This study is a prospective, observational, molecular stratification profiling study. Patients with mCRPC who have received at least one standard treatment for mCRPC will be approached to participate in MAESTRO. Patients must have archival tumour available and be willing to undergo a fresh tumour biopsy for molecular analyses. Tumour tissue (archival and fresh), research blood samples and saliva will be sent to the central laboratory for analysis to identify molecular aberrations through targeted or broader molecular analyses (e.g. exome, transcriptome) and orthogonal assays (e.g. immunohistochemistry; digital droplet PCR). When the results are available, depending on patients choice, the results will be discussed. If significant results are indicated, patients will be recommended to have follow up with a cancer geneticist to discuss the implications of these results for their personal and family's health.

There is a safety follow up 30 days after collection of study biopsy or blood samples. Patients will also be followed up for overall survival and subsequent anticancer treatment every 6 monthly via medical notes or telephone calls.

This study is a prospective, observational, molecular stratification profiling study.

mCRPC patients who have received at least one standard treatment for mCRPC will be approached to participate in MAESTRO. Patients must have archival tumour available and be willing to undergo a fresh tumour biopsy for molecular analyses. Following consent to MAESTRO, tumour tissue (archival and fresh), along with the research blood samples and saliva sample will be sent to the central laboratory for analysis to identify molecular aberrations through targeted or broader genomic analyses (e.g. exome, transcriptome) and orthogonal assays (e.g. immunohistochemistry; digital droplet PCR).

Patients will not receive any treatment as part of MAESTRO. Results of the molecular characterisation will be provided to the treating investigator to be fed back to the patient, depending on patient's choice on disclosing the results.

The following research samples are collected under as part of this study:

• Where available, excess archival tumour tissue from previous biopsies or routine surgical procedures will be retrospectively collected.
• Fresh tissue specimens will be obtained for patients who are undergoing standard of care interventions OR patient will undergo a bone marrow biopsy or an ultrasound /CT guided tumour biopsy of a safely accessible lesion. Fresh tumour specimens will be processed and/or frozen.
• Sequencing analysis of tissues will be done and results will be made available in real time. Clinically significant results will be disclosed to patients and their clinicians as per patient consent.
• Research samples for blood, serum, plasma and saliva will be collected at the time of the biopsy.

Patients who elected (optional consent) to receive sequencing results regarding incidental clinically significant findings, will be referred for genetic counselling.

Inclusion Criteria:

1. Male aged ≥18 years.
2. Histologically confirmed metastatic castrate resistant adenocarcinoma of the prostate
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 - 2.
4. Surgically or medically castrated, with testosterone levels of <50 ng/dL (<2.0 nM).
5. Confirmed metastatic disease on imaging.
6. Patients with tumour deemed by the designated investigator as safely suitable for fresh biopsy AND who are medically fit (according to local practice) to undergo a biopsy or procedure to acquire tumour tissue AND previously collected tumour specimens from prior surgery or biopsy available for analyses. An mCRPC biopsy collected within 6-months of trial entry can be used instead of this fresh biopsy if available and passes laboratory quality control requirements.
7. Willing and able to comply with the requirements of the sample collection including fresh tumour biopsy.
8. The subject is capable of understanding and complying with the protocol requirements and has given written informed consent.

Exclusion Criteria:

1. The presence of any haematological disorders, including coagulation disorders, which would be a contraindication if patient were to undergo a biopsy.
2. Any psychiatric illness/social situations that would limit compliance with study requirements.
3. Presence of any concurrent condition or situation, which, in the investigators opinion, may put the patient at significant risk, may confound the study results or may interfere significantly with the patient's participation in the study.

Participants will be recruited from participating sites in the UK. Potential participants will be identified and discussed in oncology clinics and Multi-Disciplinary Team (MDT) meetings.