A new study published in the journal JAMA surgery reported that adjuvant chemotherapy plus radiotherapy is associated with significant improvements in locoregional recurrence–free survival and favorable cancer control outcomes compared with chemotherapy alone.

Locoregional failure for patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity and mortality. Adjuvant radiotherapy (RT) can decrease locoregional failure but has not been studied in the chemotherapy era.

A randomized phase 3 trial was opened to compare adjuvant RT vs sequential chemotherapy plus RT after RC for LABC, but a third arm was added later as a randomized phase 2 trial to compare chemotherapy plus RT vs adjuvant chemotherapy alone, an emerging standard. The intent-to-treat phase 2 trial reported herein enrolled patients.

Routine follow-up and surveillance pelvic computed tomographic (CT) scans every 6 months during the first 2 years were performed. The setting was an academic centre. Patients with bladder cancer 70 years or younger having 1 or more risk factors with negative margins after radical cystectomy plus pelvic lymph node dissection were eligible.

Patients had Eastern Cooperative Oncology Group performance status of 0 to 2, no evidence of distant metastases on CT scan of the abdomen and pelvis or on chest imaging, and adequate renal, hepatic, and hematologic function. Ninety-one percent (109 of 120) had ≥ pT3 disease.

Chemotherapy plus RT included 2 cycles of gemcitabine (1000 mg/m2 intravenously on days 1, 8, and 15) and cisplatin (70 mg/m2 intravenously on day 2) before and after RT to 4500 cGy in 150 cGy twice-daily fractions over 3 weeks using 3-dimensional conformal techniques. Chemotherapy alone included 4 cycles of gemcitabine and cisplatin.

The chemotherapy plus RT arm accrued 75 patients, and the chemotherapy-alone arm accrued 45 patients, with a weighted randomization to speed accrual. Fifty-three percent (64 of 120) had urothelial carcinoma, and 46.7% (56 of 120) had squamous cell carcinoma or other. The arms were balanced except for age and tumour size, both favouring chemotherapy plus RT.

Two-year outcomes and overall adjusted hazard ratios (HRs) for chemotherapy plus RT vs chemotherapy alone were 96% vs 69% for LRFS, 68% vs 56% for disease-free survival, and 71% vs 60% for overall survival (OS). Five patients (7%) had RT-associated late grade 3 gastrointestinal tract adverse effects in the chemotherapy plus RT arm.

Adjuvant chemotherapy plus RT was reasonably well tolerated and was associated with significant improvements in LRFS and marginal improvements in disease-free survival vs chemotherapy alone in LABC. The addition of adjuvant RT should be considered for LABC. This regimen warrants further study in phase 3 trials, the researchers concluded.