Latest Assays Can Improve Prostate Cancer Workup

AMELIA ISLAND, FL.—New assays and scoring systems can improve the accuracy of prostate cancer (PCa) screening, prognostication, and risk stratification compared with the use of PSA alone, a researcher concluded in a presentation at the Florida Urological Society’s 68^th annual meeting.

Michael A. Poch, MD, from the University of South Florida and Moffitt Cancer Center in Tampa, reviewed these new tools, which include the Prostate Health Index (PHI), Prolaris, 4KScore, Oncotype DX Prostate Cancer Assay, and Decipher Prostate Cancer Biopsy.

Variability in the biology and growth of PCa can lead to under-treatment of aggressive cancers or over-treatment of non-aggressive cancers, affecting patient mortality or quality of life. Increasing data and technological advances show that PSA screening is only a first step to predicting incidence and progression of PCa and determining whether a biopsy, surveillance, or treatment is necessary.

PHI combines the results of total PSA, free PSA, and [-2]proPSA—the most PCa-specific isoform of free PSA in tumor extracts—to determine a score. A 2011 multicenter study of 892 men showed increasing PHI was associated with 4.7 times increased risk of PCa and 1.61 times increased risk of Gleason score 4+3=7 on biopsy¹. A 2013 study of 658 men showed a significant relationship between PHI and Gleason score on biopsy². The PHI score is 3 times more specific than PSA testing alone in detecting PCa, and it predicts progression during active surveillance.3

During a blinded prospective trial of 1012 men, the 4KScore Test, a blood test using 4 kallikrein biomarkers, accurately predicted biopsy outcome of Gleason score ≥7.⁴. In 10 peer-reviewed publications, 4KScore algorithms improved the prediction of histopathology, pathology, and occurrence of metastatic disease. In a 2015 literature reviews, Sanoj Punnen, MD, and colleagues stated that men with high-risk 4KScore test results could prevent an adverse or fatal cancer outcome with biopsy, whereas men with low 4KScore test results may safely defer.⁵.

Prolaris is a risk stratification tool that predicts patients’ 10-year risk of cancer progression by measuring gene expression in cell-cycle progression (CCP). A 2013 study of 413 men found cell-cycle progression score and Cancer of the Prostate Risk Assessment post-Surgical [prostatectomy] consistently predicted outcomes across the range of clinical risk ⁶.

The Oncotype DX Prostate Cancer Assay measures expression of 12 cancer-related genes from a prostate needle biopsy to calculate the Genomic Prostate Score, an analytically validated predictor of aggressive prostate cancer. The performance of the Genomic Prostate Score gives men with early-stage prostate cancer a better understanding of their treatment and risks.

The Decipher Prostate Cancer Biopsy classifies patients into low, average, and high risk, with a predictive power measured by area under the curve (AUC) of 0.87 compared with 0.67 for pre-treatment PSA screening ⁷. The AUC for predicting high-grade disease is 0.71 for Decipher compared with 0.62 for pretreatment PSA.

According to Dr Poch, Decipher may have a role in the decision-making process for prostatectomy patients who have Gleason score 3+4 disease and positive surgical margins. For example, for patients identified as having very low-risk disease, salvage therapy may be a better option than adjuvant radiation, whereas those with high-risk disease may be better served with adjuvant radiation, Dr Poch noted.

Dr Poch also noted that a patient’s numeracy is important in the patient’s ability to understand his risk and prognosis and make accurate treatment decisions. He cited a 2015 study on numeracy, time discounting, and risk attitudes ⁸, where patients with higher numeracy or time discounting scores were more likely to choose active surveillance, whereas patients with higher risk taking scores would choose radical prostatectomy.

Dr Poch concluded that the new biomarkers improve sensitivity and specificity over PSA alone, but it remains unclear which biomarker is better because there have been very few head-to-head trials comparing them.

He also said he believes the cost of testing with these tools—which ranges from $3000 to $4000—will influence the extent to which they are used in patient care.

Source

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2. Sanda M, et al. (2013) Evaluation of the Prostate Health Index (PHI) for improving prostate cancer detection and identification of clinically significant prostate cancer in the 4 to 10 ng/mL PSA range. In: Proceedings of American Urological Association Annual Meeting, San Diego
3. Loeb S, Catalona WJ.The Prostate Health Index: a new test for the detection of prostate cancer. Ther Adv Urol 2014;6:74-77
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7. Cullen J, et al. A biopsy-based 17-gene Genomic Prostate Score predicts recurrence after radical prostatectomy and adverse surgical pathology in a racially diverse population of men with clinically low- and intermediate-risk prostate cancer. Eur Urol 2015;68:123-131.
8. Lopez-Perez B, et al. Predicting prostate cancer treatment choices: The role of numeracy, time discounting, and risk attitudes. J Health Psychol 2015; published online ahead of print.