NEOADJUVANT cisplatin-based chemotherapy followed by radical cystectomy remains the gold standard for the management of muscle-invasive bladder cancer (MIBC), supported by randomised clinical trials and meta-analyses demonstrating improved survival compared with surgery alone. Validated regimens include MVAC (methotrexate, vinblastine, doxorubicin, cisplatin), cisplatin-gemcitabine, and dose-dense MVAC (dd-MVAC), with dd-MVAC offering higher pathological response rates and longer overall survival at the cost of increased toxicity. Recent trials have also incorporated immunotherapy, showing benefits from adjuvant nivolumab and perioperative durvalumab when combined with platinum-based neoadjuvant therapy.
Despite robust evidence, real-world uptake of neoadjuvant chemotherapy remains limited internationally, and anecdotal reports suggest low utilisation in Australia. Contraindications to cisplatin, including renal dysfunction, poor performance status, and comorbidities, may explain some of this underuse. Clinician uncertainty regarding the superiority of neoadjuvant versus adjuvant therapy and questions about the generalisability of trial data may also play a role.
Analysis of the BLADDA urothelial cancer registry demonstrated that neoadjuvant chemotherapy in Australian patients was associated with reduced risk of invasive bladder cancer recurrence and death. A complete pathological response was achieved in 31% of evaluable patients, aligning with results from prospective trials. Patients attaining a complete response exhibited longer event-free and overall survival compared with those with residual node-positive disease. Adjuvant chemotherapy improved event-free survival but did not significantly affect overall survival.
Over the study period, 46% of patients in BLADDA institutions received neoadjuvant chemotherapy, with utilisation increasing over time. Among patients with adequate renal function for cisplatin, 55% received neoadjuvant therapy, suggesting other unrecorded factors, including comorbidities or patient preference, may have limited uptake. Importantly, omission of neoadjuvant chemotherapy may reduce access to perioperative immunotherapy, as eligibility for adjuvant nivolumab and perioperative durvalumab is contingent on prior cisplatin-containing therapy.
While limitations include the observational nature of registry data and incomplete coverage of all Australian cases, these findings highlight the survival benefit of neoadjuvant chemotherapy in MIBC and underscore the potential to further improve patient outcomes through its increased use, particularly when combined with adjuvant or perioperative immunotherapy. Encouraging broader uptake of neoadjuvant platinum-based chemotherapy remains critical in optimising curative-intent treatment strategies.
Reference
Hiong A et al. Perioperative chemotherapy use and related outcomes in muscle-invasive bladder cancer in Australia. BJUI Compass. 2025;6(9):e70083.
