(UroToday.com) The 2022 Annual Meeting of the American Urological Association was host to a discussion section led by Dr. Roger Li regarding BCG unresponsive bladder cancer. This discussion followed the excellent presentations by Drs. Seth Lerner and Patrick Hensley.
Similar to Dr. Lerner, Dr. Li began his presentation by defining “BCG Unresponsive” high risk non-muscle invasive bladder cancer (NMIBC):
- Recurrent CIS +/- Ta or T1 within 12 months of completion of adequate BCG (At least 5 induction courses, 2 maintenance)
- Recurrent/persistent HGTa/T1 within 6 months of completion of adequate BCG
- T1HG at first evaluation after induction BCG (At least 5 induction courses)
- There is flexibility in use of 6- and 12-month time periods
Next, Dr. Li highlighted the newest (Jan 2020) FDA-approved agent in this disease space: Pembrolizumab based on results from the pivotal Keynote-057 trial.1 Keynote-057 was a phase two clinical trial of 102 patients (96 in efficacy cohort). 64% of patients had CIS alone. Complete response at 3 months was achieved in 41% of patients and, among those who achieved this outcome, 53% maintained a complete response for greater than 9 months. Toxicities were as follows:
- Any grade: 66%
- Immune mediated: 22: 3%
- Immune-mediated Grade 3-4: 3%
- Discontinuation: 9%
- Immune mediated: 22: 3%
Dr. Li next presented unpublished results from a recent meta-analysis performed by his team at Moffitt of all BCG unresponsive clinical trials. For CIS only patients, it appears that the 3, 6, and 12 months complete response rates are 41%, 38% and 25%, respectively.
Similar to Dr. Hensley, Dr. Li went on to present results from 3 series, including Dr. Hensley’s, that demonstrate that radical cystectomy for BCG progression to MIBC is associated with significantly worse outcomes.
Data from multiple contemporary series of radical cystectomy after salvage therapy was next presented. Looking at data from Keynote-057, the Nadofaragene trial, and the gem/doce series, the rate of salvage radical cystectomy was 16-40%, rate of pT2 disease or worse was 8-26%, and LN involvement was 3-12%. Looking at data from the MD Anderson Cancer Center series, specifically those with muscle invasion after BCG failure, the pT2 rate was 63%, nodal involvement was 27% and median OS was 4.1 years (compared to 9.5 years for those with pT1 disease undergoing RC following BCG failure). Clearly, there is a window of treatment that is missed once patients failing BCG progress to muscle invasion.
Similar to Dr. Hensley, Dr. Li concluded his presentation with the following regarding paradigm improvement:
- We need to understand limitations of current clinical staging
- Develop predictive biomarkers “fit for purpose”
- Clinical trial enrollment and bladder preservation by experienced clinicians
Presented by: Roger Li, MD, Assistant Professor, Urologic Oncology, Moffitt Cancer Center, Tampa, FL
Written by: Rashid Sayyid, MD, MSc – Urology Chief Resident, Augusta University/Medical College of Georgia, @rksayyid on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.
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, multicentre, phase 2 study. Lancet Oncol. 2021;22(7):919-930.