Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233

Abstract

Purpose: Multiple prospective Radiation Therapy Oncology Group (RTOG) protocols have evaluated bladder-preserving combined-modality therapy (CMT) for muscle-invasive bladder cancer (MIBC), reserving cystectomy for salvage treatment. We performed a pooled analysis of long-term outcomes in patients with MIBC enrolled across multiple studies.

Patients and methods: Four hundred sixty-eight patients with MIBC were enrolled onto six RTOG bladder-preservation studies, including five phase II studies (RTOG 8802, 9506, 9706, 9906, and 0233) and one phase III study (RTOG 8903). Overall survival (OS) was estimated using the Kaplan-Meier method, and disease-specific survival (DSS), muscle-invasive and non-muscle-invasive local failure (LF), and distant metastasis (DM) were estimated by the cumulative incidence method.

Results: The median age of patients was 66 years (range, 34 to 93 years), and clinical T stage was T2 in 61%, T3 in 35%, and T4a in 4% of patients. Complete response to CMT was documented in 69% of patients. With a median follow-up of 4.3 years among all patients and 7.8 years among survivors (n = 205), the 5- and 10-year OS rates were 57% and 36%, respectively, and the 5- and 10-year DSS rates were 71% and 65%, respectively. The 5- and 10-year estimates of muscle-invasive LF, non-muscle-invasive LF, and DM were 13% and 14%, 31% and 36%, and 31% and 35%, respectively.

Conclusion: This pooled analysis of multicenter, prospective RTOG bladder-preserving CMT protocols demonstrates long-term DSS comparable to modern immediate cystectomy studies, for patients with similarly staged MIBC. Given the low incidence of late recurrences with long-term follow-up, CMT can be considered as an alternative to radical cystectomy, especially in elderly patients not well suited for surgery.

Trial registration: ClinicalTrials.gov NCT00003930 NCT00055601.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

© 2014 by American Society of Clinical Oncology.

Figures

Fig 1.

CONSORT diagram of Radiation Therapy Oncology Group protocol 8903. MCV, methotrexate, cisplatin, and vinblastine; TURBT, transurethral resection of bladder tumor. Data adapted.

Fig 2.

CONSORT diagram of Radiation Therapy Oncology Group protocol 0233. MCV, methotrexate, cisplatin, and vinblastine; TURBT, transurethral resection of bladder tumor. Data adapted.

Fig 3.

(A) Overall survival in all patients. (B) Disease-specific survival (DSS) and bladder-intact disease-free survival (BIDFS) in all patients. (C) Overall survival in patients with clinical T2 versus T3/4 disease. (D) DSS in patients with clinical T2 versus T3/4 disease. (E) DSS in patients with a complete response after combined-modality therapy compared with patients who were nonresponders. (F) DSS in patients age 75 years or older versus patients younger than age 75 years.