SESAUA 2023: Cisplatin-Ineligible Muscle-Invasive Bladder Cancer Demonstrates Poor Long-term Outcomes Following Immediate Radical Cystectomy: Opportunity For Neoadjuvant Pembrolizumab

(UroToday.com) The 2023 SESAUA annual meeting included a bladder cancer session, featuring a presentation by Dr. Kyle Rose discussing an opportunity for neoadjuvant pembrolizumab in cisplatin-ineligible muscle-invasive bladder cancer following immediate radical cystectomy. Cisplatin-ineligible patients with muscle-invasive bladder cancer due to poor functional status and comorbidities have limited options apart from immediate radical cystectomy. Despite several ongoing clinical trials in this space, the expected survival after immediate radical cystectomy remains undefined. Dr. Rose and colleagues assessed overall survival in cisplatin-ineligible muscle-invasive bladder cancer patients undergoing immediate radical cystectomy, and compare these patients to cisplatin-ineligible patients undergoing neoadjuvant pembrolizumab.

Patients with cT2-4N0M0 muscle-invasive bladder cancer who had undergone immediate radical cystectomy were analyzed from four tertiary care centers. Criteria for cisplatin-ineligibility included:

  • Eastern Cooperative Oncology Group score >2
  • Glomerular Filtration Rate (GFR) <59
  • Grade 2 hearing loss
  • Grade 2 peripheral neuropathy
  • New York Heart Association Class III heart failure

Overall survival analysis was performed using Kaplan-Meier method, and Cox-proportional hazards modeling. For comparison, immediate radical cystectomy patients were matched using nearest neighbor propensity scoring technique against cisplatin-ineligible patients recorded from the PURE-01 prospective clinical trial with neoadjuvant pembrolizumab [1]. Patients were matched by pre-cystectomy ECOG status, GFR, age, sex, and pathologic T stage.

There were 384 cisplatin-ineligible muscle-invasive bladder cancer patients that underwent immediate radical cystectomy, while 39 cisplatin-ineligible patients received neoadjuvant pembrolizumab followed by radical cystectomy. The baseline characteristics of immediate cystectomy patients is as follows:

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In the immediate radical cystectomy arm, 118 (31%) patients were down staged (pT0-pT1) from transurethral resection alone, 30 (8%) were pT0N0, and 82 (21%) patients were node-positive on final pathology. The median overall survival for immediate radical cystectomy patients was 22.0 months (95% CI 16.0-28.0). Significantly worse overall survival occurred in patients with stage pT4N0-3 (HR 1.96, p = 0.01), but no significant differences were seen in patients with pT0-3. When comparing cisplatin-ineligible patients undergoing immediate radical cystectomy versus neoadjuvant pembrolizumab in the propensity-matched analysis, patients receiving neoadjuvant pembrolizumab experienced improved overall survival (HR 2.78, 95% 2.1-3.89) and higher complete response rate (pT0: 13.3% vs. 33%, p<0.01). As follows is the Kaplan-Meier curve for immediate radical cystectomy versus neoadjuvant pembrolizumab in cisplatin-ineligible muscle-invasive bladder cancer:

 

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Dr. Rose concluded his presentation discussing an opportunity for neoadjuvant pembrolizumab in cisplatin-ineligible muscle-invasive bladder cancer following immediate radical cystectomy with the following take-home messages:

  •  Cisplatin-ineligible patients with muscle-invasive bladder cancer undergoing immediate radical cystectomy have poor long-term oncologic outcomes, likely exacerbated by diminished functional status and medical comorbidities
  • In this multi-institutional study, patients with pT4 disease or node-positivity on final pathology expectedly experienced the worst survival
  • Given the poor long-term outcomes, neoadjuvant immunotherapy shows promise in improving survival after radical cystectomy, and double-armed prospective studies are needed to confirm this finding


Presented By: Kyle Rose, Moffitt Cancer Center, Tampa, FL

Co-Authors: Adri Durant, MD2, Marco Bandini, MD3, Heather Huelster, MD1, Megan Prunty, MD4, Adnan Fazili, MD5, Shreyas Naidu, BS1, Stephen Bardot, MD5, Laura Bukavina, MD6, Seth Lerner, MD7, Mark Tyson, MD2, Andrea Necchi, MD3, Roger Li, MD1
1.Moffitt Cancer Center, 2. Mayo Clinic Arizona, 3. San Rafaele Hospital, 4. Case Western Reserve University, 5. Ochsner Medical Center, 6. Fox Chase Cancer Center, 7. Baylor College of Medicine

 

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 Southeastern Section of the American Urological Association (SESAUA) Annual Meeting, Amelia Island, FL, Wed, Mar 15 – Sat, Mar 18, 2023.


References:

  1. Necchi A, Anichini A, Raggi D, et al. Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients with Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. J Clin Oncol 2018 Dec 1;36(34):3353-3360.