Genitourinary (GU) oncology was well represented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, with practice-relevant readouts spanning kidney, prostate, and bladder cancer. Major phase 3 trials delivered significant advances in prostate cancer, including perioperative apalutamide (Erleada) plus androgen deprivation therapy (ADT) demonstrating marked event-free survival (EFS) gains in localized high-risk disease, and talazoparib (Talzenna) plus enzalutamide (Xtandi) significantly delaying progression in homologous recombination repair (HRR)-altered metastatic castration-sensitive prostate cancer (CSPC). In non–muscle-invasive bladder cancer (NMIBC), long-term data reinforced durvalumab plus Bacillus Calmette-Guérin (BCG).
Simultaneously, trial updates emphasized the crucial balance between antitumor efficacy, toxicity, and patient quality of life across renal cell carcinoma (RCC) histologies. Looking at the various outcomes and trial updates, knowing how to implement them into clinical practice is critical. Together, these updates underscore a continued evolution toward personalized, risk-stratified treatment strategies across urologic malignancies.
LenCabo: Body composition and quality of life with lenvatinib plus everolimus vs cabozantinib in ccRCC
The phase 2 LenCabo trial (NCT05012371) was the first head-to-head comparison of contemporary second-line-or-later treatments for metastatic clear cell renal cell carcinoma (ccRCC) following progression on a PD-1-based immune checkpoint inhibitor.1 The trial’s primary analysis previously showed that lenvatinib (Lenvima) plus everolimus (Afinitor) significantly improved progression-free survival (PFS) over cabozantinib (Cabometyx), though with numerically higher rates of treatment discontinuation and grade 3 or greater adverse effects (AEs). The updated analysis examined how patient quality of life (QOL) and body composition changed with each regimen.
Of 86 patients who received at least 1 dose of assigned treatment (lenvatinib plus everolimus, n = 40; cabozantinib, n = 46), only 38 (44%) completed both baseline and day 60 Functional Assessment of Cancer Therapy-Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) assessments. The QOL comparison by FKSI-DRS at day 60 was inconclusive, but favored cabozantinib (OR, 0.51; 95% CI, 0.16-1.64; P = .26). Among the 66 patients with body composition measured at baseline and 4 months via an AI-based CT segmentation tool at the L3 vertebra, lenvatinib plus everolimus was associated with significantly higher odds of a lower body mass index (BMI; OR, 0.36; 95% CI, 0.15-0.88; P = .026), lower skeletal muscle mass index (OR, 0.30; 95% CI, 0.11-0.79; P = .014), and lower subcutaneous adiposity (OR, 0.21; 95% CI, 0.08-0.55; P = .002) compared with cabozantinib, after adjusting for baseline values, prior VEGF-targeted therapy, age, International Metastatic Database Consortium risk category, and sex. Total adipose tissue index followed the same pattern (OR, 0.23; 95% CI, 0.08-0.61; P = .003), while visceral adiposity and intermuscular adiposity did not differ significantly between arms.
“In patients progressing on PD-1 [immune checkpoint inhibition], [lenvatinib plus everolimus] was associated with significantly greater reductions in BMI, skeletal muscle mass, and subcutaneous adiposity compared with [cabozantinib] at 4 months,” the investigators concluded in the poster. “These results suggest that the superior PFS efficacy of [lenvatinib plus everolimus] in this setting is accompanied by a more pronounced catabolic effect.”
María Teresa Bourlon, MD, MS, FASCO, head of the Urologic Oncology Clinic at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City, Mexico, and editorial advisory board member for ONCOLOGY ®, called the finding clinically important for treatment selection in an interview with CancerNetwork®. “Whenever we’re prescribing a TKI in any line of treatment for RCC, we are concerned about the catabolic effect…especially reducing muscle mass and the [strength] of the patient,” she said. “These results tell us that we could expect the patients are going to be more frail, are going to lose their muscle mass, are going to lose their strength…This is a concern when we [have] an older patient from a geriatric population, a frail patient, a patient [who] has lost a lot of weight…this [presentation] is informative to rethink whether we need to give this combination or not to our patients if they’re frail, older, or have lost a lot of muscle mass.”
On the inconclusive QOL data specifically, Bourlon pointed to the study’s low completion rate as a key limitation. “It is particularly interesting in this trial that less than 50% of patients actually answered their quality-of-life questionnaire, which…limits the interpretation of the data presented,” she said. “Knowing that the result was inconclusive, we really cannot tell there’s a difference…between the combination therapy with lenvatinib/everolimus vs cabozantinib…It doesn’t lean the balance towards one or another drug at this point.”
PROTEUS: Perioperative apalutamide plus ADT in high-risk localized prostate cancer
Presented in the meeting’s plenary session, the phase 3 PROTEUS trial (NCT03767244) was the largest therapeutic trial ever conducted in localized high-risk prostate cancer, randomly assigning 2109 patients across 118 centers in 18 countries to 6 months of neoadjuvant apalutamide (Erleada) plus androgen deprivation therapy (ADT), followed by radical prostatectomy and 6 months of adjuvant apalutamide plus ADT, vs placebo plus ADT with the same surgical and duration structure.2
Presented by Mary-Ellen Taplin, MD, FASCO, chair of the Executive Committee for Clinical Research of Dana-Farber Cancer Institute, results showed a pathologic complete response/minimal residual disease rate roughly 9 times higher with apalutamide plus ADT than with placebo plus ADT, along with a statistically significant improvement in metastasis-free survival and a 29% reduction in the risk of oncologic events or death (event-free survival HR, 0.71; 95% CI, 0.63-0.80). Grade 3 or greater AEs were more frequent with apalutamide (39.6% vs 31.0% with placebo), with rash the leading cause of treatment discontinuation.
TALAPRO-3: Talazoparib plus enzalutamide in HRR-altered metastatic CSPC
In a late-breaking oral presentation, Neeraj Agarwal, MD, FASCO, Presidential Endowed Chair of Cancer Research at the Huntsman Cancer Institute of the University of Utah, presented results from the phase 3 TALAPRO-3 trial (NCT04821622), which randomly assigned 599 patients with HRR gene-altered metastatic CSPC to talazoparib plus enzalutamide or placebo plus enzalutamide, each with ADT.3
Talazoparib plus enzalutamide reduced the risk of radiographic progression or death by 52% compared with placebo plus enzalutamide (HR, 0.48), with benefit observed across both BRCA and non-BRCA HRR alterations; the 3-year radiographic PFS rates were 76.6% vs 56%. Results were simultaneously published in The New England Journal of Medicine, and the combination has since received FDA priority review for this earlier disease setting, building on its existing approval in HRR-altered metastatic castration-resistant prostate cancer based on the phase 3 TALAPRO-2 trial (NCT03395197).4,5
RAMPART: Durvalumab with or without tremelimumab vs active monitoring in resected primary RCC
The phase 3 RAMPART trial (NCT03288532), presented by James M. Larkin, MD, PhD, of the Royal Marsden NHS Foundation Trust, randomly assigned 790 patients with intermediate- or high-risk resected RCC to active monitoring, 1 year of durvalumab (Imfinzi) monotherapy, or 1 year of durvalumab plus tremelimumab (Imjudo).6 Durvalumab plus tremelimumab significantly improved disease-free survival (DFS) vs active monitoring (HR, 0.65; 95% CI, 0.45-0.93), a benefit concentrated on patients who are higher-risk (HR, 0.52) with a significant treatment-by-risk interaction; durvalumab monotherapy fell short of statistical significance (HR, 0.74; 95% CI, 0.53-1.04; 1-sided P = .041), with no such interaction observed in the intermediate-risk subgroup.
Bourlon emphasized that RAMPART’s findings do not yet unseat the current standard of care. “We have a standard of care, which is pembrolizumab [Keytruda], which has demonstrated improved overall survival [OS],” she said. “Any combination drug or monotherapy needs to prove [OS] benefit. Before that, we’re all going to be hesitant to prescribe the drug because we do have an alternative that increases overall survival… I don’t consider [durvalumab, with or without tremelimumab] standard of care, while we do have a standard of care that improves [OS], which is pembrolizumab monotherapy.”
She added that toxicity data will factor heavily into how the combination is eventually positioned: “Combination therapy might be more toxic and may lead to an increase in the rate of [AEs]…quality of life data and toxicity is going to be key for clinicians deciding [between] monotherapy vs combination therapy in the adjuvant setting.”
In an interview with CancerNetwork during ASCO, Saum Ghodoussipour, MD, director of the Bladder and Urothelial Cancer Program at Rutgers Cancer Institute and an associate professor of Surgery at Rutgers Robert Wood Johnson Medical School, suggested that there may be a place for CTLA-4-targeted combination but that the utility of risk-stratifying patients based on circulating biomarker was unclear in RCC. “There was a lot of discussion at ASCO about how ctDNA and other circulating biomarkers like KIM-1 can risk-stratify these patients. We’re getting there in bladder cancer…and we’re seeing some utility of these biomarkers, but the actual utility and benefit is not yet quite as clear in kidney cancer,” he explained.
POTOMAC: Durvalumab plus BCG in BCG-naive high-risk NMIBC
Maria De Santis, MD, Chair of Section for Interdisciplinary Genito-Urinary Cancer Medicine at the Charité Medical University Hospital, Berlin, Germany, and coinvestigators presented a 5-year OS and patient-reported outcomes (PRO) analysis from the phase 3 POTOMAC trial (NCT03528694), which randomly assigned 1018 patients with BCG-naive, high-risk NMIBC to durvalumab plus BCG induction and maintenance therapy, durvalumab plus BCG induction only, or BCG induction and maintenance alone.7
At 5 years, the OS with durvalumab plus BCG induction and maintenance showed no detriment relative to BCG alone (88% vs 86%; HR, 0.81; 95% CI, 0.54-1.19), and PRO measures with the EORTC QLQ-C30 and QLQ-NMIBC24 assessments were generally similar between arms. These data followed the trial’s previously reported DFS benefit (HR, 0.68; 95% CI, 0.50-0.93; P = .0154), which supported the FDA’s May 2026 approval of durvalumab in combination with BCG for this population.8
RADICAL/Alliance A031801: Cabozantinib with or without radium-223 in RCC with bone metastases
Rana R. McKay, MD, co-leader of the Genitourinary Oncology Disease Team at the UC San Diego Moores Cancer Center, presented interim results from the phase 2 RADICAL/Alliance A031801 trial (NCT04071223), which randomly assigned 90 evaluable patients with RCC and symptomatic bone metastases to cabozantinib with or without radium-223.9 The trial closed after its interim analysis failed to meet the prespecified futility boundary for its primary end point, symptomatic skeletal event-free survival (SSE-FS; stratified HR, 1.24; 95% CI, 0.62-2.48). A numerical improvement in OS favored the radium-223 combination (32.2 months vs 21.3 months; HR, 0.77; 95% CI, 0.42-1.41), though grade 3 or greater treatment-related AEs were more frequent with the addition of radium-223 (65.9% vs 56.8%).
Bourlon cautioned against reading too much into the trial’s secondary findings given how it closed. “Whenever you close [a trial] due to futility, you’re no longer going to be able to address other end points in the study,” she said. “It’s going to remain inconclusive because it did not recruit the predetermined number of patients and the predetermined number of events to [allow us] to interpret other end points.” On the added toxicity specifically, she added: “If we have higher grade 3 toxicity, that means we are deteriorating the quality of life of the patient…I would be very cautious [about] interpreting this combination.”
References
- Moura J, Chahoud J, Skelton WP IV, et al. Body composition and quality of life (QOL) with lenvatinib + everolimus (len + eve) vs cabozantinib (cabo) in metastatic clear cell renal cell carcinoma (ccRCC) after PD-1 inhibitor progression: results from the randomized phase II LenCabo trial. J Clin Oncol. 2026;44(suppl 16):4538. doi:10.1200/JCO.2026.44.16_suppl.4538
- Taplin ME, Gleave M, Shore ND, et al. Perioperative (neoadjuvant and adjuvant) apalutamide (APA) + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT with radical prostatectomy (RP) in high-risk localized or locally advanced prostate cancer (HR LPC/LAPC): final analysis of the PROTEUS phase 3 study. J Clin Oncol. 2026;44(suppl 17):LBA1. doi:10.1200/JCO.2026.44.17_suppl.LBA1
- Agarwal N, Matsubara N, Azad AA, et al. TALAPRO-3: talazoparib (TALA) + enzalutamide (ENZA) compared with placebo (PBO) + ENZA for the treatment of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) harboring homologous recombination repair (HRR) gene alterations. J Clin Oncol. 2026;44(suppl 17):LBA5007. doi:10.1200/JCO.2026.44.17_suppl.LBA5007
- FDA grants priority review for Pfizer’s TALZENNA plus XTANDI for the treatment of metastatic prostate cancer. News release. Pfizer Inc. July 22, 2026. Accessed July 28, 2026. https://tinyurl.com/3b77fwvx
- Fizazi K, Azad A, Matsubara N, et al. Final overall survival (OS) with talazoparib (TALA) + enzalutamide (ENZA) as first-line (1L) treatment in patients (pts) with homologous recombination repair (HRR)-deficient metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 TALAPRO-2 trial. J Clin Oncol. 2025,43(suppl 5):LBA141. doi:10.1200/JCO.2024.42.4_suppl.LBA359
- Larkin JM, Powles T, Frangou E, et al. Durvalumab monotherapy versus active monitoring for resected primary renal cell carcinoma in RAMPART: an international, phase 3, randomized controlled trial. J Clin Oncol. 2026;44(suppl 17):LBA4511. doi:10.1200/JCO.2026.44.17_suppl.LBA4511
- De Santis M, Shore ND, Nishiyama H, et al. Durvalumab (D) in combination with BCG induction and maintenance (I+M) therapy for BCG-naive, high-risk non-muscle-invasive bladder cancer (NMIBC): 5-year overall survival (OS) analysis and patient-reported outcomes (PROs) from POTOMAC. J Clin Oncol. 2026;44(suppl 16):4624. doi:10.1200/JCO.2026.44.16_suppl.4624
- FDA approves durvalumab in combination with Bacillus Calmette-Guerin for high-risk non-muscle invasive bladder cancer. News release. FDA. May 28, 2026. Accessed July 28, 2026. https://bit.ly/43wfdiu
- McKay RR, Atherton P, Ballman KV, et al. A phase 2 randomized trial of radium-223 dichloride and cabozantinib in patients (pts) with renal cell carcinoma (RCC) with bone metastases (BM): RADICAL (Alliance A031801). J Clin Oncol. 2026;44(suppl 16):4500. doi:10.1200/JCO.2026.44.16_suppl.4500
