What is the best treatment option for a patient with localized prostate adenocarcinoma, T3aN0M0, Gleason score (GS) 4+3, and a high initial Prostate-Specific Antigen (PSA) level, without evidence of distant or nodal metastasis on Prostate-Specific Membrane Antigen (PSMA) PET scan?

Treatment Recommendation for T3aN0M0, Gleason 4+3, High-Risk Localized Prostate Cancer

The optimal treatment is external beam radiation therapy (EBRT) with a minimum dose of 75.6-78 Gy combined with long-term androgen deprivation therapy (ADT) for 24-36 months. 1, 2

Risk Stratification

Your patient has high-risk localized prostate cancer based on multiple adverse features: 1, 2

• T3a disease (extraprostatic extension)
• Gleason 4+3=7 (Grade Group 3, unfavorable intermediate to high-risk)
• Extremely elevated PSA of 168 ng/mL

The Gleason 4+3 pattern is critical—this indicates predominantly poorly formed/fused/cribriform glands and carries significantly worse prognosis than Gleason 3+4, with only 63% biochemical recurrence-free survival at 5 years after surgery. 1, 3

Definitive Treatment Algorithm

Primary Treatment: EBRT + Long-Term ADT

Radiation specifications: 1, 2

• Dose: 75.6-78 Gy using 3D-CRT or IMRT with daily image guidance
• Pelvic lymph node radiation: 45 Gy (mandatory for T3 disease)
• Duration: Standard fractionation (approximately 8 weeks)

ADT specifications: 1, 2

• Agent: GnRH agonist monotherapy (leuprolide or goserelin)
• Duration: 24-36 months (NOT 4-6 months—this is inadequate for high-risk disease)
• Timing: Neoadjuvant (start 2-3 months before radiation), concomitant, and adjuvant
• Critical caveat: Combined androgen blockade (adding antiandrogen continuously) should NOT be used routinely 4, 1

Alternative Consideration: Trimodality Therapy

For patients with life expectancy >10 years, EBRT + Brachytherapy boost + Long-term ADT achieves superior outcomes (91% disease-specific survival at 9 years vs. 45% overall survival with EBRT + ADT alone). 2 However, this requires specialized expertise and careful patient selection.

Radical Prostatectomy: Generally NOT Recommended

Surgery is not the preferred option for T3a disease because: 4

• Extraprostatic extension significantly increases positive margin rates
• Would still require adjuvant radiation therapy in most cases
• Higher morbidity (80% erectile dysfunction, 49% urinary leakage) 4
• Only considered in highly selected patients with no fixation to adjacent organs 2

Critical Treatment Pitfalls to Avoid

Do NOT use short-term ADT (4-6 months) for this patient—multiple guidelines emphasize that 2-3 years of ADT is required for survival benefit in Gleason 8-10 and T3 disease. Short-term ADT achieves only 32% overall survival at 10 years versus 45% with long-term ADT. 2

Do NOT use brachytherapy monotherapy—this is contraindicated for Grade Group 4 disease. 2

Do NOT delay treatment for additional imaging beyond what you have—the PSMA PET already confirmed N0M0 status, which is sufficient for treatment planning. 1

Pre-Treatment Staging Confirmation

Your PSMA PET showing no nodal/distant metastasis is excellent, but recognize that: 5

• Bone scan is still recommended by some guidelines for Gleason ≥8 or PSA >15 ng/mL 4, 2
• However, PSMA PET is more sensitive than conventional imaging and your negative result is reassuring
• No additional imaging is needed before initiating treatment 1

ADT Flare Prevention

When starting the GnRH agonist, use antiandrogen for at least 7 days (not continuously) to prevent testosterone flare, especially given the high tumor burden suggested by PSA 168. 4 Options include:

• Bicalutamide 50 mg daily for 7-14 days
• Start antiandrogen 1 week before first GnRH injection

Post-Treatment Surveillance Protocol

1, 2

• PSA measurement: Every 6 months for first 5 years, then annually
• Digital rectal examination: Every 6 months
• Biochemical recurrence definition: PSA rise ≥2 ng/mL above nadir
• Imaging: Only if biochemical recurrence occurs or symptoms develop

Why Not Surgery First?

The evidence strongly favors radiation + ADT over surgery for T3a disease: 4, 1, 2

• No randomized trials show surgery superior to radiation for locally advanced disease
• T3a patients undergoing surgery have high rates of positive margins requiring adjuvant radiation anyway
• The combination of EBRT + long-term ADT is the Category 1 recommendation (highest level) from NCCN 1

Duration of ADT: The Evidence

The critical distinction between 4-6 months versus 24-36 months of ADT cannot be overstated. For high-risk disease (which your patient definitively has), long-term ADT provides: 2

• 45% overall survival at 10 years (vs. 32% with short-term)
• Superior disease-specific survival
• Reduced distant metastasis rates

Start treatment promptly with EBRT (75.6-78 Gy) + GnRH agonist for 24-36 months, with pelvic nodal radiation to 45 Gy. 1, 2