Systematic review and meta-analysis on trimodal therapy versus radical cystectomy for muscle-invasive bladder cancer: Does the current quality of evidence justify definitive conclusions?

Abstract

Objectives To systematically review and meta-analyze the current literature in a methodologically rigorous and transparent manner for quantitative evidence on survival outcomes among patients diagnosed with muscle-invasive bladder cancer that were treated by either trimodal therapy or radical cystectomy. Materials and methods MEDLINE, EMBASE, CENTRAL were systematically searched for comparative observational studies reporting disease-specific survival and/or overall survival on adult patients diagnosed with localized muscle-invasive bladder cancer that were exposed to either trimodal therapy or radical cystectomy. Studies qualified for meta-analysis (random effects model) if they were not at critical risk of bias (RoB). Results The literature search identified 12 eligible studies. Three (all rated as “moderate RoB”) out of 6 studies reporting on disease-specific survival qualified for quantitative analysis and yielded a pooled hazard ratio (trimodal therapy versus radical cystectomy) of 1.39 (95% confidence interval: 1.03–1.88). Four (mainly rated as “serious RoB”) out of 12 studies were included in the meta-analysis of overall survival and estimated a hazard ratio of 1.39 (1.20–1.59). Conclusion Pooled results were significant in favor of radical cystectomy. The conclusion is mainly driven by large population-based studies that are at high RoB. Hence, the certainty of these treatment estimates can be considered very low and further research will likely have an important impact on these estimates. At present, the ultimate decision between trimodal therapy and radical cystectomy should be left to the patient based on individual preferences and on the recommendation of a multidisciplinary provider team experienced with both approaches.

Outcomes for Muscle-invasive Bladder Cancer with Radical Cystectomy or Trimodal Therapy in US Veterans

“…A study by Kulkarni et al [17] that included cisplatin-based TMT with definitive dosages showed results similar to ours, albeit with a smaller cohort from a single institution. Systematic reviews have shown that the published studies comparing TMT and RC are observational and at a high risk of bias [18] , [19] . The mixed picture presented by these nonrandomized studies cannot be the basis for an assessment of superiority of treatment modalities, but rather supports a balanced discussion with patients of two treatment approaches with comparable outcomes in appropriately selected patients.…”

Sex Hormone Receptor Signaling in Bladder Cancer: A Potential Target for Enhancing the Efficacy of Conventional Non-Surgical Therapy

“…Specifically, in these patients, trimodal therapy consisting of either transurethral resection or partial cystectomy followed by radiotherapy with concurrent chemotherapy is currently considered to yield the best oncologic outcomes [ 4 , 65 ]. Although the trimodal therapy may increase quality-adjusted life years, current data on overall survival or disease-specific survival are still in favor of radical cystectomy [ 82 ]. Thus, the development of the novel radiosensitization strategies is required to replace radical cystectomy with radiotherapy as a gold standard option for some MI bladder cancers.…”

Why has the prognosis for muscle-invasive bladder cancer not significantly improved after decades of therapeutic advancements?

“…Trimodal therapy consisting of either transurethral resection of the bladder or partial cystectomy followed by radiotherapy with concurrent chemotherapy is currently considered to yield the best oncologic outcomes in select patients with muscle-invasive BCa. A recent metaanalysis demonstrated the findings in favor of radical cystectomy, with hazard ratios (95% confidence interval [CI]) of 1.39 (1.03-1.88) and 1.39 (1.20-1.59) for disease-specific survival (DSS) and overall survival (OS), respectively [6]. However, trimodal therapy in appropriately selected patients has been suggested to increase quality-adjusted life years, compared with radical cystectomy.…”