A Phase I Trial of Neoadjuvant Stereotactic Body Radiotherapy (SBRT) Prior to Radical Prostatectomy (RP) in Locally Advanced Prostate Cancer

Abstract

locked cut points of < 0.45, 0.45-0.6, > 0.6 for low, intermediate, and high, respectively. In this sub-analysis, the primary endpoint was freedom from biochemical progression (FFBP) according to PSA at randomization (≤0.5 vs > 0.5, a trial stratification variable). Cox multivariable analysis (MVA) adjusting for age, T-category, Gleason score, persistent PSA after RP, and randomization arm were performed. Secondary endpoints included clinical progression-free survival (CPFS) and time to salvage ADT. Results: Of 233 patients with tissue available, 1 was ineligible and 6 failed QC. The remaining 226 were included for analysis with a median followup of 6.3 years (IQR 6.0-7.2). High-vs. low/intermediate-GC had an HR of 2.22 (95% CI 1.37-3.58, P = 0.001) for FFBP, 2.29 (95% CI 1.32-3.98, P = 0.003) for CPFS, and 2.99 (95% CI 1.50-5.95, P = 0.002) for use of salvage ADT. In patients with PSA ≤0.5 ng/mL (165/226, 73%), the 5-year FFBP was 74% [95% CI 66-82] for low-intermediate GC compared to 59% [95% CI in patients with high-GC. High-GC patients had 5year FFBP of 13% [95% CI 0-32] when SRT was delivered at PSA > 0.5 ng/mL compared to 59% [95% CI 43-74] when PSA ≤0.5 ng/mL. Conclusion: In a contemporary phase 3 trial, patients with a high-GC were more than twice as likely than patients with low/intermediate-GC to experience biochemical and clinical progression and receive salvage ADT. High-GC patients who received SRT with PSA > 0.5 ng/mL had nearly 90% risk of recurrence by 5-years post-SRT. This data validates the clinical utility of the GC for tailoring treatment in the salvage setting.

Safety and Efficacy Study of Neoadjuvant Radiohormonal Therapy for Oligometastatic Prostate Cancer: Protocol of an Open-Label, Dose-Escalation, Single-Centre Phase I/II Clinical Trial

“…3,[14][15][16] What's more, neoadjuvant SBRT may lead to severe toxicity as reported by some studies on nonmetastatic high-risk or locally advanced prostate cancer. 12,13 But neoadjuvant conventional fractionation radiotherapy is still underexplored.…”