Exploring Clonal Evolution Leading to Prostate Cancer Recurrence
Research type
Research Study
Full title
Exploring the Mechanisms and Dynamics of Clonal Evolution leading to Recurrence in Prostate Cancer Through Evaluation of Intratumour Heterogeneity at Diagnosis and Circulating Tumour DNA at Recurrence
IRAS ID
275583
Contact name
Andrea Sottoriva
Contact email
Sponsor organisation
Institute of Cancer Research
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Although radiotherapy with hormone therapy offers a good chance of cure in localised prostate cancer, recurrence can occur, which may shorten the patient’s life. In locally advanced disease (disease that has broken through the surrounding capsule of the prostate gland), up to 30-40% of patients relapse. Cancer develops as a result of normal cells acquiring genetic mutations, and prostate cancer at diagnosis is commonly made up of different subclones - distinct regions within the patient’s cancer with different genetic mutations, each of which may behave differently and be more or less sensitive to treatments.
The IMRT clinical trial (CCR 1766) recruited 486 patients who received hormone therapy and radiotherapy to the prostate and lymph nodes in patients with locally advanced prostate cancer. The FORECAST project is undertaking whole genome sequencing from several areas of these patients’ original biopsies to determine which cancer subclones were present at diagnosis and how they evolved.
This study will collect blood samples from patients within FORECAST who have experienced a recurrence. Additionally, blood will be collected from other patients with recurrent prostate cancer and the FORECAST protocol will be used to undertake genetic sequencing of these patients’ original prostate cancers. Genetic mutations from the cancer can be detected in the blood, so-called ‘liquid biopsies’. By comparing the genetic information between the primary and relapsed cancers, we can detect which subclones present at diagnosis are ultimately responsible for the relapse, and help us to understand how prostate cancers evolve over time. This will assist us in predicting which patients are more likely to relapse, so that we may treat them most appropriately upfront, and reduce the number of patients with prostate cancer experiencing a recurrence. We will also explore the utility of liquid biopsies in biochemical-only relapse (a rising PSA with no disease visualised on scans).
REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
20/WM/0252
Date of REC Opinion
20 Oct 2020
REC opinion
Further Information Favourable Opinion