A Phase I Trial of Focal Salvage Stereotactic Body Radiation Therapy for Radiorecurrent Prostate Cancer - Beyond the Abstract

NCT03253744 is a phase 1 trial with the primary objective to identify the maximum tolerated dose (MTD) of focal, salvage stereotactic body radiation therapy (SBRT) for patients with radiorecurrent prostate cancer (i.e., local recurrence after prior external beam radiotherapy). The trial followed a classic 3+3 design with the plan to evaluate 3 increasing dose levels (DLs) of 40 Gy (DL1), 42.5 Gy (DL2), and 45 Gy (DL3) each delivered in 5 fractions. The target volume was defined by both multiparametric magnetic resonance imaging (mpMRI) and PSMA-based PET/CT with the 18F-DCFPyL radiotracer.

After treatment of the first 3 patients on DL1 was observed to be well tolerated, treatment on DL2 was initiated. Both patients treated at DL2 (42.5 Gy in 5 fractions) experienced dose limiting toxicity (grade 3 urinary incontinence for 7.5 week duration and hematuria for a 4 day duration). This prompted de-escalation and expansion on dose level 1 as it was considered the MTD. GI toxicity was minimal and the most severe toxicity was grade 2 proctitis lasting 2.5 weeks. Biochemical failure was observed in one patient at 33 months post treatment.

In conclusion, the maximum tolerated dose (MTD) of focal, salvage SBRT for in-gland recurrence after definitive, fractionated, external beam radiotherapy (EBRT) is 40Gy in 5 fractions. The most concerning toxicities observed were GU, and GI toxicities were minimal. One biochemical failure was observed after the end of the 2-year study period, comparing favorably to prior published results.

A detailed manuscript reporting the results of NCT03253744 is published in Practical Radiation Oncology (Patel et al., PRO 2023; PMID: 37442430), and a 4-minute video summary of the trial design and principal findings can be found at the following link.



Written by: Krishnan R. Patel, MD, Assistant Research Physician, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD

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