Molecular Test Helps Personalize Chemotherapy for Advanced Prostate Cancer

Around 10,000 men in the UK are diagnosed with advanced prostate cancer each year, with most deaths occurring in patients diagnosed with advanced or metastatic disease. While treatment intensification with docetaxel alongside androgen deprivation therapy (ADT) can improve survival, response rates vary, and clinicians currently lack tools to identify who will benefit most. Now, a novel molecular test can help personalize the treatment of advanced prostate cancer and avoid unnecessary side effects of chemotherapy.

Researchers at University College London (UCL, London, UK) evaluated Veracyte’s (South San Francisco, CA, USA) Decipher Prostate Genomic Classifier test, a gene expression assay performed on routinely collected prostate tissue. The test, already widely used in the US to identify localized cancers likely to spread, is the first molecular tool with randomized trial evidence showing it can guide treatment choices for metastatic disease. The test works by profiling tumor gene expression to classify patients based on predicted chemotherapy sensitivity.

The study drew on data from 1,523 patients recruited to the STAMPEDE phase III trials who had advanced prostate cancer and began treatment with ADT. Participants received additional therapies, including abiraterone or docetaxel, and were followed for a median of 14 years. Among the 832 patients with metastatic prostate cancer, researchers linked molecular test results with long-term clinical outcomes, allowing them to assess the ability of the test to predict who benefited from docetaxel chemotherapy.

The results, published in Cell, show that among the 832 patients with metastatic prostate cancer, those with high Decipher scores had a 36% reduction in risk of death after docetaxel treatment, compared to less than 4% for those with low scores. The test consistently outperformed traditional clinical tools in identifying patients most likely to benefit. This provides the first strong evidence that a routinely available molecular test can influence chemotherapy decisions in advanced prostate cancer.

The findings highlight how gene expression tests could help avoid exposing patients unlikely to benefit to toxic side effects, while guiding others toward chemotherapy for longer survival. Additional analyses identified new molecular classifiers, including a signature linked to inactivity of the tumor suppressor gene PTEN, which predicts poorer hormone therapy response but greater chemotherapy benefit. Researchers believe these discoveries pave the way for reclassifying prostate cancer into molecular subtypes for more tailored treatments.

“The ability to personalize chemotherapy decisions based on the Decipher Prostate test will greatly enhance patient care and outcomes,” said Professor Gert Attard, lead researcher at UCL Cancer Institute and UCLH. “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."

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