What is the recommended treatment approach for patients with high-risk prostate cancer based on the SWOG (Southwest Oncology Group) 1826 trial?

Treatment Approach for High-Risk Prostate Cancer Based on SWOG 1826 Trial

For patients with high-risk prostate cancer, external beam radiotherapy (EBRT) plus androgen deprivation therapy (ADT) for at least 2-3 years is the recommended treatment approach, with emerging evidence supporting the addition of novel hormonal agents or chemotherapy in selected cases.

Current Standard of Care for High-Risk Prostate Cancer

The management of high-risk prostate cancer requires aggressive multimodal therapy to optimize outcomes. Based on current guidelines:

• External beam radiotherapy (EBRT) plus hormone treatment is a category 1, level A recommendation for high-risk or locally advanced prostate cancer 1
• Radical prostatectomy (RP) plus extended pelvic lymphadenectomy is an alternative option for selected patients 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 men receiving neoadjuvant hormonal therapy and radical RT who are at high risk of prostate cancer mortality 1

Treatment Intensification Options

Recent evidence supports treatment intensification beyond traditional ADT + EBRT:

1. ADT with novel hormonal agents (doublet therapy):

   • Abiraterone, apalutamide, or enzalutamide added to ADT 1
   • The LATITUDE trial showed improved overall survival with abiraterone plus prednisone and ADT versus ADT alone (53.3 vs 36.5 months) 1

2. ADT with chemotherapy and novel hormonal agents (triplet therapy):

   • ADT with docetaxel and abiraterone or darolutamide 1
   • The NRG Oncology RTOG 0521 trial demonstrated that adding docetaxel to standard ADT+RT improved 4-year overall survival from 89% to 93% in high-risk patients 2

3. ADT with EBRT to the primary tumor for low-metastatic burden disease 1

SWOG 1826 and Related SWOG Trials

While the specific SWOG 1826 trial results are not detailed in the provided evidence, other SWOG trials have informed prostate cancer management:

• SWOG 8794 trial showed improved overall survival with adjuvant radiotherapy after radical prostatectomy compared to observation (HR 0.72; 95% CI 0.5-0.96; P=0.023) 1
• SWOG 9346 trial evaluated intermittent versus continuous ADT in metastatic prostate cancer, failing to demonstrate non-inferiority of intermittent ADT 1

Treatment Algorithm for High-Risk Prostate Cancer

1. Initial risk assessment:

   • High-risk features: Gleason score 8-10, clinical stage T3-T4, PSA >20 ng/mL 3

2. Treatment options based on patient factors:

   a) For patients suitable for definitive local therapy:

   • EBRT + long-term ADT (2-3 years) as preferred approach 1
   • Consider adding docetaxel chemotherapy for very high-risk features 2
   • Consider adding abiraterone for very high-risk features 1, 4

   b) For surgical candidates:

   • Radical prostatectomy with extended lymph node dissection 1
   • Consider adjuvant or salvage radiotherapy for positive margins or extracapsular extension 1

3. Radiation therapy specifics:

   • Minimum target dose of 70-74 Gy given in 1.8-2.0 Gy fractions 5
   • Consider intensity-modulated radiotherapy (IMRT) for dose escalation above 74 Gy 5

Common Pitfalls to Avoid

1. Inadequate ADT duration: Short-term ADT is insufficient for high-risk disease; 2-3 years of adjuvant ADT is recommended 1, 5

2. Suboptimal radiation dosing: Doses below 70 Gy result in inferior outcomes 5

3. Using ADT alone: Primary ADT alone is not recommended as standard initial treatment of non-metastatic disease 1

4. Delayed salvage therapy: Early salvage radiotherapy (PSA <0.5 ng/ml) is recommended after biochemical failure following radical prostatectomy 1, 5

5. Overlooking combination therapy: For high-risk disease, multimodal approaches are superior to single-modality treatment 5

Special Considerations

• The benefit of ADT may be less clear when combined with both EBRT and brachytherapy 3
• Neoadjuvant therapy with ADT plus docetaxel or abiraterone has shown better pathological outcomes for very-high-risk localized prostate cancer compared to ADT alone 4
• Treatment-related toxicities must be monitored, particularly with intensified regimens 1