Acute Toxicity and Early Prostate Specific Antigen Response After Two-Fraction Stereotactic Radiation Therapy for Localized Prostate Cancer Using Peri-Rectal Spacing–Initial Report of the SABR-Dual Trial

• Published in: International journal of radiation oncology, biology, physics Vol. 120; no. 5; pp. 1404 - 1409
• Main Authors: Fredman, Elisha, Moore, Assaf, Icht, Oded, Tschernichovsky, Roi, Shemesh, Danielle, Bragilovski, Dimitri, Kindler, Jonathan, Golan, Shay, Shochet, Tzippora, Limon, Dror
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2024
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - diagnostic imaging; Adenocarcinoma - pathology; Adenocarcinoma - radiotherapy; Aged; Aged, 80 and over; Dose Fractionation, Radiation; Fiducial Markers; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Prostate - diagnostic imaging; Prostate - pathology; Prostate-Specific Antigen - blood; Prostatic Neoplasms - blood; Prostatic Neoplasms - diagnostic imaging; Prostatic Neoplasms - pathology; Prostatic Neoplasms - radiotherapy; Quality of Life; Radiation Injuries; Radiosurgery - adverse effects; Radiosurgery - methods; Rectum - radiation effects; Seminal Vesicles - radiation effects
• ISSN: 0360-3016; 1879-355X; 1879-355X
• DOI: 10.1016/j.ijrobp.2024.06.038

SABR-Dual is a phase-III trial with an initial phase-I safety cohort, of 2-fraction stereotactic radiotherapy (SABR) with optional magnetic resonance imaging (MRI)-based focal boost, using peri-rectal spacing, for localized prostate cancer. This represents the initial report from the phase-I non-randomized cohort. Subjects had favorable intermediate risk (FIR) or low risk prostate adenocarcinoma, and gland volume <80 cc. All underwent radiopaque hydrogel spacer and fiducial marker placement before simulation (computed tomography and 3-tesla T2 MRI). The clinical target volume included the entire prostate, and in FIR patients, 1-2 cm of seminal vesicle. A 2-mm expansion was applied for planning target volume (PTV), and a dose of 27 Gy was prescribed to the PTV-prostate, 23 Gy to the PTV-seminal vesicle, with an optional 30 Gy simultaneous boost to an MRI-defined dominant lesion. Primary endpoint was 3-month patient-reported changes in quality of life based on the Expanded Prostate Cancer Index Composite-26, International Prostate Symptom Score, and Sexual Health Inventory for Men questionnaires. Secondary endpoints were 6-month quality of life, acute toxicity (using Common Terminology Criteria for Adverse Events version 5.0) and early Prostate specific antigen (PSA) response. Among the 20 patients in the phase-I cohort, 95% had FIR disease, and 50% received a simultaneous boost. At median follow-up of 8 months, a 3-month minimally clinically important change occurred in 1/20 (5%), 6/20 (30%), 2/20 (10%), 4/20 (20%), and 5/20 (25%) in urinary incontinence, urinary obstructive, bowel, sexual, and hormonal domains. There was a mean increase of 1 ± 5.4 in International Prostate Symptom Score and decrease of 1.8 ± 6.5 in Sexual Health Inventory for Men scores. Rates of grade 2 urinary and bowel toxicity were 10% and 0%, respectively, with no grade ≥3 toxicities. Mean PSA decrease at last follow-up was 70.4% ± 17.7%. This generalizable protocol of 2-fraction prostate SABR using peri-rectal spacing is a safe approach for ultra-hypofractionated dose-escalation, with minimal acute toxicity. Longer-term outcomes and direct comparison with standard 5-fraction SABR are being studied in the phase-III randomized portion of SABR-Dual.