Inclusion Criteria:
1. Patients must have histologically or cytologically confirmed adenocarcinoma of prostate
2. Two or more bone metastases confirmed by bone scintigraphy within 8 weeks prior to randomization
3. Symptomatic disease defined as regular use of opioid or nonopioid analgesic medication or treatment with external beam radiation therapy within the previous 12 weeks for cancer-related bone pain
4. Known castration-resistant disease, defined according to PCWG3 criteria (59) as: castrate serum testosterone level: ≤50 ng/dL (≤1.7 nmol/L)
5. Subjects who have failed initial hormonal therapy, either by orchiectomy or by using a GnRH agonist in combination with an anti-androgen, must first progress through antiandrogen withdrawal prior to being eligible. The minimum timeframe to document failure of anti-androgen withdrawal will be four weeks
6. Progressive disease based on PSA and/or radiographic PCWG3 criteria:
a. Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least one week apart. Serum PSA at screening ≥ 1ng/mL is the minimal starting value b. or radiographic disease progression based on documented bone lesions by the appearance of two or more new lesions by bone scintigraphy.
7. Patients who failed treatment with any ADT, abiraterone and/or enzalutamide for CRPC that must be terminated at least 4 weeks beforeC1D1.
8. Patients who received prior docetaxel for hormone-naïve prostate cancer should only be allowed if more than 2 years have been between the last administration of docetaxel and C1D1.
9. Male, aged ≥18 years
10. Life expectancy of greater than 6 months
11. ECOG performance status≤2 (see Appendix A)
12. Patients must have normal organ and marrow function as defined below:
* leukocytes \> 3,000/µL
* absolute neutrophil count \>1,500/µL
* platelets \>100,000/µL
* total bilirubin within normal institutional limits
* AST(SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal
* creatinine within normal institutional limits In the presence of borderline values, the participating Centers will be able to discuss individual cases with the Coordinating Center.
13. Male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 6 months after the last dose of radium-223 or docetaxel, according to guideline "Recommendation related to contraception and pregnancy testing in clinical trials", (2020\_09) (See Appendix F). Two acceptable methods of birth control thus include condom (barrier method of contraception) and one of the following is required (established use of oral, or injected or implanted hormonal method of contraception by the female partner; placement of an intrauterine device (IUD) or intrauterine system (IUS) by the female partner; additional barrier method like occlusive cap with spermicidal foam/gel/film/cream/suppository in the female partner; tubal ligation in the female partner; vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy), for more than 6 months.
14. No evidence (within 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin).
15. Participant is willing and able to give informed consent for participation in the study.
Exclusion Criteria:
1. Patients who have had radiotherapy within 4 weeks prior to C1D1.
2. Patients with known visceral metastases
3. Participation in another clinical trial with any investigational agents within 30 days prior to C1D1.
4. Concurrent use of other anticancer agents or treatments, with the following exceptions: LHRH agonists or antagonists, denosumab or bisphosphonate (eg, zoledronic acid). Ongoing treatment should be kept at a stable schedule; however, if medically required, a change of dose, compound, or both is allowed.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
6. Patients who received systemic radiotherapy (e.g. samarium, strontium etc.) for the treatment of bone metastases.
7. Patients who received blood transfusion or erythropoietin within the last 4 weeks prior to start of study treatment.
8. Patients who received prior treatment with Radium-223.
9. Patients with malignant lymphadenopathy exceeding 3 cm in short-axis diameter, or symptomatic nodal disease, i.e. scrotal, penile or leg edema.
10. Other primary tumor (other than CRPC) including hematological malignancy present within the last 5 years (except non-melanoma skin cancer or low-grade superficial bladder cancer).
11. Maintenance treatment with corticosteroids corresponding to a prednisolone or prednisone dose above 10 mg/day. The dose must have been stable for at least 5 days.
12. Patients with imminent or established spinal cord compression based on clinical findings and/or magnetic resonance imaging.
13. Positive test for HIV in case of known positivity to human immunodeficiency virus (HIV).
* Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen\[HBsAg\] test at screening) or hepatitis C Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible.
* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
