What is the optimal treatment for a 73‑year‑old man with Gleason 9 prostate cancer who is otherwise fit (ECOG 0‑1) and has a life expectancy of ≥10 years?

Optimal Treatment for a 73-Year-Old Fit Patient with Gleason 9 Prostate Cancer

For a 73-year-old fit patient (ECOG 0-1, life expectancy ≥10 years) with Gleason 9 prostate cancer, the preferred treatment is external beam radiotherapy (IMRT/VMAT with daily IGRT) to the prostate at 76-78 Gy combined with long-term androgen deprivation therapy for 2-3 years plus abiraterone acetate for 2 years. 1 This trimodality approach achieves 9-year disease-specific survival of 91% and represents the highest-quality evidence for this aggressive disease. 2

Primary Treatment Recommendation: Radiation-Based Trimodality Therapy

The cornerstone of curative treatment for Gleason 9 disease is dose-escalated external beam radiation (≥75.6 Gy) combined with long-term ADT (2-3 years). 3, 1 This combination provides superior outcomes compared to either modality alone, with 10-year overall survival of approximately 72% and biochemical control rates of 77%. 4

Radiation Dose and Technique

• Deliver 76-78 Gy to the prostate using intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with daily image-guided radiotherapy (IGRT). 1
• When organ-at-risk constraints permit, add a focal boost to the MRI-defined dominant intraprostatic lesion to maximize local control. 1
• Dose escalation above 75.6 Gy is critical for Gleason 8-10 disease, as lower doses (<75.6 Gy) result in 24% 5-year local failure rates versus essentially 0% with higher doses plus ADT. 4

Androgen Deprivation Therapy Duration

Long-term ADT for 2-3 years is mandatory—not optional—for Gleason 9 disease. 3, 1, 5 The RTOG 92-02 trial definitively demonstrated that long-term ADT (2+ years) achieves 45% 10-year overall survival in Gleason 8-10 patients versus only 32% with short-term ADT (4 months), representing a 40% relative improvement in survival (P=0.0061). 3, 2

Addition of Abiraterone Acetate

Add abiraterone acetate (with prednisone) for 2 years to the ADT plus radiation regimen. 1 This intensification improves overall survival by approximately 30-40% in high-risk, node-positive patients and represents the most recent guideline recommendation from the 2024 European Association of Urology. 1

Alternative High-Efficacy Option: Brachytherapy Boost

For patients with good baseline urinary function (low International Prostate Symptom Score), external beam radiation combined with a brachytherapy boost, long-term ADT, and 2 years of abiraterone achieves the highest reported disease-specific survival (91% at 9 years) for Gleason 9-10 disease. 2, 6, 7

• This "trimodality" approach (EBRT + brachytherapy + ADT) reduces distant metastasis rates to 8% at 5 years compared to 24% with either surgery or EBRT alone. 7
• The brachytherapy boost delivers extremely dose-escalated radiation (biological equivalent dose >100 Gy) that cannot be safely achieved with external beam alone. 6
• Critical caveat: Brachytherapy can worsen obstructive urinary symptoms and requires specialized expertise; patients with pre-existing bladder outlet obstruction, very large or very small prostates, or prior transurethral resection of the prostate are poor candidates. 3, 2

Why Radical Prostatectomy Is Not Preferred

Radical prostatectomy is not the optimal primary treatment for Gleason 9 disease in this patient. 1, 2 The evidence is compelling:

• Surgery achieves only 36% progression-free survival for Gleason 8-10 disease, with nearly half of patients (49%) requiring local salvage therapy and 30% requiring systemic salvage. 3, 2, 6
• Even when surgery is performed, it must be followed by extended pelvic lymph node dissection, adjuvant radiotherapy, and long-term ADT—essentially reproducing the trimodality regimen with added surgical morbidity. 1
• Comparative studies show that EBRT+brachytherapy with ADT reduces prostate cancer-specific mortality by 62% (HR 0.38,95% CI 0.21-0.68) and distant metastasis by 73% (HR 0.27,95% CI 0.17-0.43) compared to radical prostatectomy. 7
• Expected surgical complications include erectile dysfunction in up to 80% and urinary incontinence requiring ≥1 pad daily in up to 49% of patients. 8

If surgery is chosen despite these data, it must include extended pelvic lymph node dissection (removing all node-bearing tissue from the external iliac vein to Cooper's ligament) because this detects nodal metastases twice as often as limited dissection. 3, 8

Staging and Pre-Treatment Workup

Before initiating treatment, complete the following staging:

• Bone scan to exclude metastatic disease (mandatory for Gleason 8-10). 2
• Pelvic CT or MRI (or preferably PSMA-PET if available) to assess for lymph node involvement. 1, 2
• If imaging confirms nodal involvement (cN1), pelvic nodal irradiation must be included in the radiation field, and the patient should receive the full regimen of radiation + long-term ADT + 2 years of abiraterone. 1

Critical Pitfalls to Avoid

1. Never use short-term ADT (≤6 months) for Gleason 9 disease. Short-term ADT reduces 10-year survival from 45% to 32% compared to long-term ADT. 3, 2

2. Never use ADT alone without radiation. ADT monotherapy does not provide curative intent and does not improve survival for localized disease. 8, 2

3. Never use brachytherapy as monotherapy for Gleason 9 disease; it is markedly inferior to combined approaches and achieves poor biochemical control. 3, 2

4. Do not omit abiraterone in node-positive or very high-risk patients, as it provides a substantial survival benefit per the most recent 2024 guidelines. 1

5. Do not use radiation doses <75.6 Gy for Gleason 9 disease; dose escalation is essential for local control. 4

Monitoring and Follow-Up

• PSA testing every 3-6 months for early detection of biochemical recurrence. 1
• Monitor for ADT-related adverse effects including osteoporosis (consider bone density screening and bisphosphonates), metabolic syndrome, and cardiovascular risk. 1
• Encourage regular exercise to mitigate ADT-related fatigue and improve quality of life. 1
• After radiation, PSA should reach ≤1 ng/mL within 16 months; biochemical recurrence is defined as PSA rise ≥2 ng/mL above the nadir. 8

Optional Intensification for Very High-Risk Features

If the patient has multiple adverse features (e.g., clinical T3b-T4, nodal involvement, PSA >20 ng/mL), consider adding docetaxel chemotherapy as an additional intensification strategy, though this is more commonly reserved for higher-volume metastatic disease. 1