External beam radiotherapy and concurrent gemcitabine for muscle-invasive bladder cancer: Toxicities and early outcomes.

Abstract

443 Background: To report toxicities and early outcomes of external beam radiotherapy (EBRT) with concurrent gemcitabine for muscle-invasive bladder cancer (MIBC) Methods: Between 9/04 - 4/15, 85 patients (median age 77) with MIBC (cT2-T4, Nx-3) underwent transurethral resection (TUR) (39 complete, 43 incomplete, 2 unknown) followed by EBRT (median dose 64.8Gy) with concurrent gemcitabine (20-27 mg/m2) twice weekly. 25 patients (29%) received neoadjuvant chemotherapy. Patients were followed q3 months with imaging, cystoscopy and/or cytology. Early ( < 90 days) and late ( > 90 days) toxicities were graded according to the Common Terminology Criteria for Adverse Events (v4.0). Median followup was 19.5 months; 74 (87%) had > 3 month followup. Kaplan-Meier and Cox regression were used for survival and multivariate analyses. Results: Acute grade ≥ 3 hematologic, gastrointestinal or genitourinary toxicity occurred in 18%, 1.5% and 1.3% of patients, respectively. 73/85 (86%) patients received full EBRT course without interruption. 78/85 (92%) received > 50% of the prescribed gemcitabine. The most common reason for a gemcitabine interruption/dose reduction was hematologic (80%). Late grade 3 toxicity included hematuria (n = 5), urinary obstruction (n = 4) and cystitis (n = 1). The 2-year freedom from in-bladder recurrence and bladder-intact survival was 53% and 60%, respectively. The 2-year distant metastasis-free, disease-specific and overall survivals were 66%, 69% and 62%, respectively. A complete TUR was associated with improvements in 2 year bladder-intact (73% vs 51%, p = 0.01), disease-specific (87% vs 54%, p = 0.001), distant metastasis-free (83% vs 52%, p < 0.0001) and overall survival (78% vs 50%, p = 0.003) compared with incomplete TUR. Neoadjuvant chemotherapy and nodal status had no significant impact on survival outcomes. Conclusions: EBRT with concurrent gemcitabine is well-tolerated for MIBC, even in an elderly population. Hematologic (acute) and genitourinary (late) toxicities are most common. Survival outcomes in this unselected population are comparable to prior trials, although longer followup is needed. A complete TUR prior to chemoradiation is strongly recommended.