Abstract
Background: Muscle-invasive bladder cancer (MIBC) is associated with high recurrence and mortality rates. While cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy remains the standard of care, many patients are ineligible for cisplatin. Recent advances in immunotherapy and biomarker research are reshaping perioperative strategies, aiming to personalize treatment and improve outcomes. Methods: We conducted a comprehensive narrative review of the recent literature and clinical trials on the perioperative treatment of MIBC. We focused on published phase II and III trials assessing neoadjuvant and adjuvant strategies, including immunotherapy, antibody-drug conjugates (ADCs), combination regimens, and circulating tumor DNA (ctDNA)-based approaches. Results: Numerous trials (e.g., PURE-01, ABACUS, NABUCCO, AURA, NIAGARA) have demonstrated the feasibility and efficacy of immune checkpoint inhibitors (ICIs) in both cisplatin-eligible and -ineligible populations. Combination strategies, including ICIs plus chemotherapy or ADCs, have shown promising pathological complete response rates and event-free survival. In the adjuvant setting, nivolumab improved disease-free survival and received regulatory approval. Biomarkers such as PD-L1 and ctDNA are emerging tools for predicting treatment response and recurrence risk, although prospective validation is ongoing. Conclusions: The treatment paradigm for MIBC is shifting toward multimodal and biomarker-driven approaches. Integration of ICIs into perioperative management, especially in combination with chemotherapy or ADCs, may enhance outcomes. ctDNA shows potential as a predictive and prognostic biomarker, guiding therapeutic decisions and surveillance. Future research should focus on refining patient selection, optimizing treatment sequencing, and validating ctDNA-guided strategies to personalize care while minimizing overtreatment.