1. Able and willing to provide written informed consent
2. Aged 18 or over
3. Polymetastatic disease defined as one of the following:
i. ≥5 bone metastases
ii. ≥1 unequivocal visceral metastases
4. Eastern Cooperative Oncology Group (ECOG) Performance status 0 to 2
5. No medical contra-indications to an Androgen receptor signalling inhibitor (ARSI) or docetaxel (with or without prednisolone).
6. Patients should be either of the following:
i. Planned to start long-term Luteinizing Hormone Releasing Hormone (LHRH) suppression, or
ii. Have started long-term LHRH antagonist within the last14 weeks, or
iii. Have started LHRH agonist within the last 16 weeks. When antiandrogens (eg bicalutamide) are used in combination with an LHRH agonist to prevent flare,
patients have to have started within 18 weeks of starting antiandrogens.
7. Patients should be planned for addition of docetaxel (PARADIGM-D) or ARSI (PARADIGM-A) within 14 weeks after start of LHRH antagonist ( 16 weeks if LHRH agonist is started
without anti-androgen) or 18 weeks from start of anti-androgen with a target of 6 cycles or continuation until progression respectively.
8. No concomitant medical conditions likely to reduce life expectancy.
9. Patient agrees to be followed up in the recruiting centre and to having sequential plasma samples collected as per the study protocol.
1. Concurrent or planned for (i.e. prior to development of castration resistance), treatment with oestrogen, radiotherapy or surgery to the primary tumour.
(N.B Patients may also be eligible if randomised to any of the following experimental drugs; PARPi, PD-1/PD-L1 , AKTi, PSMA-lutetium, if given in combination with SOC(i.e. ADT + docetaxel or ARSI) treatment in an open-label clinical trial, or to the placebo arm in an open-label clinical trial following discussion and approval of the CI/delegate. Patients can participate in other observational studies.)
2. Prior systemic therapy for prostate cancer other than for LHRHa +/- anti-androgen (started within the time limits defined in inclusion criterion 7).
3. Metastatic brain disease or leptomeningeal disease.
4. Any surgery planned prior to Cycle 4 Day 1 (C4 D1)
5. Other current malignancy or malignancy diagnosed or relapsed within the past 5 years (other than non-melanomatous skin cancer, stage 0 melanoma in situ and non-muscle invasive bladder cancer).
6. Patients who consent to the whole-body magnetic resonance imaging (WBMRI) translational sub-study should have no contraindications to MRI as per local guidelines.