A Phase I Trial of Focal Salvage Stereotactic Body Radiation Therapy for Radiorecurrent Prostate Cancer.

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.

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.

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.

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.

Practical radiation oncology. 2023 Jul 11 [Epub ahead of print]

Krishnan R Patel, Nicholas R Rydzewski, Erica Schott, Theresa Cooley-Zgela, Holly Ning, Jason Cheng, Kilian Salerno, Erich P Huang, Peter A Pinto, Liza Lindenberg, Esther Mena, Peter Choyke, Baris Turkbey, Deborah E Citrin

Radiation Oncology Branch, National Cancer Institute, NIH, Bethesda, MD. Electronic address: ., Radiation Oncology Branch, National Cancer Institute, NIH, Bethesda, MD., Biometric Research Branch, National Cancer Institute, NIH, Rockville, MD. Electronic address: ., Urologic Oncology Branch, National Cancer Institute, NIH, Bethesda, MD., Molecular Imaging Branch, National Cancer Institute, NIH, Bethesda, MD.