Adjuvant Radiotherapy Enhances Control of High-Risk Bladder Cancer

Recent findings suggest that adjuvant radiotherapy significantly reduces the risk of locoregional recurrence in patients with high-risk muscle-invasive bladder cancer (MIBC) following radical cystectomy and perioperative chemotherapy. The study, published in the Journal of Clinical Oncology, indicates potential benefits for disease-free and overall survival, though these were not statistically significant.

The phase 3 randomized controlled trial was conducted at four academic centers in India, involving 153 patients with nonmetastatic MIBC. The trial's participants were primarily treated with neoadjuvant (71%) or adjuvant chemotherapy (20%) alongside undergoing radical cystectomy and pelvic nodal dissection.

The patients were randomly assigned to receive either adjuvant radiotherapy using intensity-modulated radiotherapy (IMRT) delivering 50.4 Gy in 28 fractions, or observation. Radiotherapy began within eight weeks of surgery or the last chemotherapy session. After a median follow-up of 47 months, the primary outcome, 2-year locoregional recurrence-free survival, was notably higher in the radiotherapy group at 87.1%, compared to 76.0% in the observation group (hazard ratio, 0.43; P = .04).

Additionally, although not reaching statistical significance, the radiotherapy arm showed improved rates of disease-free survival (71.6% vs 58.7%), bladder cancer-specific survival (79.6% vs 65.0%), and overall survival (70.4% vs 57.4%).

Of the patients experiencing disease recurrence, roughly 31% developed distant metastases, with similar rates observed across both study arms. Locoregional recurrence, however, was significantly less frequent in those receiving pelvic radiotherapy (7.9%) compared to those under observation (25.6%; odds ratio, 0.25).

Serious adverse effects within the initial three months were infrequent, with 1.6% of radiotherapy patients and 4.2% of those in the observation group affected. Notably, 17.5% of patients in the radiotherapy cohort experienced grade 2 symptoms like diarrhea or proctitis. Later stage grade 3 or 4 adverse events occurred in 17% of radiotherapy patients compared to 10.5% in the observation group.

The study authors, led by Dr Vedang Murthy from the Tata Memorial Centre in Mumbai, underscore the potential of adjuvant pelvic IMRT to enhance locoregional control with minimal added severe toxicity. They emphasize that these results bolster the integration of radiotherapy into the adjuvant treatment regimen for patients with high-risk MIBC. However, it should be noted that 14 patients did not receive the intended radiotherapy, and the absence of immunotherapy in the trial limits the applicability of findings to current clinical practices.