Flaig, Thomas W.

TPS913 Background: A subset of patients with MIBC who receive neoadjuvant therapy (NAT) prior to radical cystectomy (RC) have a pathologic complete response (pCR) at the time of RC. With pCR rates of 22-42% in patients with MIBC following NAT (+/- ICI), whether a subset of patients with good clinical response to NAT can avoid RC is an important unanswered question, especially with the development of more active systemic therapies. HCRN 16-257 evaluated maintenance nivolumab in lieu of cystectomy in patients with MIBC who experienced clinical complete response (cCR) following neoadjuvant GC and nivolumab. The cCR rate was 48%, but 8/33 (24%) patients who elected bladder preservation subsequently underwent cystectomy for local disease recurrence. The RETAIN trial also evaluated omission of local therapy following neoadjuvant therapy with a 2-year bladder preservation rate in patients with ≤T1 disease following NAC of 54% (22/41). Of the 9/25 (36%) patients on that trial developed metastatic disease, 8/9 developed localized disease before metastasizing. These data illustrate the critical role that local therapy plays in patients with MIBC. For this reason, we believe that radiotherapy to the bladder combined with ICI will improve bladder intact event-free survival (BI-EFS). This trial also allows for patients to opt for bladder preservation based on a good clinical response to NAT. Methods: This is a single arm, phase 2 trial (NCT07061964) evaluating risk-adapted bladder preservation therapy for patients with MIBC following NAT. NAT consists of any NCCN guideline concordant therapy for MIBC. Patients with cT2-T4aN0M0 MIBC who complete NAT will be eligible if they have ≤T1 disease on post-NAT TURBT, confirmed by biopsies of prior tumor sites and systematic sampling (left/right lateral walls, dome, posterior wall, trigone). Patients will receive 55 Gray (Gy) in 20 fractions of radiotherapy (RT) to the bladder with 1 year of pembrolizumab. The primary objective is to evaluate whether 3-year BI-EFS is at least 70% in participants with < = T1 (without multifocal CIS) following NAT and RT with 1 year of pembrolizumab. Secondary objectives include local muscle invasive recurrence-free survival, metastasis-free survival (MFS), overall survival (OS), the rate of salvage cystectomy, and evaluation of the frequency and severity of toxicities in participants who receive RT and pembrolizumab. Plasma and urine will be banked for future correlative studies. S2427 was activated in September 2025 with an accrual goal of 111 patients. Clinical trial information: NCT07061964 .

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non–muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)–unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non–muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non–muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody–drug conjugates for metastatic bladder cancer.

PURPOSE The combination of gemcitabine and cisplatin (GC) is a standard therapy for metastatic urothelial carcinoma. Based on data that angiogenesis plays a role in urothelial carcinoma growth and progression, a randomized placebo-controlled trial was performed with the primary objective of testing whether patients treated with GC and bevacizumab (GCB) have superior overall survival (OS) than patients treated with GC and placebo (GCP). PATIENTS AND METHODS Between July 2009 and December 2014, 506 patients with metastatic urothelial carcinoma without prior chemotherapy for metastatic disease and no neoadjuvant or adjuvant chemotherapy within 12 months were randomly assigned to receive either GCB or GCP. The primary end point was OS, with secondary end points of progression-free survival, objective response, and toxicity. RESULTS With a median follow-up of 76.3 months among alive patients, the median OS was 14.5 months for patients treated with GCB and 14.3 months for patients treated with GCP (hazard ratio for death = 0.87; 95% CI, 0.72 to 1.05; two-sided stratified log-rank P = .14). The median progression-free survival was 8.0 months for GCB and 6.7 months for GCP (hazard ratio = 0.77; 95% CI, 0.63 to 0.95; P = .016). The proportion of patients with grade 3 or greater adverse events did not differ significantly between both arms, although increased bevacizumab-related toxicities such as hypertension and proteinuria occurred in the bevacizumab-treated arm. CONCLUSION The addition of bevacizumab to GC did not result in improved OS. The observed median OS of about 14 months is consistent with prior phase III trials of cisplatin-based chemotherapy.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non–muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non–muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org . Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.