The Top 5 Genitourinary Cancer Advancements in 2025

The past year brought significant, practice-changing data across urologic oncology, cementing new standards of care for prostate, kidney, and bladder cancers. Research emphasized the value of intensification, personalized biomarker-driven approaches, and strategic maintenance therapy.

Here are the top 5 stories from 2025 about the advancements in prostate, kidney, and bladder cancers.

mHSPC Regimens Are Distinguished by Drug Interactions and Disease Volume

For patients with metastatic hormone-sensitive prostate cancer (mHSPC), selecting an androgen receptor pathway inhibitor (ARPI) requires careful consideration of both disease burden and drug-drug interactions. Ganesh V. Raj, MD, PhDhighlights that outcomes across trials for agents like apalutamide (Erleada), enzalutamide (Xtandi), darolutamide (Nubeqa), and abiraterone (Zytiga)/prednisone often differ based on whether a patient has high- or low-volume disease, with overall survival (OS) benefits seen across various combinations. Furthermore, drug interaction profiles are key; abiraterone/prednisone generally has the lowest interaction risk, while enzalutamide and apalutamide show a higher potential for drug-drug interactions, influencing treatment safety and selection.

ARANOTE Trial Aligns With Prior ARPI Plus ADT Studies in mHSPC

The phase 3 ARANOTE trial demonstrated that adding darolutamide to androgen deprivation therapy (ADT) significantly extended radiographic progression-free survival (rPFS) for patients with mHSPC.

The rPFS hazard ratio (HR) was 0.54, a result that aligns closely with prior studies using other ARPIs combined with ADT. This benefit was observed across both high- and low-volume disease subgroups. While the OS data are not yet mature enough to reach statistical significance (HR, 0.81), the trend and secondary end points are consistent with established ARPI regimens. Importantly, darolutamide plus ADT demonstrated a manageable safety profile similar to ADT alone, though a higher risk of bone fracture was noted, emphasizing the need for bone-protective agents.

Mar Reviews First-Line Therapy in Metastatic Non-Clear Cell RCC

The treatment landscape for metastatic non-clear cell renal cell carcinoma (nccRCC) has been significantly advanced by the use of doublet therapies. The NCCN guidelines prefer the combinations of lenvatinib (Lenvima) plus pembrolizumab (Keytruda) and cabozantinib (Cabometyx) plus nivolumab (Opdivo) for first-line therapy.

Data from the KEYNOTE-B61 trial support the lenvatinib/pembrolizumab regimen, which demonstrated an objective response rate (ORR) of 50.6% and a disease control rate of 82.3% across various nccRCC histologies. While trial enrollment is always encouraged due to the disease's diverse drivers, the high response rates and manageable safety profile, with hypertension being the most common severe adverse event, establish these doublets as strong standard-of-care options.

Tumor-Associated Macrophages May Improve Outcomes in Metastatic RCC

Research into metastatic ccRCC uggests that CD163-positive tumor-associated macrophages (TAMs), typically associated with immune suppression in other cancers, correlate with improved outcomes when patients receive first-line nivolumab (anti–PD-1 therapy).

In an analysis of the HCRN GU16-260 trial, a high density of these TAMs was associated with a significantly better ORR (65% vs 15% for low density) and a longer PFS (median 16.6 months vs 5.5 months). Spatial analysis further indicated that highly exhausted CD8-positive tumor-infiltrating lymphocytes are enriched in the immediate proximity of these CD163-positive TAMs, highlighting a specialized niche that may contribute to the enhanced anti–PD-1 efficacy.

Considering Practice-Changing Maintenance Options in Bladder Cancer

The JAVELIN Bladder 100 trial has established avelumab (Bavencio) as the standard switch maintenance therapy for advanced, metastatic urothelial carcinoma.

This practice-changing trial demonstrated a significant OS and PFS benefit for patients who achieved disease control (complete response, partial response, or stable disease) after initial platinum-based chemotherapy (eg, gemcitabine/cisplatin). For the majority of eligible patients, starting avelumab maintenance immediately after chemotherapy is now the standard of care, though treatment contraindications, such as active autoimmune disease, still require individual patient consideration.