Pract Radiat Oncol 2023 Jul 11
A Phase I Trial of Focal Salvage Stereotactic Body Radiation Therapy for Radiorecurrent Prostate Cancer.
Abstract
Purpose
NCT03253744 was a phase I trial to identify the maximally tolerated dose (MTD) of image-guided, focal, salvage stereotactic body radiotherapy (SBRT) for patients with locally radiorecurrent prostate cancer. Additional objectives included biochemical control and imaging response.
Methods and materials
The trial design included three dose levels (DLs): 40Gy (DL1), 42.5Gy (DL2), and 45Gy (DL3) in 5 fractions delivered ≥48 hours apart. The prescription dose was delivered to the MRI and PSMA imaging-defined tumor volume. Dose escalation followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities were scored until two years after completion of SBRT using CTCAE v5.0 criteria. Escalation was halted if two dose limiting toxicities occurred, defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT, and any grade 3 GU or grade 4 GI toxicity thereafter.
Results
Between 08/2018 and 05/2022, 8 patients underwent salvage focal SBRT with a median follow-up of 35 months. No DLTs were observed on DL1. Two patients were enrolled in DL2 and experienced grade 3 GU toxicities, prompting de-escalation and expansion (n=6) at the MTD (DL1). The most common toxicities observed were G2+ GU toxicities, with only a single G2 GI toxicity and no G3+ GI toxicities. One patient experienced biochemical failure (PSA nadir + 2.0) at 33 months.
Conclusions
The MTD for focal salvage SBRT for isolated intraprostatic radiorecurrence was 40Gy in 5 fractions producing a 100% 24-month bPFS, with one post-study failure at 33 months. The most frequent clinically significant toxicity was late grade 2+ GU toxicity.
Related Questions
What urethral dose constraints would you use off-trial for reirradiating the prostate using SBRT?
The short answer to this question is that there is no evidence-based answer. Below is a review for anyone interested. Background: The recognition of local recurrence as a pattern of failure seems to be growing, perhaps in part due to the increased utilization of advanced imaging (as previously discu...
Would you offer salvage radiation for a local recurrence of prostate cancer that was initially treated with SBRT?
At this time, I’m not sure there is enough data to recommend a course of re-irradiation after primary SBRT outside of a clinical trial, although I do know some who offer it. The majority of the data regarding re-irradiation for local recurrence after RT comes from smaller retrospective reports, alth...
Has use of PSMA PETCT revealed increased local failures than previously known after definitive prostate EBRT with biochemical failure?
Prior to the advent of PET imaging, the published rates of local recurrence (LR) after definitive RT vary widely in phase III trials from ≈ 1% (e.g., PCS IV) to ≈ 30% (e.g., PROG 9509). The heterogeneity is likely explained by several factors including (1) differences in baseline risk of local recur...
After definitive prostate RT, when do you prescribe ADT for local salvage (EBRT, HDR, LDR)?
For patients with localized recurrence after definitive radiotherapy, re-irradiation without ADT is a reasonable course of action and the one I usually favor. There are no current clinical trials that have been reported to demonstrate the benefit of ADT in this setting, but this practice is consiste...