Radical Cystectomy or Trimodality Therapy for MIBC: A Multi-institutional Analysis

By Emily Menendez - May 23, 2023

Previous studies have attempted to compare the efficacy of bladder preservation with radical cystectomy for the treatment of muscle-invasive bladder cancer (MIBC), yet many of these trials shut down due to insufficient accrual. Since no other similar trials are currently planned, Zlotta et al utilized propensity scores to compare trimodality therapy (consisting of maximal transurethral resection of bladder tumor followed by concurrent chemoradiation) with radical cystectomy to further test treatment efficacy for MIBC.

The research team’s multi-institutional, retrospective analysis included 722 patients with clinical stage T2–T4N0M0 MIBC who were treated at 3 different university centers located in the United States and Canada between January 2005 and December 2017. A total of 440 patients underwent radical cystectomy, while 282 received trimodality therapy. Each patient had solitary tumors less than 7 cm in size and no extensive or multifocal carcinoma in situ. Some patients had unilateral hydronephrosis.
The primary end point of the trial was metastasis-free survival (MFS). Secondary end points included overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS).

Any differences in survival outcomes by treatment were analyzed using propensity scores incorporated in propensity score matching (PSM) with logistic regression and 3:1 matching with replacement and inverse probability treatment weighting (IPTW).

In the PSM analysis, the 3:1 matched cohort consisted of 1119 patients; 837 underwent radical cystectomy with a median follow-up of 4.38 years, and 282 received trimodality therapy with a median follow-up of 4.88 years. The 5-year MFS rate was 74% for radical cystectomy and 75% for trimodality therapy with IPTW, and both were 74% with PSM. No difference in MFS was seen in IPTW (subdistribution hazard ratio [SHR], 0.89; 95% CI, 0.67-1.20; P=.40) or PSM (SHR, 0.93; 95% CI, 0.71-1.24; P=.64).

The 5-year CSS rate for radical cystectomy compared with trimodality therapy was 81% versus 84% with IPTW and 83% versus 85% with PSM. The 5-year DFS rate was 73% versus 74% with IPTW, and both were 76% with PSM. No differences in CSS (IPTW: SHR, 0.72; 95% CI, 0.50-1.04; P=.071 and PSM: SHR, 0.73; 95% CI, 0.52-1.02; P=.057) and DFS (IPTW: SHR, 0.87; 95% CI, 0.65-1.16; P=.35 and PSM: SHR, 0.88; 95% CI, 0.67-1.16; P=.37) were seen between radical cystectomy and trimodality therapy.

OS was greatest in trimodality therapy (IPTW: 66% [95% CI, 61-71] vs 73% [95% CI, 68-78]; hazard ratio [HR], 0.70; 95% CI, 0.53-0.92; P=.010 and PSM: 72% [95% CI, 69-75] vs 77% [95% CI, 72-81]; HR, 0.75; 95% CI, 0.58-0.97; P=.0078). The outcomes for radical cystectomy and trimodality therapy were not statistically different among centers for CSS and MFS (P=.22-.90). Salvage cystectomy was done in 38 (13%) trimodality therapy patients. Pathological stage in the 440 radical cystectomy patients was pT2 in 124 (28%), pT3-4 in 194 (44%), and node-positive in 114 (26%). The median number of nodes removed was 39, the soft tissue positive margin rate was 1% (n=5), and the perioperative mortality rate was 2.5% (n=11).

This study demonstrates the similar oncologic outcomes of radical cystectomy and trimodality therapy for the treatment of patients with MIBC. Trimodality therapy may act as a promising treatment for suitable candidates with MIBC, not only patients with significant comorbidities for whom surgery is not an option.