Molecular Testing Steers Personalized Chemotherapy for Advanced Prostate Cancer Patients

Recent research led by University College London highlights the potential of molecular profiling of tumors to customize chemotherapy treatments for men with advanced prostate cancer. The study demonstrates that analyzing the gene expression patterns in prostate tumor tissue can identify which patients are more likely to benefit from chemotherapy, particularly docetaxel, and consequently improve survival outcomes. This approach enables clinicians to avoid unnecessary side effects in patients unlikely to respond to such treatments.

The pivotal study, published in the journal Cell, involved 1,523 participants from the STAMPEDE phase III trial, all diagnosed with metastatic prostate cancer and undergoing androgen deprivation therapy (ADT). ADT works by blocking male hormones like testosterone that fuel prostate cancer growth. The trial examined the benefit of adding drugs like abiraterone or docetaxel to ADT over a median follow-up of 14 years.

Results revealed that patients with high Decipher Prostate scores, determined through a gene expression test called the Decipher Prostate Genomic Classifier (manufactured by Veracyte), experienced a 36% reduction in the risk of death when treated with docetaxel. Conversely, those with lower scores saw a much smaller benefit, with less than 4% reduction in mortality risk. These findings suggest that using molecular profiling can effectively predict chemotherapy sensitivity, allowing for more personalized and effective treatment strategies.

This test represents the first molecular assay supported by randomized trial evidence to guide therapy in metastatic prostate cancer. It is already widely utilized in the United States for assessing localized prostate cancer risks; now, its application extends into guiding treatment decisions for advanced stages, marking a significant advancement in personalized oncology.

Professor Gert Attard, a leading researcher at UCL Cancer Institute, emphasized the importance of these findings, stating that they enable the identification of patients who are most likely to benefit from chemotherapy, thereby enhancing outcomes and minimizing unnecessary toxicity. The ability to tailor treatment plans based on tumor biology signifies a milestone in prostate cancer management.

Prostate cancer remains a major health concern, with approximately 55,100 new cases annually in the UK and around 12,000 deaths each year. The disease is the second leading cause of cancer-related death among men, predominantly affecting those diagnosed with advanced or metastatic disease.

The development of this molecular test underscores the potential of combining tumor profiling with clinical trials to refine treatment strategies. Collaborations between UCL, industry partners like Veracyte, and charitable organizations exemplify how innovation can translate into real-world benefits for patients.

As Dr. Emily Grist, another lead researcher, notes, the discovery of molecular signatures such as PTEN inactivity provides further insights into tumor behavior, predicting response to therapies and guiding future personalized treatment approaches. This innovative research paves the way for more refined and effective management of prostate cancer, focusing on molecular characteristics to optimize patient care.