Objectives: Although the standard treatment for nonmetastatic muscle-invasive bladder cancer is cystectomy and neoadjuvant chemotherapy, there is interest in bladder-preserving therapy as an alternative, and there is uncertainty about the need for and optimal extent of lymph node dissection and optimal chemotherapy regimens and timing of administration.
Data sources: Electronic databases (Ovid MEDLINE®, January 1990 to October 2014; Cochrane Central Register of Controlled Trials through September 2014; Cochrane Database of Systematic Reviews through September 2014; Health Technology Assessment through Third Quarter 2014; National Health Sciences Economic Evaluation Database through Third Quarter 2014; and Database of Abstracts of Reviews of Effects through Third Quarter 2014); references lists; and clinical trials registries.
Review methods: We selected randomized controlled trials, nonrandomized controlled clinical trials, and nonrandomized cohort studies with concurrent comparators that evaluated bladder-preserving therapies against one another or versus radical cystectomy, that evaluated the effectiveness of lymph node dissection or effects of extent of dissection, and that compared neoadjuvant or adjuvant chemotherapy versus another chemotherapy regimen or versus no chemotherapy. The quality of included studies was assessed, data were extracted, and results were summarized qualitatively.
Results: One randomized controlled trial with methodological limitations found no difference between bladder-preserving external beam radiation therapy (60 Gray) versus radical cystectomy plus radiation therapy (40 Gray) in median survival duration, although bladder-preserving treatment was associated with increased risk of local or regional recurrence (35.8% vs. 6.8%) (strength of evidence: insufficient). Cohort studies of bladder-preserving treatments versus radical cystectomy had methodological shortcomings and reported inconsistent results, precluding reliable conclusions (strength of evidence: insufficient).
Cohort studies suggested that lymph node dissection was associated with lower risk of mortality than no lymph node dissection and that more extensive lymph node dissection with cystectomy might be more effective than less extensive lymph node dissection at improving survival, but studies had methodological limitations, there was some inconsistency in results, and there was variability in the lymph node dissection techniques evaluated (strength of evidence: low).
Six randomized controlled trials consistently found neoadjuvant chemotherapy with cisplatin-based combination regimens to be associated with decreased risk, or a trend toward decreased risk, of mortality versus no neoadjuvant chemotherapy, including three trials that evaluated current regimens (cisplatin, methotrexate, and vinblastine; methotrexate, vinblastine, doxorubicin, and cisplatin) (strength of evidence: moderate). Four trials found adjuvant chemotherapy to be associated with decreased risk of mortality versus no adjuvant chemotherapy, but no trial reported a statistically significant effect and there was some inconsistency in findings (strength of evidence: low). One trial and two cohort studies found no clear differences between neoadjuvant and adjuvant use of methotrexate, vinblastine, doxorubicin, and cisplatin in survival (strength of evidence: low).
Evidence on harms, effectiveness of treatments for muscle-invasive bladder cancer in patient subgroups (including older patients, patients with comorbidities, and patients with renal dysfunction), and comparative effectiveness of different chemotherapy regimens was too limited to reach reliable conclusions.
Conclusions: Neoadjuvant chemotherapy with cisplatin-based regimens improved survival in patients with muscle-invasive bladder cancer, and extended lymph node dissection during cystectomy might be more effective than standard lymph node dissection for improving survival. More research is needed to clarify the effectiveness of bladder-preserving therapies versus radical cystectomy and define patient subgroups in which such therapies may be an option.