Favorable toxicity of chemoradiation for muscle-invasive bladder cancer in elderly, frail patients.
Authors: Moore Assaf , Zhang Zhigang , Bochner Bernard H. , Donahue Timothy F. , Rosenberg Jonathan E. , Iyer Gopa , Funt Samuel Aaron , Bajorin Dean F. , Teo Min Yuen , Aggen David Henry , Gorovets Daniel , Guttmann David , Zelefsky Michael J. , Kollmeier Marisa 
Published: February 2022

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Background: Chemoradiation (CRT) for bladder cancer provides comparable outcomes to radical cystectomy; however, concerns regarding toxicity, particularly in elderly, frail patients limit its utilization. Methods: We identified 150 consecutive patients who underwent definitive CRT for T1-4N0M0 bladder cancer at Memorial Sloan Kettering Cancer Center between 2005 and 2020. Most were men (71.3%), elderly (median age, 77.5 years), had high Charlson Comorbidity Index (CCMI) score (median, 7), were nonsurgical candidates (65.3%), Stage T2 (75.3%) and had a macroscopically complete TURBT (65%). 24% of patients received neoadjuvant platinum-based chemotherapy. Concurrent gemcitabine was used in 98.7%. 116 (77.3%) patients underwent 45Gy to the pelvic lymphatics/whole bladder followed by bladder boost (median total dose, 66.6 Gy) and 34 patients (22.7%) received 55 Gy in 20 fractions to the whole bladder/ urethra only. Fiducial markers for image-guidance were used in 55% (83/150) of cases. Patients were followed post-treatment with toxicity assessment, cytology/cystoscopy and imaging every 3 months year 1, every 6 months for years 2-3 and annually thereafter. Acute (≤3 months) and late ( > = 3 months) gastrointestinal (GI) and genitourinary (GU) toxicities were assessed according to CTCAE v4.0. Complete response (CR) was defined as no evidence of disease at 3-month follow up. Survival outcomes were estimated using the Kaplan-Meier method. Median follow up was 31 months (range, 0-155 months). Results: The majority (94%) completed the prescribed course of radiation. Acute grade 3 GU and GI toxicities occurred in 2% and 5.3% of patients, respectively. No acute grade 4 toxicity was recorded. The most common GU and GI toxicities were radiation cystitis and diarrhea. Late grade ≥2 GU and GI toxicity occurred in 11.2% and 0.7% or cases, respectively. One late grade 4 GI toxicity was recorded (small bowel obstruction 7 months after completion of CRT). 80% (n = 120) of patients achieved a CR. Of complete responders, 30% (36/120) developed recurrent disease at a median time of 13.8 months (range, 3.2- 90.4). Among them, local only vs regional/distant recurrence rates were 72.2% and 27.8%, respectively. Of entire cohort, 40% of patients were alive and 31% had died with no evidence of disease at last follow up. While the estimated 5-year OS was 48% (95% CI, 39%, 59%), the estimated 5-year disease-specific mortality rate was 31% (95% CI, 24%, 40%). On univariate analysis, younger age (p < 0.001), receipt of neoadjuvant chemotherapy (p = 0.006) and surgical candidacy (p = 0.041) were predictive of improved OS. On multivariate analysis, only younger age was significant (p = 0.006). Conclusions: CRT had a favorable toxicity profile and encouraging cancer control outcomes in this unselected, mostly elderly and frail patient cohort.