Researchers at Cedar-Sinai have developed a novel way to identify which prostate cancer patients will develop aggressive types of the disease based on the genes that are activated in each individual tumor.
The study, “Integrated Classification of Prostate Cancer Reveals a Novel Luminal Subtype with Poor Outcome,” published in Cancer Research, divides prostate cancer patients into three distinct subtypes, may help clinicians provide more effective, tailored treatments to each patient.
“These findings raise the possibility that by determining the gene expression profile of a patient’s tumor, physicians may be able to identify aggressive disease at the outset of diagnosis and start treatment earlier,” Sungyong You, PhD, an instructor in the Cedars-Sinai Department of Surgery and the first author of the study, said in a press release.
Currently, researchers rely on the Gleason grade to determine which cancers will develop into dangerous forms of the disease. This score ranks the cancer cells from 2 to 10 based on how similar they are to normal prostate cells. The higher the grade, the higher the risk of patients having a poor outcome.
But this method is not accurate enough, and some patients may not receive the appropriate treatments, such as radiation, hormone therapy, or removal of the prostate, in a timely manner, while others may be receiving unnecessary treatments that are associated with severe side effects.
In the past, other studies had already used genetic data to identify distinct subtypes of prostate cancer, but this is the first large-scale study that actually links the subtypes to clinical outcomes based solely on the genes that are expressed in each tumor.
In this study, researchers analyzed the genetic profiles of 1,321 human prostate cancer samples to create the three subtypes, which they called PCS1, PCS2, and PCS3. These were then matched with the clinical outcomes of more than 4,600 patients, showing that each subtype was associated with a distinct outcome.
These findings can greatly enhance the management of prostate cancer patients. In fact, one of the greatest problems clinicians face is knowing which patients will develop aggressive forms of the disease and require more aggressive treatment.
“About 60 percent of prostate cancer patients we treat won’t progress to aggressive cancer. The problem was that we didn’t have a way of knowing which patients fall into that 60 percent,” said Michael Freeman, PhD, director of Cancer Biology and Therapeutics Research in the Cedars-Sinai Department of Biomedical Sciences and the study’s principal investigator. “We hope our findings help physicians provide more patients with optimal treatments, resulting in healthier outcomes.”
In their study, the researchers found that patients who were included in the PCS1 subtype were more likely to develop an aggressive form of the disease, with increased risk of spreading into other regions of the body and consequently poorer outcomes. The other two subtypes, PCS2 and PCS3, progressed more slowly.
One important finding was that even when patients had been assigned low Gleason grades, if they had a PCS1 subtype they would still have worse outcomes. Previously, patients with low Gleason grade scores did not receive treatment and were just closely monitored. But the new findings suggest that surveillance may not be enough for some of these patients.
The researchers also showed that the new subtyping can be performed in circulating tumor cells. Therefore, a simple blood test may be used in the future to distinguish which patients require treatment from those who don’t, and to monitor how the tumor is evolving during treatment.