Redefining standards: a comprehensive systematic review of practice changing advances in GU oncology from ASCO and ESMO 2025

Background: The year 2025 has been a transformative moment in GU oncology, with paradigm-shifting clinical trial results presented at major conferences and rapidly published. These developments are recasting therapeutic standards across bladder, kidney, prostate, penile, and testicular cancers through novel mechanisms and refined personalization. Objectives: This systematic review aimed to identify, synthesize, and critically evaluate pivotal phase II and III randomized controlled trials presented at ASCO/ESMO 2025 or published in 2025, focusing on innovative therapeutic strategies across GU malignancies. Methods: Conducted per PRISMA 2020 guidelines, the review involved exhaustive searches of conference proceedings, PubMed/MEDLINE, and Embase (January-December 2025). Included studies were phase II and III RCTs in GU oncology reporting overall or progression-free survival for novel therapies. Study selection, data extraction, and risk-of-bias assessment using the Cochrane RoB 2 tool were performed. Results: Lu]Lu-PSMA-617 to standard therapy significantly improved radiographic PFS in PSMA-positive mHSPC. Docetaxel scheduling was optimized (ARASAFE), and an AI model (STAMPEDE) identified patients for AR inhibitor benefit. Novel agents like saruparib and pasritamig showed promise. (4) In testicular cancer, de-escalated therapy was established for seminoma (SAKK 01/10). (5) In penile cancer, chemotherapy optimization progressed. Conclusion: The 2025 evidence establishes multiple new standards of care across GU cancers, emphasizing biomarker-driven strategies, immunotherapy integration, novel resistance mechanisms, and treatment optimization. This synthesis provides an evidence-based framework for updating guidelines and highlights the move toward more personalized management, while noting persistent challenges and future research needs.