (10.5%), the mutations were in non–RCC-associated genes, investigators reported in JAMA Oncology.

Of the non–RCC-associated mutations, CHEK2 was particularly common among patients with clear cell RCC (ccRCC), occurring in eight patients with ccRCC and two with non ccRCC (nccRCC). The overall odds ratio for this mutation among the study cohort was 3.0, compared with the general population (95% confidence interval 1.3-5.8; P = .003). “Although there are currently no RCC-specific screening recommendations for individuals with CHEK2 mutations, there may be incremental screening for other cancers, justifying including this gene on RCC panel tests,” wrote Maria Carlo, MD, and her coauthors.

Germline FH mutations were seen in seven patients, all with nccRCC. This higher rate of hereditary leiomyomatosis and RCC (HLRCC) was higher than previously reported in the literature, and clinical cues to the diagnosis were few among the study patients. Even though clues pointing to HLRCC were seen when tumor samples were submitted for histopathology to the genitourinary specialists at the study site, “it is unclear whether nonspecialist pathologists would be able to draw the same conclusions,” wrote Dr. Carlo and her colleagues.

Renal cell cancer–associated mutations were significantly more common in patients with nccRCC than in the ccRCC group: 9/74 (11.7%) nccRCC patients had an RCC-associated mutation, compared with 3/177 of the ccRCC group (P = .001).

The patient’s course of therapy could be guided by the mutation identified in 10% (eight) of the nccRCC patients, “none of which would have been identified with somatic-only sequencing,” wrote Dr. Carlo and associates. “Our results suggest that germline mutations in cancer-associated genes in patients with advanced RCC may be prevalent, and many of these mutations can be used to guide therapy.”

The 254 patients (median age 56 years, 70.5% male, 83.1% non-Hispanic white) were drawn from 267 patients with American Joint Committee on Cancer (AJCC) stage III or IV RCC participating in clinical trials at Memorial Sloan Kettering Cancer Center, New York, where Dr. Carlo practices as an oncologist. The patients included in the cohort were those who consented to germline sequencing and results disclosure.

To determine which pathogenic variants were identified by the study protocol that would have been missed by current testing standards, the investigators assumed that for those who met guidelines, the multigene test panel would probe for VHL, VH, FLCN, MET, SDHB, SDHD, BAP1, TSC1, TSC2, TP53, and MITF. If another mutation was picked up by the next-generation sequencing used in the study, or if a mutation was found in an individual who otherwise would not have been tested, the finding was considered incremental and attributable to the study protocol.

Implications of the additional mutations picked up by the tumor-germline sequencing approach go beyond the patient, said the researchers, who have seen several of the study participants’ family members receive positive test results for cancer-associated mutations as well. “Relatives who are also found to carry FH mutations should be considered for RCC screening. Early detection may increase the likelihood of cure and survivorship,” wrote Dr. Carlo and her coinvestigators.

Dr. Carlo reported serving as a consultant for Pfizer. Other authors reported multiple associations with pharmaceutical companies. The study was funded by the National Institutes of Health, the J. Randall and Kathleen L. MacDonald Kidney Cancer Research Fund, and the Robert and Kate Niehaus Center for Inherited Cancer Genomics at Memorial Sloan Kettering Cancer Center.

SOURCE: Carlo M et al. JAMA Oncol. 2018 Jul 5. doi: 10.1001/jamaoncol.2018.1986.

CHICAGO – Pembrolizumab monotherapy shows promising efficacy and tolerability in treatment-naive patients with advanced clear cell renal cell carcinoma (accRCC), according to findings from the phase 2 KEYNOTE-427 study.

At a median follow-up of 12 months, the overall response rate in 110 study participants with at least one post-baseline assessment was 38%. Three patients (2.7%) achieved a complete response and 39 (35.5%) achieved a partial response, David F. McDermott, MD, reported at the annual meeting of the American Society of Clinical Oncology.

“The disease control rate was 59%,” he said.

Overall, 67% of the patients experienced a reduction in tumor burden, 14% experienced at least an 80% reduction, and 7% experienced a 100% reduction of their target lesion, said Dr. McDermott of Beth Israel Deaconess Medical Center, Boston.

“Most tumor responses occurred early in the course of therapy,” he noted.

The median time to response was 2.8 months, and the median duration of response was not reached at data cutoff, but 74.8% of responders had a response lasting at least 6 months.

An analysis by International Metastatic Renal Cell Carcinoma Database Criteria (IMDC) category showed a confirmed overall response rate (ORR) of 32% among 41 patients with favorable risk, and 42% in 69 patients with intermediate or poor risk.

“Nine of 17 patients in the poor risk group achieved a major response,” Dr. McDermott noted. “Complete and durable responders were seen in all IMDC subgroups.”

In 46 patients with increased PD-L1 expression or a combined positive score of at least 1 the confirmed ORR was 50.0%, and in 53 patients with low PD-L1 expression and a combined positive score less than 1 it was 26%. The ORR was 45% in the remaining patients in whom PD-L1testing could not be performed.

“Of note, all of the complete responses were seen in the PD-L1-high or CPS-greater-than-1 group,” he said.

Median progression-free survival was 8.7 months, and median overall survival has not been reached.

Tolerability of pembrolizumab in this study was acceptable and consistent with that seen with pembrolizumab monotherapy in other tumor types. Although 80% of patients experienced a treatment-related adverse event, the events mainly included fatigue, pruritus, diarrhea, rash, and arthralgia, occurring in 12.7% to 27.3% of patients, he said.

Grade 3/4 events occurred in 21.8% of patients and one patient experienced a fatal grade 5 case of pneumonitis, he added, noting that 11% of patients discontinued treatment because of a treatment-related adverse event.

Overall, 61 patients discontinued therapy, and 33 of those discontinued because of disease progression.

Programmed death-1 (PD-1) inhibitor-based combination therapies have been shown to have clinical benefit when used first-line in accRCC, but data with respect to the clinical impact of first-line PD-1 inhibitor monotherapy are lacking, Dr. McDermott explained.

KEYNOTE-427 was a single-arm, open-label, two-cohort study evaluating the efficacy and safety of pembrolizumab as first-line monotherapy in accRCC and advanced non–clear cell RCC (anccRCC). Patients had accRCC or anccRCC, measurable disease, no prior systemic therapy and Karnofsky Performance Status score of 70% or greater. They were treated with intravenous pembrolizumab at a dose of 200 mg every 3 weeks, and response was assessed at week 12, then every 6 weeks thereafter until week 54, then every 12 weeks.

The current analysis focused on the accRCC cohort and showed that in treatment-naive patients with histologically confirmed accRCC and measurable disease, pembrolizumab shows promising antitumor activity across IMDC risk groups, he said.

“Encouraging activity was also observed in key subgroups, such as the IMDC intermediate/poor risk group ... and patients with [programmed death-ligand 1]-positive tumors,” he said. “The findings ... provide support for the exploration of pembrolizumab in the adjuvant setting and will allow investigators to put the benefit of anti-PD-1-based combination therapies in better context,” he concluded, noting that KEYNOTE-564, a study of pembrolizumab in the adjuvant setting is currently enrolling, and the current study (KEYNOTE-427) cohort B exploring pembrolizumab monotherapy in anccRCC patients is ongoing.

Merck sponsored the study. Dr. McDermott reported consulting or advisory roles with Array BioPharma, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Merck, Novartis, Pfizer, and X4 Pharma. His institution has received research funding from Prometheus Laboratories.

SOURCE: McDermott DF et al., ASCO 2018 Abstract 4500.

CHICAGO – Pembrolizumab monotherapy shows promising efficacy and tolerability in treatment-naive patients with advanced clear cell renal cell carcinoma (accRCC), according to findings from the phase 2 KEYNOTE-427 study.

At a median follow-up of 12 months, the overall response rate in 110 study participants with at least one post-baseline assessment was 38%. Three patients (2.7%) achieved a complete response and 39 (35.5%) achieved a partial response, David F. McDermott, MD, reported at the annual meeting of the American Society of Clinical Oncology.

“The disease control rate was 59%,” he said.

Overall, 67% of the patients experienced a reduction in tumor burden, 14% experienced at least an 80% reduction, and 7% experienced a 100% reduction of their target lesion, said Dr. McDermott of Beth Israel Deaconess Medical Center, Boston.

“Most tumor responses occurred early in the course of therapy,” he noted.

The median time to response was 2.8 months, and the median duration of response was not reached at data cutoff, but 74.8% of responders had a response lasting at least 6 months.

An analysis by International Metastatic Renal Cell Carcinoma Database Criteria (IMDC) category showed a confirmed overall response rate (ORR) of 32% among 41 patients with favorable risk, and 42% in 69 patients with intermediate or poor risk.

“Nine of 17 patients in the poor risk group achieved a major response,” Dr. McDermott noted. “Complete and durable responders were seen in all IMDC subgroups.”

In 46 patients with increased PD-L1 expression or a combined positive score of at least 1 the confirmed ORR was 50.0%, and in 53 patients with low PD-L1 expression and a combined positive score less than 1 it was 26%. The ORR was 45% in the remaining patients in whom PD-L1testing could not be performed.

“Of note, all of the complete responses were seen in the PD-L1-high or CPS-greater-than-1 group,” he said.

Median progression-free survival was 8.7 months, and median overall survival has not been reached.

Tolerability of pembrolizumab in this study was acceptable and consistent with that seen with pembrolizumab monotherapy in other tumor types. Although 80% of patients experienced a treatment-related adverse event, the events mainly included fatigue, pruritus, diarrhea, rash, and arthralgia, occurring in 12.7% to 27.3% of patients, he said.

Grade 3/4 events occurred in 21.8% of patients and one patient experienced a fatal grade 5 case of pneumonitis, he added, noting that 11% of patients discontinued treatment because of a treatment-related adverse event.

Overall, 61 patients discontinued therapy, and 33 of those discontinued because of disease progression.

Programmed death-1 (PD-1) inhibitor-based combination therapies have been shown to have clinical benefit when used first-line in accRCC, but data with respect to the clinical impact of first-line PD-1 inhibitor monotherapy are lacking, Dr. McDermott explained.

KEYNOTE-427 was a single-arm, open-label, two-cohort study evaluating the efficacy and safety of pembrolizumab as first-line monotherapy in accRCC and advanced non–clear cell RCC (anccRCC). Patients had accRCC or anccRCC, measurable disease, no prior systemic therapy and Karnofsky Performance Status score of 70% or greater. They were treated with intravenous pembrolizumab at a dose of 200 mg every 3 weeks, and response was assessed at week 12, then every 6 weeks thereafter until week 54, then every 12 weeks.

The current analysis focused on the accRCC cohort and showed that in treatment-naive patients with histologically confirmed accRCC and measurable disease, pembrolizumab shows promising antitumor activity across IMDC risk groups, he said.

“Encouraging activity was also observed in key subgroups, such as the IMDC intermediate/poor risk group ... and patients with [programmed death-ligand 1]-positive tumors,” he said. “The findings ... provide support for the exploration of pembrolizumab in the adjuvant setting and will allow investigators to put the benefit of anti-PD-1-based combination therapies in better context,” he concluded, noting that KEYNOTE-564, a study of pembrolizumab in the adjuvant setting is currently enrolling, and the current study (KEYNOTE-427) cohort B exploring pembrolizumab monotherapy in anccRCC patients is ongoing.

Merck sponsored the study. Dr. McDermott reported consulting or advisory roles with Array BioPharma, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Merck, Novartis, Pfizer, and X4 Pharma. His institution has received research funding from Prometheus Laboratories.

SOURCE: McDermott DF et al., ASCO 2018 Abstract 4500.

CHICAGO – Pembrolizumab monotherapy shows promising efficacy and tolerability in treatment-naive patients with advanced clear cell renal cell carcinoma (accRCC), according to findings from the phase 2 KEYNOTE-427 study.

At a median follow-up of 12 months, the overall response rate in 110 study participants with at least one post-baseline assessment was 38%. Three patients (2.7%) achieved a complete response and 39 (35.5%) achieved a partial response, David F. McDermott, MD, reported at the annual meeting of the American Society of Clinical Oncology.

“The disease control rate was 59%,” he said.

Overall, 67% of the patients experienced a reduction in tumor burden, 14% experienced at least an 80% reduction, and 7% experienced a 100% reduction of their target lesion, said Dr. McDermott of Beth Israel Deaconess Medical Center, Boston.

“Most tumor responses occurred early in the course of therapy,” he noted.

The median time to response was 2.8 months, and the median duration of response was not reached at data cutoff, but 74.8% of responders had a response lasting at least 6 months.

An analysis by International Metastatic Renal Cell Carcinoma Database Criteria (IMDC) category showed a confirmed overall response rate (ORR) of 32% among 41 patients with favorable risk, and 42% in 69 patients with intermediate or poor risk.

“Nine of 17 patients in the poor risk group achieved a major response,” Dr. McDermott noted. “Complete and durable responders were seen in all IMDC subgroups.”

In 46 patients with increased PD-L1 expression or a combined positive score of at least 1 the confirmed ORR was 50.0%, and in 53 patients with low PD-L1 expression and a combined positive score less than 1 it was 26%. The ORR was 45% in the remaining patients in whom PD-L1testing could not be performed.

“Of note, all of the complete responses were seen in the PD-L1-high or CPS-greater-than-1 group,” he said.

Median progression-free survival was 8.7 months, and median overall survival has not been reached.

Tolerability of pembrolizumab in this study was acceptable and consistent with that seen with pembrolizumab monotherapy in other tumor types. Although 80% of patients experienced a treatment-related adverse event, the events mainly included fatigue, pruritus, diarrhea, rash, and arthralgia, occurring in 12.7% to 27.3% of patients, he said.

Grade 3/4 events occurred in 21.8% of patients and one patient experienced a fatal grade 5 case of pneumonitis, he added, noting that 11% of patients discontinued treatment because of a treatment-related adverse event.

Overall, 61 patients discontinued therapy, and 33 of those discontinued because of disease progression.

Programmed death-1 (PD-1) inhibitor-based combination therapies have been shown to have clinical benefit when used first-line in accRCC, but data with respect to the clinical impact of first-line PD-1 inhibitor monotherapy are lacking, Dr. McDermott explained.

KEYNOTE-427 was a single-arm, open-label, two-cohort study evaluating the efficacy and safety of pembrolizumab as first-line monotherapy in accRCC and advanced non–clear cell RCC (anccRCC). Patients had accRCC or anccRCC, measurable disease, no prior systemic therapy and Karnofsky Performance Status score of 70% or greater. They were treated with intravenous pembrolizumab at a dose of 200 mg every 3 weeks, and response was assessed at week 12, then every 6 weeks thereafter until week 54, then every 12 weeks.

The current analysis focused on the accRCC cohort and showed that in treatment-naive patients with histologically confirmed accRCC and measurable disease, pembrolizumab shows promising antitumor activity across IMDC risk groups, he said.

“Encouraging activity was also observed in key subgroups, such as the IMDC intermediate/poor risk group ... and patients with [programmed death-ligand 1]-positive tumors,” he said. “The findings ... provide support for the exploration of pembrolizumab in the adjuvant setting and will allow investigators to put the benefit of anti-PD-1-based combination therapies in better context,” he concluded, noting that KEYNOTE-564, a study of pembrolizumab in the adjuvant setting is currently enrolling, and the current study (KEYNOTE-427) cohort B exploring pembrolizumab monotherapy in anccRCC patients is ongoing.

Merck sponsored the study. Dr. McDermott reported consulting or advisory roles with Array BioPharma, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Merck, Novartis, Pfizer, and X4 Pharma. His institution has received research funding from Prometheus Laboratories.

SOURCE: McDermott DF et al., ASCO 2018 Abstract 4500.

Levels of activity of a protein linked to malignancy could help predict if and when patients with renal cell carcinoma are likely to experience a recurrence, investigators report.

In a retrospective cohort study, the researchers looked at surgical specimens from 303 patients with localized clear cell renal cell carcinoma who had surgery between 1993 and 2011. The specimens were stained for antibodies against three key proteins; eukaryotic initiation factor 4E (eIF4E), eukaryotic initiation factor 4E binding protein 1 (4EBP1), and phospho eukaryotic initiation factor 4E binding protein 1 (p-4EBP1), reported Osamu Ichiyanagi, MD, of Yamagata (Japan) University, and colleagues. The study was published in Clinical Genitourinary Cancer.

The 4EBP1/eIF4E axis is known to regulate protein synthesis associated with malignant behavior. Researchers found that while the expression levels for the three proteins were similar between the recurrence-free and recurrence groups, patients who did not experience a recurrence had significantly lower activity in the 4EBP1/eIF4E axis.

The analysis showed that having intermediate or strong activation of the 4EBP1/eIF4E axis was an independent predictor of the risk of recurrence, as was Fuhrman grade 3/4 and pathological T stage of pT1b or above.

Only two patients who had weak activation of the 4EBP1/eIF4E axis experienced a recurrence (one early, one late).

Overall, 31 patients experienced an early recurrence – defined as recurrence within 5 years – and 16 patients experienced a recurrence after 5 years. Strong activation of the 4EBP1/eIF4E axis was an independent predictor of early recurrence.

About one-third of patients with nonmetastatic renal cell carcinoma who are curatively treated with nephrectomy experience a tumor recurrence, most commonly a distant metastasis. Late recurrence is known to occur in 6%-12% of patients.

“We show here for the first time that activation level of the 4EBP1/eIF4E axis in localised ccRCC may contribute not only to tumour recurrence but also to the timing of recurrence following curative nephrectomy,” wrote Dr. Ichiyanagi and coauthors. “Our data indicate that this activation may impact ER [early recurrence] and LR [late recurrence] events differentially.”

The study also found that more patients experienced recurrence after curative nephrectomy, suggesting that the 4EBP1/eIF4E axis became strongly activated after this.

The study was supported by Yamagata University Faculty of Medicine and the Japan Society for Promotion of Science. No conflicts of interest were declared.

SOURCE: Ichiyanagi O et al. Clin Genitourin Cancer. 2018 June 8. doi: 10.1016/j.clgc.2018.06.002.

Levels of activity of a protein linked to malignancy could help predict if and when patients with renal cell carcinoma are likely to experience a recurrence, investigators report.

In a retrospective cohort study, the researchers looked at surgical specimens from 303 patients with localized clear cell renal cell carcinoma who had surgery between 1993 and 2011. The specimens were stained for antibodies against three key proteins; eukaryotic initiation factor 4E (eIF4E), eukaryotic initiation factor 4E binding protein 1 (4EBP1), and phospho eukaryotic initiation factor 4E binding protein 1 (p-4EBP1), reported Osamu Ichiyanagi, MD, of Yamagata (Japan) University, and colleagues. The study was published in Clinical Genitourinary Cancer.

The 4EBP1/eIF4E axis is known to regulate protein synthesis associated with malignant behavior. Researchers found that while the expression levels for the three proteins were similar between the recurrence-free and recurrence groups, patients who did not experience a recurrence had significantly lower activity in the 4EBP1/eIF4E axis.

The analysis showed that having intermediate or strong activation of the 4EBP1/eIF4E axis was an independent predictor of the risk of recurrence, as was Fuhrman grade 3/4 and pathological T stage of pT1b or above.

Only two patients who had weak activation of the 4EBP1/eIF4E axis experienced a recurrence (one early, one late).

Overall, 31 patients experienced an early recurrence – defined as recurrence within 5 years – and 16 patients experienced a recurrence after 5 years. Strong activation of the 4EBP1/eIF4E axis was an independent predictor of early recurrence.

About one-third of patients with nonmetastatic renal cell carcinoma who are curatively treated with nephrectomy experience a tumor recurrence, most commonly a distant metastasis. Late recurrence is known to occur in 6%-12% of patients.

“We show here for the first time that activation level of the 4EBP1/eIF4E axis in localised ccRCC may contribute not only to tumour recurrence but also to the timing of recurrence following curative nephrectomy,” wrote Dr. Ichiyanagi and coauthors. “Our data indicate that this activation may impact ER [early recurrence] and LR [late recurrence] events differentially.”

The study also found that more patients experienced recurrence after curative nephrectomy, suggesting that the 4EBP1/eIF4E axis became strongly activated after this.

The study was supported by Yamagata University Faculty of Medicine and the Japan Society for Promotion of Science. No conflicts of interest were declared.

SOURCE: Ichiyanagi O et al. Clin Genitourin Cancer. 2018 June 8. doi: 10.1016/j.clgc.2018.06.002.

Levels of activity of a protein linked to malignancy could help predict if and when patients with renal cell carcinoma are likely to experience a recurrence, investigators report.

In a retrospective cohort study, the researchers looked at surgical specimens from 303 patients with localized clear cell renal cell carcinoma who had surgery between 1993 and 2011. The specimens were stained for antibodies against three key proteins; eukaryotic initiation factor 4E (eIF4E), eukaryotic initiation factor 4E binding protein 1 (4EBP1), and phospho eukaryotic initiation factor 4E binding protein 1 (p-4EBP1), reported Osamu Ichiyanagi, MD, of Yamagata (Japan) University, and colleagues. The study was published in Clinical Genitourinary Cancer.

The 4EBP1/eIF4E axis is known to regulate protein synthesis associated with malignant behavior. Researchers found that while the expression levels for the three proteins were similar between the recurrence-free and recurrence groups, patients who did not experience a recurrence had significantly lower activity in the 4EBP1/eIF4E axis.

The analysis showed that having intermediate or strong activation of the 4EBP1/eIF4E axis was an independent predictor of the risk of recurrence, as was Fuhrman grade 3/4 and pathological T stage of pT1b or above.

Only two patients who had weak activation of the 4EBP1/eIF4E axis experienced a recurrence (one early, one late).

Overall, 31 patients experienced an early recurrence – defined as recurrence within 5 years – and 16 patients experienced a recurrence after 5 years. Strong activation of the 4EBP1/eIF4E axis was an independent predictor of early recurrence.

About one-third of patients with nonmetastatic renal cell carcinoma who are curatively treated with nephrectomy experience a tumor recurrence, most commonly a distant metastasis. Late recurrence is known to occur in 6%-12% of patients.

“We show here for the first time that activation level of the 4EBP1/eIF4E axis in localised ccRCC may contribute not only to tumour recurrence but also to the timing of recurrence following curative nephrectomy,” wrote Dr. Ichiyanagi and coauthors. “Our data indicate that this activation may impact ER [early recurrence] and LR [late recurrence] events differentially.”

The study also found that more patients experienced recurrence after curative nephrectomy, suggesting that the 4EBP1/eIF4E axis became strongly activated after this.

The study was supported by Yamagata University Faculty of Medicine and the Japan Society for Promotion of Science. No conflicts of interest were declared.

SOURCE: Ichiyanagi O et al. Clin Genitourin Cancer. 2018 June 8. doi: 10.1016/j.clgc.2018.06.002.

In hindsight, a widely used prognostic model for patients with metastatic renal cell carcinoma (mRCC) has been shown to be effective at stratifying patient risk, and may inform the design of future clinical trials.

By retrospectively comparing clinical outcomes with risk categories determined by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, Brian I Rini, MD, of the Cleveland Clinic, and his colleagues found notable differences in progression-free survival, overall survival, and objective response rates between the different risk categories among patients with mRCC treated with sunitinib (Sutent) in a major clinical trial.

“These benchmark values can aid current and future design and interpretation of clinical trials in mRCC. Results of this analysis demonstrate clear differences in patient outcomes based on IMDC prognostic risk group,” they wrote. The report was published in Clinical Genitourinary Cancer.

They also found that the Memorial Sloan Kettering Cancer Center (MSKCC) model appeared to be similar in prognostic utility to the IMDC model, and that either model could be useful for counseling patients about prognosis and treatment options.

They based their conclusions on an analysis of data from a phase 3 clinical trial comparing sunitinib with interferon alfa in patients with mRCC. Patients in this study were grouped according to prognostic risk category by the MSKCC criteria, which overlap with the IMDC criteria in five of six areas.

In the current study, Dr. Rini and his associates applied the IMDC criteria to the same population, and derived benchmark values for outcomes by IMDC risk groups based on radiologic tumor progression measurements performed by independent reviewers on images of patients in the intention-to-treat population.

They also conducted an analysis of data from investigator measurements of tumor progression, and compared the results with the independently reviewed radiologic data for patients outcomes according to the MSKCC model.

SOURCE: Rini B et al. Clin Genitourin Cancer. 2018 May 3. doi: 10.1016/j.clgc.2018.04.005.

In hindsight, a widely used prognostic model for patients with metastatic renal cell carcinoma (mRCC) has been shown to be effective at stratifying patient risk, and may inform the design of future clinical trials.

By retrospectively comparing clinical outcomes with risk categories determined by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, Brian I Rini, MD, of the Cleveland Clinic, and his colleagues found notable differences in progression-free survival, overall survival, and objective response rates between the different risk categories among patients with mRCC treated with sunitinib (Sutent) in a major clinical trial.

“These benchmark values can aid current and future design and interpretation of clinical trials in mRCC. Results of this analysis demonstrate clear differences in patient outcomes based on IMDC prognostic risk group,” they wrote. The report was published in Clinical Genitourinary Cancer.

They also found that the Memorial Sloan Kettering Cancer Center (MSKCC) model appeared to be similar in prognostic utility to the IMDC model, and that either model could be useful for counseling patients about prognosis and treatment options.

They based their conclusions on an analysis of data from a phase 3 clinical trial comparing sunitinib with interferon alfa in patients with mRCC. Patients in this study were grouped according to prognostic risk category by the MSKCC criteria, which overlap with the IMDC criteria in five of six areas.

In the current study, Dr. Rini and his associates applied the IMDC criteria to the same population, and derived benchmark values for outcomes by IMDC risk groups based on radiologic tumor progression measurements performed by independent reviewers on images of patients in the intention-to-treat population.

They also conducted an analysis of data from investigator measurements of tumor progression, and compared the results with the independently reviewed radiologic data for patients outcomes according to the MSKCC model.

SOURCE: Rini B et al. Clin Genitourin Cancer. 2018 May 3. doi: 10.1016/j.clgc.2018.04.005.

In hindsight, a widely used prognostic model for patients with metastatic renal cell carcinoma (mRCC) has been shown to be effective at stratifying patient risk, and may inform the design of future clinical trials.

By retrospectively comparing clinical outcomes with risk categories determined by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model, Brian I Rini, MD, of the Cleveland Clinic, and his colleagues found notable differences in progression-free survival, overall survival, and objective response rates between the different risk categories among patients with mRCC treated with sunitinib (Sutent) in a major clinical trial.

“These benchmark values can aid current and future design and interpretation of clinical trials in mRCC. Results of this analysis demonstrate clear differences in patient outcomes based on IMDC prognostic risk group,” they wrote. The report was published in Clinical Genitourinary Cancer.

They also found that the Memorial Sloan Kettering Cancer Center (MSKCC) model appeared to be similar in prognostic utility to the IMDC model, and that either model could be useful for counseling patients about prognosis and treatment options.

They based their conclusions on an analysis of data from a phase 3 clinical trial comparing sunitinib with interferon alfa in patients with mRCC. Patients in this study were grouped according to prognostic risk category by the MSKCC criteria, which overlap with the IMDC criteria in five of six areas.

In the current study, Dr. Rini and his associates applied the IMDC criteria to the same population, and derived benchmark values for outcomes by IMDC risk groups based on radiologic tumor progression measurements performed by independent reviewers on images of patients in the intention-to-treat population.

They also conducted an analysis of data from investigator measurements of tumor progression, and compared the results with the independently reviewed radiologic data for patients outcomes according to the MSKCC model.

SOURCE: Rini B et al. Clin Genitourin Cancer. 2018 May 3. doi: 10.1016/j.clgc.2018.04.005.

Cancer immunotherapy using checkpoint inhibitors may achieve greater mortality reductions in men than they do in women, new research has suggested.

In a meta-analysis and systematic review published in Lancet Oncology, researchers analyzed 20 randomized, controlled trials of immune checkpoint inhibitors that included detail on overall survival and patients’ sex; altogether, these studies involved 11,351 patients with advanced or metastatic cancers.

They found that while men treated with checkpoint inhibitors had a significant 28% reduced risk of death, compared with male controls, the survival benefit in women was smaller (14% reduced risk of death, compared with female controls).

Fabio Conforti, MD, from the European Institute of Oncology, Milan, and coauthors commented that the magnitude of the difference between the effect seen men and that in women was clinically significant.

“The pooled reduction of risk of death was double the size for male patients than for female patients – a difference that is similar to the size of the difference in survival benefit observed between patients with non–small cell lung cancer with PD-L1 positive (greater than 1%) tumors versus negative tumors, who were treated with anti-PD-1,” they wrote.

This difference between the benefit seen men and that in women was evident across all the subgroups in the study, which included subgroups based on cancer histotype, line of treatment, drugs used, and type of control.

However there was greater heterogeneity in the magnitude of the effect of checkpoint inhibitors on mortality in men than there was in women. The authors suggested this could be explained by the fact that the drugs have lower efficacy in women and this may therefore reduce the variability of results when compared with those in men.

SOURCE: Conforti F et al. Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045(18)30261-4.

Cancer immunotherapy using checkpoint inhibitors may achieve greater mortality reductions in men than they do in women, new research has suggested.

In a meta-analysis and systematic review published in Lancet Oncology, researchers analyzed 20 randomized, controlled trials of immune checkpoint inhibitors that included detail on overall survival and patients’ sex; altogether, these studies involved 11,351 patients with advanced or metastatic cancers.

They found that while men treated with checkpoint inhibitors had a significant 28% reduced risk of death, compared with male controls, the survival benefit in women was smaller (14% reduced risk of death, compared with female controls).

Fabio Conforti, MD, from the European Institute of Oncology, Milan, and coauthors commented that the magnitude of the difference between the effect seen men and that in women was clinically significant.

“The pooled reduction of risk of death was double the size for male patients than for female patients – a difference that is similar to the size of the difference in survival benefit observed between patients with non–small cell lung cancer with PD-L1 positive (greater than 1%) tumors versus negative tumors, who were treated with anti-PD-1,” they wrote.

This difference between the benefit seen men and that in women was evident across all the subgroups in the study, which included subgroups based on cancer histotype, line of treatment, drugs used, and type of control.

However there was greater heterogeneity in the magnitude of the effect of checkpoint inhibitors on mortality in men than there was in women. The authors suggested this could be explained by the fact that the drugs have lower efficacy in women and this may therefore reduce the variability of results when compared with those in men.

SOURCE: Conforti F et al. Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045(18)30261-4.

Cancer immunotherapy using checkpoint inhibitors may achieve greater mortality reductions in men than they do in women, new research has suggested.

In a meta-analysis and systematic review published in Lancet Oncology, researchers analyzed 20 randomized, controlled trials of immune checkpoint inhibitors that included detail on overall survival and patients’ sex; altogether, these studies involved 11,351 patients with advanced or metastatic cancers.

They found that while men treated with checkpoint inhibitors had a significant 28% reduced risk of death, compared with male controls, the survival benefit in women was smaller (14% reduced risk of death, compared with female controls).

Fabio Conforti, MD, from the European Institute of Oncology, Milan, and coauthors commented that the magnitude of the difference between the effect seen men and that in women was clinically significant.

“The pooled reduction of risk of death was double the size for male patients than for female patients – a difference that is similar to the size of the difference in survival benefit observed between patients with non–small cell lung cancer with PD-L1 positive (greater than 1%) tumors versus negative tumors, who were treated with anti-PD-1,” they wrote.

This difference between the benefit seen men and that in women was evident across all the subgroups in the study, which included subgroups based on cancer histotype, line of treatment, drugs used, and type of control.

However there was greater heterogeneity in the magnitude of the effect of checkpoint inhibitors on mortality in men than there was in women. The authors suggested this could be explained by the fact that the drugs have lower efficacy in women and this may therefore reduce the variability of results when compared with those in men.

SOURCE: Conforti F et al. Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045(18)30261-4.