What is the role of adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer?

Role of Adjuvant Radiation Therapy After Radical Prostatectomy

Adjuvant radiation therapy should be offered to patients with adverse pathologic findings after radical prostatectomy, including seminal vesicle invasion, positive surgical margins, or extraprostatic extension, as it reduces the risk of biochemical recurrence, local recurrence, and clinical progression of prostate cancer. 1

Patient Selection for Adjuvant RT

Adjuvant radiation therapy is most beneficial for patients with:

• Adverse pathologic features:
  • Positive surgical margins (especially if diffuse >10 mm or ≥3 sites)
  • Seminal vesicle invasion
  • Extraprostatic extension
• Short PSA doubling times (<9 months)
• Persistent serum PSA levels after surgery 1

Evidence Supporting Adjuvant RT

Multiple randomized controlled trials have demonstrated benefits of adjuvant RT:

• SWOG 8794 trial (425 patients, 12.6 years median follow-up):

  • Reduced risk of PSA relapse and disease recurrence
  • Improved 10-year biochemical failure-free survival in high-risk patients (36% vs 12%, p=.001)
  • Showed improved overall and metastasis-free survival 1

• EORTC trial (1005 patients):

  • 5-year biochemical progression-free survival significantly improved with RT for patients with positive surgical margins (78% vs 49%)
  • No benefit observed for patients with negative surgical margins 1

• German study by Wiegel et al. (268 patients with pT3 disease):

  • Postoperative radiation improved 5-year biochemical progression-free survival (72% vs 54%; HR, 0.53) 1

Timing of Adjuvant RT

• Should be administered after recuperation from surgery, typically within 1 year 1
• Should be administered before PSA exceeds 1.5 ng/mL 1
• Earlier administration (when PSA is lower) is associated with better outcomes 1

Target Volumes and Dosing

• The defined target volumes include the prostate bed 1
• Pelvic lymph nodes may be irradiated, but pelvic radiation is not always necessary 1
• Median doses of 70-74 Gy using intensity-modulated RT (IMRT) have shown excellent biochemical relapse-free survival rates (93% at 3 and 5 years) 2

Special Considerations for Lymph Node Positive Disease

For patients with positive lymph nodes found during or after radical prostatectomy:

1. ADT (androgen deprivation therapy) is a category 1 option
2. Observation is a category 2A recommendation for very low-risk or low-risk patients (category 2B for intermediate, high, or very high risk)
3. Addition of pelvic RT to ADT (category 2B) may improve biochemical recurrence-free survival and cancer-specific survival 1

Salvage vs. Adjuvant RT

• Salvage RT is administered after biochemical recurrence (PSA ≥0.2 ng/mL with confirmatory level) 1
• Adjuvant RT is administered before biochemical recurrence
• Effectiveness of salvage RT is greatest when administered at lower PSA levels 1
• PSA should be monitored every 6-12 months for the first 5 years after radical prostatectomy, as 77% of recurrences occur within this period 3

Potential Side Effects

Radiation therapy after prostatectomy may cause:

• Urinary toxicity (grade 3 GU toxicity in 4-8% of patients)
• Gastrointestinal toxicity (generally mild)
• Urethral strictures (reported in 6% of patients)
• Sexual dysfunction 2

Higher doses (>70 Gy) may increase the risk of severe side effects, though modern techniques like IMRT have improved the safety profile 2, 4

Follow-up After Treatment

• PSA monitoring every 6-12 months for the first 5 years, then annually
• Annual digital rectal examination to monitor for local recurrence and colorectal cancer
• Bone mineral density assessment for patients receiving ADT, with calcium and vitamin D supplementation recommended 1

Adjuvant RT after radical prostatectomy has demonstrated clear benefits in reducing biochemical recurrence and disease progression in patients with adverse pathologic features, with emerging evidence suggesting improvements in metastasis-free and overall survival.