Abstract
INTRODUCTION: Small cell bladder cancer is an aggressive histological subtype and represents one of the most common extra-pulmonary small cell carcinomas. Treatment options include radical cystectomy, chemotherapy, radiotherapy, or combinations of these three. However, the optimal treatment approach remains unknown. This meta-analysis assesses the current literature on non-metastatic SCBC and analyzes different treatment approaches. METHODS: A comprehensive search was conducted in four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Library) utilizing the search terms "small or neuroendocrine AND cancer OR Carcinoma OR Tumor OR Malignan* OR oncolog* OR metastati* OR neoplasm AND bladder or urothelial or Urologic" from inception until March 2024. Eligible papers reported treatment and overall survival (OS) of non-metastatic SCBC patients. A meta-analysis was conducted comparing treatments with radical cystectomy- and radiotherapy-based approaches in addition to the use of chemotherapy. RESULTS: In total, 12 articles were included in the present systematic review and meta-analysis. Regarding the comparison between radical cystectomy-based treatment and radiotherapy-based treatment, comparable OS was observed between both groups as the reported hazard ratio (HR) was found to be 1.04 (95 % confidence intervals [CI]: 0.90, 1.20, p = 0.6). After including chemotherapy in the analysis, it was observed that using radical cystectomy or radiotherapy with the addition of chemotherapy showed better OS with lower HR (0.53 [95 %CI: 0.39, 0.73], p < 0.0001) compared with radical cystectomy or radiotherapy without chemotherapy. The median OS of radical cystectomy or radiotherapy with chemotherapy was higher than that of radical cystectomy or radiotherapy without chemotherapy, and chemotherapy alone as follows: 30.89 (95 %CI: 23.82, 40.08), 19.67 (95 %CI: 16.26, 23.80), and 19.20 (95 %CI: 16.55, 22.28), respectively. CONCLUSION: In this systematic review and meta-analysis, no OS difference was observed in patients undergoing radical cystectomy-based or radiotherapy-based treatments. The addition of chemotherapy to local therapy seems to improve OS. However, given the high heterogeneity of the included studies, these results should be interpreted cautiously.