Genomic Data Advances Precision Medicine for Prostate Cancer

As disease treatments continue to advance and become more personalized, researchers are increasingly relying on genomic data to accelerate the development of precision medicine for a range of conditions.

Recently, investigators have shifted their focus to prostate cancer, a condition that impacts about one in eight American men. While prostate cancer is prevalent across all patient populations, black men in the US have a higher lifetime risk of the disease – and a higher rate of mortality from the disease – than their white counterparts.

In a review conducted by Mount Sinai researchers and published in Cancer Reports, the team noted that these disparities are likely due to socioeconomic factors, problems with care access, and tumor biology.

For their review, Mount Sinai researchers focused on the biological differences in the development of prostate cancer across ethnicities.

"We provide a comprehensive review of the significant research in recent years that has examined the molecular and genomic reasons for unequal cancer burden in African American and Caucasian American populations and acknowledge the challenges that lie ahead," said senior author Ashutosh K. Tewari, MD, of the Icahn School of Medicine at Mount Sinai.

"This article provides specific guidelines for managing prostate cancer in African American men based on their disease's biology and makes a significant contribution to the ongoing national effort to improve African American men's outcomes from prostate cancer."

Although recent evidence has suggested that equivalence in socioeconomic factors results in equal mortality outcomes for African American men with prostate cancer, higher incidence still remains, the group stated.

Researchers examined the molecular and genomic differences in prostate cancer between black men and white men to highlight innovative treatments. This included immunotherapies explicitly aimed at black populations to reverse prostate cancer disparities.

Going forward, researchers could use these differences to improve the diagnosis and treatment of prostate cancer in black men, ultimately reducing incidence and mortality rates associated with the disease.

"Understanding the specific biology of prostate cancer in African American men and integrating clinical and genomic data will enable a precision medicine approach to treating African American men and contribute to the ongoing efforts to improve outcomes in this population," said co-author Sujit S. Nair, PhD.

Researchers from Johns Hopkins Kimmel Cancer Center are also examining genomic data to accelerate precision medicine for prostate cancer.

In a study published in JAMA Oncology, the team studied prostate cancer samples from 352 participants in the NRG/RTOG 9601 clinical trial. The trial compared radiation therapy alone with radiation therapy combined with hormone therapy.

Researchers found that the Decipher test, which measures the activity of 22 genes among seven known cancer pathways, independently estimated participants’ risk of metastasis, death from prostate cancer, and overall survival.

The test also guided treatment recommendations for recurrence of prostate cancer after surgery, which could help identify which patients are most likely to benefit from hormone therapy.

“The findings may be practice-changing, and will give oncologists additional information to help guide decisions on whether to offer patients hormone therapy,” said senior study author Phuoc Tran, MD, PhD, professor of radiation oncology and molecular radiation sciences and co-director of the Cancer Invasion and Metastasis Program at the Johns Hopkins Kimmel Cancer Center.

The Decipher test uses genomic classifier scores determined from the genomic characteristics of the tumor to stratify patients into three groups. Lower scores correlate with a more favorable prognosis.

These genomic classifiers helped researchers predict participants’ risk of distant metastases, prostate cancer-specific death, and overall survival – even after adjusting for participants’ age, race and ethnicity, Gleason score, extent of tumor spread, prostate-specific antigen level, and whether they were receiving hormone therapy.

“Patients with lower scores do better overall, but they do not benefit as much from adding on hormone therapy because they are low risk. Patients with higher scores have worse disease and, therefore, benefit the most from adding the hormone therapy,” said Tran.

The results show the potential for genetic data to help target prostate cancer treatments.

“The way that we treat many patients in the clinic now is based on pathological and clinical factors, such as age, stage, grade, and imaging. Those have been very helpful, but you can only go so far with these rough markers,” said Tran.

“Hormone therapy unfortunately has a whole host of side effects, such as lack of libido, lack of erections and fatigue, and over time can increase the risk of diabetes, heart attack or stroke, so you only want to prescribe it if it is clearly beneficial.”

The information provided by the Decipher test can guide precision medicine efforts to help providers direct hormone therapies to those most likely to benefit from them.

“Our study demonstrated that Decipher is prognostic in its ability to determine cancer metastasis and also prostate cancer-specific survival and overall survival. It also was able to determine the benefit of patients receiving hormones or no hormones,” Tran concluded.