BackgroundThe rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30–47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re‑I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re‑I.Materials and methodsWe retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re‑I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0–2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent.ResultsFrom January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7–50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2‑year progression free survival (PFS) was 100% and 81.5%, respectively, while 2‑year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12–39 months. Re‑I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia).ConclusionLinac-based SBRT is a safe technique for performing Re‑I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.