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Multicenter Study
. 2025 Nov:212:111113.
doi: 10.1016/j.radonc.2025.111113. Epub 2025 Aug 21.

Refining prognostic stratification in salvage radiotherapy for prostate cancer: a retrospective multicenter cohort study using PSMA-PET and machine learning

Federica Medici  1 , Daniel M Aebersold  2 , Jozefina Casuscelli  3 , Louise Emmett  4 , Stefano Fanti  5 , Andrea Farolfi  6 , Matthias Guckenberger  7 , George Hruby  8 , Stefan A Koerber  9 , Stephanie A Thoma  10 , Jan C Peeken  11 , Paul Rogowski  12 , Sophia Scharl  13 , Mohamed Shelan  14 , Simon K B Spohn  15 , Iosif Strouthos  16 , Marco Vogel  17 , Thomas Wiegel  18 , Constantinos Zamboglou  19 , Nina-Sophie Schmidt-Hegemann  20 , Alessio G Morganti  21 , Savino Cilla  22
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Free article
Multicenter Study

Refining prognostic stratification in salvage radiotherapy for prostate cancer: a retrospective multicenter cohort study using PSMA-PET and machine learning

Federica Medici et al. Radiother Oncol. 2025 Nov.
Free article

Abstract

Background: Salvage radiotherapy (SRT) is the standard treatment for biochemical recurrence (bREC) after radical prostatectomy (RP), yet optimal radiation dose, field size, and the role of advanced imaging like PSMA-PET remain unclear. This study assessed the impact of SRT dose and the prognostic role of PSMA-PET on 2-year biochemical relapse-free survival (bRFS) in patients with localized disease.

Methods: In this retrospective multicenter study, 255 patients treated with SRT across 11 centers were selected from a database of 1,201 cases. Inclusion criteria included PSA persistence/recurrence (≥0.1 ng/mL) post-RP and negative PSMA-PET for nodal or distant metastases. Patients receiving androgen deprivation therapy or with PSA > 0.5 ng/mL pre-SRT were excluded. Prognostic factors were identified using LASSO analysis and modeled with CART analysis. The primary endpoint was 2-year bRFS.

Results: With a median follow-up of 33 months, 2-year bRFS was 88.2 %. Lower pre-SRT PSA (<0.2 ng/mL), PSMA-PET negativity, longer PSA doubling time, older age, favorable ISUP grades (1-2), and shorter intervals from surgery to bREC were associated with improved bRFS. CART analysis demonstrated that PSMA-PET findings significantly influenced prognosis in patients with PSA levels below 0.2 ng/mL, while PSA-doubling time was predictive in patients with PSA 0.2-0.5 ng/mL. SRT dose and elective nodal irradiation did not significantly affect bRFS.

Conclusions: This study underscores the complexity of prognostic modeling in SRT for prostate cancer, highlighting the value of PSMA-PET and CART for refined risk stratification.

Keywords: Androgen deprivation therapy; Biochemical recurrence; Biochemical relapse-free survival; ISUP grade; Metastasis-free survival; PSMA-PET; Pathological T stage; Prognostic factors; Prophylactic lymph node irradiation; Prostate cancer; Radical prostatectomy; Radiotherapy dosing; Salvage radiotherapy; Therapeutic intensification.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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