Bladder Preservation Therapy Using Proton Boost Concurrently Combined With Intra-Arterial Chemotherapy For Invasive Bladder Cancer

The purpose of the present study is to retrospectively analyze the clinical outcomes of bladder preservation therapy using proton boost for muscle-invasive bladder cancer. Between August 1990 and February 2014, we treated patients with stage T2-3N0M0 bladder cancer with the following protocol: patients were treated with concurrent chemoradiation therapy (CRT) as a bladder preservation therapy. Transurethral resection of the bladder tumor was performed for reduction of tumor volume and pathological examination for tumor invasion before CRT. Three cycles of intra-arterial chemotherapy consisting of MTX 30mg/m2 and CDDP 50mg/m2were administered every 3 weeks during small-pelvis irradiation by X ray (41.4 Gy/23 fractions). Upon on completion of CRT, patients were evaluated by transurethral biopsy to confirm disappearance of cancer cells, and patients without residual tumor received boost irradiation (36.3 Gy equivalent/11 fractions) using proton beams. In the present study, we focus on the clinical outcomes of 72 patients (male: 54, female: 18) who were treated with this protocol; their median age was 66 years (range, 36-89 years). Median follow-up time was 36 months (range, 2-237 months). Recurrences developed in 18 patients (25.0%); initial recurrence sites were bladder alone in 9, both bladder and distant organs in 2, lymph nodes in 4, distant organs alone in 2, and renal pelvis in 1. Recurrences at the bladder were observed in 11 cases (15.3%): seven tumors were noninvasive, and bladder function was preserved in 5 of them. Until the last follow-up, 9 patients died of disease recurrences, but 6 patients died of intercurrent diseases without any signs of recurrence. The 5-year rates of overall survival, local control, and bladder preservation were 71.4%, 83.4%, and 86.3%, respectively. Treatment-related late toxicities of grade 3-4 were observed in 3 patients: urinary hemorrhage, urethral stricture, and ureter stricture in each. There were no grade 3 gastrointestinal toxicities. Statistical analyses revealed that multiple tumors (P=.04), T3 (P=.014), and existence of hydronephrosis before treatment (P=.021) were prognostic factors for overall survival, and multiple tumors (P