Cisplatin-based neoadjuvant chemotherapy (NAC) improves survival in muscle-invasive urothelial cancer (MIUC), yet pathological complete response (pCR) is achieved in a minority of patients. Relative dose intensity (RDI) is a potentially modifiable determinant of chemotherapy efficacy, but its impact during NAC in MIUC remains unexplored. This multicentre retrospective study included patients with MIUC treated with cisplatin-gemcitabine NAC followed by radical cystectomy. RDI was calculated from original administration records and categorised as ≥ 85% versus <85%. The primary endpoint was pCR (ypT0N0M0). Secondary endpoints included overall survival (OS) and event-free survival (EFS). A total of 330 patients were included; 66% maintained RDI≥85%. Overall pCR rate was 25.2%. Patients with RDI≥85% achieved higher pCR rates compared with those with RDI<85% (29.7% vs 16.2%; p = 0.008). RDI≥85% remained independently associated with pCR in multivariable analysis (OR = 2.10; p = 0.032). Preserved RDI was also associated with improved EFS (HR = 0.65; p = 0.039) and OS (HR = 0.53; p = 0.026) at univariate analysis. Achievement of pCR was strongly associated with superior EFS (HR = 0.23; p < 0.001) and OS (HR = 0.35; p = 0.009). Preservation of cisplatin RDI≥85% during NAC is independently correlated with higher pCR rates and associated to a better survival trend in MIUC. Optimisation of chemotherapy delivery represents a clinically actionable strategy to enhance neoadjuvant efficacy.
The oncologist. 2026 Jul 02 [Epub ahead of print]
Giuseppe Neola, Fabiano Flauto, Carmine Caso, Giuseppina Montuori, Marco Maruzzo, Eleonora Lai, Giuseppe Luigi Banna, Michele Maffezzoli, Mimma Rizzo, Francesco Massari, Veronica Mollica, Sarah Scagliarini, Vincenza Conteduca, Patrizia Giannatempo, Alessandro Rametta, Brigida Anna Maiorano, Gaetano Facchini, Edoardo Lenci, Rosa Tambaro, Francesco Grillone, Davide Bosso, Felice Crocetto, Ciro Imbimbo, Alberto Servetto, Roberto Bianco, Luigi Formisano
Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy., Oncology Unit 3, Istituto Oncologico Veneto - IOV IRCCS, Padova, Italy., Portsmouth Hospitals University NHS Trust, Portsmouth, United Kingdom., Department of Medicine and Surgery, University Hospital of Parma - Medical Oncology Unit, University of Parma, Parma, Italy., Medical Oncology Unit, Azienda Ospedaliera Universitaria Consorziale Policlinico di Bari, Bari, Italy., Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., UOC di Oncologia, Azienda Ospedaliera di Rilievo Nazionale Cardarelli di Napoli, Naples, Italy., Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, Foggia, Italy., Genitourinary Medical Oncology - Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy., Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy., Oncology Unit, S. Maria Delle Grazie Hospital, Pozzuoli, Naples, Italy., Medical Oncology Unit, Azienda Ospedaliera Ospedali Riuniti Marche Nord, Pesaro, Italy., Uro-Gynecological Oncology, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Naples Italy., SOC Oncologia PO Pugliese-Ciaccio Azienda Ospedaliera Universitaria Renato Dulbecco, Catanzaro, Italy., Medical Oncology Unit, Ospedale del Mare, 80147 Naples, Italy., Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Italy.