Objective: To determine whether patients with metastatic non‐clear‐cell renal cell carcinoma ( RCC ) benefit from cytoreductive nephrectomy ( CN ). Patients and Methods: We used the Surveillance, Epidemiology, and End Results ( SEER ) programme to identify a population‐based sample of 4914 patients diagnosed with metastatic RCC between 2000 and 2009. Of the 4914 patients, 591 had non‐clear‐cell histology. The median follow‐up was 20 months. The primary outcome measure was RCC ‐specific mortality. Results: Approximately 64% of patients underwent CN . Patients with non‐clear‐cell histology who underwent CN had lower RCC ‐specific and all‐cause mortality than those who did not ( P < 0.001 in both cases). After adjustment for age, gender, race, marital status, year of diagnosis, geographical location and histology, the associations between CN and lower RCC ‐specific mortality (hazard ratio [ HR ] 0.62, 95% confidence interval [ CI ] 0.48–0.80, P < 0.001) and between CN and all‐cause mortality ( HR 0.45, 95% CI 0.37–0.55, P < 0.001) remained highly significant. Among patients diagnosed between 2006 and 2009 (targeted therapy era), the results remained unchanged ( HR 0.50, 95% CI 0.34–0.72, P < 0.001 and HR 0.43, 95% CI 0.31–0.59, P < 0.001, respectively). An interaction model found lower all‐cause mortality for all histologies after CN . Conclusions: Patients from the SEER programme with metastatic non‐clear‐cell RCC , including those treated in the targeted therapy era, appear to derive a survival benefit from CN , an association which remained significant regardless of histological subtype. This observation suggests that CN should remain standard in patients with advanced RCC who are deemed to be surgical candidates.

Purpose: The phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control) in metastatic castration-resistant prostate cancer (mCRPC) with tumor homologous recombination repair (HRR) gene alterations. We present exploratory analyses on the use of circulating tumor DNA (ctDNA) testing as an additional method to identify patients with mCRPC with HRR gene alterations who may be eligible for olaparib treatment. Patients and Methods: Plasma samples collected during screening in PROfound were retrospectively sequenced using the FoundationOne®Liquid CDx test for BRCA1, BRCA2 (BRCA), and ATM alterations in ctDNA. Only patients from Cohort A (BRCA/ATM alteration positive by tissue testing) were evaluated. We compared clinical outcomes, including radiographic progression-free survival (rPFS) between the ctDNA subgroup and Cohort A. Results: Of the 181 (73.9%) Cohort A patients who gave consent for plasma sample ctDNA testing, 139 (76.8%) yielded a result and BRCA/ATM alterations were identified in 111 (79.9%). Of these, 73 patients received olaparib and 38 received control. Patients’ baseline demographics and characteristics, and the prevalence of HRR alterations were comparable with the Cohort A intention-to-treat (ITT) population. rPFS was longer in the olaparib group versus control [median 7.4 vs. 3.5 months; hazard ratio (HR), 0.33; 95% confidence interval (CI), 0.21–0.53; nominal P < 0.0001], which is consistent with Cohort A ITT population (HR, 0.34; 95% CI, 0.25–0.47). Conclusions: When tumor tissue testing is not feasible or has failed, ctDNA testing may be a suitable alternative to identify patients with mCRPC carrying BRCA/ATM alterations who may benefit from olaparib treatment.