What is the best treatment approach for a patient with early-stage prostate cancer, classified as cT1c N0 (clinical tumor stage 1c, no regional lymph node involvement) with unfavorable intermediate-risk disease and an initial Prostate-Specific Antigen (PSA) level of 5.8, considering Stereotactic Body Radiation Therapy (SBRT) followed by Androgen Deprivation Therapy (ADT)?

Treatment of cT1c N0 Unfavorable Intermediate-Risk Prostate Cancer with SBRT and ADT

Yes, you can treat this patient with SBRT followed by short-term ADT (4-6 months), as this approach is explicitly recommended by current European guidelines for unfavorable intermediate-risk prostate cancer. 1

Guideline-Based Recommendation

The 2024 EAU-EANM-ESTRO-ESUR guidelines provide a weak recommendation to offer ultrahypofractionated IMRT/IGRT or SBRT using either 36.25 Gy (40 Gy to the prostate) in 5 fractions or 42.7 Gy in 7 fractions delivered on alternate days for intermediate-risk disease. 1 This should be combined with short-term ADT (4-6 months) for unfavorable intermediate-risk patients. 1

Why This Approach Works

• SBRT has demonstrated superior outcomes in unfavorable intermediate-risk disease: A large propensity-weighted analysis of 28,028 patients showed that SBRT without ADT was associated with improved overall survival compared to conventional radiotherapy with ADT (HR 0.81,95% CI 0.67-0.99, P=0.04). 2

• The PSA of 5.8 ng/mL is favorable: This relatively low PSA within the intermediate-risk range suggests better prognosis, though the "unfavorable" designation (likely due to Gleason 3+4 with >50% cores positive, or Gleason 4+3, or multiple intermediate-risk factors) still warrants ADT addition. 1, 3, 4

• Short-term ADT improves outcomes: Multiple randomized trials (TROG 9601, DFCI 95096, RTOG 8610) demonstrated cancer-specific survival benefit when 4-6 months of ADT is added to radiotherapy in intermediate-risk disease. 1

Specific Treatment Protocol

SBRT Dosing Options

Choose one of these evidence-based regimens:

• 36.25 Gy in 5 fractions (or 40 Gy to prostate with margin reduction) delivered on alternate days 1
• 42.7 Gy in 7 fractions delivered on alternate days 1

ADT Duration and Timing

• Duration: 4-6 months total 1
• Timing: Neoadjuvant and concurrent with SBRT is the most common approach, though the exact timing remains somewhat flexible 1, 5
• Agent options: LHRH agonist (with antiandrogen cover to prevent flare) or LHRH antagonist 1

Critical Caveats and Pitfalls

Patient Selection Matters

• Good urinary function is essential: SBRT can exacerbate obstructive symptoms, so patients with significant baseline lower urinary tract symptoms may be better candidates for surgery. 1, 6
• Confirm "unfavorable" classification: Ensure the patient truly has unfavorable features (Gleason 4+3, or >50% positive cores, or multiple intermediate-risk factors) rather than favorable intermediate-risk disease, as this affects ADT necessity. 3, 4

Alternative Approaches to Consider

• Brachytherapy boost: For unfavorable intermediate-risk patients with good urinary function, HDR or LDR brachytherapy boost combined with IMRT/VMAT plus short-term ADT (4-6 months) is an alternative option with a weak recommendation. 1
• Conventional dose-escalated RT: IMRT/VMAT with 76-78 Gy or moderate hypofractionation (60 Gy/20 fx or 70 Gy/28 fx) combined with short-term ADT has a strong recommendation and longer follow-up data. 1

Evidence Strength Considerations

• SBRT carries only a weak recommendation in the 2024 EAU guidelines, reflecting that while safe and effective, it has shorter follow-up data compared to conventional fractionation. 1
• No level 1 evidence exists for SBRT specifically in unfavorable intermediate-risk disease with long-term oncologic outcomes, though emerging data is promising. 5, 2
• Pelvic nodal irradiation is NOT standard with SBRT for intermediate-risk disease; only the prostate should be treated. 5

Expected Outcomes and Monitoring

Biochemical Control

• 2-year biochemical control: 82-100% 5
• 3-year biochemical control: 56-100% 5
• PSA should reach ≤1.0 ng/mL within 16 months after completion of treatment 6, 7

Toxicity Expectations

• Acute GU toxicity (Grade 2+): 0-89% (highly variable by technique) 5
• Chronic GU toxicity (Grade 2+): 2-56.7% 5
• Acute GI toxicity (Grade 2+): 0-18% 5
• Chronic GI toxicity (Grade 2+): 0-40% 5

Follow-up Schedule

• PSA every 6 months for first 5 years, then annually 7
• Biochemical recurrence defined as: PSA rise ≥2 ng/mL above nadir 7

When NOT to Use This Approach

Do not offer SBRT if:

• Patient has significant baseline obstructive urinary symptoms (consider surgery instead) 6
• Patient has favorable intermediate-risk disease with life expectancy >10 years and prefers active surveillance (this is a reasonable option for highly selected favorable intermediate-risk patients) 1, 3
• Patient has cribriform or intraductal histology (these patients should be excluded from less aggressive approaches) 1