Eligibility for Registration for a STAMPEDE2 Trial ID Number

Inclusion Criteria:

1. At least 18 years old.

2. Histological confirmation of prostate adenocarcinoma or a strong clinical suspicion of prostate cancer with a plan to confirm the diagnosis formally before any future randomisation.

3. Confirmation of metastatic site(s) on CT/MRI and either bone or PET scan. Patients with metastatic disease meeting any of the following criteria are eligible:
   a. Metastatic disease to the bone (in any distribution).
   b. Non-regional lymph node metastases of any size or distribution. Lymph nodes that are only visible on PET will not be eligible as sites of metastasis.
   Note: If lymph nodes are the only site of metastases, then at least one must be at least 1.5cm in short axis AND outside of the pelvis.
   c. Visceral metastases of any size or distribution.

4. Clinical presentation is:
   a. de novo.
   OR
   b. relapsed with:
   1) continuing hormone sensitivity in the opinion of the investigator, and;
   2) all hormone treatments (e.g., ADT and ARPI) will have been completed ≥2 years prior to any future randomisation into any of the comparisons, and;
   3) will have received ≤3 years total of ADT at the point of randomisation into any comparison.
   Note: the dates will be checked again at randomisation. It is the responsibility of the investigator to account for the time between registration and randomisation into any comparison

5. Long-term androgen deprivation therapy (ADT) has started or there is an intention to start for a minimum of 2 years.

6. WHO performance status 0-2 or if WHO Performance Status 3, deemed to be due to metastatic burden and expected to improve with ADT.
   Note: Improvement to WHO status 0-2 will be checked again at randomisation into any subsequent comparison.

7. Willing and able to comply with trial treatments.

8. Patient has signed informed consent form for registration into the STAMPEDE2 Trial platform.

Exclusion Criteria:

1. Clinically and pathologically overt small cell carcinoma.

2. Metastatic brain disease or leptomeningeal disease.

3. Any active malignancies (ie, progressing or requiring any treatment in the previous 36 months) other than prostate cancer (except non-muscle invasive bladder cancer; non-melanomatous skin cancer or a malignancy that is considered cured with minimal risk of recurrence).

4. Any other medical condition that in the investigator`s opinion means the participant is unfit or unsuitable for long-term ADT or the trial treatments in the comparison for which they are being considered.