(UroToday.com) The 2026 GU ASCO annual meeting featured a urothelial carcinoma session and a presentation by Dr. Edward Uchio discussing a cohort A post hoc analysis of the KEYNOTE-057 trial assessing the outcomes in participants with BCG-unresponsive high-risk non-muscle invasive bladder cancer who underwent radical cystectomy after pembrolizumab.
Radical cystectomy with pelvic lymph node dissection is the current standard of care for patients with BCG-unresponsive non-muscle invasive bladder cancer, but it is associated with significant morbidity and a negative impact on quality of life. Based on results from cohort A of the phase 2 KEYNOTE-057 trial, pembrolizumab monotherapy is a bladder-sparing treatment option for patients with BCG-unresponsive high-risk non-muscle invasive bladder cancer with CIS with or without papillary disease.1 A post hoc analysis of KEYNOTE-057 suggested that pembrolizumab may provide a clinically meaningful delay in radical cystectomy.2 At ASCO GU 2026, Dr. Uchio and colleagues presented updated outcomes of patients in cohort A of KEYNOTE-057 who underwent radical cystectomy after discontinuing pembrolizumab after a median follow-up of 6 years.
Adults in cohort A with histologically confirmed BCG-unresponsive high-risk non-muscle invasive bladder cancer with CIS who were ineligible for or declined radical cystectomy received pembrolizumab 200 mg IV Q3W for ≤2 years:
End points of this analysis were to evaluate cystectomy-free survival for complete and non–complete responders, time to cystectomy, pathologic staging at radical cystectomy, and subsequent therapies/procedures other than radical cystectomy following pembrolizumab discontinuation. Cystectomy free survival was calculated from the first dose of pembrolizumab until death or radical cystectomy, and time to cystectomy was calculated from the last dose of pembrolizumab. Complete responders were defined as patients with the best overall response of complete response.
There were 96 patients enrolled in cohort A, of which 44 underwent radical cystectomy after discontinuing pembrolizumab (1 additional patient since the previous analysis). The median follow-up was 72.6 months (range: 62.5-83.1). Before undergoing radical cystectomy, 13/44 patients had initial complete response, and 31/44 never had a complete response:
The median cystectomy free survival (95% CI) was 56.8 months (30.9-NR) for patients with complete response and 18.5 months (7.8-36.5) for patients without complete response, with 12-month cystectomy free survival rates of 87.2% and 54.1%, respectively:
The median time to cystectomy was 15.0 months (range: 9.0-69.8) for patients with a complete response and 6.4 months (4.0-42.2) for patients without a complete response. There were 13 of 44 patients who underwent subsequent therapy/procedures following pembrolizumab discontinuation, including intravesical therapy (n = 6), neoadjuvant systemic therapy (n = 5), treatment for locally advanced/metastatic urothelial carcinoma (n = 5), and radiation therapy (n = 2). Additionally, six patients (13.6%) had upstaging to muscle-invasive bladder cancer at radical cystectomy:
Dr. Uchio concluded his presentation discussing a cohort A post hoc analysis of the KEYNOTE-057 trial with the following take-home points:
- Long-term results from this post hoc analysis of KEYNOTE-057 continue to suggest that intravenous pembrolizumab can offer durable bladder preservation in high-risk BCG-unresponsive non-muscle invasive bladder cancer with CIS, with sustained delays of radical cystectomy among initial responders and minimal additional upstaging
- Patients with a complete response had > 3-fold longer median cystectomy-free survival than non-responders
- These results suggest that pembrolizumab can provide durable responses and can delay the time to subsequent radical cystectomy in most patients
Presented by: Edward M. Uchio, MD, University of California, Irvine Medical Center, Orange, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2026 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 26 – Sat, Feb 28, 2026.
References:
- Balar AV, Kamat AM, Kulkarni GS, et al. Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): An open-label, single-arm, multicenter, phase 2 study. Lancet Oncol. 2021 Jul;22(7):919-930.
- Necchi A, Roumiguié M, Kamat AM, et al. Pembrolizumab monotherapy for high-risk non-muscle-invasive bladder cancer without carcinoma in situ and unresponsive to BCG (KEYNOTE-057): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2024 Jun;25(6):720-730.