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VEGFR TKIs have clinical activity in mRCC refractory to IC therapy, possibly impacted by the mechanism of prior combination therapy.

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Background:Biomarkers for metastatic castration-resistant prostatic cancer (mCRPC) are an unmet medical need.Methods:The prognostic and predictive value for survival and response to salvage hormonal therapy (SHT) of baseline testosterone level (TL) was analysed in a cohort of 101 mCRPC patients participating in 9 non-hormonal first-line chemotherapy phase II–III trials. Inclusion criteria in all trials required a TL of <50 ng dl−1.Results:Median age: 70 years; visceral metastases: 19.8% median prostate-specific antigen (PSA): 50.7 ng ml−1; median TL: 11.5 ng dl−1. Median overall survival (OS; 24.5 months) was significantly longer if baseline TL was above (High TL; n=52) than under (Low TL; n=49) the TL median value (32.7 vs 22.4 months, respectively; P=0.0162, hazard ratio (HR)=0.6). The presence of anaemia was an unfavourable prognostic factor (median OS: 20.6 vs 28.4 months; P=0.0025, HR=1.88 (CI95%: 1.01–3.48)). Patients presenting both anaemia and low testosterone had a worse outcome compared to those with one or none of them (median OS: 17.9 vs 22.4 vs 38.1 months; P=0.0024). High vs Low TL was associated with PSA response rate (55.6% vs 21.7%) in 41 patients receiving SHT.Conclusion:Testosterone level under castration range was a prognostic factor for survival mCRPC patients. The PSA response to SHT differed depending on TLs. Testosterone levels might help in treatment decision.

Despite intense drug development in the last decade in metastatic urothelial carcinoma and the incorporation of novel compounds to the treatment armamentarium, chemotherapy remains a key treatment strategy for this disease. Platinum-based combinations are still the backbone of first-line therapy in most cases. The role of chemotherapy in the second line has been more ill-defined due to the complexity of this setting, where patient selection remains critical. Nevertheless, two regimens, one in monotherapy (i.e. vinflunine) and one in combination with antiangiogenics (i.e. docetaxel + ramucirumab) have shown efficacy. Immunotherapy through checkpoint inhibition has revealed remarkably durable benefit in a small proportion of patients in the first and second line and is currently the preferred partner for combinations with chemotherapy. Difficult populations such as patients with liver metastases or those progressing to checkpoint inhibition represent a medical challenge and selective ways of delivering cytotoxics, like the antibody–drug conjugates, might represent a valid alternative. This article reviews the current role of chemotherapy in the management of advanced urothelial carcinoma and the ongoing and coming studies involving this treatment strategy.