Data Support Trimodality Therapy in Suitable Candidates With MIBC

"In the absence of randomized trials, which are unlikely to be carried out in the near term, this study provides the best evidence possible supporting that trimodality therapy, in the setting of multidisciplinary shared decision making, should be offered to all eligible candidates with muscle-invasive bladder cancer as an oncologically equivalent alternative to radical cystectomy," according to the study authors.

Radical cystectomy and bladder-preserving trimodality therapy produced similar outcomes when used to treat patients with muscle-invasive bladder cancer (MIBC), according to findings from a retrospective study published in the Lancet Oncology.

When analyzed using inverse probability treatment weighting (IPTW), the rate of metastasis-free survival (MFS) at 5 years was 74% (95% CI, 70%-78%) with radical cystectomy vs 75% (95% CI, 70%-80%) with trimodality therapy (subdistribution HR [SHR], 0.89; 95% CI, 0.67-1.20; P = .40). The rates of cancer-specific survival at 5 years were 81% (95% CI, 77%-85%) vs 84% (95% CI, 79%-89%), respectively (SHR, 0.72; 95% CI, 0.50-1.04; P = .071), and the rates of disease-free survival (DFS) at 5 years were 73% (95% CI, 69%-77%) vs 74% (95% CI, 69%-79%), respectively (SHR, 0.87; 95% CI, 0.65-1.16; P = .35), with trimodality therapy vs cystectomy.

When analyzed using propensity score matching (PSM), the 5-year MFS rate was 74% (95% CI, 70%-77%) with cystectomy and 74% (95% CI, 68%-79%) with trimodality therapy (SHR 0.93; 95% CI, 0.71-1.24; P = .64). The 5-year cancer-specific survival rates were 83% (95% CI, 80%-86%) vs 85% (95% CI, 80%-89%), respectively (SHR, 0.73; 95% CI, 0.52-1.02; P = .057), and the 5-year DFS rates were 76% (95% CI, 72%-80%) vs 76% (95% CI, 71%-81%), respectively (SHR, 0.88; 95% CI, 0.67-1.16; P = .37).

Moreover, the 5-year overall survival (OS) rate was 66% (95% CI, 61%-71%) with cystectomy vs 73% (95% CI, 68%-78%) with trimodality therapy according to IPTW (HR, 0.70; 95% CI, 0.53-0.92; P = .010). The corresponding figures according to PSM were 72% (95% CI, 69%-75%) vs 77% (95% CI, 72%-81%), respectively (HR, 0.75; 95% CI, 0.58-0.97; P = .0078).

“Using 2 different statistical methods to balance treatment groups in the absence of randomised trials, this multicenter study showed that there was no difference in [MFS], cancer-specific survival, or [DFS] between trimodality therapy and radical cystectomy in selected patients with [MIBC] in the modern era,” the investigators wrote. “Patients included in our analyses would have been eligible for both procedures. Outcomes for radical cystectomy and trimodality therapy were not different among centers.”

In total, 722 patients with clinical stage T2 to T4N0M0 muscle-invasive urothelial carcinoma of the bladder received treatment between January 2005 and December 2017, and were assessed in this retrospective analysis. Of this population, 440 underwent radical cystectomy and 282 underwent trimodality therapy. The median follow-up was 4.38 years (interquartile range [IQR], 1.6-6.7) in the cystectomy cohort and 4.88 years (IQR, 2.8-7.7) in the trimodality cohort.

After 3:1 matching, the median age in the cystectomy cohort was 71.4 years (IQR, 66.0-77.1), and the median age in the trimodality therapy cohort was 71.6 years (IQR, 64.0-78.9). Both cohorts were mostly comprised of male patients (75% vs 76%, respectively; P = .65).

As part of trimodality therapy, patients underwent a maximal transurethral resection of bladder tumor followed by repeat resection if their tumor remained macroscopically visible. Investigators then administered concurrent radiosensitising chemotherapy and radiotherapy.

Radical cystectomy consisted of cystoprostatectomy among male patients and anterior exenteration among female patients. Both groups underwent bilateral pelvic lymph node dissection and urinary diversion.

The primary end point was MFS. Secondary end points included OS, cancer-specific survival, DFS, and distant metastatic and regional failure-free survival.

Investigators removed a median of 39 (IQR, 21-57) nodes among patients who underwent radical cystectomy. Local recurrence developed in 3% of patients. The soft tissue positive margin rate was 1.0%, and the 90-day perioperative mortality rate was 2.5%.

Additionally, 13% of those who received trimodality therapy (n = 38) underwent salvage cystectomy; this population had a 5-year cancer-specific survival rate of 85% (95% CI, 79%-89%). The corresponding rate among those who didn’t undergo the salvage treatment was 84% (95% CI, 73%-96%; P = .69). The 5-year MFS rate in the trimodality cohort was 80% (95% CI, 73%-87%) in those who received neoadjuvant or adjuvant chemotherapy vs 73% (95% CI, 65%-81%) in those who didn’t (P = .14).

A major limitation to this study was its retrospective design, which may have introduced unaccounted-for residual confounders and imbalances between the cohorts, according to the investigators. Moreover, socioeconomic and other differences between the institutions involved may have affected outcomes.

“In the absence of randomized trials, which are unlikely to be carried out in the near term, this study provides the best evidence possible supporting that trimodality therapy, in the setting of multidisciplinary shared decision making, should be offered to all eligible candidates with muscle-invasive bladder cancer as an oncologically equivalent alternative to radical cystectomy,” the investigators concluded. “Hopefully, our results will renew interest and further support undertaking a randomized trial in this space.”

Reference

Zlotta AR, Ballas LK, Niemierko A, et al. Radical cystectomy versus trimodality therapy for muscle-invasive bladder cancer: a multi-institutional propensity score matched and weighted analysis. Lancet Oncol. 2023;24(6):669-681. doi:10.1016/S1470-2045(23)00170-5