PROSTATE CANCER GENETICS AND BIOLOGY

The genomic profiles of prostate cancers in African-American men and men of European ancestry show several differences, researchers report.

"This study strongly supports the idea that samples from African-American patients need to be included in future molecular studies and clinical trials for new prostate-cancer therapies," Dr. Joshua D. Campbell of Boston University School of Medicine told Reuters Health by email.

African-American men have a higher incidence of prostate cancer, present with more advanced disease at an earlier age, and have increased mortality from the disease compared with European Americans. Whether genomic alterations differ between these groups and contribute to clinical outcomes remains unclear.

Dr. Campbell, also at Broad Institute of MIT and Harvard, in Cambridge, Massachusetts, and colleagues evaluated prostate-cancer genomic alterations associated with race and investigated tumor genomic features in primary and metastatic disease in 250 African-American men and 611 European-American men from four publicly available data sets.

Tumors from African-American men showed significantly higher frequencies of somatic mutations in ZFHX3 (6.0% vs. 2.1%), ETV3 deep deletions (6.3% vs. 2.3%), and deletions in ZFHX3 (8.8% vs. 3.4%) and NKX3-1 (10.5% vs. 5.4%).

In contrast, deletions in PTEN were significantly less common in African-American men (5.3%) than in European American men (15.3%), the researchers report in Clinical Cancer Research.

In a separate analysis of 3,454 men with localized and metastatic prostate cancer, frequencies of several genomic alterations were significantly higher in tumors from African-American men than in European-American men, including CCND1 amplification, HGF amplification, KMT2D truncation, MYC amplification, SPOP point mutation, and overall alterations in KEL, NOTCH2, and PTCH1.

There were no significant differences between African-American and European-American men in currently clinically actionable genes.

"We were able to find genes that were more frequently mutated in prostate cancers from African-American patients including ZFHX3, ETV3, and MYC," Dr. Campbell said. "These associations had not been previously reported, although other studies had already found that some genes were less frequently mutated in tumors from this population (e.g., the TMPRSS2-ERG fusion and PTEN deletions)."

"We found that the frequency of mutations in DNA repair genes and other genes that are targets of current therapeutics are similar between men with African ancestry compared to other groups," he said. "This suggests that current prostate-cancer therapies should be beneficial in people of both African and European ancestry as long as they are applied equitably."

Dr. Timothy Rebbeck of Harvard T. H. Chan School of Public Health and Dana Farber Cancer Institute, in Boston, who earlier reviewed variation in prostate-cancer genetics by race, ethnicity and geography, told Reuters Health by email, "We have known for a while that there are differences in genomic features of prostate tumors. The fact that this study reported differences is therefore consistent with the literature, but it was interesting to see in this paper that many of the clinically relevant molecular events do not differ by race."

"This work needs to be confirmed before the data can be translated to clinical practice, but if there are similarities in molecular profiles across races for relevant therapies, this could guide therapeutic decisions," said Dr. Rebbeck, who was not involved in the new research. "However, these data don't provide data on treatment responses, so studies that extend these molecular differences to actual treatment responses or outcomes still need to be done."

SOURCE: https://bit.ly/2Ca76iM Clinical Cancer Research, online July 10, 2020.

In a study reported in the Journal of Urology, Wang et al found that tests for small noncoding RNAs isolated from urinary exosomes accurately distinguished patients with vs without prostate cancer and patients with low- vs intermediate- or high-risk disease. 

Study Details

The investigators describe the development and performance of three separate tests:

• The miR Sentinel^TM  PCa test, which distinguishes patients with prostate cancer from persons with no evidence of prostate cancer
• The miR Sentinel CS Test, which distinguishes between low-risk  (Grade Group 1) and intermediate- and high-risk disease (Grade Group 2–5)
• The miR Sentinel HG Test, which distinguishes low- and favorable intermediate-risk prostate cancer (Grade Group 1 or 2) from high-risk disease (Grade Group 3–5).

The tests were validated in case-control samples in a training cohort of 836 subjects (268 with no cancer, 568 with cancer) and a testing cohort of 600 subjects (300 with no cancer, 300 with cancer).

Key Findings

In the training cohort, the Sentinel PCa Test showed a sensitivity of 94% and specificity of 96% for predicting presence of cancer (positive predictive value [PPV] = 98%, negative predictive value [NPV] = 88%). The Sentinel CS Test showed a sensitivity of 93% and specificity of 91% for prediction of Grade Group 2 or higher cancer (PPV = 91%, NPV = 93%). The Sentinel HG Test showed a sensitivity of 95% and specificity of 96% for the prediction of Grade Group 3 or higher cancer (PPV = 91%, NPV = 98%).

In the testing cohort, the Sentinel PCa Test demonstrated a sensitivity of 94% and specificity of 92% for predicting presence of cancer (PPV = 92%, NPV = 94%). The Sentinel CS Test showed a sensitivity of 93% and specificity of 90% for prediction of Grade Group 2 or higher cancer (PPV = 91%, NPV = 92%). The Sentinel HG Test showed a sensitivity of 94% and specificity of 96% for the prediction of Grade Group 3 or higher cancer (PPV = 91%, NPV = 97%).

The investigators concluded, “In this comprehensive evaluation of the urinary exosome–based miR Sentinel PCa, CS, and HG Tests, high accuracy for identifying the presence of cancer and the presence of high-grade cancer was demonstrated. These data demonstrate that the evaluation of a panel of urinary exosomal small noncoding RNAs offers the ability to accurately and noninvasively screen, diagnose, characterize, and monitor prostate cancer.”