Background: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970). Methods: Patients with post-radical prostatectomy PSA levels of ≥0.1–2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD2_1.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire—Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up. Results: From April 2021 to June 2022, thirty men with a median age of 72 years (range 55–82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18–1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0–0.48 ng/mL). Conclusions: Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy.

We aimed to evaluate whether progression-directed radiation therapy (PDRT) can prolong the initiation of a subsequent systemic therapy regimen in a cohort of patients with oligoprogressive NSCLC. A retrospective analysis was conducted on NSCLC patients who underwent PDRT for extracranial oligoprogressive NSCLC, defined as limited (up to five) progressing lesions following initial complete, partial, or stable response to systemic therapy according to REC1ST 1.1 and/or PERCIST 1.0 criteria. Cox proportional hazard regressions were performed to identify factors influencing time to next treatment (TTNT), which was considered the primary endpoint. Forty patients were analyzed. First, second, and ≥3 lines of systemic therapy were administered in 22 (58.2%), 14 (27.2%), and 4 (14.6%) cases, respectively. The median total dose was 36 Gy (range: 12–60) in five fractions (1–10), with a median biological effective dose for tumor control (BED10) of 52 Gy (26.4–151.2). After a median follow-up of 11 months (2–50), PDRT delayed further systemic therapy in 32 (80.0%) treatments. Median TTNT was not reached at 8 months (1–47) with a one-year Kaplan–Meier estimate of 81.4% (95% CI: 75.0% to 87.8%). No >grade 3 adverse event was observed. On multivariate analysis, patients with ≥3 lines of systemic therapy and/or with larger CTV volumes did not benefit from PDRT. Despite the use of sub-ablative doses, our findings show that PDRT represents an effective, safe, and viable option for oligoprogressive NSCLC. Patients irradiated early during their systemic treatment course, with a low volume of disease and nonmetastatic oligoprogression, could derive substantial benefits from PDRT.