Subtyping Prostate Cancer May Improve Outcomes

Subtyping cancer has been seen to improve treatment and survival rates among patients with various types of the disease, including those with breast cancer. Researchers now believe that prostate cancer can be subtyped based on cell of origin as luminal A, luminal B, and basal cell subtypes, according to a study presented at the American Society of Clinical Oncology 2017 Genitourinary Cancers Symposium.

While luminal B prostate cancer was observed to have the worst prognosis, these patients may benefit the most from androgen deprivation therapy (ADT), which may lead to more targeted treatments.

“The cell of origin of prostate cancer is unknown,” said researcher Felix Feng, MD, who presented the study.

The investigators hypothesized that prostate cancer could be better characterized based on cell subtypes, similar to other hormone-associated cancers. This method would likely improve treatment and outcomes for patients with prostate cancer.

In the study, the researchers used the PAM50 classifier test to calculate the prevalence of 50 classifier genes and 5 control genes to identify basal and luminal cell involvement with the disease. The study authors analyzed 1567 biopsies from high-risk patients who underwent radical prostatectomy, according to the presentation.

They discovered that prostate cancer can be split into 3 different subtypes. Based on heat maps from the test, similar to those conducted for breast cancer, the 3 subtypes were able to be distinguished from each other, according to the study.

“Given the similarity between these heat maps, it suggests that the underlying biology between breast and prostate cancer is somewhat similar,” Dr Feng said.

The authors then confirmed their findings by analyzing another 6300 cancer samples, which suggests the test can be widely repeated. However, the most important factor was to discover if subtyping the disease was clinically meaningful.

Further research showed that patients with luminal B disease had worse outcomes, compared with the other subtypes. The rate of 10-year survival was 41% for luminal A and 39% for basal subtypes, but luminal B was only 29%, according to the study. Both luminal A and basal subtypes were discovered to have a 10-year rate of not experiencing distant metastasis of 73%, while luminal B was found to have a rate of 53%.

For disease-specific survival, patients with the luminal A subtype had a 10-year rate of 89%, patients with the basal cell subtype had a survival rate of 82%, whereas the luminal B subtype had a 69% survival rate. Compared with the luminal B subtype, the other subtypes had a significantly lower rate of metastatic progression, according to the study authors.

Additionally, the investigators found that certain biological pathways are upregulated or downregulated in the subtypes. In the luminal subtypes, androgen receptor signaling is higher, whereas proliferation pathways are increased in basal and luminal B prostate cancers. Specifically, in the basal subtype, pathways that are implicated in epithelial mesenchymal transition and the immune system are upregulated.

The authors also discovered that patients with luminal B disease seemed to benefit the most from ADT, with an indication that other patients may experience disease worsening with the treatment.

To further assess which patients would benefit from ADT, the authors said that a new trial should subtype patients, and randomize them to receive salvage radiation therapy with placebo or apalutamide.

“This subtyping approach may provide a molecular strategy for treatment selection for patients with aggressive, but potentially curable, cancers,” Dr Feng concluded.