Utility of PCa markers in African-Americans differs

Two urinary biomarkers for detection of prostate cancer have differing utility in African-American men undergoing prostate biopsy.

San Francisco-Two urinary biomarkers for detection of prostate cancer have differing utility in African-American men undergoing prostate biopsy. Urinary PCA3 improved the ability to predict the presence of any and high-grade prostate cancer in this group, whereas the TMPRSS2:ERG urinary assay did not add significantly to standard detection and risk stratification tools, reported Jonathan L. Silberstein, MD, at the Genitourinary Cancers Symposium in San Francisco.

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These urinary biomarkers had been validated previously in Caucasian men. “There was very little data before this study to demonstrate that urinary biomarker tests had any utility in African-American men,” said Dr. Silberstein, chief of urologic oncology at Tulane Cancer Center, New Orleans. “I would say that this study shows that not only are they of value in African-Americans, but it’s really important that we understand how limited traditional serum PSA and free PSA are in this patient population. As a result, some of these novel biomarkers, in particular PCA3, may have a real important role for this patient population.”

Dr. Silberstein and colleagues collected urine following digital rectal examination (DRE) in 304 men, 182 of whom were African-American, without known prostate cancer prior to biopsy. PCA3 and TMPRSS2:ERG RNA copies were quantified using transcription-mediated amplification assays.

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Prediction models for prostate cancer and high-grade prostate cancer were created using standard of care variables (age, race, family history of prostate cancer, prior prostate biopsy and abnormal DRE) plus PSA. Biomarkers of PCA3 and TMPRSS2:ERG were added to determine whether they increase the models’ performance compared with the base model. The final model constructed combined standard of care variables and PSA with both of the biomarkers.

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Some 139 of the 304 patients (46%) were diagnosed with prostate cancer. PCA3 and TMPRSS2:ERG scores were greater in men with prostate cancer than in those without. The median PCA3 scores were 52.81 in those with versus 34.98 in those without prostate cancer, and the median TMPRSS2:ERG scores were 3.42 and 6.88, respectively. Men with prostate cancer more often had three or more cores, ≥33.3% cores, >50% involvement of greatest biopsy core, and Epstein-significant prostate cancer (p<.01).

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PCA3 added to the standard of care variables plus PSA model improved prediction for the detection of any prostate cancer in the overall cohort (0.747 vs. 0.677; p<.0001), in African-American men only (0.711 vs. 0.638; p=.0002), and in non-African-American men (0.781 vs. 0.732; p=.0016).

PCA3 also added to the model for the prediction of high-grade (>Gleason 6) prostate cancer for the overall cohort (0.804 vs. 0.78; p=.0002) and the African-American subset only (0.759 vs. 0.717; p=.0003) but not in the non-African-American subset.

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Decision curve analysis demonstrated significant net benefit with the addition of PCA3 compared with standard of care variables plus PSA.

Next: TMPRSS2:ERG doesn't improve concordance

TMPRSS2:ERG doesn’t improve concordance

For African-American men, TMPRSS2:ERG did not improve concordance statistics for the detection of any or high-grade prostate cancer.

“Novel biomarkers should not be across-the-board tests,” Dr. Silberstein said. “I don’t think they’re of tremendous value to use routinely in every patient. But when you have discordant information-for example, if the biopsies are continuing to show me low-risk prostate cancer but the MRIs show an aggressive lesion-then I really think you need additional information to help you sort it through.”

“Our study demonstrates that for many African-American patients, PCA3 can help diagnose prostate cancer and particularly higher grade lesions,” he added. “So when I see an African-American patient who is reluctant to have a prostate biopsy, or had a previously negative biopsy with a persistently elevated PSA, PCA3 has real clinical value. Additionally, if I have a patient with significant comorbidities and a marginally elevated PSA who is unlikely to benefit from the diagnosis of a low-grade tumor, PCA3 in an African-American can influence my decision to biopsy.”

Dr. Silberstein has received honoraria from and served as a consultant/adviser to Astellas Pharma and Medivation. Two of his co-authors have disclosed relationships with several pharmaceutical and/or device companies.