Patterns of Relapse Following Radiation Therapy of Intermediate-Risk Prostate Cancer in the PROFIT Randomized Trial

Conventionally fractionated radiation therapy (CFRT) and hypofractionated RT (HFRT) are established treatments for intermediate-risk (IR) prostate cancer (PCa), with differing dose per fraction. However, their comparative patterns of failure remain unclear. This stuy aims to analyze the distinct relapse patterns of HFRT versus CFRT in terms of local progression-free survival (LPFS), pelvic lymph node metastasis-free survival (pnMFS), extrapelvic lymph node MFS (epnMFS), and bone MFS (bMFS).

Patients with IR PCa included in French and Australian centers in the "PROstate Fractionated Irradiation Trial (PROFIT)" study (NCT00304759), a phase 3, multicenter, randomized controlled trial. Using molecular positron emission tomography imaging, magnetic resonance imaging, and bone scintigraphy, the anatomic sites of relapse were retrospectively identified in biochemically relapsing patients after HFRT or CFRT. LPFS, pnMFS, epnMFS, and bMFS were compared between both treatment arms using Kaplan-Meier analyses.

With a median follow-up of 6.4 years, 274 patients (130 HFRT and 144 CFRT) were included, among whom 35 (24.3%) in the HFRT arm and 28 (19.4%) in the CFRT arm experienced relapse. Median time to relapse varied by site: 4.9 years locally, 3.96 years for pelvic lymph nodes, 2.95 years for extrapelvic lymph nodes, and 3.6 years for bone metastasis. No significant differences were found between HFRT and CFRT arms in LPFS, pnMFS, epnMFS, or bMFS.

Relapse rates after HFRT or CFRT are low, with no discernible variance in anatomical relapse patterns between treatments. Tailored management strategies considering these relapse patterns could optimize care of IR patients, including initial staging and microboosting of dominant lesions.