What are the indications for Radiation Therapy (RT) in prostate cancer?

Indications for Radiation Therapy in Prostate Cancer

Radiation therapy (RT) is indicated for patients with prostate cancer across all risk categories, with specific recommendations based on disease risk stratification, patient factors, and treatment goals aimed at optimizing survival and quality of life.

Risk-Based Indications for RT

Low-Risk Prostate Cancer

• RT is an option for men with low-risk disease as an alternative to active surveillance or radical prostatectomy 1
• For low-risk patients, RT can be delivered as:
  • External beam radiation therapy (EBRT) with dose escalation (75.6-79 Gy) 1
  • Brachytherapy as monotherapy 1
• ADT should NOT be added to RT for low-risk patients except when needed to reduce prostate size for brachytherapy 1

Intermediate-Risk Prostate Cancer

• RT is a standard treatment option for intermediate-risk disease 1
• Recommended RT approaches include:
  • Dose-escalated hypofractionated EBRT 1
  • Combined EBRT-brachytherapy (LDR or HDR) 1
• For unfavorable intermediate-risk patients, RT should be combined with short-term (4-6 months) ADT 1
• Moderate hypofractionation is appropriate for intermediate-risk patients 1

High-Risk/Locally Advanced Prostate Cancer

• RT with long-term ADT is a primary treatment option for high-risk and locally advanced disease 1
• For patients with high-risk prostate cancer, clinicians should recommend the addition of long-course (18-36 months) ADT with radiation therapy 1
• RT approaches for high-risk disease include:
  • Dose-escalated EBRT (75-80 Gy) with whole pelvic nodal irradiation 1
  • Combined EBRT-brachytherapy with ADT 1
• Neoadjuvant and concurrent ADT for 4-6 months is recommended for men receiving radical RT for high-risk disease 1
• Adjuvant ADT for 2-3 years is recommended for high-risk patients receiving RT 1

Specific RT Indications by Clinical Scenario

Primary Treatment

• RT as definitive primary treatment for localized disease across all risk groups 1
• RT with ADT for locally advanced disease (T3-T4) 1
• RT with elective nodal irradiation for high-risk patients, which has shown improved biochemical failure-free survival and distant metastasis-free survival 1

Salvage Treatment

• Salvage RT to the prostate bed for biochemical recurrence after radical prostatectomy 1
• Early salvage RT (PSA <0.5 ng/ml) is recommended for better outcomes 1

Adjuvant Setting

• Post-operative RT is not routinely recommended after radical prostatectomy 1
• Patients with positive surgical margins or extra-capsular extension should be informed about the pros and cons of adjuvant RT 1

Technical Considerations for RT Delivery

• Dose escalation (>75 Gy) is recommended for all risk categories to improve biochemical control 1, 2
• Daily image-guided RT (IGRT) is essential for target margin reduction and treatment accuracy when delivering higher doses 1
• Moderate hypofractionation is appropriate for high-risk patients who are candidates for EBRT 1
• Ultra-hypofractionation in high-risk patients with elective nodal coverage is not currently recommended outside clinical trials 1

Evidence Quality and Treatment Outcomes

• Multiple randomized trials demonstrate that dose escalation improves biochemical control but has not consistently shown overall survival benefits 2
• Combined RT and ADT has shown improvements in:
  • Biochemical control
  • Local control
  • Distant metastases rates
  • Disease-specific survival
  • Overall survival (particularly in high-risk patients) 3, 4
• The POP-RT trial demonstrated that whole pelvis IMRT for high-risk patients improved biochemical failure-free survival (HR 0.23) and distant metastasis-free survival (HR 0.35) compared to prostate-only RT 1

Common Pitfalls and Caveats

1. ADT Duration: Ensure appropriate ADT duration based on risk category - short-term (4-6 months) for intermediate-risk and long-term (18-36 months) for high-risk disease 1

2. Radiation Dose: Conventional dose of 70 Gy is no longer considered adequate; doses of 75-80 Gy are now standard 1, 2

3. Treatment Toxicity: Higher radiation doses are associated with increased late GI and GU toxicity (21% vs 15% and 12% vs 7%, respectively) 2, requiring careful consideration of the risk-benefit ratio

4. Patient Selection: Not all patients are suitable for RT; contraindications include prior pelvic irradiation, active inflammatory disease of the rectum, or a permanent indwelling Foley catheter 1

5. Timing of Salvage RT: Early initiation of salvage RT (PSA <0.5 ng/ml) after biochemical recurrence post-prostatectomy yields better outcomes 1

In summary, RT is a cornerstone treatment for prostate cancer with specific indications based on risk stratification. The combination of RT with appropriate duration of ADT for intermediate and high-risk disease has demonstrated significant improvements in disease control and survival outcomes.