Background: Previous randomized clinical trials have shown an improvement in overall survival in patients with metastatic castration resistant prostate cancer (mCRPC), who have already failed other therapies, treated with 177Lu-PSMA radioligand therapy (RLT). Although 177Lu-PSMA RLT has shown exciting treatment responses in men with mCRPC and suggests a low toxicity profile, it has not been widely investigated in patients with metastatic hormone-sensitive prostate cancer (HSPCa). As of today, treatment with systemic drugs is proof of concept in advanced or metastatic HSPCa, as well as in other cancer types, and leads to improved oncological outcome, potentially by eradicating micro-metastatic disease. As a bone-seeking calcium mimetic, Radium-223 (Ra-223) is incorporated into new bone stroma, predominantly within sclerotic metastatic deposits. The high-energy of the alpha-particle radiation generates double-stranded DNA breaks, offering a potent and highly localized cytotoxic effect in the target areas. In a phase 3, randomized, double-blind, placebo-controlled study, Ra-223 has proven to significantly improve overall survival (by a treatment comprising 1 injection per month, at a dose of 50 kBq per kilogram of body weight intravenously), as compared with placebo. The optimal therapy in patients with oligometastatic bone HSPCa after previous curative treatment has not yet been defined. Methods: This is a single center, interventional, one-arm phase I-II study that prospectively investigates if a treatment strategy in which two types of cytotoxic RLT, i.e., an alpha-emitter and a beta-emitter, alternatively offered to patients with oligometastatic HSPCa, is feasible and safe. Eight patients with low volume, PSMA expressing, radiological progressive HSPCa (minimal 2 bone metastases, maximal 5, and at 0 to 3 lymph node metastases) will be recruited. In these patients, loco-regional radiotherapy or surgery is not an option anymore. The PSA doubling time in participating patients should be less than 6 months. Primary endpoint: To assess the feasibility and safety in patients with bone metastatic, oligometastatic HSPCa, treated by Ra-223 RLT alternated with ¹⁷⁷Lu-PSMA RLTSecondary endpoints: Toxicity and (serious) adverse events will be monitored and reported in concordance with the NCI CTCAE v5.0; Assessment of the xerostomia inventory; Prostate-specific antigen (PSA) levels on follow-up at 3, 6 and 12-months; Investigative Treatment: Patients enrolled in the trial will receive three intravenous applications of Radium-223, in a dose of 5.5 kBq/kg body weight at t = 0 weeks, t = 4 weeks and t = 8 weeks (±1), and two intravenous applications of 7.4 GBq 177Lu-PSMA RLT at t = 6 weeks and t = 12 weeks (±1). Clinical trial information: NL81658.029.22.