Targeted Radiotherapy in Androgen-suppressed Prostate Cancer Patients.

For many men with metastatic prostate cancer, the cancer develops resistance to successive systemic therapies and eventually all treatment options are exhausted and the patient succumbs to their disease. It is therefore vital to find ways of evading prostate cancer resistance. Stereotactic body radiotherapy (SBRT) has the advantage that it destroys cancerous tissue irrespective of the underlying genetic deficit within the progressing metastasis. If the resistant clones are localized to 1-2 metastases and can be destroyed or ablated, the patient can continue to receive the benefit of their systemic (androgen deprivation) treatment (Abiraterone or Enzalutamide) which may continue to control the remainder of their disease for many months, possibly even years. SBRT is a recognised technique for the elimination of isolated metastases in other tumour sites achieving local control of metastasis in 80-90% of cases. This is achieved with very few side effects. In the TRAP trial, the investigators wish to establish whether it is beneficial to target 1 or 2 metastatic sites with SBRT or whether patients will develop polymetastatic progression. Patients enrolled on the trial will receive 30 Gy in 5 fractions on alternate days over 10 days. They will continue their androgen deprivation treatment throughout and following SBRT. Side effects will be closely monitored throughout and patients will be seen at the end of radiotherapy and then 4 weeks after treatment. Thereafter patients will undergo trial follow up three monthly which will includes Prostate Specific Antigen (PSA) monitoring. In addition to the above procedures, the investigators will use a combination of whole body (WB) diffusion weighted (DW) magnetic resonance imaging (WB DW MRI) and circulating tumour (ct) deoxyribonucleic acid (DNA), 'ct DNA' biomarker analysis with the aim of identifying those patients which benefit most from the combination of SBRT and androgen deprivation treatment. WB DW MRI is a novel MRI technique which shows improved sensitivity compared to standard MRI. The marker ctDNA enables the investigators to explore genomic characterisation and variation of metastases and compare findings with previously explored genome mutations in prostate cancer patients.