Comparison of sequential versus concurrent chemoradiation regimens in non-metastatic muscle-invasive bladder cancer

Abstract

Purpose: The treatment approach for non-metastatic bladder cancer is guided by an invasion of the muscular layer of the bladder wall. Radical cystectomy is the recommended treatment for muscle-invasive disease. However, it has considerable morbidity and mortality and is not suited for many patients. Trimodality therapy consisting of chemoradiation after transurethral resection of bladder tumor offers a definitive approach with bladder-sparing potential. However, there is a lack of research defining the optimal combination of chemotherapy and radiation in this setting.

Materials and methods: We extracted patient data from the National Cancer Database to compare survival outcomes and demographic factors in 2,227 non-metastatic bladder cancer patients who were treated with chemotherapy sequential to or concurrently with radiation. Sequential treatment was defined as chemotherapy beginning >14 days before radiation, and concurrent was defined as beginning within 14 days of the first radiation.

Results: The sequential treatment group patients were younger (mean age, 74 vs. 78 years; p < 0.001) with more advanced disease. We found no difference in overall survival between patients who received chemotherapy sequential to radiation and those who received concurrent chemoradiation only (p = 0.533).

Conclusion: Our data are concordant with a previous prospective study, and support that chemotherapy prior to radiation does not decrease survival outcomes relative to patients receiving only concurrent chemoradiation. Given that the sequential group had an overall higher stage but no difference in survival, downstaging chemotherapy prior to radiation may be helpful in these patients. Further studies including a larger, multi-institutional clinical trial are indicated to support clinical decision-making.

Keywords: Chemoradiotherapy; Survival analysis; Urinary bladder neoplasms.

Fig. 1.

Flowchart of selection of study patients from National Cancer Database (NCDB). NA, Not Applicable; IS, In situ; AJCC, American Joint Committee on Cancer; N0, No regional lymph node involvement; M0, No distant metastasis; NOS, Not otherwise specified.

Fig. 2.

(A) Kaplan-Meier curve of overall survival time in patients with non-metastatic bladder cancer treated with either sequential chemotherapy followed by radiation therapy (Upfront Chemo then RT, blue line, n = 554) or concurrent chemotherapy and radiation therapy (Concurrent Chemo then RT, red line, n = 1,673). (B) Kaplan-Meier curve of overall survival time after matching (Upfront Chemo then RT, blue line, n=554; Concurrent Chemo then RT, red line, n = 554).