ASCO GU 2018: Evaluation of prostate cancer risk in men with PSA 1.5

San Francisco, CA ( There is growing evidence that genomic classification of malignancies, including prostate cancer, may help overcome the heterogeneity and inherent subjective flaws of clinical staging systems. Genomic tests for prostate cancer abound, with many addressing PCa in its various clinical stages. Some are based on prostate biopsy tissue, while others are based on prostatectomy or metastatectomy specimens.

The utility of PSA alone as a screening tool has been called into question. With international guidelines and task forces increasingly recommending shared decision making with regards to PSA testing, it is important to understand the potential pitfalls of PSA testing alone. Ultimately, the goal is better identification of high-risk prostate cancer and decreased detection of low-risk prostate cancer.

Combining PSA with some of the novel genomic markers may help increase the yield of PSA testing. In this study, the authors evaluate the ability of three of those genomic tests or biomarkers (PHI [prostate health index], 4KScore, and SelectMDx) in men with PSA < 1.5 ng/mL; men at relatively low risk of PCa.

All three tests have been extensively evaluated in the past. PHI is evaluated using p2PSA, total PSA, and free PSA in serum. 4KScore incorporates four kallikrein protein biomarkers: total PSA, free PSA, intact PSA, human kallikrein protein, and clinical information. The SelectMDx, a urine test done following a digital rectal exam, measures mRNA levels of the homeobox C6 and distal-less homeobox 1 biomarkers. In terms of cutoffs for predicting absence of HG PCa - PHI score < 52.7 suggests absence of HG PCa; 4KScore < 20% suggests absence of HG PCa; SelectMDx score of 0% indicates absence of HG PCa.

652 men were screened for PCa an annual Prostate Cancer Awareness Week the institution – during each of those weeks in 2012, 2015, and 2016, a different test was concurrently assessed. In 2012, PHI; in 2015, 4KScore; in 2016, SelectMDx. Between 67-80 patients each year men the inclusion criteria of PSA < 1.5.

Interestingly, no patients with a PSA < 1.5 had a SelectMDx > 0% and/or phi > 52.7. Only one patient had a 4KScore of 27%, indicating a risk for HG PCa. However, none of these patients had follow-up biopsy to provide histopathologic confirmation.

Beyond what their original methods and title suggests, the authors completed the same for men with PSA between 1.5 and 3.99. In this cohort, 2.9% (4/135), 7.4% (4/54), and 2.3% (2/85) had positive phi, 4KScore, and SelectMDx results, respectively.

Based on these results, the authors clearly indicate that a cutoff of 4 for PSA would exclude miss patients with HG PCa, which we already knew. More importantly, the risk of HG PCa in men with PSA < 1.5 is close to 0%, based on these biomarkers. Ultimately, the lack of histopathology and follow-up limits the conclusions.

Speaker: Whitney Stanton

Co-Authors: E. David Crawford, Paul Arangua, John Hoenemeyer, Francisco G. La Rosa, Adrie van Bokhoven, M. Scott Lucia, Wendy Poage, Priya N. Werahera

Institution(s): University of Colorado

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA