Background The 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 methods We 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. Results From 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). Conclusion Linac-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.

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Patients who undergo radium-223 treatment for metastatic castration-resistant prostate cancer (mCRPC) generally have a long history of androgen deprivation therapy and/or steroid therapy, which leads to bone loss and causes osteoporosis. Notably, Osteoporosis in combination with metastatic bone disease increases the risk of bone fracture. An 84-year-old man with multi-metastatic bone CRPC underwent six administrations of intravenous radium-223, which induced a good biochemical and clinical response. However, two months following the treatment, the patient reported acute pain localized to the lumbar spine mimicking bone progression disease and presented with stable prostate-specific antigen levels. A prostate-specific membrane antigen-positron emission tomography scan showed no tracer uptake in that site, whereas a magnetic resonance imaging scan and subsequent vertebral biopsy confirmed the absence of cancer progression and showed the presence of vertebral crushing of L4-L5, which was probably due to an osteoporotic process. The patient had never received bisphosphonate therapy and refused it during α-emitting therapy with radium-223. The osteoporotic process, in association with metastatic bone disease, more easily leads to bone fractures that have an important impact on performance status, quality of life and prognosis quoad vitam in patients with advanced prostate cancer. Use of bisphosphonates or anti-RANKL antibody appears to be effective in improving bone mineral density. Notably, patients with multi-metastatic bone disease who undergo radium-223 therapy should be treated in conjunction with anti-osteoporotic therapy (bisphosphonates or anti-RANKL antibody) and adequate calcium and vitamin D supplementation. Early recognition and differentiation of osteoporotic processes when determining the progression of cancer-associated bone disease is crucial in evaluating the response to radium-223 therapy and, consequently, for further therapeutic decision making.