Is stereotactic body radiotherapy (36.25 Gy in five fractions) with short‑term androgen‑deprivation therapy an evidence‑based curative option for a medically fit man with unfavourable intermediate‑risk prostate cancer (Gleason 4+3 or 3+4 with >50 % core involvement, PSA 10–20 ng/mL, clinical stage T2b‑c)?

SBRT for Unfavorable Intermediate-Risk Prostate Cancer

SBRT at 36.25 Gy in 5 fractions combined with short-term ADT (6 months) is an evidence-based curative option for medically fit men with unfavorable intermediate-risk prostate cancer, though the evidence base is less robust than for conventional fractionation with ADT. 1

Risk Classification and Treatment Rationale

Unfavorable intermediate-risk disease is defined by the presence of any of the following: primary Gleason pattern 4 (Gleason 4+3), ≥50% positive biopsy cores, or presence of >1 NCCN intermediate-risk factor (T2b-c, PSA 10-20 ng/mL, or Gleason 7). 2 Your patient with Gleason 4+3 or 3+4 with >50% core involvement clearly meets unfavorable intermediate-risk criteria. 2

Patients with unfavorable intermediate-risk disease have significantly worse outcomes than favorable intermediate-risk patients, with higher rates of distant metastasis and prostate cancer-specific mortality, making them more likely to benefit from combined modality therapy. 2

SBRT Evidence and Recommendations

Validated SBRT Regimens

The NCCN recommends two validated SBRT regimens for definitive treatment: 36.25 Gy in 5 fractions or 42.7 Gy in 7 fractions. 1 The 36.25 Gy/5fx regimen you are considering is specifically endorsed by major guidelines. 1

Multi-institutional registry data for SBRT at 36.25 Gy/5fx demonstrates:

• 2-year biochemical disease-free survival of 94.5% for intermediate-risk patients 3
• 7-year biochemical disease-free survival of 89.6% for intermediate-risk patients 4
• Minimal acute and late toxicity, with no Grade 3+ genitourinary or gastrointestinal toxicity reported 3

Critical Requirement: Combination with ADT

For unfavorable intermediate-risk disease, SBRT must be combined with 6 months of androgen deprivation therapy. 1 This recommendation is based on strong evidence from conventional fractionation studies showing that short-term ADT (4-6 months) significantly improves outcomes in intermediate-risk disease. 2

Dose-escalated radiotherapy with short-term ADT in intermediate-risk patients demonstrates:

• Improved prostate cancer-specific mortality (adjusted HR 0.297; 95% CI 0.128-0.685; P=0.004) 5
• Reduced distant metastasis (adjusted HR 0.347; 95% CI 0.176-0.685; P=0.002) 5
• Improved biochemical control (HR 0.516; 95% CI 0.360-0.739; P<0.001) 5

The benefit of ADT is particularly pronounced in patients with Gleason 4+3 and ≥50% positive cores—exactly the unfavorable features your patient has. 5

Standard Treatment Alternatives

For comparison, standard evidence-based options for unfavorable intermediate-risk disease include:

• Conventional external beam radiotherapy (74-78 Gy) + 4-6 months ADT: This has Level I evidence with 10-year overall survival improvement from 54% to 61% (p=0.03). 2
• Radical prostatectomy with pelvic lymph node dissection: This is also a standard option. 2

Technical Requirements and Contraindications

SBRT should only be performed at centers with:

• Appropriate image-guided delivery systems 1, 6
• Physics expertise and quality assurance programs 1, 6
• Clinical experience with SBRT delivery 1, 6

Absolute contraindications include prior pelvic irradiation, active inflammatory bowel disease, and permanent indwelling Foley catheter. 6

Relative contraindications include very low bladder capacity, chronic moderate-to-severe diarrhea, bladder outlet obstruction requiring suprapubic catheter, and inactive ulcerative colitis. 6

Critical Caveats

Evidence Gap for SBRT in Unfavorable Intermediate-Risk

While SBRT is endorsed by guidelines, the evidence base is less robust than for conventional fractionation with ADT. 2 Most SBRT studies have not specifically analyzed unfavorable intermediate-risk as a distinct subgroup, and follow-up is shorter than conventional fractionation trials. 3, 4

One study specifically analyzing intermediate-risk subgroups found that patients with "high intermediate-risk" features (Gleason 4+3 or Gleason 3+4 with PSA 10-20) had significantly worse 7-year biochemical disease-free survival of 79.3% compared to 93.5% for low intermediate-risk patients. 4 This suggests that unfavorable features predict worse outcomes even with SBRT.

Nodal Coverage Limitation

SBRT to prostate only does not allow for pelvic nodal irradiation. 1 If nodal coverage is deemed necessary based on nomogram risk estimates, conventional IMRT to the pelvis (45 Gy) with prostate boost should be used instead of SBRT. 1

ADT Duration is Non-Negotiable

The 6-month ADT duration is critical and should not be shortened. 1 Evidence shows that even 4 months of ADT provides significant benefit in intermediate-risk disease, but 6 months is the guideline-recommended duration for unfavorable features. 2, 1

Staging Requirements

Before proceeding with SBRT, staging with cross-sectional imaging (CT or MRI) and bone scan should be considered for unfavorable intermediate-risk patients to exclude occult metastatic disease. 2