Clinical complete response as a surrogate for pathological response in bladder cancer: a systematic review and...

To evaluate the concordance between clinical complete response (cCR) and pathological complete response (pCR) in muscle-invasive bladder cancer (MIBC) to assess the surrogacy and prognostic value of cCR for guiding bladder-sparing strategies.

In this prospectively registered systematic review and meta-analysis (CRD420251066540), we searched MEDLINE, EMBASE, and Web of Science in June 2025 for studies reporting clinical and pathological complete response rates in patients with MIBC undergoing neoadjuvant therapy followed by radical cystectomy (RC). Pooled concordance was estimated via random-effects meta-analysis. Risk-of-bias was assessed using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I).

Out of 1947 individual records, 10 (n = 894) retrospective and three (n = 181) prospective studies comprising 1075 patients were included. Restaging modalities for cCR assessment included transurethral resection of the bladder (TURB; n = 188, two studies), computed tomography (n = 221, two studies), magnetic resonance imaging (MRI; n = 122, two studies), and fluorodeoxyglucose positron emission tomography (n = 45). One study (n = 56) used perioperative cystoscopy, while the remaining five studies (n = 499) combined imaging with cystoscopy or TURB. The concordance (n = 779, nine studies) between cCR and pCR was 0.51 (95% confidence interval [CI] 0.42-0.60), the concordance (n = 536, seven studies) between non-cCR and non-pCR was 0.84 (95% CI 0.70-0.92). Most studies were rated as having moderate concerns regarding bias, and one as serious due to examiner-dependent bias of cystoscopy-based cCR assessment.

Current evidence does not support relying on the current definition of cCR alone, which poorly predicts pCR, to guide treatment decisions. Ongoing trials assessing the combination of MRI plus TURB with urine and/or blood based circulating tumour DNA may help refine cCR evaluation and support the sole introduction of bladder-sparing approaches in patients with MIBC who respond to neoadjuvant systemic therapy.