Residual CIS after Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle Invasive Bladder Cancer: Implications for Neoadjuvant Trials


  • Complete response is the de facto primary endpoint for NAC trials in locally advanced UC.
  • Residual CIS-only after NAC and RC had similar survival to patients with complete response in a large cohort.
  • Residual CIS-only may be considered for inclusion as an endpoint for survival in NAC trials.
  • CR as the sole endpoint in NAC trials may not capture many patients who are deriving benefit.
Purpose: To better define surrogate endpoints for neoadjuvant chemotherapy (NAC) trials in patients with muscle-invasive bladder cancer. We compared survival in patients with carcinoma in-situ (CIS) only vs. complete response following NAC and radical cystectomy (RC).

Materials and Methods: Patients with cT2-4N0M0 disease treated with NAC and RC between 2001 and 2018 were stratified by response: complete response (CR, pT0N0), partial response (PR, pTaN0, pT1N0+/-CIS), CIS-only (pTisN0), stable disease (SD, pT2N0), or progressive disease (PD, >pT2N0). Primary endpoints were overall survival (OS) and risk of recurrence in patients with CIS-only vs. CR. Multivariable Cox proportional hazards regression model was used for OS and a competing risks proportional hazards model was used for risk of recurrence.

Results: Of 1,406 patients in our institution cohort, 340 patients met inclusion criteria. Kaplan-Meier mean estimates of OS for CR and CIS-only were 108.9 months (95% CI 89.7–127.9) and 125.8 months (95% CI 112.3–139.3), respectively (P = 0.13). Cox proportional hazards model found no difference in OS between patients with PR (HR 1.06, 95% CI 0.33–2.58, P = 0.897) or CIS-only (HR 0.422, 95% CI 0.15–1.18, P = 0.101) when compared to CR. The risk of recurrence was similar between patients with CIS-only (HR 0.73, 95% 0.29–1.84, P = 0.49) and PR (HR 1.32, 95% CI 0.54–3.29, P = 0.54) when compared to CR on competing risks analysis.

Conclusions: Residual CIS-only after NAC and RC demonstrated similar survival outcomes when compared to patients with pathologic CR. Further study in large multi-institutional cohorts may further validate CIS-only as an additional surrogate endpoint after NAC and may inform future trials.

Andrew T. Gabrielson, MD,1 Marcus J. Daniels, MD,1 Julian Rowe MD,1 Ridwan Alam, MD, MPH,1 Esther J. Lee, BS,1 Andres Matoso, MD,2 Anthony De Felice, MHS, BS,1 Noah Hahn, MD,1,3 Jean Hoffman-Censits, MD,1,3 Trinity J. Bivalacqua, MD, PhD,1 Max Kates, MD,1

  1. James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD
  2. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD
  3. Department of Medical Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD

Source: Gabrielson A, Daniels M, Rowe J, "Residual CIS after neoadjuvant chemotherapy and radical cystectomy for muscle invasive bladder cancer: Implications for neoadjuvant trials." Urologic Oncology: Seminars and Original Investigations. 2022.
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