START-MET HS Prostate Cancer. : SbrT & Androgen Receptor Therapy METastatic HSPC

Phase III Study of Stereotactic Body Radiation Therapy (SBRT) Plus Standard of Care in Castration Sensitive Oligometastatic Prostate Cancer Patients.

Phase III study of stereotactic body radiation therapy (SBRT) plus standard of care in castration sensitive oligometastatic prostate cancer patients, defined as androgen deprivation therapy plus radiotherapy to the primary tumor in previously not treated patients and second generation hormonal treatments (Apalutamide/Abiraterone+Prednisone/Enzalutamide) vs androgen deprivation therapy plus radiotherapy to the primary tumor in previously not treated patients plus second generation hormonal treatments, for the treatment of oligometastatic prostate cancer.

A total of 266 patients with a histological diagnosis of metastatic hormone sensitive prostate cancer, with limited disease (≤ 3 lesions based on CT and Bone Scan and ≤ 5 lesions based on Choline or PSMA PET/TC) at the diagnosis or in an oligorrecurrent stage will be included in the study. Candidates will be first screened for metastatic sites through bone scintigraphy and computerised tomography (CT) scans. Those who meet the ≤3 metastatic sites criteria will be second screened for metastatic sites based on Choline or PSMA PET/TC, which will be used to define the treatment volume of metastatic disease with SBRT/HIGRT and to confirm the oligometastatic status before the inclusion in the study.

Once included in the study, patients will be randomize (1:1) to standard of care + SBRT vs standard of care.

• Interventional arm: STANDARD OF CARE + SBRT (all metastatic lesions). ADT+ RT to the primary tumor (previously not treated) + Second generation hormonal treatment
• Control arm: STANDARD OF CARE. ADT+ RT to the primary tumor (previously not treated) + Second generation hormonal treatment

Patients will be stratified according to prior local treatment (yes/no) or the new imaging technique used (Choline vs PSMA PET/TC).

Inclusion Criteria:

1. Patients with a histological diagnosis of prostate cancer.

2. Castration sensitive prostate cancer patients.

3. Oligometastatic disease defined as less than or equal 3 lesions based on CT and Bone Scan and less than or equal 5 lesions based on Choline or PSMA PET/TC. Bone metastases (including the spine) or/and lymph nodes metastases.

4. Informed consent is obtained from the patient.

5. Adequate bone-marrow, liver and renal function:

   • Haemoglobin ≥10 g/dL, Leucocytes ≥ 2000/mm^3, Neutrophils ≥1500/mm^3, platelets ≥1000007mm^3
   • GOT, GPT and Total Bilirrubin ≤1.5*ULN (Upper limit of normality)
   • Creatinine ≤1.5*ULN or Creatinine Clearance ≥50 ml/min^-1

Exclusion Criteria:

1. Lack of a histological diagnosis of prostate cancer.
2. Castration resistant prostate cancer patients according to PCWG3[30].
3. Metastatic disease defined as greater than or equal 3 lesions based on CT and Bone Scan and greater than or equal 5 lesions based on Choline or PSMA PET/TC.
4. Visceral metastases.
5. Tumor stage T4 according to AJCC 8th Edition Cancer staging form.
6. Prior treatment with docetaxel, second generation hormonal treatments (Apalutamide/Abiraterone+Prednisone/Enzalutamide) or bone antiresorptive therapy.
7. Presence of symptoms or signs that are indicative of urgent surgery/radiotherapy as the first treatment for the metastases disease.
8. Lesions that require SBRT treatment that exceed critical organ tolerance limits, or do not meet the criteria for the prescription of SBRT techniques used.
9. History of another neoplastic pathology which is not a currently controlled with the exception basal cell carcinomas.
10. Presence of a cardiopathy or metabolic disorder that does not recommend the treatment with second generation hormonal treatments, or the presence of inflammatory bowel disease or other pathology that does not recommend the treatment with radiotherapy.
11. Lack of informed consent or the patient's ability to give consent.
12. Participation in other clinical trials at the time of inclusion or in the 3 previous months.