Safety and efficacy of platinum-based neoadjuvant chemotherapy with gemcitabine at 800 mg/m ² vs. 1000 mg/m ² in muscle-invasive bladder cancer: A multicenter retrospective study.

Abstract

773 Background: Platinum-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the gold standard treatment for muscle-invasive bladder cancer (MIBC). Gemcitabine plus platinum agents is preferred over MVAC due to similar efficacy and reduced toxicity. However, the optimal gemcitabine dose for balancing safety and efficacy remains unclear. Methods: This multicenter retrospective study included 517 patients with MIBC who received 2–4 cycles of platinum-based NAC with gemcitabine, followed by RC. Patients were divided into two groups based on gemcitabine dosage: the 800 mg/m 2 group and the 1000 mg/m 2 group. The incidence of myelosuppressive hematological adverse events (AEs) was compared between the two groups. Multivariable Cox proportional hazards regression analyses were conducted to assess the impact of gemcitabine dose on cancer-specific survival (CSS) and overall survival (OS). Results: The median age and follow-up duration were 70 years and 55 months, respectively. Of the 517 patients, 348 (67%) received gemcitabine at a dose of 800 mg/m 2 , and 169 (33%) received 1000 mg/m 2 . The rates of grade ≥3 neutropenia and febrile neutropenia did not differ significantly between the 800 mg/m 2 and 1000 mg/m 2 groups (70% vs. 70%, P = 0.958; 4.1% vs. 5.4%, P = 0.523, respectively). However, the incidence of grade ≥3 thrombocytopenia was significantly lower in the 800 mg/m 2 group compared to the 1000 mg/m 2 group (20% vs. 33%, P < 0.001). CSS and OS were significantly shorter in the 800 mg/m 2 group than in the 1000 mg/m 2 group ( P = 0.012 and P < 0.001, respectively). After adjustment for confounding variables, gemcitabine at 800 mg/m 2 was not significantly associated with shorter CSS ( P = 0.471; hazard ratio [HR]: 1.298; 95% confidence interval [CI]: 0.639–2.636) or OS ( P = 0.308; HR: 1.351; 95% CI: 0.758–2.410). Conclusions: Gemcitabine at a dose of 800 mg/m 2 may reduce the incidence of grade ≥3 thrombocytopenia without compromising oncological outcomes. Multivariable analysis for CSS. Factor P value HR 95% CI Age Continuous 0.683 1.006 0.979–1.033 Sex Male 0.738 0.919 0.561–1.506 Performance status Continuous 0.569 1.154 0.705–1.889 Body mass index Continuous 0.853 1.005 0.950–1.065 Cisplatin-based regimens Received 0.215 0.665 0.348–1.268 Tumor grade Grade 3 0.012 2.040 1.170–3.557 Pathological T stage ≥ pT3 0.024 1.805 1.079–3.017 Pathological N stage ≥ pN1 <0.001 2.742 1.663–4.522 Surgical margin Positive 0.086 1.870 0.916–3.816 Urinary diversion Neobladder 0.085 0.665 0.418–1.058 Gemcitabine dose 800 mg/m2 0.471 1.298 0.639–2.636