T. Y. T. De Souza, L. Souhami, R. N. Asso, C. Martinez, W. Kassouf, R. R. Saleh, S. L. Faria, M. Duclos, R. Rajan, A. Aprikian, S. Tanguay, R. Sanchez-Salas, and F. Cury; McGill University Health Centre, Montreal, QC, Canada
Purpose/Objective(s):Trimodality therapy (TMT) has become increasingly recognized as a viable option for patients (pts) with muscle invasive bladder cancer (MIBC). This study aims to assess the effectiveness and safety of TMT using hypofractionated intensity modulated radiation therapy (HIMRT) combined with weekly gemcitabine for MIBC pts. Materials/
Methods: Between 2008 and 2021, 103 pts with MIBC underwent transurethral resection of bladder tumor (TURBT) followed by HIMRT 50 Gy/20 fractions to the entire empty bladder and ± 40 Gy/20 fractions to pelvic nodes (PLN) with concurrent weekly gemcitabine (100 mg/m2). Pts were followed up for a minimum of 12 months. At presentation, they were staged as follows: 87.5% stage 2, 10.5% stage 3 and 2% stage 4. Clinical characteristics such as age, gender, ECOG performance status, complete or incomplete TURBT, clinical stage, and presence of carcinoma in situ were evaluated for their predictive value using multivariable analysis (MVA) using Cox proportional-hazards model. Overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and bladder preservation rates were estimated using the Kaplan-Meier method. Acute and late toxicities were graded according to Common Terminology Criteria for Adverse Events version 4.0. Results: The median follow-up was 51 months (range: 15-170) with a median age of 75 years (interquartile range [IQR] 66–80). 79% of pts had a complete TURBT. At 3-month cystoscopy, 83.5% of pts achieved a complete response (CR). Median OS was 49 months. 5-year OS, LRFS, DMFS, cystectomy-free survival and intact bladder survival rates were 59.2%, 77.6%, 77.4%, 87.4% and 56.5%, respectively. On MVA, lack of CR correlated with a significantly higher risk of local recurrence (hazard ratio 3.01; p=0.018), while ECOG =2 plus stage 3 or 4 disease impacted on OS. Seventy-three pts (70.9%) received HIMRT to the bladder + PLN, while 30 pts (29%) received to the bladder only, with no significant outcomes difference between the two groups. Among the 23 pts with local recurrence, 12 were MIBC and underwent salvage radical cystectomy. Of the 11 who had a non-invasive recurrence, 4 were carcinoma in situ (pTis) and 4 were papillary urothelial carcinoma (pTa) and 3 were pT1. Acute gastrointestinal (GI), genitourinary (GU), and hematological toxicities grade =3 were 6.3%, 3.5%, and 8.5%, respectively. Late GI and GU toxicities grade =3 were 3.5% and 0.7%, respectively. Conclusion: Bladder preservation with HIMRT combined with concurrent low-dose weekly gemcitabine is a well-tolerated, effective, and attractive alternative for MIBC treatment in this, generally, elderly population. This approach yields comparable outcomes to radical cystectomy, providing encouraging functional and oncologic results.
