Renal Cell Carcinoma

Researchers have developed what they say is a clinically useful prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) treated with the second-generation androgen receptor inhibitor enzalutamide.

Knowledge of prognosis gained by the model, which includes 11 variables routinely collected from patients, may help clinicians make decisions on the aggressiveness with which to pursue active therapy and could also help shape trial designs that utilize combinations with androgen receptor–directed therapies, the research team wrote in Annals of Oncology.

Led by Andrew J. Armstrong, MD, of Duke University, Durham, N.C., the researchers randomly split patients from the PREVAIL trial database (enzalutamide vs. placebo) 2:1 into training (n = 1,159) and testing (n = 550) sets.

They noted that, in the PREVAIL trial, enzalutamide significantly reduced the risk of death by 29% (hazard ratio, 0.71; P less than .001), compared with placebo.

Using the training set, the research team analyzed 23 predefined variables based on previous work demonstrating their potential importance in mCRPC outcomes. A multivariable model predicting overall survival (OS) was then developed and the HR and 95% confidence interval were established for each potentially prognostic variable.

The final validated multivariable model included 11 independent prognostic variables: albumin, alkaline phosphatase, hemoglobin, lactate dehydrogenase, neutrophil-lymphocyte ratio, number of bone metastases, presence of pain, pattern of spread, prostate specific antigen, time from diagnosis to randomization, and treatment.

The 11-variable model provided a significant separation between low-risk and high-risk patients (HR, 0.35; 95% CI, 0.27-0.46) and between low-risk (HR, 0.20; 95% CI, 0.14-0.29) and intermediate-risk (HR, 0.40; 95% CI, 0.30-0.53) versus high-risk patients.

Median OS for low-risk, intermediate-risk, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached, 34.2 months, and 21.1 months, respectively.

“This model has potential clinical utility for individual and trial-level survival, potential outcomes prognostication, and clinical trial design of novel treatment approaches in this population,” the research team concluded.

The researchers said their model had several advantages over others because it was developed and validated in a contemporary treatment setting that reflected current practice. However, they cautioned that while the variables in their model had “strong biologic rationale” outcomes for individuals in contemporary practice may differ from those in clinical trial populations.

“External validation is recommended in a broader, nontrial population of men with mCRPC. Accordingly, the prognostic model presented in this paper and in general, should not displace the well-informed clinical judgment of health care professionals treating individual patients,” they wrote.

The research was supported by Medivation and Astellas Pharma (the codevelopers of enzalutamide).

SOURCE: Armstrong AJ et al. Ann Oncol. 2018 Sept 10. doi: 10.1093/annonc/mdy406.

Researchers have developed what they say is a clinically useful prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) treated with the second-generation androgen receptor inhibitor enzalutamide.

Knowledge of prognosis gained by the model, which includes 11 variables routinely collected from patients, may help clinicians make decisions on the aggressiveness with which to pursue active therapy and could also help shape trial designs that utilize combinations with androgen receptor–directed therapies, the research team wrote in Annals of Oncology.

Led by Andrew J. Armstrong, MD, of Duke University, Durham, N.C., the researchers randomly split patients from the PREVAIL trial database (enzalutamide vs. placebo) 2:1 into training (n = 1,159) and testing (n = 550) sets.

They noted that, in the PREVAIL trial, enzalutamide significantly reduced the risk of death by 29% (hazard ratio, 0.71; P less than .001), compared with placebo.

Using the training set, the research team analyzed 23 predefined variables based on previous work demonstrating their potential importance in mCRPC outcomes. A multivariable model predicting overall survival (OS) was then developed and the HR and 95% confidence interval were established for each potentially prognostic variable.

The final validated multivariable model included 11 independent prognostic variables: albumin, alkaline phosphatase, hemoglobin, lactate dehydrogenase, neutrophil-lymphocyte ratio, number of bone metastases, presence of pain, pattern of spread, prostate specific antigen, time from diagnosis to randomization, and treatment.

The 11-variable model provided a significant separation between low-risk and high-risk patients (HR, 0.35; 95% CI, 0.27-0.46) and between low-risk (HR, 0.20; 95% CI, 0.14-0.29) and intermediate-risk (HR, 0.40; 95% CI, 0.30-0.53) versus high-risk patients.

Median OS for low-risk, intermediate-risk, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached, 34.2 months, and 21.1 months, respectively.

“This model has potential clinical utility for individual and trial-level survival, potential outcomes prognostication, and clinical trial design of novel treatment approaches in this population,” the research team concluded.

The researchers said their model had several advantages over others because it was developed and validated in a contemporary treatment setting that reflected current practice. However, they cautioned that while the variables in their model had “strong biologic rationale” outcomes for individuals in contemporary practice may differ from those in clinical trial populations.

“External validation is recommended in a broader, nontrial population of men with mCRPC. Accordingly, the prognostic model presented in this paper and in general, should not displace the well-informed clinical judgment of health care professionals treating individual patients,” they wrote.

The research was supported by Medivation and Astellas Pharma (the codevelopers of enzalutamide).

SOURCE: Armstrong AJ et al. Ann Oncol. 2018 Sept 10. doi: 10.1093/annonc/mdy406.

Researchers have developed what they say is a clinically useful prognostic model for overall survival in chemotherapy-naive men with metastatic castration-resistant prostate cancer (mCRPC) treated with the second-generation androgen receptor inhibitor enzalutamide.

Knowledge of prognosis gained by the model, which includes 11 variables routinely collected from patients, may help clinicians make decisions on the aggressiveness with which to pursue active therapy and could also help shape trial designs that utilize combinations with androgen receptor–directed therapies, the research team wrote in Annals of Oncology.

Led by Andrew J. Armstrong, MD, of Duke University, Durham, N.C., the researchers randomly split patients from the PREVAIL trial database (enzalutamide vs. placebo) 2:1 into training (n = 1,159) and testing (n = 550) sets.

They noted that, in the PREVAIL trial, enzalutamide significantly reduced the risk of death by 29% (hazard ratio, 0.71; P less than .001), compared with placebo.

Using the training set, the research team analyzed 23 predefined variables based on previous work demonstrating their potential importance in mCRPC outcomes. A multivariable model predicting overall survival (OS) was then developed and the HR and 95% confidence interval were established for each potentially prognostic variable.

The final validated multivariable model included 11 independent prognostic variables: albumin, alkaline phosphatase, hemoglobin, lactate dehydrogenase, neutrophil-lymphocyte ratio, number of bone metastases, presence of pain, pattern of spread, prostate specific antigen, time from diagnosis to randomization, and treatment.

The 11-variable model provided a significant separation between low-risk and high-risk patients (HR, 0.35; 95% CI, 0.27-0.46) and between low-risk (HR, 0.20; 95% CI, 0.14-0.29) and intermediate-risk (HR, 0.40; 95% CI, 0.30-0.53) versus high-risk patients.

Median OS for low-risk, intermediate-risk, and high-risk groups (testing set) defined by prognostic risk tertiles were not yet reached, 34.2 months, and 21.1 months, respectively.

“This model has potential clinical utility for individual and trial-level survival, potential outcomes prognostication, and clinical trial design of novel treatment approaches in this population,” the research team concluded.

The researchers said their model had several advantages over others because it was developed and validated in a contemporary treatment setting that reflected current practice. However, they cautioned that while the variables in their model had “strong biologic rationale” outcomes for individuals in contemporary practice may differ from those in clinical trial populations.

“External validation is recommended in a broader, nontrial population of men with mCRPC. Accordingly, the prognostic model presented in this paper and in general, should not displace the well-informed clinical judgment of health care professionals treating individual patients,” they wrote.

The research was supported by Medivation and Astellas Pharma (the codevelopers of enzalutamide).

SOURCE: Armstrong AJ et al. Ann Oncol. 2018 Sept 10. doi: 10.1093/annonc/mdy406.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Expression of programmed death-1 (PD1) mRNA may predict outcomes after anti-PD1 therapy across cancer types, according to investigators.

High levels of PD1 mRNA were significantly associated with response to anti-PD1 monotherapy, investigators found in an analysis of tumor samples from 117 patients with advanced cancers who had received either nivolumab or pembrolizumab.

Further validation of PD1 mRNA is warranted to help select patients who might benefit from an anti-PD1 treatment strategy, wrote investigator Aleix Prat, MD, PhD, of Hospital Clínic of Barcelona, and his coinvestigators.

“Identification of reproducible biomarkers that can be applied to predict benefit of anti-PD1 monotherapy might be of clinical value,” Dr. Prat and his coinvestigators note. The report is in Annals of Oncology.

Previous studies support use of PDL1 expression by immunohistochemistry as a biomarker for pembrolizumab in non–small-cell lung cancer; however, that biomarker has some technical limitations, and has not been predictive in other cancer types and with other anti-PD1 drugs including nivolumab, Dr. Prat and his coinvestigators said.

The 117 tumor samples evaluated for PD1 mRNA expression comprised 59 advanced melanomas, 32 non–small-cell lung cancers, 14 renal cell cancers, and 12 other tumors, according to the report. Sixty-two of the patients had been treated with pembrolizumab, and 55 received nivolumab.

About one-quarter of the samples (28.2%) were classified as “PD1-high” with a preestablished cutoff value developed by Dr. Prat and his coinvestigators.

The overall response rate was 51.5% for the patients who had PD1-high tumors, versus 23.8% for the remaining tumors (P less than .001). Those non-PD1-high tumors, when grouped as PD1-intermediate and PD1-low, had overall response rates of 26.6% and 15.0%, respectively.

Median progression-free survival was 8.17 months for PD1-high tumors and 3.18 months for the rest of the tumors (P = .011), the report shows. Similarly, overall survival was a median of 23.4 months for PD1-high tumors and 14.9 months for the rest (P = .330).

Dr. Prat and his colleagues detailed earlier investigations validating PD1 mRNA as a biomarker, including an analysis of PD1 and immune-related gene expression in 10,078 samples from 34 cancer types in The Cancer Genome Atlas.

In that analysis, PD1 was strongly correlated with a group of 30 genes that were “significantly enriched” in biological processes including CD8-T-cell activation, the investigators said.

Moreover, high levels of PD1 mRNA expression were strongly correlated with overall response rates reported in the literature for anti-PD1 monotherapy, they added.

They also reported results of an analysis they used to develop the PD1-high cutoff value. That analysis was based on PD1 mRNA expression in 773 tumor samples across 17 tumor types.

“Our results are consistent with the hypothesis that identification of a preexisting and stable adaptive immune response using PD1 mRNA expression predicts outcome across cancer-types following anti-PD1 monotherapy,” the researchers wrote.

The work was partially sponsored by Instituto de Salud Carlos III, Spanish Society of Medical Oncology, Banco Bilbao Vizcaya Argentaria Foundation, Pas a Pas, Save the Mama, and the Breast Cancer Research Foundation. Dr. Prat disclosed an advisory role with Nanostring Technologies.

SOURCE: Paré L et al. Ann Oncol. 2018 Aug 27. doi: 10.1093/annonc/mdy335.

Once again, a study has shown that when it comes to managing patients with serious advanced malignancies – in this case, metastatic renal cell carcinoma – experience matters.

A review of data on 41,836 patients with metastatic renal cell carcinoma (mRCC) treated at 1,222 facilities (TFs) showed that across all cohorts, including patients with known liver and lung metastases who received systemic therapies, treatment-center volume was significantly associated with longer survival, reported Daniel M. Geynisman, MD of Fox Chase Cancer Center in Philadelphia, and his colleagues.

“These findings may help define the optimal treatment environment for the management of patients with mRCC. The improved survival outcomes at higher-volume TFs should also be a call to improve mRCC management at lower-volume facilities. Given the negative externalities of care regionalization, focus should shift toward policies that help equalize mRCC management at lower-volume TFs by expanding treatment options, clinical trial access, and specialized resource availability,” the researchers wrote. Their report is in European Urology.

The investigators noted that several studies have demonstrated that patients with localized RCC treated at high-volume centers had better postoperative outcomes and few complications following surgery for renal cancer, but whether treatment volume makes a difference for patients with metastatic disease was less clear.

To get a better understanding of the association between case volume and outcomes for patients with advanced RCC, the investigators searched the National Cancer Database for information on all U.S. patients with mRCC from 2004 through 2013 for whom survival data were available.

To confirm the association with volume, they created five cohorts with increasingly restrictive inclusion criteria, as follows:

• Cohort A: All patients with survival data (41,836 patients).
• Cohort B: Patients with mRCC who received active treatment of any kind (27,557).
• Cohort C: Patients treated with systemic therapy with or without primary surgery (19,138).
• Cohort D: Patients treated with systemic therapy at the reporting facility (12,000).
• Cohort E: Patients with known sites of metastases (4,933).

The investigators also conducted sensitivity analyses on subcohorts of patients who did not receive nephrectomies in cohorts C, D, and E.

They found in a multivariable analysis that increased volume, measured as cases per year, was associated with reduced overall mortality across all cohorts.

For example, in cohort A, the hazard ratio (HR) for overall mortality for TFs caring for a mean of 5 patients per year was 0.92, compared with 0.84 for centers with 10 cases per year, and 0.74 for TFs caring for a mean of 20 patients per year (P less than .001). Similarly, the respective HRs for patients in cohort E were 0.88, 0.79, and 0.72 (P less than .001).

The overall probability of mortality was also significantly lower in higher-volume centers for those patients in cohorts C, D, and E who did not undergo nephrectomy.

The investigators acknowledged that the study was limited by the retrospective nature of the database information, and by the absence of data on treatment regimens used at specific facilities, which may explain mechanisms of the effects they observed.

The investigators did not specify a study funding source. Dr. Geynisman reported having no conflicts of interest.

SOURCE: Joshi SS et al. Eur Urol. 2018 Sep;74[3]:387-93.

Once again, a study has shown that when it comes to managing patients with serious advanced malignancies – in this case, metastatic renal cell carcinoma – experience matters.

A review of data on 41,836 patients with metastatic renal cell carcinoma (mRCC) treated at 1,222 facilities (TFs) showed that across all cohorts, including patients with known liver and lung metastases who received systemic therapies, treatment-center volume was significantly associated with longer survival, reported Daniel M. Geynisman, MD of Fox Chase Cancer Center in Philadelphia, and his colleagues.

“These findings may help define the optimal treatment environment for the management of patients with mRCC. The improved survival outcomes at higher-volume TFs should also be a call to improve mRCC management at lower-volume facilities. Given the negative externalities of care regionalization, focus should shift toward policies that help equalize mRCC management at lower-volume TFs by expanding treatment options, clinical trial access, and specialized resource availability,” the researchers wrote. Their report is in European Urology.

The investigators noted that several studies have demonstrated that patients with localized RCC treated at high-volume centers had better postoperative outcomes and few complications following surgery for renal cancer, but whether treatment volume makes a difference for patients with metastatic disease was less clear.

To get a better understanding of the association between case volume and outcomes for patients with advanced RCC, the investigators searched the National Cancer Database for information on all U.S. patients with mRCC from 2004 through 2013 for whom survival data were available.

To confirm the association with volume, they created five cohorts with increasingly restrictive inclusion criteria, as follows:

• Cohort A: All patients with survival data (41,836 patients).
• Cohort B: Patients with mRCC who received active treatment of any kind (27,557).
• Cohort C: Patients treated with systemic therapy with or without primary surgery (19,138).
• Cohort D: Patients treated with systemic therapy at the reporting facility (12,000).
• Cohort E: Patients with known sites of metastases (4,933).

The investigators also conducted sensitivity analyses on subcohorts of patients who did not receive nephrectomies in cohorts C, D, and E.

They found in a multivariable analysis that increased volume, measured as cases per year, was associated with reduced overall mortality across all cohorts.

For example, in cohort A, the hazard ratio (HR) for overall mortality for TFs caring for a mean of 5 patients per year was 0.92, compared with 0.84 for centers with 10 cases per year, and 0.74 for TFs caring for a mean of 20 patients per year (P less than .001). Similarly, the respective HRs for patients in cohort E were 0.88, 0.79, and 0.72 (P less than .001).

The overall probability of mortality was also significantly lower in higher-volume centers for those patients in cohorts C, D, and E who did not undergo nephrectomy.

The investigators acknowledged that the study was limited by the retrospective nature of the database information, and by the absence of data on treatment regimens used at specific facilities, which may explain mechanisms of the effects they observed.

The investigators did not specify a study funding source. Dr. Geynisman reported having no conflicts of interest.

SOURCE: Joshi SS et al. Eur Urol. 2018 Sep;74[3]:387-93.

Once again, a study has shown that when it comes to managing patients with serious advanced malignancies – in this case, metastatic renal cell carcinoma – experience matters.

A review of data on 41,836 patients with metastatic renal cell carcinoma (mRCC) treated at 1,222 facilities (TFs) showed that across all cohorts, including patients with known liver and lung metastases who received systemic therapies, treatment-center volume was significantly associated with longer survival, reported Daniel M. Geynisman, MD of Fox Chase Cancer Center in Philadelphia, and his colleagues.

“These findings may help define the optimal treatment environment for the management of patients with mRCC. The improved survival outcomes at higher-volume TFs should also be a call to improve mRCC management at lower-volume facilities. Given the negative externalities of care regionalization, focus should shift toward policies that help equalize mRCC management at lower-volume TFs by expanding treatment options, clinical trial access, and specialized resource availability,” the researchers wrote. Their report is in European Urology.

The investigators noted that several studies have demonstrated that patients with localized RCC treated at high-volume centers had better postoperative outcomes and few complications following surgery for renal cancer, but whether treatment volume makes a difference for patients with metastatic disease was less clear.

To get a better understanding of the association between case volume and outcomes for patients with advanced RCC, the investigators searched the National Cancer Database for information on all U.S. patients with mRCC from 2004 through 2013 for whom survival data were available.

To confirm the association with volume, they created five cohorts with increasingly restrictive inclusion criteria, as follows:

• Cohort A: All patients with survival data (41,836 patients).
• Cohort B: Patients with mRCC who received active treatment of any kind (27,557).
• Cohort C: Patients treated with systemic therapy with or without primary surgery (19,138).
• Cohort D: Patients treated with systemic therapy at the reporting facility (12,000).
• Cohort E: Patients with known sites of metastases (4,933).

The investigators also conducted sensitivity analyses on subcohorts of patients who did not receive nephrectomies in cohorts C, D, and E.

They found in a multivariable analysis that increased volume, measured as cases per year, was associated with reduced overall mortality across all cohorts.

For example, in cohort A, the hazard ratio (HR) for overall mortality for TFs caring for a mean of 5 patients per year was 0.92, compared with 0.84 for centers with 10 cases per year, and 0.74 for TFs caring for a mean of 20 patients per year (P less than .001). Similarly, the respective HRs for patients in cohort E were 0.88, 0.79, and 0.72 (P less than .001).

The overall probability of mortality was also significantly lower in higher-volume centers for those patients in cohorts C, D, and E who did not undergo nephrectomy.

The investigators acknowledged that the study was limited by the retrospective nature of the database information, and by the absence of data on treatment regimens used at specific facilities, which may explain mechanisms of the effects they observed.

The investigators did not specify a study funding source. Dr. Geynisman reported having no conflicts of interest.

SOURCE: Joshi SS et al. Eur Urol. 2018 Sep;74[3]:387-93.

A proactive side-effect management strategy enabled many patients with high-risk renal cell carcinoma (RCC) to stay on adjuvant sunitinib therapy in a recent clinical trial, researchers report.

With dose interruptions, dose reductions, and supportive medical therapy, adverse events on adjuvant sunitinib were predictable, manageable, and reversible, according to their report on the S-TRAC (Sunitinib as Adjuvant Treatment for High-Risk Renal Cell Carcinoma Following Nephrectomy) trial.

Patients did report reduced health-related quality of life, but with the exception of diarrhea and loss of appetite, those changes were generally not clinically significant, the investigators wrote. The report is in Annals of Oncology.

The safety profile for sunitinib was acceptable in adjuvant RCC treatment in S-TRAC, with no safety signals observed, said Michael Staehler, MD, PhD, department of urology, Ludwig Maximilian University of Munich, and his coauthors.

“It is likely proactive management contributed to preservation of global health status and quality of life, and alleviation of treatment-related symptoms, thereby enabling patients to remain on effective adjuvant therapy,” Dr. Staehler and his coauthors said.

Sunitinib is approved by the Food and Drug Administration for adjuvant treatment of patients at high risk of recurrent RCC after nephrectomy. That was based in part on previously reported results of the phase 3 S-TRAC study, which showed a 24% reduction in risk of a disease-free survival event versus placebo.

For the 306 patients randomized to sunitinib, 71% stayed on treatment for at least 8 months, reaching cycle 6 of therapy, while 56% finished the full year of treatment, Dr. Staehler and his coauthors said in this new report on S-TRAC focused on adverse events and patient-reported outcomes.

The most common adverse events in the sunitinib arm of S-TRAC included diarrhea in 56.9%, versus 21.4% in the placebo arm, palmar-plantar erythrodysesthesia (PPE) in 50.3% versus 10.2% for placebo, and hypertension in 36.9% versus 11.8% for placebo. The frequency of serious adverse events was similar between arms, according to the investigators, at 21.9% for sunitinib and 17.1% for placebo.

Adverse events were the most common reason for dose reduction, cited in 34.6% of cases, and for dose interruption, reported in 46.4%, they said.

Treatment discontinuations due to adverse events occurred in 28.1%, usually because of PPE.

The S-TRAC study investigators used the EORTC QLQ-C30 instrument to evaluate patient experience during treatment.

That evaluation included an analysis of global health status/quality of life score that favored placebo, with a mean difference in the overall means of –4.76. Although statistically significant (P greater than or equal to .0001), the point estimate of the difference was below the commonly accepted threshold that would indicate clinically meaningful deterioration, investigators said.

Similar patterns that were statistically significant but not clinically meaningful were seen for symptoms including fatigue and pain. However, patient-reported scores for diarrhea and loss of appetite did reach the level of a clinically meaningful difference.

But only one patient permanently discontinued sunitinib because of diarrhea, and none permanently discontinued because of loss of appetite, Dr. Staehler and his coauthors noted.

The work was sponsored by Pfizer. Dr. Staehler reported honoraria, consulting fees, and research grants from Pfizer, Bayer, GSK, Roche, BMS, Novartis, Exelixis, and AVEO. Coauthors reported disclosures related to Merck, Sanofi, Astellas, Celldex, Acerta, Janssen, and others.

SOURCE: Staehler M et al. Ann Oncol. 2018 Aug 23. doi: 10.1093/annonc/mdy329.

A proactive side-effect management strategy enabled many patients with high-risk renal cell carcinoma (RCC) to stay on adjuvant sunitinib therapy in a recent clinical trial, researchers report.

With dose interruptions, dose reductions, and supportive medical therapy, adverse events on adjuvant sunitinib were predictable, manageable, and reversible, according to their report on the S-TRAC (Sunitinib as Adjuvant Treatment for High-Risk Renal Cell Carcinoma Following Nephrectomy) trial.

Patients did report reduced health-related quality of life, but with the exception of diarrhea and loss of appetite, those changes were generally not clinically significant, the investigators wrote. The report is in Annals of Oncology.

The safety profile for sunitinib was acceptable in adjuvant RCC treatment in S-TRAC, with no safety signals observed, said Michael Staehler, MD, PhD, department of urology, Ludwig Maximilian University of Munich, and his coauthors.

“It is likely proactive management contributed to preservation of global health status and quality of life, and alleviation of treatment-related symptoms, thereby enabling patients to remain on effective adjuvant therapy,” Dr. Staehler and his coauthors said.

Sunitinib is approved by the Food and Drug Administration for adjuvant treatment of patients at high risk of recurrent RCC after nephrectomy. That was based in part on previously reported results of the phase 3 S-TRAC study, which showed a 24% reduction in risk of a disease-free survival event versus placebo.

For the 306 patients randomized to sunitinib, 71% stayed on treatment for at least 8 months, reaching cycle 6 of therapy, while 56% finished the full year of treatment, Dr. Staehler and his coauthors said in this new report on S-TRAC focused on adverse events and patient-reported outcomes.

The most common adverse events in the sunitinib arm of S-TRAC included diarrhea in 56.9%, versus 21.4% in the placebo arm, palmar-plantar erythrodysesthesia (PPE) in 50.3% versus 10.2% for placebo, and hypertension in 36.9% versus 11.8% for placebo. The frequency of serious adverse events was similar between arms, according to the investigators, at 21.9% for sunitinib and 17.1% for placebo.

Adverse events were the most common reason for dose reduction, cited in 34.6% of cases, and for dose interruption, reported in 46.4%, they said.

Treatment discontinuations due to adverse events occurred in 28.1%, usually because of PPE.

The S-TRAC study investigators used the EORTC QLQ-C30 instrument to evaluate patient experience during treatment.

That evaluation included an analysis of global health status/quality of life score that favored placebo, with a mean difference in the overall means of –4.76. Although statistically significant (P greater than or equal to .0001), the point estimate of the difference was below the commonly accepted threshold that would indicate clinically meaningful deterioration, investigators said.

Similar patterns that were statistically significant but not clinically meaningful were seen for symptoms including fatigue and pain. However, patient-reported scores for diarrhea and loss of appetite did reach the level of a clinically meaningful difference.

But only one patient permanently discontinued sunitinib because of diarrhea, and none permanently discontinued because of loss of appetite, Dr. Staehler and his coauthors noted.

The work was sponsored by Pfizer. Dr. Staehler reported honoraria, consulting fees, and research grants from Pfizer, Bayer, GSK, Roche, BMS, Novartis, Exelixis, and AVEO. Coauthors reported disclosures related to Merck, Sanofi, Astellas, Celldex, Acerta, Janssen, and others.

SOURCE: Staehler M et al. Ann Oncol. 2018 Aug 23. doi: 10.1093/annonc/mdy329.

A proactive side-effect management strategy enabled many patients with high-risk renal cell carcinoma (RCC) to stay on adjuvant sunitinib therapy in a recent clinical trial, researchers report.

With dose interruptions, dose reductions, and supportive medical therapy, adverse events on adjuvant sunitinib were predictable, manageable, and reversible, according to their report on the S-TRAC (Sunitinib as Adjuvant Treatment for High-Risk Renal Cell Carcinoma Following Nephrectomy) trial.

Patients did report reduced health-related quality of life, but with the exception of diarrhea and loss of appetite, those changes were generally not clinically significant, the investigators wrote. The report is in Annals of Oncology.

The safety profile for sunitinib was acceptable in adjuvant RCC treatment in S-TRAC, with no safety signals observed, said Michael Staehler, MD, PhD, department of urology, Ludwig Maximilian University of Munich, and his coauthors.

“It is likely proactive management contributed to preservation of global health status and quality of life, and alleviation of treatment-related symptoms, thereby enabling patients to remain on effective adjuvant therapy,” Dr. Staehler and his coauthors said.

Sunitinib is approved by the Food and Drug Administration for adjuvant treatment of patients at high risk of recurrent RCC after nephrectomy. That was based in part on previously reported results of the phase 3 S-TRAC study, which showed a 24% reduction in risk of a disease-free survival event versus placebo.

For the 306 patients randomized to sunitinib, 71% stayed on treatment for at least 8 months, reaching cycle 6 of therapy, while 56% finished the full year of treatment, Dr. Staehler and his coauthors said in this new report on S-TRAC focused on adverse events and patient-reported outcomes.

The most common adverse events in the sunitinib arm of S-TRAC included diarrhea in 56.9%, versus 21.4% in the placebo arm, palmar-plantar erythrodysesthesia (PPE) in 50.3% versus 10.2% for placebo, and hypertension in 36.9% versus 11.8% for placebo. The frequency of serious adverse events was similar between arms, according to the investigators, at 21.9% for sunitinib and 17.1% for placebo.

Adverse events were the most common reason for dose reduction, cited in 34.6% of cases, and for dose interruption, reported in 46.4%, they said.

Treatment discontinuations due to adverse events occurred in 28.1%, usually because of PPE.

The S-TRAC study investigators used the EORTC QLQ-C30 instrument to evaluate patient experience during treatment.

That evaluation included an analysis of global health status/quality of life score that favored placebo, with a mean difference in the overall means of –4.76. Although statistically significant (P greater than or equal to .0001), the point estimate of the difference was below the commonly accepted threshold that would indicate clinically meaningful deterioration, investigators said.

Similar patterns that were statistically significant but not clinically meaningful were seen for symptoms including fatigue and pain. However, patient-reported scores for diarrhea and loss of appetite did reach the level of a clinically meaningful difference.

But only one patient permanently discontinued sunitinib because of diarrhea, and none permanently discontinued because of loss of appetite, Dr. Staehler and his coauthors noted.

The work was sponsored by Pfizer. Dr. Staehler reported honoraria, consulting fees, and research grants from Pfizer, Bayer, GSK, Roche, BMS, Novartis, Exelixis, and AVEO. Coauthors reported disclosures related to Merck, Sanofi, Astellas, Celldex, Acerta, Janssen, and others.

SOURCE: Staehler M et al. Ann Oncol. 2018 Aug 23. doi: 10.1093/annonc/mdy329.

Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic, clear cell renal cell carcinoma (RCC), according to results of the randomized, phase 3 CARMENA trial.

Overall survival was not inferior in the sunitinib arm of the trial, which comprised 450 patients who were suitable candidates for nephrectomy and had MSKCC intermediate or poor risk disease.

These findings contrast with those of previous retrospective studies suggesting patients undergoing nephrectomy who were treated with targeted therapies had an overall survival benefit, according to Bernard Escudier, MD, of Gustave Roussy Institute, Villejuif, France, and his coauthors.

“Given the many approved options for systemic targeted therapy that are now available, the reassessment of the role of surgery in disease management is important,” Dr. Escudier and his colleagues noted. The report is in the New England Journal of Medicine.

The CARMENA trial enrolled 450 out of a planned 576 patients in 79 European centers between September 2009 and September 2017. A total of 226 were randomized to sunitinib alone and 224 to nephrectomy and sunitinib.

With a median follow-up of 50.9 months and 326 deaths, the hazard ratio for death was 0.89 (95% confidence interval, 0.71-1.10). The upper boundary of the 95% CI for noninferiority was 1.20, according to the report.

Median overall survival was 18.4 months for the sunitinib alone arm, and 13.9 months for the nephrectomy-plus-sunitinib arm. While the study was statistically underpowered because of incomplete enrollment, that “trend in longer overall survival” supports the findings favoring sunitinib alone in this noninferiority trial, the authors noted.

Safety results were as expected based on previous trial results, according to the investigators. Grade 3/4 adverse events occurred in 91 patients (42.7%) in the sunitinib group, and 61 (32.8%) in the nephrectomy-sunitinib group, they reported. Nine patients in the sunitinib group had grade 3/4 renal or urinary tract disorders, versus 1 in the nephrectomy-sunitinib group (P = .051).

These findings confirm current clinical practice guidelines on the use of systemic targeted therapy in patients with poor-risk metastatic RCC, according to the authors.

However, targeted therapy in this setting has evolved considerably since the CARMENA trial was designed.

Sunitinib remains one of the most commonly used treatments in patients with good or intermediate prognosis metastatic RCC; however, recent randomized trials show the superiority of the c-MET inhibitor cabozantinib and the immune checkpoint inhibitor combination of nivolumab plus ipilimumab over sunitinib.

Those newer agents will likely become initial treatment options for intermediate- and poor-risk groups, according to the authors.

Both cabozantinib and nivolumab plus ipilimumab are listed as first-line treatment options for intermediate- and poor-risk patients in the most recent clinical practice guidelines from the National Comprehensive Cancer Network.

Nephrectomy may have a role for symptom control in some patients with metastatic RCC, based on results of previous retrospective studies suggesting benefit.

“There is no ‘one size fits all’ approach,” Dr. Escudier and his coauthors wrote. “The multimodal approach of individualized treatment provides appropriate management of metastatic renal-cell carcinoma.”

Dr. Escudier reported personal fees from Bristol-Myers Squibb, EUSA Pharma, Ipsen, Novartis, Pfizer, and Roche outside the submitted work. Coauthors reported disclosures with Bayer, MSD, Janssen, Astellas, Bouchara, Ferring, and others.

SOURCE: Méjean A et al. N Engl J Med. 2018 Aug 2. doi: 10.1056/NEJMoa1803675.

Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic, clear cell renal cell carcinoma (RCC), according to results of the randomized, phase 3 CARMENA trial.

Overall survival was not inferior in the sunitinib arm of the trial, which comprised 450 patients who were suitable candidates for nephrectomy and had MSKCC intermediate or poor risk disease.

These findings contrast with those of previous retrospective studies suggesting patients undergoing nephrectomy who were treated with targeted therapies had an overall survival benefit, according to Bernard Escudier, MD, of Gustave Roussy Institute, Villejuif, France, and his coauthors.

“Given the many approved options for systemic targeted therapy that are now available, the reassessment of the role of surgery in disease management is important,” Dr. Escudier and his colleagues noted. The report is in the New England Journal of Medicine.

The CARMENA trial enrolled 450 out of a planned 576 patients in 79 European centers between September 2009 and September 2017. A total of 226 were randomized to sunitinib alone and 224 to nephrectomy and sunitinib.

With a median follow-up of 50.9 months and 326 deaths, the hazard ratio for death was 0.89 (95% confidence interval, 0.71-1.10). The upper boundary of the 95% CI for noninferiority was 1.20, according to the report.

Median overall survival was 18.4 months for the sunitinib alone arm, and 13.9 months for the nephrectomy-plus-sunitinib arm. While the study was statistically underpowered because of incomplete enrollment, that “trend in longer overall survival” supports the findings favoring sunitinib alone in this noninferiority trial, the authors noted.

Safety results were as expected based on previous trial results, according to the investigators. Grade 3/4 adverse events occurred in 91 patients (42.7%) in the sunitinib group, and 61 (32.8%) in the nephrectomy-sunitinib group, they reported. Nine patients in the sunitinib group had grade 3/4 renal or urinary tract disorders, versus 1 in the nephrectomy-sunitinib group (P = .051).

These findings confirm current clinical practice guidelines on the use of systemic targeted therapy in patients with poor-risk metastatic RCC, according to the authors.

However, targeted therapy in this setting has evolved considerably since the CARMENA trial was designed.

Sunitinib remains one of the most commonly used treatments in patients with good or intermediate prognosis metastatic RCC; however, recent randomized trials show the superiority of the c-MET inhibitor cabozantinib and the immune checkpoint inhibitor combination of nivolumab plus ipilimumab over sunitinib.

Those newer agents will likely become initial treatment options for intermediate- and poor-risk groups, according to the authors.

Both cabozantinib and nivolumab plus ipilimumab are listed as first-line treatment options for intermediate- and poor-risk patients in the most recent clinical practice guidelines from the National Comprehensive Cancer Network.

Nephrectomy may have a role for symptom control in some patients with metastatic RCC, based on results of previous retrospective studies suggesting benefit.

“There is no ‘one size fits all’ approach,” Dr. Escudier and his coauthors wrote. “The multimodal approach of individualized treatment provides appropriate management of metastatic renal-cell carcinoma.”

Dr. Escudier reported personal fees from Bristol-Myers Squibb, EUSA Pharma, Ipsen, Novartis, Pfizer, and Roche outside the submitted work. Coauthors reported disclosures with Bayer, MSD, Janssen, Astellas, Bouchara, Ferring, and others.

SOURCE: Méjean A et al. N Engl J Med. 2018 Aug 2. doi: 10.1056/NEJMoa1803675.

Sunitinib alone was not inferior to nephrectomy followed by sunitinib in patients with metastatic, clear cell renal cell carcinoma (RCC), according to results of the randomized, phase 3 CARMENA trial.

Overall survival was not inferior in the sunitinib arm of the trial, which comprised 450 patients who were suitable candidates for nephrectomy and had MSKCC intermediate or poor risk disease.

These findings contrast with those of previous retrospective studies suggesting patients undergoing nephrectomy who were treated with targeted therapies had an overall survival benefit, according to Bernard Escudier, MD, of Gustave Roussy Institute, Villejuif, France, and his coauthors.

“Given the many approved options for systemic targeted therapy that are now available, the reassessment of the role of surgery in disease management is important,” Dr. Escudier and his colleagues noted. The report is in the New England Journal of Medicine.

The CARMENA trial enrolled 450 out of a planned 576 patients in 79 European centers between September 2009 and September 2017. A total of 226 were randomized to sunitinib alone and 224 to nephrectomy and sunitinib.

With a median follow-up of 50.9 months and 326 deaths, the hazard ratio for death was 0.89 (95% confidence interval, 0.71-1.10). The upper boundary of the 95% CI for noninferiority was 1.20, according to the report.

Median overall survival was 18.4 months for the sunitinib alone arm, and 13.9 months for the nephrectomy-plus-sunitinib arm. While the study was statistically underpowered because of incomplete enrollment, that “trend in longer overall survival” supports the findings favoring sunitinib alone in this noninferiority trial, the authors noted.

Safety results were as expected based on previous trial results, according to the investigators. Grade 3/4 adverse events occurred in 91 patients (42.7%) in the sunitinib group, and 61 (32.8%) in the nephrectomy-sunitinib group, they reported. Nine patients in the sunitinib group had grade 3/4 renal or urinary tract disorders, versus 1 in the nephrectomy-sunitinib group (P = .051).

These findings confirm current clinical practice guidelines on the use of systemic targeted therapy in patients with poor-risk metastatic RCC, according to the authors.

However, targeted therapy in this setting has evolved considerably since the CARMENA trial was designed.

Sunitinib remains one of the most commonly used treatments in patients with good or intermediate prognosis metastatic RCC; however, recent randomized trials show the superiority of the c-MET inhibitor cabozantinib and the immune checkpoint inhibitor combination of nivolumab plus ipilimumab over sunitinib.

Those newer agents will likely become initial treatment options for intermediate- and poor-risk groups, according to the authors.

Both cabozantinib and nivolumab plus ipilimumab are listed as first-line treatment options for intermediate- and poor-risk patients in the most recent clinical practice guidelines from the National Comprehensive Cancer Network.

Nephrectomy may have a role for symptom control in some patients with metastatic RCC, based on results of previous retrospective studies suggesting benefit.

“There is no ‘one size fits all’ approach,” Dr. Escudier and his coauthors wrote. “The multimodal approach of individualized treatment provides appropriate management of metastatic renal-cell carcinoma.”

Dr. Escudier reported personal fees from Bristol-Myers Squibb, EUSA Pharma, Ipsen, Novartis, Pfizer, and Roche outside the submitted work. Coauthors reported disclosures with Bayer, MSD, Janssen, Astellas, Bouchara, Ferring, and others.

SOURCE: Méjean A et al. N Engl J Med. 2018 Aug 2. doi: 10.1056/NEJMoa1803675.

Although the two major subtypes of papillary renal cell carcinoma (PRCC) differ on a variety of measures of aggressiveness, subtype is not independently prognostic, according to a retrospective cohort study conducted by the German Network of Kidney Cancer.

Investigators led by Iris Polifka, an intern at the Institute of Pathology at the University Hospital Erlangen (Germany), characterized 376 renal tumors initially diagnosed as PRCC. They reviewed histologic features and performed immunohistochemical staining for a range of markers.

Main study results, which were reported in Human Pathology, showed that 65.4% of the tumors were PRCC subtype 1 and 34.6% were PRCC subtype 2. The former more commonly had foamy macrophages and expressed cytokeratin 7, whereas the latter more commonly had abundant cytoplasm, expressed E-cadherin and p53, and had high MIB1 expression (staining of more than 15% of cells), which indicated a high proliferation rate (P less than .05 for each). The latter also had higher stage and higher grade.

Univariate analysis in the entire study cohort showed that racemase expression and cytokeratin 7 expression were favorable prognostic factors for overall survival, whereas presence of abundant cytoplasm and psammoma bodies, high MIB1 expression, and PRCC subtype 2 were unfavorable prognostic factors.

However, in multivariate analysis, only four factors were independent predictors of death: high tumor MIB1 expression (hazard ratio, 2.465; P = .033), higher T stage (P = .036), metastases (HR, 4.334; P = .011), and age older than the median of 63 years at surgery (HR, 2.384; P = .005). Notably, tumor subtype did not independently predict this outcome.

“[T]he better [overall survival] in PRCC1 is mainly a reflection of its encapsulated nature associated with lower TNM stage … while enhanced proliferation might add to the aggressive nature of high grade and high stage tumors independently from PRCC subtype,” the investigators propose.

“PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2,” they conclude.

The investigators disclosed that they had no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Polifka I et al. Hum Pathol. 2018 Aug 16. doi: 10.1016/j.humpath.2018.08.006.

Although the two major subtypes of papillary renal cell carcinoma (PRCC) differ on a variety of measures of aggressiveness, subtype is not independently prognostic, according to a retrospective cohort study conducted by the German Network of Kidney Cancer.

Investigators led by Iris Polifka, an intern at the Institute of Pathology at the University Hospital Erlangen (Germany), characterized 376 renal tumors initially diagnosed as PRCC. They reviewed histologic features and performed immunohistochemical staining for a range of markers.

Main study results, which were reported in Human Pathology, showed that 65.4% of the tumors were PRCC subtype 1 and 34.6% were PRCC subtype 2. The former more commonly had foamy macrophages and expressed cytokeratin 7, whereas the latter more commonly had abundant cytoplasm, expressed E-cadherin and p53, and had high MIB1 expression (staining of more than 15% of cells), which indicated a high proliferation rate (P less than .05 for each). The latter also had higher stage and higher grade.

Univariate analysis in the entire study cohort showed that racemase expression and cytokeratin 7 expression were favorable prognostic factors for overall survival, whereas presence of abundant cytoplasm and psammoma bodies, high MIB1 expression, and PRCC subtype 2 were unfavorable prognostic factors.

However, in multivariate analysis, only four factors were independent predictors of death: high tumor MIB1 expression (hazard ratio, 2.465; P = .033), higher T stage (P = .036), metastases (HR, 4.334; P = .011), and age older than the median of 63 years at surgery (HR, 2.384; P = .005). Notably, tumor subtype did not independently predict this outcome.

“[T]he better [overall survival] in PRCC1 is mainly a reflection of its encapsulated nature associated with lower TNM stage … while enhanced proliferation might add to the aggressive nature of high grade and high stage tumors independently from PRCC subtype,” the investigators propose.

“PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2,” they conclude.

The investigators disclosed that they had no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Polifka I et al. Hum Pathol. 2018 Aug 16. doi: 10.1016/j.humpath.2018.08.006.

Although the two major subtypes of papillary renal cell carcinoma (PRCC) differ on a variety of measures of aggressiveness, subtype is not independently prognostic, according to a retrospective cohort study conducted by the German Network of Kidney Cancer.

Investigators led by Iris Polifka, an intern at the Institute of Pathology at the University Hospital Erlangen (Germany), characterized 376 renal tumors initially diagnosed as PRCC. They reviewed histologic features and performed immunohistochemical staining for a range of markers.

Main study results, which were reported in Human Pathology, showed that 65.4% of the tumors were PRCC subtype 1 and 34.6% were PRCC subtype 2. The former more commonly had foamy macrophages and expressed cytokeratin 7, whereas the latter more commonly had abundant cytoplasm, expressed E-cadherin and p53, and had high MIB1 expression (staining of more than 15% of cells), which indicated a high proliferation rate (P less than .05 for each). The latter also had higher stage and higher grade.

Univariate analysis in the entire study cohort showed that racemase expression and cytokeratin 7 expression were favorable prognostic factors for overall survival, whereas presence of abundant cytoplasm and psammoma bodies, high MIB1 expression, and PRCC subtype 2 were unfavorable prognostic factors.

However, in multivariate analysis, only four factors were independent predictors of death: high tumor MIB1 expression (hazard ratio, 2.465; P = .033), higher T stage (P = .036), metastases (HR, 4.334; P = .011), and age older than the median of 63 years at surgery (HR, 2.384; P = .005). Notably, tumor subtype did not independently predict this outcome.

“[T]he better [overall survival] in PRCC1 is mainly a reflection of its encapsulated nature associated with lower TNM stage … while enhanced proliferation might add to the aggressive nature of high grade and high stage tumors independently from PRCC subtype,” the investigators propose.

“PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2,” they conclude.

The investigators disclosed that they had no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Polifka I et al. Hum Pathol. 2018 Aug 16. doi: 10.1016/j.humpath.2018.08.006.

Hypofractionated radiation therapy (RT) may be a more viable treatment option for oligometastatic renal cell carcinoma (RCC) than is generally recognized, a recent literature review has suggested.

Advances in stereotactic RT offer “new opportunities in RCC management” with limited toxicity, reported Francesca De Felice, PhD, of Sapienza University in Rome and her coauthor. The authors suggested that future studies investigate RT in combination with immunotherapy.

“Due to the assumption that RCC is a radioresistant tumor,” the authors wrote in Critical Reviews in Oncology/Hematology, “RT has long been considered a futile approach to manage primary disease” and is predominantly used for treatment of distant metastases with palliative intent. “This review provides highlights in current RCC strategies to potentially suggest a more tailored treatment approach in clinical daily practice.”

The investigators concluded that hypofractionated RT (greater than 3 Gy/fraction) deserves more serious consideration. “It has enormous advantages,” the authors wrote, “assuring ablative doses to the target meanwhile preserving surrounding normal tissues. Using stereotactic technique, surprising high local control rates have been achieved in several tumors (such as lung, liver, and bone), in both primary and oligometastatic setting[s].”

In five studies, single-dose RT (ranging from 8 to 24 Gy) was used to treat patients with RCC and extracranial metastases. Of the patients in these studies, 89% of them achieved local control, median overall survival (OS) ranged from 11.7 months to 21 months, and severe RT-related toxicity occurred 0%-4% of the time.

“Although [there is a] high level of data heterogeneity,” the authors wrote, “this systematic review suggested that stereotactic RT is associated with excellent local control rates and low toxicity incidence. Thus, if feasible, stereotactic RT represents an effective and safe approach to treat RCC metastasis.”

The authors cautioned that “the optimal high dose required for local tumor control has not yet been defined.”

The authors suggested that, in the future, immunotherapy in combination with RT may “produce synergistic effects, resulting in better response rate and duration, given the known immune-modulated abscopal effect of RT.” First, questions about treatment sequencing, dosing, and patient selection would need to be answered. “Further research should be aimed at these clinical needs in order to achieve the maximum benefit to RCC patient[s].”

This study did not receive specific funding.

SOURCE: Felice F et al. Crit Rev Oncol Hematol. 2018 Aug 1. doi: 10.1016/j.critrevonc.2018.06.002

Hypofractionated radiation therapy (RT) may be a more viable treatment option for oligometastatic renal cell carcinoma (RCC) than is generally recognized, a recent literature review has suggested.

Advances in stereotactic RT offer “new opportunities in RCC management” with limited toxicity, reported Francesca De Felice, PhD, of Sapienza University in Rome and her coauthor. The authors suggested that future studies investigate RT in combination with immunotherapy.

“Due to the assumption that RCC is a radioresistant tumor,” the authors wrote in Critical Reviews in Oncology/Hematology, “RT has long been considered a futile approach to manage primary disease” and is predominantly used for treatment of distant metastases with palliative intent. “This review provides highlights in current RCC strategies to potentially suggest a more tailored treatment approach in clinical daily practice.”

The investigators concluded that hypofractionated RT (greater than 3 Gy/fraction) deserves more serious consideration. “It has enormous advantages,” the authors wrote, “assuring ablative doses to the target meanwhile preserving surrounding normal tissues. Using stereotactic technique, surprising high local control rates have been achieved in several tumors (such as lung, liver, and bone), in both primary and oligometastatic setting[s].”

In five studies, single-dose RT (ranging from 8 to 24 Gy) was used to treat patients with RCC and extracranial metastases. Of the patients in these studies, 89% of them achieved local control, median overall survival (OS) ranged from 11.7 months to 21 months, and severe RT-related toxicity occurred 0%-4% of the time.

“Although [there is a] high level of data heterogeneity,” the authors wrote, “this systematic review suggested that stereotactic RT is associated with excellent local control rates and low toxicity incidence. Thus, if feasible, stereotactic RT represents an effective and safe approach to treat RCC metastasis.”

The authors cautioned that “the optimal high dose required for local tumor control has not yet been defined.”

The authors suggested that, in the future, immunotherapy in combination with RT may “produce synergistic effects, resulting in better response rate and duration, given the known immune-modulated abscopal effect of RT.” First, questions about treatment sequencing, dosing, and patient selection would need to be answered. “Further research should be aimed at these clinical needs in order to achieve the maximum benefit to RCC patient[s].”

This study did not receive specific funding.

SOURCE: Felice F et al. Crit Rev Oncol Hematol. 2018 Aug 1. doi: 10.1016/j.critrevonc.2018.06.002

Hypofractionated radiation therapy (RT) may be a more viable treatment option for oligometastatic renal cell carcinoma (RCC) than is generally recognized, a recent literature review has suggested.

Advances in stereotactic RT offer “new opportunities in RCC management” with limited toxicity, reported Francesca De Felice, PhD, of Sapienza University in Rome and her coauthor. The authors suggested that future studies investigate RT in combination with immunotherapy.

“Due to the assumption that RCC is a radioresistant tumor,” the authors wrote in Critical Reviews in Oncology/Hematology, “RT has long been considered a futile approach to manage primary disease” and is predominantly used for treatment of distant metastases with palliative intent. “This review provides highlights in current RCC strategies to potentially suggest a more tailored treatment approach in clinical daily practice.”

The investigators concluded that hypofractionated RT (greater than 3 Gy/fraction) deserves more serious consideration. “It has enormous advantages,” the authors wrote, “assuring ablative doses to the target meanwhile preserving surrounding normal tissues. Using stereotactic technique, surprising high local control rates have been achieved in several tumors (such as lung, liver, and bone), in both primary and oligometastatic setting[s].”

In five studies, single-dose RT (ranging from 8 to 24 Gy) was used to treat patients with RCC and extracranial metastases. Of the patients in these studies, 89% of them achieved local control, median overall survival (OS) ranged from 11.7 months to 21 months, and severe RT-related toxicity occurred 0%-4% of the time.

“Although [there is a] high level of data heterogeneity,” the authors wrote, “this systematic review suggested that stereotactic RT is associated with excellent local control rates and low toxicity incidence. Thus, if feasible, stereotactic RT represents an effective and safe approach to treat RCC metastasis.”

The authors cautioned that “the optimal high dose required for local tumor control has not yet been defined.”

The authors suggested that, in the future, immunotherapy in combination with RT may “produce synergistic effects, resulting in better response rate and duration, given the known immune-modulated abscopal effect of RT.” First, questions about treatment sequencing, dosing, and patient selection would need to be answered. “Further research should be aimed at these clinical needs in order to achieve the maximum benefit to RCC patient[s].”

This study did not receive specific funding.

SOURCE: Felice F et al. Crit Rev Oncol Hematol. 2018 Aug 1. doi: 10.1016/j.critrevonc.2018.06.002

The incidence of metastatic renal cell carcinoma (RCC) continues to rise, according to a recent study. In turn, skeletal-related events are also becoming more common.

Many patients with metastatic disease have skeletal involvement, so knowledge of skeletal-related events (SREs) is more important than ever, reported Masood Umer, MD, of Aga Khan University Hospital in Karachi, Pakistan, and his coauthors. SREs include nerve compression, hypercalcemia, impending fractures, and pathological fractures, any one of which may require medical or surgical intervention.

Beyond SREs, “bone metastases in RCC [have a] negative impact on progression-free survival and overall survival of patients treated with systemic therapies,” the authors wrote in Annals of Medicine and Surgery.

The authors conducted a literature review of skeletal metastasis in RCC, which included 947 patients, assessing incidence and discussing appropriate medical and surgical interventions.

A total of 26.7% of patients with RCC also had skeletal metastasis. The most common sites of metastasis were the proximal femur, pelvis, and spine. It was estimated that 85% of patients with metastatic RCC may experience SREs and related complications, with an average of more than two events per individual.

A multimodal approach is required, potentially involving surgical and medical interventions. For isolated bony metastases and fractures, surgery is often beneficial. Denosumab is the leading medical treatment; compared with zoledronic acid, denosumab prolongs time to first SRE by a median of approximately 8 months and reduces risk of first SRE by almost 20%. Risks of osteonecrosis are similar between agents.

The authors noted that research concerning the impact of targeted therapies on rates of bone metastasis and SREs is limited by patient exclusions in clinical trials. Granted, these agents have likely made for better outcomes.

“Advancement in targeted therapy in recent decades [has] made some improvement in treatment of SREs and has helped in improving patent’s quality of life, but still we are in need of further improvement in treatment modalities,” they concluded

This study did not receive specific funding.

SOURCE: Umer M et al. Ann Med Surg. 2018 Jan 21. doi: 10.1016/j.amsu.2018.01.002.

The incidence of metastatic renal cell carcinoma (RCC) continues to rise, according to a recent study. In turn, skeletal-related events are also becoming more common.

Many patients with metastatic disease have skeletal involvement, so knowledge of skeletal-related events (SREs) is more important than ever, reported Masood Umer, MD, of Aga Khan University Hospital in Karachi, Pakistan, and his coauthors. SREs include nerve compression, hypercalcemia, impending fractures, and pathological fractures, any one of which may require medical or surgical intervention.

Beyond SREs, “bone metastases in RCC [have a] negative impact on progression-free survival and overall survival of patients treated with systemic therapies,” the authors wrote in Annals of Medicine and Surgery.

The authors conducted a literature review of skeletal metastasis in RCC, which included 947 patients, assessing incidence and discussing appropriate medical and surgical interventions.

A total of 26.7% of patients with RCC also had skeletal metastasis. The most common sites of metastasis were the proximal femur, pelvis, and spine. It was estimated that 85% of patients with metastatic RCC may experience SREs and related complications, with an average of more than two events per individual.

A multimodal approach is required, potentially involving surgical and medical interventions. For isolated bony metastases and fractures, surgery is often beneficial. Denosumab is the leading medical treatment; compared with zoledronic acid, denosumab prolongs time to first SRE by a median of approximately 8 months and reduces risk of first SRE by almost 20%. Risks of osteonecrosis are similar between agents.

The authors noted that research concerning the impact of targeted therapies on rates of bone metastasis and SREs is limited by patient exclusions in clinical trials. Granted, these agents have likely made for better outcomes.

“Advancement in targeted therapy in recent decades [has] made some improvement in treatment of SREs and has helped in improving patent’s quality of life, but still we are in need of further improvement in treatment modalities,” they concluded

This study did not receive specific funding.

SOURCE: Umer M et al. Ann Med Surg. 2018 Jan 21. doi: 10.1016/j.amsu.2018.01.002.

The incidence of metastatic renal cell carcinoma (RCC) continues to rise, according to a recent study. In turn, skeletal-related events are also becoming more common.

Many patients with metastatic disease have skeletal involvement, so knowledge of skeletal-related events (SREs) is more important than ever, reported Masood Umer, MD, of Aga Khan University Hospital in Karachi, Pakistan, and his coauthors. SREs include nerve compression, hypercalcemia, impending fractures, and pathological fractures, any one of which may require medical or surgical intervention.

Beyond SREs, “bone metastases in RCC [have a] negative impact on progression-free survival and overall survival of patients treated with systemic therapies,” the authors wrote in Annals of Medicine and Surgery.

The authors conducted a literature review of skeletal metastasis in RCC, which included 947 patients, assessing incidence and discussing appropriate medical and surgical interventions.

A total of 26.7% of patients with RCC also had skeletal metastasis. The most common sites of metastasis were the proximal femur, pelvis, and spine. It was estimated that 85% of patients with metastatic RCC may experience SREs and related complications, with an average of more than two events per individual.

A multimodal approach is required, potentially involving surgical and medical interventions. For isolated bony metastases and fractures, surgery is often beneficial. Denosumab is the leading medical treatment; compared with zoledronic acid, denosumab prolongs time to first SRE by a median of approximately 8 months and reduces risk of first SRE by almost 20%. Risks of osteonecrosis are similar between agents.

The authors noted that research concerning the impact of targeted therapies on rates of bone metastasis and SREs is limited by patient exclusions in clinical trials. Granted, these agents have likely made for better outcomes.

“Advancement in targeted therapy in recent decades [has] made some improvement in treatment of SREs and has helped in improving patent’s quality of life, but still we are in need of further improvement in treatment modalities,” they concluded

This study did not receive specific funding.

SOURCE: Umer M et al. Ann Med Surg. 2018 Jan 21. doi: 10.1016/j.amsu.2018.01.002.

Expression of leptin could help differentiate benign renal oncocytomas from chromophobe renal cell carcinoma (RCC), results of a recent pathology study suggest.

Renal oncocytomas had significantly increased nuclear expression of leptin, compared with the eosinophilic subtype of chromophobe RCC, according to the study.

If translated into clinical urology and pathology practice, quantification of leptin expression could help in the difficult task of differentiating between these renal lesions, according to the investigators, led by Glenda Gobe, PhD, of the Kidney Disease Research Group at the University of Queensland in Brisbane, Australia.

“This may have a major clinical impact in reducing unnecessary intervention and treatment-related harm,” Dr. Gobe and her colleagues reported in Pathology.

They obtained archived paraffin blocks from human renal tumor tissue obtained between 2009 and 2014. Paraffin sections were immunostained for leptin and leptin receptors.

The investigators evaluated 30 chromophobe RCC specimens – 15 eosinophilic and 15 noneosinophilic variants – and 15 renal oncocytomas. They also included 30 clear cell RCCs, the most common histological subtype of RCC, to verify immunohistochemistry (IHC) staining patterns.

Results showed that both leptin and leptin receptor IHC was significantly increased in tumor versus in matched, noncancerous kidney tissue.

Expression of both leptin and leptin receptor was highest for renal oncocytomas versus both the chromophobe and clear cell RCCs. On closer scrutiny, the investigators said, nuclear expression of leptin in renal oncocytomas had a significantly higher intensity versus chromophobe RCC.

“This important finding could prove to be helpful in the distinction between chromophobe RCC and renal oncocytoma,” Dr. Gobe and her coauthors wrote in their report.

In a subgroup analysis, they found a significantly increased nuclear leptin intensity for the renal oncocytomas as compared to the eosinophilic variants of chromophobe RCC (P = .016 by Dunn’s multiple comparisons test).

By contrast, testing did not reveal a significant difference for renal oncocytomas versus noneosinophilic chromophobe RCC (P = .0939) or versus clear cell RCC (P greater than .999).

Leptin, secreted by adipose cells that help regulate energy balance through inhibition of hunger, may play a role in carcinogenesis, according to investigators. Studies to date have shown that the hormone may impact carcinogenesis through cell proliferation, inhibition of apoptosis, and other potential mechanisms.

Applying this biomarker in clinical practice could more reliably characterize renal lesions with no or limited malignant potential, according to the investigators.

“The distinction of renal oncocytoma from chromophobe RCC will dictate different management pathways, as renal oncocytoma is benign while chromophobe RCC is a malignant subtype which will require further surveillance,” Dr. Gobe and her coinvestigators wrote.

The University of Malaya, Kuala Lumpur, Malaysia, funded the study. Dr. Gobe and her coauthors stated that they had no conflicts of interest.

SOURCE: Gobe G et al. Pathology. 2018 Aug;50(5):504-10.

Expression of leptin could help differentiate benign renal oncocytomas from chromophobe renal cell carcinoma (RCC), results of a recent pathology study suggest.

Renal oncocytomas had significantly increased nuclear expression of leptin, compared with the eosinophilic subtype of chromophobe RCC, according to the study.

If translated into clinical urology and pathology practice, quantification of leptin expression could help in the difficult task of differentiating between these renal lesions, according to the investigators, led by Glenda Gobe, PhD, of the Kidney Disease Research Group at the University of Queensland in Brisbane, Australia.

“This may have a major clinical impact in reducing unnecessary intervention and treatment-related harm,” Dr. Gobe and her colleagues reported in Pathology.

They obtained archived paraffin blocks from human renal tumor tissue obtained between 2009 and 2014. Paraffin sections were immunostained for leptin and leptin receptors.

The investigators evaluated 30 chromophobe RCC specimens – 15 eosinophilic and 15 noneosinophilic variants – and 15 renal oncocytomas. They also included 30 clear cell RCCs, the most common histological subtype of RCC, to verify immunohistochemistry (IHC) staining patterns.

Results showed that both leptin and leptin receptor IHC was significantly increased in tumor versus in matched, noncancerous kidney tissue.

Expression of both leptin and leptin receptor was highest for renal oncocytomas versus both the chromophobe and clear cell RCCs. On closer scrutiny, the investigators said, nuclear expression of leptin in renal oncocytomas had a significantly higher intensity versus chromophobe RCC.

“This important finding could prove to be helpful in the distinction between chromophobe RCC and renal oncocytoma,” Dr. Gobe and her coauthors wrote in their report.

In a subgroup analysis, they found a significantly increased nuclear leptin intensity for the renal oncocytomas as compared to the eosinophilic variants of chromophobe RCC (P = .016 by Dunn’s multiple comparisons test).

By contrast, testing did not reveal a significant difference for renal oncocytomas versus noneosinophilic chromophobe RCC (P = .0939) or versus clear cell RCC (P greater than .999).

Leptin, secreted by adipose cells that help regulate energy balance through inhibition of hunger, may play a role in carcinogenesis, according to investigators. Studies to date have shown that the hormone may impact carcinogenesis through cell proliferation, inhibition of apoptosis, and other potential mechanisms.

Applying this biomarker in clinical practice could more reliably characterize renal lesions with no or limited malignant potential, according to the investigators.

“The distinction of renal oncocytoma from chromophobe RCC will dictate different management pathways, as renal oncocytoma is benign while chromophobe RCC is a malignant subtype which will require further surveillance,” Dr. Gobe and her coinvestigators wrote.

The University of Malaya, Kuala Lumpur, Malaysia, funded the study. Dr. Gobe and her coauthors stated that they had no conflicts of interest.

SOURCE: Gobe G et al. Pathology. 2018 Aug;50(5):504-10.

Expression of leptin could help differentiate benign renal oncocytomas from chromophobe renal cell carcinoma (RCC), results of a recent pathology study suggest.

Renal oncocytomas had significantly increased nuclear expression of leptin, compared with the eosinophilic subtype of chromophobe RCC, according to the study.

If translated into clinical urology and pathology practice, quantification of leptin expression could help in the difficult task of differentiating between these renal lesions, according to the investigators, led by Glenda Gobe, PhD, of the Kidney Disease Research Group at the University of Queensland in Brisbane, Australia.

“This may have a major clinical impact in reducing unnecessary intervention and treatment-related harm,” Dr. Gobe and her colleagues reported in Pathology.

They obtained archived paraffin blocks from human renal tumor tissue obtained between 2009 and 2014. Paraffin sections were immunostained for leptin and leptin receptors.

The investigators evaluated 30 chromophobe RCC specimens – 15 eosinophilic and 15 noneosinophilic variants – and 15 renal oncocytomas. They also included 30 clear cell RCCs, the most common histological subtype of RCC, to verify immunohistochemistry (IHC) staining patterns.

Results showed that both leptin and leptin receptor IHC was significantly increased in tumor versus in matched, noncancerous kidney tissue.

Expression of both leptin and leptin receptor was highest for renal oncocytomas versus both the chromophobe and clear cell RCCs. On closer scrutiny, the investigators said, nuclear expression of leptin in renal oncocytomas had a significantly higher intensity versus chromophobe RCC.

“This important finding could prove to be helpful in the distinction between chromophobe RCC and renal oncocytoma,” Dr. Gobe and her coauthors wrote in their report.

In a subgroup analysis, they found a significantly increased nuclear leptin intensity for the renal oncocytomas as compared to the eosinophilic variants of chromophobe RCC (P = .016 by Dunn’s multiple comparisons test).

By contrast, testing did not reveal a significant difference for renal oncocytomas versus noneosinophilic chromophobe RCC (P = .0939) or versus clear cell RCC (P greater than .999).

Leptin, secreted by adipose cells that help regulate energy balance through inhibition of hunger, may play a role in carcinogenesis, according to investigators. Studies to date have shown that the hormone may impact carcinogenesis through cell proliferation, inhibition of apoptosis, and other potential mechanisms.

Applying this biomarker in clinical practice could more reliably characterize renal lesions with no or limited malignant potential, according to the investigators.

“The distinction of renal oncocytoma from chromophobe RCC will dictate different management pathways, as renal oncocytoma is benign while chromophobe RCC is a malignant subtype which will require further surveillance,” Dr. Gobe and her coinvestigators wrote.

The University of Malaya, Kuala Lumpur, Malaysia, funded the study. Dr. Gobe and her coauthors stated that they had no conflicts of interest.

SOURCE: Gobe G et al. Pathology. 2018 Aug;50(5):504-10.

What appears at first glance to be a renal vascular tumor may in fact be a rare type of renal cell carcinoma (RCC), authors of a case study cautioned.

A tumor recovered from a 62-year old woman who underwent a partial nephrectomy for an incidentally discovered asymptomatic left renal mass contained arborizing vessels that mimicked hemangioma. Immunohistochemical staining of the tumor highlighted the vascular component but masked epithelial cells, a situation that, in the absence of other clues, might cause a misdiagnosis, reported Kanika Taneja, MD, from the Henry Ford Cancer Institute in Detroit, and her colleagues.

The authors were tipped off to an unusual presentation, however, by mixed signals from immunohistochemical staining, leading them to an admittedly fuzzy diagnosis of “unclassified hemangioma-like RCC.”

“This case highlights that renal cell carcinoma must be strongly considered in the differential diagnosis of renal vascular tumors, and broadens the spectrum of histologies that may mimic hemangioma,” they wrote in Human Pathology.

Although there are a few recent reports in the medical literature of clear cell RCC tumors that mimic hemangiomas, the authors noted that, “to our knowledge, non–clear cell hemangioma-like renal cell carcinoma has not been previously reported.”

The tumor in question was removed from the patient with clear surgical margins during a partial nephrectomy.

Gross examination showed a 2.6 by 2.5 by 2.5 cm, well-circumscribed, tan-brown hemorrhagic mass. On microscopic examination the tumor had hemangioma-like features and lacked typical clear cell morphology, and immunohistochemical staining did little to clarify the picture.

Specifically, although staining highlighted the epithelial component of the tumor, the investigators saw what they described as “an abnormal combination of positive markers” that are normally used to distinguish clear cell from papillary histologies, effectively throwing a monkey wrench into the diagnostic works.

The marker profile in this case included cytokeratin 7, high molecular weight cytokeratin, and carbonic anhydrase IX, but only minimal labeling for alpha-methylacyl-CoA racemase and absence of GATA3.

To add to the confusion, fluorescent in situ hybridization “revealed negative studies for chromosome 3p, trisomy 7 or 17, and MITF family translocations, failing to further place this unique neoplasm into a definitive category,” Dr. Taneja and her colleagues wrote, adding that further study of the tumor may help to clarify whether it represents a distinct tumor type or is simply an unusual pattern caused by degeneration and involution of a known tumor type.

The authors did not disclose a study funding source, but reported having no conflicts of interest.

SOURCE: Taneja K et al. Hum Pathol. 2017 Nov 2. doi: 10.1016/j.humpath.2017.09.015.

What appears at first glance to be a renal vascular tumor may in fact be a rare type of renal cell carcinoma (RCC), authors of a case study cautioned.

A tumor recovered from a 62-year old woman who underwent a partial nephrectomy for an incidentally discovered asymptomatic left renal mass contained arborizing vessels that mimicked hemangioma. Immunohistochemical staining of the tumor highlighted the vascular component but masked epithelial cells, a situation that, in the absence of other clues, might cause a misdiagnosis, reported Kanika Taneja, MD, from the Henry Ford Cancer Institute in Detroit, and her colleagues.

The authors were tipped off to an unusual presentation, however, by mixed signals from immunohistochemical staining, leading them to an admittedly fuzzy diagnosis of “unclassified hemangioma-like RCC.”

“This case highlights that renal cell carcinoma must be strongly considered in the differential diagnosis of renal vascular tumors, and broadens the spectrum of histologies that may mimic hemangioma,” they wrote in Human Pathology.

Although there are a few recent reports in the medical literature of clear cell RCC tumors that mimic hemangiomas, the authors noted that, “to our knowledge, non–clear cell hemangioma-like renal cell carcinoma has not been previously reported.”

The tumor in question was removed from the patient with clear surgical margins during a partial nephrectomy.

Gross examination showed a 2.6 by 2.5 by 2.5 cm, well-circumscribed, tan-brown hemorrhagic mass. On microscopic examination the tumor had hemangioma-like features and lacked typical clear cell morphology, and immunohistochemical staining did little to clarify the picture.

Specifically, although staining highlighted the epithelial component of the tumor, the investigators saw what they described as “an abnormal combination of positive markers” that are normally used to distinguish clear cell from papillary histologies, effectively throwing a monkey wrench into the diagnostic works.

The marker profile in this case included cytokeratin 7, high molecular weight cytokeratin, and carbonic anhydrase IX, but only minimal labeling for alpha-methylacyl-CoA racemase and absence of GATA3.

To add to the confusion, fluorescent in situ hybridization “revealed negative studies for chromosome 3p, trisomy 7 or 17, and MITF family translocations, failing to further place this unique neoplasm into a definitive category,” Dr. Taneja and her colleagues wrote, adding that further study of the tumor may help to clarify whether it represents a distinct tumor type or is simply an unusual pattern caused by degeneration and involution of a known tumor type.

The authors did not disclose a study funding source, but reported having no conflicts of interest.

SOURCE: Taneja K et al. Hum Pathol. 2017 Nov 2. doi: 10.1016/j.humpath.2017.09.015.

What appears at first glance to be a renal vascular tumor may in fact be a rare type of renal cell carcinoma (RCC), authors of a case study cautioned.

A tumor recovered from a 62-year old woman who underwent a partial nephrectomy for an incidentally discovered asymptomatic left renal mass contained arborizing vessels that mimicked hemangioma. Immunohistochemical staining of the tumor highlighted the vascular component but masked epithelial cells, a situation that, in the absence of other clues, might cause a misdiagnosis, reported Kanika Taneja, MD, from the Henry Ford Cancer Institute in Detroit, and her colleagues.

The authors were tipped off to an unusual presentation, however, by mixed signals from immunohistochemical staining, leading them to an admittedly fuzzy diagnosis of “unclassified hemangioma-like RCC.”

“This case highlights that renal cell carcinoma must be strongly considered in the differential diagnosis of renal vascular tumors, and broadens the spectrum of histologies that may mimic hemangioma,” they wrote in Human Pathology.

Although there are a few recent reports in the medical literature of clear cell RCC tumors that mimic hemangiomas, the authors noted that, “to our knowledge, non–clear cell hemangioma-like renal cell carcinoma has not been previously reported.”

The tumor in question was removed from the patient with clear surgical margins during a partial nephrectomy.

Gross examination showed a 2.6 by 2.5 by 2.5 cm, well-circumscribed, tan-brown hemorrhagic mass. On microscopic examination the tumor had hemangioma-like features and lacked typical clear cell morphology, and immunohistochemical staining did little to clarify the picture.

Specifically, although staining highlighted the epithelial component of the tumor, the investigators saw what they described as “an abnormal combination of positive markers” that are normally used to distinguish clear cell from papillary histologies, effectively throwing a monkey wrench into the diagnostic works.

The marker profile in this case included cytokeratin 7, high molecular weight cytokeratin, and carbonic anhydrase IX, but only minimal labeling for alpha-methylacyl-CoA racemase and absence of GATA3.

To add to the confusion, fluorescent in situ hybridization “revealed negative studies for chromosome 3p, trisomy 7 or 17, and MITF family translocations, failing to further place this unique neoplasm into a definitive category,” Dr. Taneja and her colleagues wrote, adding that further study of the tumor may help to clarify whether it represents a distinct tumor type or is simply an unusual pattern caused by degeneration and involution of a known tumor type.

The authors did not disclose a study funding source, but reported having no conflicts of interest.

SOURCE: Taneja K et al. Hum Pathol. 2017 Nov 2. doi: 10.1016/j.humpath.2017.09.015.