Recommended Radiotherapy Approach for High-Risk Prostate Cancer
For high-risk prostate cancer, the recommended radiotherapy approach is external beam radiation therapy (EBRT) combined with long-term androgen deprivation therapy (ADT) for 24-36 months, with the option of adding brachytherapy boost for improved disease control. 1
Standard Treatment Approach
- EBRT using intensity modulated radiation therapy (IMRT) techniques should be employed to provide highly conformal treatment to the prostate 1
- Long-term ADT (24-36 months) should be administered as an adjunct to radiotherapy for high-risk prostate cancer patients (Strong Recommendation; Evidence Level: Grade A) 1
- Pelvic lymph node irradiation should be considered for patients with high-risk disease 1
- Doses between 78 and 80+ Gy provide improved PSA-assessed disease control for high-risk disease 1
- Image-guided radiation therapy (IGRT) is required if dose ≥78 Gy to improve oncologic cure rates and reduce side effects 1
Combined Modality Approach
- Combination therapy of EBRT with brachytherapy (either low-dose or high-dose rate) can be considered to improve coverage of the periprostatic space 1
- The addition of brachytherapy to EBRT has shown reduced risk of recurrence in high-risk patients 1
- Analysis of 12,745 high-risk patients found that treatment with brachytherapy plus EBRT lowered disease-specific mortality compared with EBRT alone (HR, 0.77; 95% CI, 0.66–0.90) 1
- Trimodality treatment (EBRT + brachytherapy + ADT) has shown excellent outcomes with 9-year progression-free survival and disease-specific survival rates reaching 87% and 91%, respectively 1
ADT Duration Considerations
- For patients receiving EBRT alone, the optimal minimum ADT duration appears to be more than 18 months, with evidence supporting 24-36 months 2, 1
- For patients receiving EBRT plus brachytherapy boost, the optimal minimum ADT duration may be 18 months or possibly less 2
- The EORTC 22961 trial showed that 36 months of ADT improved 5-year overall survival compared to 6 months (84.8% vs 81.0%, HR 1.42; 95% CI 1.09–1.85) 1
- Neoadjuvant and concurrent ADT for 4–6 months followed by adjuvant ADT for a total of 24-36 months is recommended 1
Treatment Selection Considerations
- Patients with obstructive urinary symptoms may be better candidates for surgical approaches rather than radiotherapy 3
- If radiotherapy is chosen for patients with obstructive symptoms, brachytherapy should be used cautiously as it can exacerbate urinary obstructive symptoms 3, 1
- Patients should be informed that ADT with radiation increases the likelihood and severity of adverse treatment-related events on sexual function and can cause other systemic side effects (Strong Recommendation; Evidence Level: Grade B) 1
Emerging Evidence
- Recent studies suggest that the PSA response to neoadjuvant ADT before EBRT (PSA nadir) may influence long-term biochemical tumor-control outcomes 4
- Some evidence suggests that combined EBRT and brachytherapy without ADT may provide good outcomes in select high-risk patients, with one study showing 5-year biochemical failure-free survival of 84.8% 5
- However, this remains controversial as the strongest evidence still supports the use of ADT with radiotherapy for high-risk disease 1
Common Pitfalls and Caveats
- Primary ADT alone (without radiotherapy) is not recommended as standard initial treatment for non-metastatic high-risk prostate cancer 1, 3
- Ensure proper patient selection for brachytherapy, as patients with very large or very small prostate, high IPSS scores, or previous TURP may be at increased risk for side effects 1
- Post-implant dosimetry should be performed to document the quality of brachytherapy implants 1
- Daily prostate localization techniques should be used to improve treatment accuracy and reduce side effects 1
By following this evidence-based approach to radiotherapy for high-risk prostate cancer, clinicians can optimize disease control while minimizing treatment-related toxicity.