Prostate Cancer Subtyping May Lead to More Personalized Care

It may be possible to provide more personalized patient care for prostate cancer with a test that is already commercially available. A study led by scientists at UC San Francisco (UCSF) and the University of Michigan have found a test commonly used in breast cancer may also be able to identify which men with aggressive prostate cancer will benefit from androgen deprivation therapy (ADT).

The researchers examined the clinical and genetic differences between luminal and basal subtypes in prostate cancer in nearly 4,000 samples from retrospective and prospective cohorts. They found men with luminal B tumors respond better to postoperative ADT than men with non–luminal B tumors. The findings, which have been published in JAMA Oncology, offer novel insight into prostate cancer biology and point to a potential clinical tool to personalize ADT treatment for prostate cancer.

The researchers divided prostate tumors into three subtypes based on genetic patterns. Their results revealed that starting ADT postoperatively prevents the spread of prostate cancer in only luminal B, a particularly aggressive form that affects about one-third of those with the disease. 

The PAM50 test has been used for more than a decade to identify which breast cancers are the best candidates for hormonal therapy. However, no such tool has been available for prostate cancer. But the current study suggests PAM50 can also distinguish between the three prostate cancer subtypes.

 “We’ve clearly shown that there are different molecular subtypes of prostate cancer and that a test widely used in breast cancer can also potentially be used to help individualize therapy for prostate cancer patients as well,” said senior study author Felix Feng, MD, a UCSF associate professor of Radiation Oncology, Urology, and Medicine in San Francisco.

A biomarker to distinguish between the three prostate cancer subtypes (luminal B, luminal A and basal) could lead to more personalized treatment for prostate cancer patients and help many men avoid the adverse side effects associated with ADT.

The retrospective study focused on 1,567 prostate cancer samples from high-risk patients who had undergone radical prostatectomy. The team identified the three distinct gene expression profiles and confirmed the findings in thousands of prostate cancer samples.

The researchers report that luminal B disease was the most aggressive, with metastases recurring in about half of the patients over 10 years, compared to about one quarter of the patients with the luminal A or basal subtype. They observed that ADT treatments were more effective with luminal B tumors, but may have worsened the prognosis in the other types of tumors.

A large prospective clinical trial involving as many as 100 clinical research sites is now planned. It will use the PAM50 assay to identify men by their cancer subtype and randomly assign them to treatment with radiation and placebo or radiation and ADT.