What is the best treatment for a patient with Gleason 8 localized prostate cancer and a Prostate-Specific Antigen (PSA) level of 8?

Treatment for Gleason 8 Localized Prostate Cancer with PSA 8

For a patient with Gleason 8 localized prostate cancer and PSA 8 ng/mL, the optimal treatment is external beam radiation therapy (IMRT/VMAT plus IGRT) with long-term androgen deprivation therapy (ADT) for 2-3 years. This approach provides the best balance of cancer control and survival outcomes for this high-risk disease 1.

Risk Classification and Staging

This patient has high-risk localized prostate cancer based on:

• Gleason score 8 (high-risk criterion regardless of other factors)
• PSA 8 ng/mL (intermediate range, but Gleason 8 supersedes this)

Before proceeding with treatment, appropriate staging should include:

• Bone scintigraphy (bone scan) 1
• Pelvic MRI to assess local extent and lymph node involvement 1

Treatment Options and Recommendations

First-Line Recommendation: Radiation Therapy + ADT

• External beam radiation therapy (IMRT/VMAT plus IGRT) with 76-78 Gy in combination with long-term ADT (2-3 years) 1
• This combination has shown superior survival outcomes in high-risk disease 1
• The RTOG 92-02 trial demonstrated a significant overall survival advantage with long-term ADT (2 years) specifically in patients with Gleason 8-10 disease 1

Alternative Options:

1. Radiation therapy with brachytherapy boost + long-term ADT

   • For patients with good urinary function 1
   • IMRT/VMAT plus IGRT with brachytherapy boost (either HDR or LDR) and long-term ADT (2-3 years) 1

2. Radical prostatectomy with extended pelvic lymph node dissection

   • Viable option for selected patients as part of multimodal therapy 1
   • Should include extended pelvic lymph node dissection 1
   • May require adjuvant therapy based on pathological findings 1
   • 5-year progression-free survival rate of approximately 36% has been reported for patients with Gleason scores of 8 or greater after radical prostatectomy 1

Evidence Supporting Radiation + ADT Approach

The superiority of radiation therapy with long-term ADT is supported by:

• The NCCN guidelines identify radiation with long-term ADT as the preferred treatment for high-risk disease 1
• EAU guidelines strongly recommend IMRT/VMAT plus IGRT with 76-78 Gy in combination with long-term ADT (2-3 years) 1
• Multiple randomized trials have shown survival benefits with the addition of long-term ADT to radiation therapy in high-risk patients 1
• The RTOG 92-02 trial specifically showed overall survival advantage for Gleason 8-10 patients with long-term ADT (45% vs 32%, p=0.0061) 1

Outcomes and Prognosis

• With optimal treatment, 10-year cancer-specific survival can reach 85% for patients with high-grade prostate cancer 2
• For patients with Gleason 8 disease and PSA ≤10 ng/mL, 5-year biochemical recurrence-free survival rates of approximately 64-66% can be expected 3
• Patients with Gleason 9-10 have significantly worse outcomes compared to those with Gleason 8, highlighting the importance of aggressive treatment for Gleason 8 disease 4

Important Considerations

• Adjuvant radiation therapy should be considered after radical prostatectomy for patients with adverse pathological features (pT3 disease or positive margins) 1
• Whole gland or focal therapy is not recommended for high-risk disease 1
• Active surveillance is not appropriate for high-risk disease 1
• Brachytherapy alone is not recommended for high-grade disease 1

Follow-up Recommendations

• Regular PSA monitoring every 3-6 months for the first 5 years, then annually
• PSA should fall to a very low level and remain stable after radiation therapy
• PSA should be undetectable (<0.1 ng/mL) after radical prostatectomy
• Rising PSA after treatment requires prompt evaluation for recurrence

By selecting external beam radiation therapy with long-term ADT, this patient has the best chance for optimal cancer control and survival with manageable side effects.