Prostate Cancer Genomic Heterogeneity

Cancer is a genetic disease, caused by mutations in genes that lead to increased cell proliferation and survival. Importantly, the genetic changes vary dramatically between individual prostate cancer patients and the specific combination of mutations within a patient's cancer is thought to determine tumour aggressiveness and clinical outcome.

Personalized medicine approaches aim to decipher the genetic code of a patient's tumour in order to identify cancers which will behave aggressively and need treatment. However, extensive intra-tumour heterogeneity (ITH) has been discovered in several solid tumour types, complicating the identification of the relevant genetic changes as they may not be present throughout the entire tumour and are likely to be missed by tumour biopsies. ITH is thus a major hurdle for the implementation of personalized cancer treatment approaches.

Investigators have developed genetic technologies that allow them to measure ITH in solid tumours and they now want to apply these to patients with prostate cancer to define the extent and the clinical importance of ITH in this disease which is currently unknown. This will involve looking at the control of genes in the cancer cells which make some tumours more aggressive than others. This may help in predicting which tumours are important and need to be targeted and those that could be left so that too much tissue damage does not occur as a result of therapy. Finding out why some cancer cells spread and others do not may also help to identify novel molecular targets that could be used to prevent the development of metastases.

Patients with suspected prostate cancer usually have scans and then prostate biopsies. These biopsies are needed by the pathologist to make a proper diagnosis and cannot be used for full genetic analysis. So, investigators will ask patients whether they would be willing to give some extra samples of tissue while undergoing these routine biopsies.

Defining ITH in prostate cancer will provide important insights into the genetics of prostate cancer development and metastatic progression and is a key prerequisite for the development of reliable personalized cancer medicine approaches. Thus this study will significantly advance researchers' efforts to predict which tumours are dangerous and in need of urgent treatment and those that could safely be left untreated which would spare these patients the unnecessary side effects. Investigators think that this research work will have a major impact on the use of next generation sequencing in the management of prostate cancer through an in-depth understanding of how common are differences between and within individual cancer lesions. Investigators also want to find out whether these differences, if they exist, are important in tumour development and spread to other areas. Investigators think that the characterization of these differences will allow them to successfully use this information to group patients undergoing treatment using molecular 'signatures' so that treatment is targeted rather than applied in a 'sledge-hammer' approach. Investigators believe that without studies like PROGENY, doctors will instead rely on data from single tumour biopsies which can be misleading since single biopsies may not have sampled the most aggressive tumour area. Finally, investigators think that PROGENY will reveal how prostate cancers evolve over time and which of these changes lead to metastases and ultimately kill the patient. These are called phylogenetic studies and will help work out the main (or 'trunk') genomic changes from later events in 'branches'. This may allow researchers to focus their drug discovery efforts on the common 'trunk' genomic changes.

Inclusion criteria

• Treatment naïve group

• Men with no prior diagnosis of prostate cancer undergoing prostate biopsy based on identified lesions on imaging
• Men with a raised PSA above 15ng/ml
• Men giving informed consent

Treated men

• Men undergoing tissue biopsy for suspicion of prostate cancer recurrence following previous local or systemic therapy based on identified lesions in multi-parametric MRI, bone-scan, choline PET/CT, or PET/MRI

Exclusion criteria

• 1. Unable to have MRI scan or CT scan, or in whom artefact would reduce scan quality
• Unable to have prostate biopsy
• Unable to undergo biopsy for metastatic evaluation
• On immunosuppression or predefined immunosuppressed state
• A coagulopathy predisposing to bleeding
• Unable to give informed consent