What are the indications for adjuvant radiotherapy (RT) in carcinoma of the urinary bladder?

Adjuvant Radiotherapy Indications for Bladder Cancer

Adjuvant radiotherapy should be considered for patients with pT3/pT4 pN0-2 urothelial bladder cancer after radical cystectomy, particularly those with positive surgical margins and/or positive lymph nodes, as these patients face pelvic failure rates of 40-45% at 5 years. 1

Primary Indications for Adjuvant RT

High-Risk Pathologic Features (Post-Cystectomy)

• Locally advanced disease (pT3-4) with or without nodal involvement (pN0-2) represents the clearest indication for adjuvant RT 1
• Positive surgical margins at any pT stage—these patients have particularly high pelvic failure rates (68% in some series) and may derive the greatest survival benefit 1, 2
• Positive pelvic lymph nodes identified during lymphadenectomy, especially with extranodal extension 1

The NCCN guidelines specifically state that although no conclusive data demonstrate improvements in overall survival, adjuvant radiation is reasonable in this population given the high local failure rates (20-45%) and relatively good tolerability 1.

Evidence Base and Outcomes

• One randomized study of 236 patients with pT3a-pT4a disease demonstrated improvement in 5-year disease-free survival and local control compared with surgery alone 1
• A more recent randomized phase II trial (120 patients with pT3-4 or node-positive disease) showed significant improvement in local control for chemoradiation (96% vs 69% at 3 years), though overall survival improvement was not statistically significant 1
• Late grade ≥3 gastrointestinal toxicity was low in these trials 1
• A large US database study suggested an overall survival benefit specifically for patients with positive surgical margins (hazard ratio 0.73, p=0.047) 2

Radiation Dose and Technique

Standard Dosing

• 45 to 50.4 Gy to the treatment field without concurrent chemotherapy is the standard approach 1
• Treatment fields should encompass the cystectomy bed and pelvic lymph nodes at risk 1
• Boost doses of 54-60 Gy may be considered for involved resection margins and areas of extranodal extension if feasible based on normal tissue constraints 1

Alternative Dosing (Older Guidelines)

• Earlier NCCN recommendations suggested 40-45 Gy with or without concurrent cisplatin 1
• The safety of higher doses, especially with neobladder reconstruction, requires further study 1

Sequencing with Chemotherapy

For patients who did not receive neoadjuvant chemotherapy, it may be reasonable to sandwich adjuvant radiation between cycles of adjuvant chemotherapy 1. However:

• Radiation and multidrug chemotherapy should not be given concurrently in the adjuvant setting 1
• The safety and efficacy of concurrent sensitizing chemotherapy with radiation in the adjuvant setting needs further study 1
• Patients who received neoadjuvant chemotherapy should not receive additional adjuvant chemotherapy after partial cystectomy 1

Patients Who Should NOT Receive Adjuvant RT

• Patients with ≤pT2 disease with no nodal involvement or lymphovascular invasion are considered lower risk and adjuvant RT is not indicated 1
• Patients with adequate surgical margins and pT2 or less disease have sufficiently low pelvic failure rates that adjuvant RT is not warranted 1

Special Consideration: Partial Cystectomy

For highly selected patients who undergo partial cystectomy, adjuvant radiotherapy or chemotherapy may be considered based on pathologic risk factors including positive nodes, positive margins, high-grade lesions, and pT3-4 lesions (category 2B recommendation) 1.

Current Practice Patterns

Important caveat: Despite these indications, use of adjuvant RT in the United States has been decreasing over time, from 3.1% in 2004 to 1.7% in 2013 2. Current utilization rates are approximately 1.4% for pT3 disease, 4.0% for pT4 disease, and 5.2% for positive surgical margins 2. This underutilization may represent a missed opportunity for local control in appropriately selected high-risk patients.

Key Clinical Pitfall

The most critical error is failing to identify patients with positive surgical margins or extranodal extension who would benefit most from adjuvant RT. These patients have the highest pelvic failure rates and appear to derive the greatest benefit from adjuvant radiation 1, 2. Careful pathologic review and multidisciplinary discussion are essential for identifying appropriate candidates.