The past year produced practice-changing data across urologic oncology, solidifying new standards of care for prostate, kidney and bladder cancers and underscoring the value of treatment intensification, biomarker-driven approaches and strategic maintenance therapy.
In metastatic hormone-sensitive prostate cancer (mHSPC), clinicians must weigh disease burden and drug‑drug interaction profiles when selecting an androgen receptor pathway inhibitor (ARPI). Outcomes differ by high‑ versus low‑volume disease, with overall‑survival benefits observed across multiple ARPI combinations. Experts note that abiraterone plus prednisone carries the lowest risk of drug interactions, while enzalutamide and apalutamide have higher interaction potential, a factor that increasingly guides regimen choice.
The phase 3 ARANOTE trial showed that adding darolutamide to androgen‑deprivation therapy substantially extended radiographic progression‑free survival in mHSPC, with an rPFS hazard ratio of 0.54. The benefit was seen in both high‑ and low‑volume disease subgroups. Overall‑survival data remain immature (HR 0.81) but trends and secondary endpoints are consistent with prior ARPI‑plus‑ADT studies. Darolutamide plus ADT demonstrated a safety profile similar to ADT alone, though an increased risk of bone fractures highlights the importance of bone‑protective measures.
Treatment of metastatic non‑clear cell renal cell carcinoma (nccRCC) has moved toward doublet regimens. NCCN guidelines now favor lenvatinib plus pembrolizumab and cabozantinib plus nivolumab as first‑line options. KEYNOTE‑B61 data support lenvatinib/pembrolizumab, reporting an objective response rate of 50.6% and a disease control rate of 82.3% across diverse nccRCC histologies. Hypertension was the most common severe adverse event. Given the heterogeneity of nccRCC, clinical trial enrollment remains encouraged, but these doublets represent strong standard‑of‑care choices.
Emerging translational data in metastatic clear‑cell RCC suggest a paradoxical association between CD163‑positive tumor‑associated macrophages (TAMs) and improved outcomes with first‑line nivolumab. In an analysis of the HCRN GU16‑260 trial, high densities of CD163+ TAMs correlated with a higher objective response rate (65% vs 15%) and longer progression‑free survival (median 16.6 vs 5.5 months). Spatial profiling indicated enrichment of highly exhausted CD8+ tumor‑infiltrating lymphocytes in close proximity to these macrophages, pointing to a specialized immune niche that may enhance anti–PD‑1 efficacy.
JAVELIN Bladder 100 has established avelumab as the standard switch‑maintenance therapy for advanced metastatic urothelial carcinoma. The trial showed significant overall‑survival and progression‑free‑survival benefits for patients who achieved disease control after platinum‑based chemotherapy. For most eligible patients, initiating avelumab immediately after chemotherapy is now standard practice, with individualization required for patients with contraindications such as active autoimmune disease.
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