Accelerated Hypo-Fractionated Radiation Therapy for Elderly Frail Bladder Cancer Patients Unfit for Surgery or Chemotherapy

Abstract

Frail elderly patients with potentially curable muscle-invasive bladder cancer are often unsuitable candidates for surgery or tri-modality therapy as they are unfit for chemotherapy and unable to complete a six-week course of radiotherapy. We hypothesized that accelerated hypofractionated radiotherapy, as a single modality, would improve outcomes for this population of patients. Patients with confirmed muscle-invasive or high-risk T1 transitional cell carcinoma of the bladder, stage T1-T4aN0M0, who underwent transurethral resection of bladder tumor (TURBT) and were not suitable for cystectomy or chemotherapy were eligible for this retrospective analysis. All patients were treated with curative intent to a dose of 45 Gy in 15 fractions. Comorbidity burden was assessed by Charlson Comorbidity Index (CCI). Weekly symptom assessment and physical examination was performed during treatment, followed by cystoscopy and cytology sample commencing at a mean of 3 months after completion of treatment. Cystoscopy, cytology, and computed tomography imaging were used to evaluate treatment outcome. Endpoints for this study included local control and complete local response (stable or absence of bladder tumor) as well as overall, disease-free, and cancer-specific survival analyzed by the Kaplan-Meier method. Seventeen patients with a median age of 87 (range, 81-95 years), mostly male (82%) and age-adjusted CCI >3 were included during 2010 to 2015. Pre-treatment staging was T2N0 in 76% of patients and hydronephrosis was evident in 47% of patients. TURBT was considered incomplete in 65% of patients. Radiation therapy technique has evolved over the years from 3-D CRT (47%) to VMAT (53%). Almost all patients (94%) completed radiotherapy, with a median treatment time of twenty days. Median follow-up was 10.6 months. Acute grade 3 gastrointestinal or genitourinary toxicities occurred in 6% and 24%, respectively. No grade 4 toxicity was documented. Acute/late Diarrhea of any grade occurred in 29% of patients treated with 3-D technique, but in none of the patients treated with VMAT (p=0.002). Local control within the bladder was achieved in 69% of patients evaluated by cystoscopy or imaging, and complete local response was 69% of patients who underwent cystoscopy. Overall survival at 1 year was 45%, and cancer-specific survival at 1 and 2 years were 85% and 70%, respectively. Of the surviving patients at the end of follow-up, 80% were without evident of disease and 60% had a functioning bladder. Accelerated hypo-fractionated radiotherapy alone provides excellent local control in elderly patients unfit for concomitant chemoradiotherapy. Contemporary radiation techniques such as VMAT were associated with reduced bowel toxicity compared with 3-D CRT.