Stereotactic Focal Radiotherapy as an Alternative Treatment to Active Surveillance for Low and Intermediate Risk Prostate Cancer

The stereotactic radiation therapy procedure involves at first placement of 3-4 fiducial markers, a planning computed tomography (CT) scan as well as a planning MRI, both fused thereafter based on fiducial markers. The delay between fiducial markers placement and planning CT Scan - MRI must be of at least 10 days. SBRT delivers 36.25 Gy in 5 fractions prescribed on the 80% isodose or higher. The fractions are delivered with a CyberKnife device every other day for 2 weeks. If constraints to organs at risk can be fulfilled with other radiation therapy devices, the latter can be used for treatment as well. Organs-at-risk (rectal wall, bladder wall, bladder neck, urethra, as well as contralateral neurovascular bundles, contralateral external sphincter and contralateral pudendal vessels) are delineated (see constraints used in the first citation). Gross target volume (GTV) is delineated on the MRI while considering the hypointense T2-weighted nodule, the hypointense apparent diffusion coefficient, and the hyperintense perfusion zone. At first, the GTV is expanded by 1cm in all directions to generate the clinical target volume (CTV). The CTV is then cropped to the limits of the prostate. If the volume ratio CTV/Prostate is under 30%, the expansion margin of the GTV is increased progressively within the prostate by 0.1 cm increments so that the CTV achieves at least 30% of the prostate volume. Hence, a maximum of 1.5 cm margin around the GTV is allowed and encouraged. The CTV is then expanded by 3 mm to generate the planning target volume (PTV).

• Inclusion Criteria (all the criteria must be fulfilled ) :

• a. Localized prostate adenocarcinoma CAPRA score ≤ 5. This lesion is considered the Index lesion
• b. Macroscopic tumor PIRADS score >4 on multiparametric MRI
• c. The biopsies must be pathologic in or in the direct vicinity (the same prostatic zone defined as a quarter volume of the prostate (PZ)) of the MRI pathologic nodule
• d. The absence of MRI pathologic criteria (PIRADS ≤3) in a Gleason score ≤ 6 (3+3)-ISUP Grade1 zone outside of the single Index lesion is considered clinically non-significant and does not preclude inclusion
• e. The lesion can be plurifocal in a same intent to treat PZ
• f. WHO Performance Status 0-1
• g. No major urinary symptoms with IPSS score ≤15 and urinary continence ICIQ score =0
• h. Patient is candidate for AS
• Exclusion Criteria :

• a. Age at diagnosis < 50 years
• b. Time between initial diagnostic biopsies and randomization > 4 months, or radiation therapy initiation > 6 months
• c. Cribriform or Intraductal histologic components
• d. Gleason Score ≥7 (3+4)-ISUP Grade 2 biopsy outside the intent to treat PZ
• e. Multicentric pathologic MRI (PIRADS ≥4) outside a same PZ
• f. Initial PSA > 20 ng/ml
• g. Regional pathologic nodes or metastases
• h. Androgen-deprivation therapy
• i. Any cancer within the last 5 years except skin basocellular carcinoma or any uncontrolled cancer
• j. Urethral stenosis
• k. Recurrent prostatitis (at least 3 episodes within the last 3 years)
• l. Any inflammatory collagen disease.
• m. Contraindication to repeated prostatic biopsies or MRI