The 2025 ASCO Annual Meeting has officially concluded. Our sincere thanks to the global oncology community and ASCO for creating such a remarkable forum advancing cancer care. Here we highlight the most impactful updates in genitourinary tumors from this year’s meeting.
Kidney Cancer: Long-Term Data and Novel Agents Redefining Standards
Kidney cancer is at a pivotal turning point, with new long-term data and novel therapies shaping the future of care.
- With more than 5 years of follow-up, KEYNOTE-564 reaffirmed the benefit of adjuvant therapy with the PD-1 inhibitor pembrolizumab in high-risk, clear cell renal cell carcinoma (RCC), improving both disease-free survival and overall survival vs placebo (Abstract 4514).
- In advanced disease, the 9-year update from CheckMate 214 confirmed durable survival outcomes with the PD-1 inhibitor nivolumab plus the CTLA-4 monoclonal antibody ipilimumab over the tyrosine kinase inhibitor sunitinib, with a delayed overall survival benefit emerging in favorable-risk patients (Abstract 4505).
- The 5-year results from LITESPARK-004 showed sustained efficacy with the hypoxia-inducible factor–2 alpha (HIF-2a) inhibitor belzutifan in von Hippel–Lindau disease–associated renal cell carcinoma, central nervous system hemangioblastomas, and pancreatic neuroendocrine tumors, along with a continued reduction in surgical interventions (Abstract 4507).
Emerging Strategies in Advanced RCC
Emerging strategies in advanced renal cell carcinoma also gained attention.
- The phase I TRAVERSE trial of the CD70–chimeric antigen receptor (CAR) T-cell therapy ALLO-316 showed a 33% objective response rate in tumors with CD70 expression ≥ 50% (Abstract 4508).
- The phase I ARC-20 trial reported a 41% objective response rate with the combination of casdatifan (HIF-2α inhibitor) plus cabozantinib (tyrosine kinase inhibitor) in previously treated patients across all International Metastatic RCC Database Consortium risk groups (Abstract 4506). These results have prompted progression to a phase III trial (PEAK-1).
- In STELLAR-002, the novel multitargeted tyrosine kinase inhibitor zanzalintinib plus the nivolumab yielded a 63% objective response rate, whereas the triplet of zanzalintinib, nivolumab, and the monoclonal antibody relatlimab yielded a 33% objective response rate—both with acceptable safety including low rates of palmar-plantar erythrodysesthesia (Abstract 3101).
- The PDIGREE trial explored treatment sequences following induction nivolumab plus ipilimumab in metastatic clear cell RCC (Abstract 4516). Of 1,111 enrolled patients, two-thirds transitioned to protocol-defined second-line therapy. We are looking forward to seeing the results of later steps evaluating the sequential treatments after disease progression with nivolumab plus ipilimumab.
- Finally, in the translocation RCC AREN1721 trial, despite early closure due to slow accrual, treatment with nivolumab plus the tyrosine kinase inhibitor axitinib significantly extended median progression-free and overall survival vs monotherapy with nivolumab, without unexpected toxicity (Abstract 4521).
“Kidney cancer is at a pivotal turning point, with new long-term data and novel therapies shaping the future of care.”— EMRE YEKEDÜZ, MD, AND YÜKSEL ÜRÜN, MD
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Bladder Cancer: Organ-Sparing and Biomarker-Driven Innovations
Preoperative and perioperative approaches continue to evolve in non–muscle-invasive and muscle-invasive bladder cancers, aiming to enhance treatment responses while incorporating bladder-sparing strategies.
- In the phase III ENLIGHTED trial, padeliporfin (vascular-targeted photodynamic therapy) demonstrated a 73% complete response rate with manageable toxicity in patients with low-grade, upper tract urothelial carcinoma, supporting its potential as an organ-sparing alternative (Abstract LBA4513).
- In non–muscle-invasive bladder cancer, the CREST study showed that the PD-1 inhibitor sasanlimab plus bacillus Calmette-Guérin (BCG) improved 3-year event-free survival in patients with carcinoma in situ and T1 tumors vs BCG alone (Abstract 4517).
- In the BCG shortage context, a randomized trial comparing BCG plus mitomycin with BCG alone in non–muscle-invasive bladder cancer showed similar efficacy and safety, but BCG plus mitomycin required fewer BCG doses and had higher treatment adherence (Abstract LBA4504).
For muscle-invasive bladder cancer, several perioperative strategies have emerged.
- In cisplatin-ineligible, muscle-invasive bladder cancer, the CLONEVO trial showed that neoadjuvant use of the CDK4/6 inhibitor abemaciclib led to promising downstaging and biomarker modulation (ClinicalTrials.gov identifierNCT03837821; Abstract 4520).
- The SURE-02 trial reported a 38.7% clinical complete response rate with neoadjuvant therapy consisting of the antibody-drug conjugate sacituzumab govitecan-hziy plus pembrolizumab, allowing for bladder preservation in a subset of patients (Abstract 4518).
- The NIAGARA trial’s exploratory analysis revealed that circulating tumor DNA (ctDNA)-positive status before radical cystectomy was associated with a lower likelihood of achieving pathologic complete response, whereas greater ctDNA clearance indicated an added benefit from perioperative treatment with the immune checkpoint inhibitor durvalumab plus chemotherapy (Abstract 4503).
Collectively, these data reflect continued refinement of bladder cancer treatment through novel agents and biomarker-driven strategies.
Metastatic Urothelial Cancer: Advancing Targeted and Chemotherapy-Free Options
Key advances in metastatic urothelial cancer were also highlighted at the meeting.
- In cisplatin-ineligible patients, CheckMate 901 showed that nivolumab plus ipilimumab improved overall survival vs chemotherapy—but the benefit did not meet statistical significance (Abstract 4500).
- In the maintenance setting, the monoclonal antibody avelumab plus sacituzumab govitecan improved progression-free survival vs avelumab alone, in the phase II JAVELIN Bladder Medley trial (Abstract 4501).
- The exploratory analysis from the phase III EV-302 trial confirmed high complete response rates and durable benefit with the antibody-drug conjugate enfortumab vedotin-ejfv plus pembrolizumab over chemotherapy (Abstract 4502).
- A phase Ib/II study of the NECTIN4 antibody-drug conjugate 9MW2821 plus the monoclonal antibody toripalimab demonstrated an 87.5% objective response rate in treatment-naive patients with metastatic urothelial cancer, with manageable safety (Abstract 4519).
These findings support chemotherapy-free and targeted strategies, including antibody-drug conjugates and immune checkpoint inhibitors, as emerging standards across treatment lines in metastatic urothelial cancer.
Prostate Cancer: Intensifying Therapy and Embracing Precision
During the meeting, significant advancements in prostate cancer emphasized treatment intensification and precision-based strategies for localized and castration-sensitive disease.
- A meta-analysis from the ICECaP trial showed that although adding docetaxel to androgen-deprivation therapy and radiotherapy did not significantly improve metastasis-free or overall survival in high-risk, localized prostate cancer overall, a subset of patients with very high–risk features may benefit from this approach, supporting biomarker-guided personalization (Abstract 5013). (See a video with the presenter of this clinical trial on The ASCO Post Newsreels at ascopost.com/videos.)
- The phase III trial of CAN-2409 plus a prodrug, using a tumor-targeted adenoviral HSV-thymidine kinase gene therapy, demonstrated a 30% reduction in recurrence or death when added to standard radiotherapy (with or without short-course androgen-deprivation therapy). This strategy did not seem to increase severe toxicity in patients with intermediate- to high-risk localized prostate cancer (Abstract 5000).
- For nonmetastatic high-risk patients, a validated multimodal artificial intelligence tool accurately identified those deriving the greatest benefit from intensified androgen receptor pathway inhibitor therapy (Abstract 5027).
- In oligometastatic castration-sensitive prostate cancer, the Metacure trial showed durable prostate-specific antigen (PSA) control with short-course, intensified androgen-deprivation therapy plus stereotactic body radiation therapy (Abstract 5014). (See a video with the presenter of this clinical trial on The ASCO Post Newsreels at ascopost.com/videos.)
- In metastatic castration-sensitive prostate cancer, the IRONMAN registry confirmed the prognostic value of PSA > 0.2 ng/mL at 6 and 12 months (Abstract 5002).
- STAMPEDE data revealed that PTEN inactivation was predictive of docetaxel benefit (Abstract 5003).
- Long-term data from the phase III trials ARCHES (Abstract 5005) and ARANOTE (Abstract 5004) confirmed survival and quality-of-life benefits with the androgen receptor inhibitors enzalutamide and darolutamide. (See videos with the presenters of both these clinical trials on The ASCO Post Newsreels at ascopost.com/videos.)
- The AMPLITUDE trial showed that the PARP inhibitor niraparib plus abiraterone improved outcomes in homologous recombination repair (HRR)-altered metastatic castration-sensitive prostate cancer, supporting earlier use of PARP inhibitors (Abstract LBA5006). (See a video with the presenter of this clinical trial on The ASCO Post Newsreels at ascopost.com/videos.)
Metastatic Castration-Resistant Prostate Cancer: Novel Combinations and New Targets
Multiple studies in metastatic castration-resistant prostate cancer explored novel combination strategies and emerging targets.
- The PARP inhibitor olaparib plus the radiopharmaceutical radium-223 significantly improved radiographic progression–free survival over radium-223 alone, regardless of HRR status, in the phase III COMRADE trial (Abstract 5007).
- Niraparib plus the PD-1 inhibitor cetrelimab showed superior progression-free and overall survival vs niraparib alone after chemoimmunotherapy induction in aggressive-variant prostate cancer (Abstract 5008).
- A B7-H3 antibody-drug conjugate, DB-1311/BNT324, showed promising efficacy in heavily pretreated patients (Abstract 5015).
- In a phase I study, pasritamig (a first-in-class, bispecific T-cell engager targeting human kallikrein 2) showed good tolerability and PSA50 (≥ 50% decrease in PSA level from baseline) responses (Abstract 5017).
- Combining nivolumab plus ipilimumab with 177-lutetium–PSMA-617 (LuPSMA) in the ANZUP 2001 trial (Abstract TPS271) or with stereotactic body radiation therapy in the CheckPRO trial (Abstract 5018) led to increased toxicity. Although the ANZUP 2001 trial showed improved PSA progression-free survival, the CheckPRO trial did not demonstrate an added benefit.
- The use of LuPSMA increased clonal hematopoiesis mutations, in the exploratory analysis of the TheraP trial (Abstract 5020), warranting further long-term evaluation.
“Significant advancements in prostate cancer emphasized treatment intensification and precision-based strategies for localized and castration-sensitive disease.”— EMRE YEKEDÜZ, MD, AND YÜKSEL ÜRÜN, MD
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Rare Disease Focus: Penile Cancer
- In an open-label, randomized, noninferiority trial of adjuvant therapy for high-risk penile cancer, platinum plus fluorouracil showed similar activity compared with platinum plus paclitaxel (Abstract LBA5012). However, the platinum-plus-fluorouracil arm had higher rates of hematologic and gastrointestinal toxicities and greater erectile dysfunction–related bother.
DISCLOSURE: Dr. Yekedüz reported no conflicts of interest. Dr. Ürün has served on advisory boards for as well as received honoraria from or served as a consultant to Abdi-İbrahim Pharmaceuticals, Astellas, AstraZeneca, Bristol Myers Squibb, Eczacıbaşı, GEN Ilaç, GSK, Janssen, Merck, MSD, Nobelpharma, Novartis, Pfizer, and Roche.
Dr. Yekedüz practices in the Department of Medical Oncology, Ankara University School of Medicine, Ankara, Türkiye, and in the Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston. Dr. Ürün practices in the Department of Medical Oncology, Ankara University School of Medicine, Ankara, Türkiye.
