Oligo-metastatic prostate cancer (OMPCa) is considered as an intermediated state between localized and poly-metastatic disease. Various retrospective studies and prospective clinical trials are carrying out to validate whether patients with OMPCa could benefit from local treatment for both primary and metastatic lesions. The investigators here to conduct a unique clinical trial which OMPCa patients were confirmed by conventional imaging, and received a long-term enhanced systemic therapy accompanied by tumor-directed therapy.

Recent studies showed that metastatic lesion of prostate cancer may originate from both the primary and the existing metastatic lesion, thus, disease with limited number of metastatic lesions were considered as oligo-metastatic prostate cancer (OMPCa), an intermediated state between localized and poly-metastatic disease. For patients with newly diagnosed OMPCa, serval studies revealed that prostate radiation therapy could improve their clinical outcomes. For patients with oligo-recurrent prostate cancer, they could also be benefit from stereotactic ablative radiation therapy to the metastatic lesion. The investigators thus designed a distinct clinical trial including patients who were confirmed as oligo-metastatic disease by conventional imaging modality (CT, MRI and ECT) rather than PSMA PET-CT. This study also aimed to evaluate the therapeutic effects of tumor-directed treatment under the background of long-term enhanced systemic therapy, including abiraterone, enzalutamide or apalutamide. Here, the investigators proposed that, for patients with de novo oligo-metastatic prostate cancer, enhanced systemic treatment combined with radical treatment of primary lesion and radiotherapy of all accessible metastatic lesions may prolong their survival time without affecting their quality of life.

Inclusion Criteria:

1. Histologically or cytologically confirmed de novo prostate adenocarcinoma (can be accompanied by neuroendocrine differentiation, but accounts for less than 10% of the total tumor components);

2. Aged between 18 and 80;

3. M1a/b disease with presence of 1-5 visible metastases (detected by bone scan (ECT), chest, abdominal and pelvic CT or MRI). Biopsy of the suspected metastases is recommended to the patients. If the patients refused to the biopsy, additional PSMA-PET/CT or regional MRI should be performed to confirm the metastatic lesions.

4. The metastatic lesions should meet the following the criteria:

   1. Metastases are limited to bone or lymph nodes;
   2. Visceral metastases are not allowed;
   3. Radiographic observed pelvic lymph node metastasis with a diameter of >2cm should also be considered as one metastatic lesion.
   4. If the lymph nodes are the only detected metastatic lesions, at least one metastatic lymph node should be outside the pelvis.

5. ECOG performance status of 0 or 1;

6. PSA less than 100ng/ml at diagnosis;

7. No more than one month's systemic treatment before enrollment (including castration (surgical or medical castration), castration combined with traditional anti-androgen therapy (flutamide or bicalutamide));

8. No previous pelvic radiotherapy history;

9. The primary lesion of prostate cancer has not received any form of local treatment (surgery, radiotherapy, cryotherapy, radiofrequency ablation, etc.); TURP is allowed, if the aim of the surgery is to relieve lower urinary tract symptom but not to treat the tumor.

10. The metastatic lesions of prostate cancer have not received any form of local treatment (surgery, radiotherapy, cryotherapy, radiofrequency ablation, etc.);

11. Written informed consent;

12. Willing and expected to comply with treatment and follow up schedule.

13. Life expectancy > 10 years.

Exclusion Criteria:

1. Received prior local treatment for primary lesion or metastatic lesions, including radical prostatectomy, radical radiotherapy, surgery or radiotherapy to metastatic lesion;

2. Received prior systemic treatment for prostate cancer longer than 1 month;

3. Received prior castration combined with new-generation androgen signaling pathway inhibitors such as abiraterone, apalutamide or enzalutamide; castration combined with docetaxel chemotherapy;

4. Had any visceral metastases (liver, lung, brain etc.);

5. Histologically or cytologically confirmed small cell carcinoma;

6. Unable to tolerate the treatment for primary and metastatic lesion;

7. Unwilling to accept potential related adverse events caused by treatment for primary and metastatic lesion;

8. Had any other previous or current malignant disease, except for curatively treated skin basal cell carcinoma or other tumors cured for more than 5 years;

9. Had other severe disorders, such as:

   1. Unstable cardiac disease,
   2. Myocardial infarction less than 6 months prior to enrollment,
   3. Clinically significant cardiac failure requiring treatment, defined as New York Heart Association (NYHA) class III,
   4. Uncontrolled hypertension,
   5. Severe neurological or psychological disorder including dementia or epilepsy,
   6. Uncontrolled active infection,
   7. Acute gastric ulcer,
   8. Hypercalcemia,
   9. Chronic obstructive pulmonary lung disease requiring hospitalization,
   10. Any other significant disorders that in the investigator's opinion means the participant is unfit for any of the study treatments;

10. Had participated in other clinical trial before enrollment.

11. Had contraindications to radiotherapy or unsuitable for radical radiotherapy evaluated by radiologists and physicists.