Stereotactic Intensity-modulated Radiotherapy After Radical Prostatectomy (SCIMITAR): 4-Year Outcomes of a Phase 2 Clinical Trial.

Abstract

In the phase 2 SCIMITAR trial, stereotactic body radiotherapy (SBRT; 30-34 Gy in 5 fractions) was delivered to the prostatic fossa after radical prostatectomy in 100 patients requiring postoperative RT, with or without nodal RT and androgen deprivation therapy (ADT). The primary endpoint was 4-yr biochemical recurrence (BCR)-free survival (BCR-FS), with events defined as BCR (prostate-specific antigen ≥0.2 ng/ml above nadir), salvage ADT, or death. Outcomes were compared to individual patient data (IPD) from a phase 3 trial of conventionally fractionated RT (CFRT) using inverse probability of treatment weighting and Fine-Gray models. At median follow-up of 53 mo, the 4-yr BCR-FS rate was 60% (95% confidence interval [CI] 50-70%). The IPD analysis revealed that for men not receiving ADT, the risk of BCR was lower with SBRT than with CFRT (subdistribution hazard ratio [sHR] 0.49, 95% CI 0.29-0.84; p = 0.008). For men receiving ADT, there was no significant difference in BCR risk between SBRT and CFRT (sHR 1.58, 95% CI 0.81-3.11; p = 0.18), although the asymmetrically broad 95%CI and directionality of the point estimate suggest that a higher BCR risk with SBRT cannot be ruled out. The 4-yr cumulative incidence rates for late grade ≥2 gastrointestinal and genitourinary toxicities were 6.6% and 32%, respectively. At 48 mo, the proportion of patients reporting a decline of more than two times the minimal clinically important difference in urinary incontinence, urinary irritative/obstructive, bowel, and sexual domains was 23%, 6.7%, 13%, and 9.7%, respectively. SBRT to the prostatic fossa appears to be safe and effective through 4 yr.