Researchers identify indicators predicting lethal outcomes in high grade prostate cancer

Prostate cancer is one of the most common cancers among men in the United States; one in nine men will be diagnosed during his lifetime. When they are diagnosed, a patient’s disease is graded from 1 to 5 based on how aggressive it is, with 5 being the most aggressive.

Patients with grades 4/5 disease are at the highest risk of poor outcomes or death from the disease; however, there are no immunologic or genomic indicators that can help physicians determine the best course of treatment for this group of patients.

Moffitt Cancer Center researchers are hoping to change that. The team conducted studies to determine if genomic heterogeneity in tumors from grade 4/5 prostate cancer patients can be exploited to identify patient subsets that are at higher risk for lethal outcomes and therefore may benefit from targeted treatment strategies.

The studies from these researchers focused on transcriptomic interactions between the tumor immune content score and the Decipher score, a 22-gene classifier that provides a score predicting the probability that cancer will spread. They analyzed data from 8,071 prostate cancer patient samples of any disease grade (6,071 prostatectomy and 2,000 treatment naïve) in the Decipher Genomics Resource Information Database (GRID) registry. Each of the patient sample swas also given an immune content score (ICS) that was derived using the mean expression of 264 immune cell-specific genes.

All T=the samples were separated into four distinct immunogenomic subsets based on their results: ICS high/Decipher high, ICS low/Decipher high, ICS high/Decipher low and ICS low/Decipher low. These researchers discovered that approximately 25% of all grade 4/5 patient samples were in the ICS high/Decipher high subset.

The ICS high/Decipher high patient samples were further evaluated for the association between immunogenomic subtypes and radiation response signatures and they found that the ICS high/Decipher high subset were genomically more radiosensitive, meaning these tumors would respond well to radiation therapy. They determined that this subset also had a higher abundance of T cells and monocyte/macrophages. However, the research team says further research is needed to unravel the biologic mechanisms of this association.

These results will aid in the subtyping of aggressive prostate cancer patients who may benefit from combined immune-radiotherapy modalities.

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