Introduction and objective
Prior randomized controlled trials (RCT) comparing bladder preservation to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC) closed early due to lack of accrual. In the absence of level 1 data, we compared trimodality therapy (TMT, maximal transurethral resection of bladder tumor followed by concurrent chemoradiation) to RC.
Methods
703 patients with cT2-T3/4aN0M0 MIBC were retrospectively analyzed. 421 RC and 282 TMT, eligible for both TMT or RC, treated at the Massachusetts General Hospital, Boston; Princess Margaret Cancer Centre, Toronto; and University of Southern California, Los Angeles between 2005-2017 were included. To compare homogeneous cohorts, all patients had solitary tumors <7cm, no or unilateral hydronephrosis, and no multifocal carcinoma in situ. Treatment propensity scores were estimated using logistic regression. Patients were matched 1:1 without replacement. Covariates included age, sex, clinical T stage, hydronephrosis, presence or absence of CIS, (neo)adjuvant chemotherapy and ECOG status. Primary endpoint was metastasis-free survival. Overall survival (OS) was estimated with adjusted Cox models; cancer-specific survival (CSS), distant failure-free survival, pelvic nodal failure-free survival and metastasis-free survival (distant and pelvic nodal failure) were estimated with adjusted competing risk models. The analysis was performed as intent-to-treat.
Results
After matching 534 patients (267 RC vs 267 TMT), age (70.9 vs 71.4), cT2 stage (89 vs 90%), presence of hydronephrosis (12 vs 10%) were similar between RC and TMT cohorts. At 5 years, metastasis-free (78 vs 76%, p=0.93), CCS (83 vs 84%, p=0.45), distant failure-free (80 vs 78%, p=0.91), and pelvic nodal failure-free (96 vs 92%, p=0.10) survival were not statistically different between RC and TMT, whereas OS favored TMT (67 vs 75%, p=0.02). Outcomes for RC and TMT were not different among centers. Final pT stage of 421 RC was: pT0 14%, pT1 7%, pT2 29%, pT3/4 42% and N+ 24%. Peri RC mortality was 2.1%. Median number of nodes removed was 40. NMIBC recurrence occurred in 57/278 (20.5%) TMT patients. Salvage cystectomy was performed in 38 TMT patients (13%).
Conclusions
This large multi-institutional contemporary study supports that TMT for select MIBC patients, eligible for both procedures, provides oncologic outcomes equivalent to RC. TMT should not be reserved to non surgical candidates only but offering TMT to all suitable candidates could provide patients with a choice of treatments.
Source of funding
N/A