Assessing clinical complete response after neoadjuvant systemic therapy in muscle-invasive bladder cancer: a systematic review

Reliable assessment of clinical complete response (cCR) is essential to facilitate bladder-sparing treatment approaches in patients with muscle-invasive bladder cancer (MIBC) undergoing neoadjuvant systemic therapy, yet there is no agreement on the choice of diagnostic modalities for its assessment. We aimed to summarize strategies for assessing cCR in MIBC to facilitate development of bladder-preservation strategies. In this prospectively registered systematic review (CRD420251088678), we searched MEDLINE, Embase, and Web of Science in July 2025 for studies reporting on cCR in MIBC patients undergoing neoadjuvant therapy prior to definitive local therapy or bladder preservation strategies. Risk-of-bias (RoB) was assessed using ROBINS-I tool. Out of 1696 individual records, 41 studies comprising 3588 patients were included in this systematic review. Majority of studies used cisplatin-based neoadjuvant therapies (n = 2941, 23 studies), with eight studies including perioperative immunotherapy (n = 647). For cCR evaluation, 12 studies (n = 1064) used only medical imaging (including CT, MRI, or FDG-PET/CT), three studies (n = 231) performed re-TURBT, one study (n = 56) used cystoscopy, and the remaining 25 studies (n = 2237) assessed cCR through combinations of medical imaging and clinical evaluation. Reported cCR rates ranged from 4.2% to 45% for CT, 15% to 78% for MRI, 76% for FDG-PET/CT, 25% to 46% for TURBT, 50% for cystoscopy, and 7.4% to 87% in studies combining medical imaging with local clinical evaluation. Most studies were rated as having moderate RoB concerns, while one preliminary report was classified as having serious RoB due to limited sample size. We found substantial heterogeneity in cCR assessment modalities, limiting comparability across bladder-sparing studies and highlighting the need for standardization. Data on patients receiving neoadjuvant chemo-immunotherapy remain scarce, and none incorporated urinary tumor DNA in cCR definitions. Serial MRI, with or without invasive assessment, appears promising for selecting candidates for bladder preservation.