Testing the molecular profile of tumours identifies which patients with advanced prostate cancer are more likely to benefit from chemotherapy and live longer, sparing patients less likely to benefit from unpleasant side effects, according to a new study led by UCL researchers.
Published in Cell, the study is the first strong evidence that a gene expression test performed on routinely collected prostate tissue can help guide therapy choices for prostate cancer patients whose cancer has spread to other parts of the body (metastatic cancer). The test is called the Decipher Prostate Genomic Classifier test and is manufactured by Veracyte.
The study included 1,523 patients recruited to the STAMPEDE phase III trials, that had been diagnosed with advanced prostate cancer and started treatment with androgen deprivation therapy (ADT), which blocks male hormones such as testosterone that can drive prostate cancer growth. The STAMPEDE trials tested the additional benefit of adding abiraterone or docetaxel to ADT and the study patients were followed up for a median of 14 years.
Among the 832 patients with metastatic prostate cancer, those with high Decipher Prostate scores had a 36% reduction in the risk of death after treatment with docetaxel, while those with lower Decipher scores had a reduction in the risk of death that was estimated at less than 4%.
This finding is significant as while docetaxel chemotherapy improves survival for some patients, it also reduces quality of life. This test may be used to identify which patients are likely to have docetaxel-sensitive tumours and live longer with docetaxel chemotherapy treatment.
The Decipher Prostate test is already widely used in the US to help identify localised prostate cancer more likely to spread. It becomes the first molecular test with clinical evidence from a randomised trial showing it can guide treatment choices for metastatic prostate cancer.
Professor Gert Attard, lead researcher at UCL Cancer Institute and UCLH, said: "The STAMPEDE trial has resulted in several changes to the way patients presenting with advanced prostate cancer are treated. Now through large-scale molecular analysis linked to long-term follow-up, for the first time we identify groups of patients recruited to the trial who had very different benefit from treatment. The ability to personalise chemotherapy decisions based on the Decipher Prostate test will greatly enhance patient care and outcomes.
"By identifying which patients are most likely to have a survival benefit from chemotherapy, we can avoid unnecessary side effects and develop alternative treatments for people with metastatic prostate cancer who are unlikely to benefit."
There are around 55,100 new prostate cancer cases in the UK every year and 12,000 men are expected to die from prostate cancer this year. Prostate cancer is the second most common cause of cancer death in males in the UK, accounting for 14% of all cancer deaths in this group. Most prostate cancer deaths occur in patients who first presented with advanced or metastatic disease.
Treatment intensification with docetaxel, in addition to standard-of-care androgen deprivation therapy (ADT), can improve survival for patients with metastatic prostate cancer. However, response rates vary, and clinicians have limited tools to identify who is likely to benefit and who is not. Veracyte's Decipher Prostate test addresses this gap by providing a more personalised approach to treatment decisions.
UCL Business (UCLB), the commercialisation company for UCL, brokered Veracyte's collaboration with UCL to bring together the company's expertise in profiling expression patterns in tumours with UCL's expertise in clinical trials and cancer biology. In addition to identifying the first commercially available test that can predict docetaxel efficacy, the collaboration has also identified several new molecular classifiers that predict outcomes of patients.
Dr Emily Grist, a lead researcher of this study at UCL Cancer Institute, added: "One of our additional discoveries is of a signature that identifies inactivity of the tumour suppressor gene PTEN. This both predicts shorter life expectancy with hormone therapy and greater benefit from chemotherapy, as compared to those with PTEN activity.
"I believe our study is a milestone in efforts to re-classify prostate cancer into distinct molecular groups. The long-term impact will be bespoke treatments based on tumour molecular profiles that should improve outcomes for patients."
Harriet Story, Senior Business Manager for UCLB, said: "This collaboration between UCL and Veracyte demonstrates the potential of gene expression tests to revolutionise cancer treatment by identifying patients who will benefit from docetaxel chemotherapy. It's deeply satisfying to see the outputs of this UCL research already available as a reimbursed test in the US to help metastatic prostate cancer patients receive more personalised treatment - impact made possible by UCL's collaboration with a global diagnostics developer."
Simon Grieveson, Assistant Director of Research at Prostate Cancer UK, said: "Around 10,000 men are diagnosed with advanced prostate cancer every year in the UK.
"We're thrilled to have supported this innovative research in partnership with Movember which could help to predict upfront which men will benefit most from the addition of chemotherapy - helping some men live longer, while others can avoid the side effects of unnecessary treatment.
"This is a fantastic example of charities, academic researchers and industry collaborating to deliver real impact for men affected by prostate cancer."
Funding to support UCL research costs in the collaboration with Veracyte were provided by Prostate Cancer UK, Cancer Research UK, the John Black Charitable Foundation and the Prostate Cancer Foundation, amongst others.
The STAMPEDE trial is funded by Cancer Research UK and led by researchers at the UCL MRC Clinical Trials Unit and UCL Cancer Institute. The trial aims to find new treatment approaches for advanced prostate cancer.
