Multigene Assay Validated for Risk Assessment in Prostate Cancer

There has been a preponderance in the healthcare industry to overtreat early-stage, slow-progressing prostate cancer, often subjecting patients to unwarranted, life-altering treatments.

Phil Febbo, MD

There has been a preponderance in the healthcare industry to overtreat early-stage, slow-progressing prostate cancer, often subjecting patients to unwarranted, life-altering treatments. According to Genomic Health Inc, provider of genomic-based diagnostic tests, increased surveillance should be the primary outcome in patients with clinically localized prostate cancer (PC). To prevent overtreatment in such patients, they have developed the Oncotype DX test that allows clinical risk assessment for differentiating between high-risk and low-risk patients with prostate cancer (PC).

Oncotype DX prostate cancer assay is a multigene RT-PCR expression assay compatible with fixed paraffin-embedded diagnostic prostate needle biopsies. The assay measures expression of 12 cancer-related genes (AZGP1,KLK2,SRD5A2,FAM13c,FLNC,GSN,TPM2,GSTM2,TPX2,BGN,COL1A1, andSFRP4) and five reference genes that are algorithmically combined to calculate the Genomic Prostate Score (GPS) ranging from 0 (low) to 100 (high). This 17-gene biopsy-based assay has been analytically and subsequently validated as a predictor of aggressive PC.1,2

Two studies published recently inUrology Practicevalidate the benefits of incorporating Oncotype DX score into the therapeutic decision-making process. In the first study, the authors assess the economics of active surveillance for prostate cancer under the Patient Protection and Affordable Care Act (PPACA)3. They conclude that while multiple aspects of the PPACA are likely to impact the choice and delivery of active surveillance for prostate cancer management, active surveillance is an attractive option for managing prostate cancer in the new healthcare environment.

Marc Dall'Era, MD, vice chair of urology at the University of California, Davis Comprehensive Cancer Center and part of the study said, "Despite increasing awareness of active surveillance as a viable alternative to immediate intervention in men with clinically low-risk prostate cancer, its adoption has been limited largely due to physician and patient concerns around the accuracy of disease risk assessment." He added that publication of the latest study along with earlier clinical results are likely to positively impact treatment recommendations by urologists in patients with NCCN-classified very low to low-intermediate risk.

In another study in the same journal, the Oncotype DX GPS was clinically validated to predict the likelihood of adverse surgical pathology in men with NCCN-classified very low, low, or low-intermediate risk prostate cancer.4While the biological risk predicted by GPS differed from NCCN clinical risk alone in 39% of patients, overall 18% of recommendations changed between active surveillance and immediate treatment after GPS. The relative increase in recommendations for active surveillance was 24%. Thirty percent of the initial recommendation of radical prostatectomy was changed to active surveillance after GPS. Overall, urologists indicated that incorporating GPS was useful in 85% and 79% of cases, respectively, including when biological risk confirmed the clinical risk category.

With these advances, active surveillance has become a standard alternative to immediate curative intervention in certain men with prostate cancer. It is now included in the treatment guidelines of the American Urological Association (AUA), European Association of Urology (EAU), and the National Comprehensive Cancer Network (NCCN).5-7

According to the molecular testing section of the NCCN guidelines, Genomic Health's Oncotype DX prostate cancer test may provide prognostic information beyond standard clinical data for patients who have Gleason score 7 or disease that extends beyond the prostatic capsule on radical prostatectomy.8

The Oncotype DX test has also been recommended for Medicare coverage. Palmetto GBA, a Medicare administrative contractor that assesses molecular diagnostic technologies, is recommending coverage of the Oncotype DX prostate cancer test for qualified Medicare patients throughout the United States. This proposal is not active presently and will go through Medicare’s review process including a public comment period before finalization and notification.9

Phil Febbo, MD, chief medical officer, Genomic Health concludes, "These data from actual patient charts add an important real-life perspective on the value of our test. Combined with 14 studies including more than 2000 patients and a recent favorable draft local coverage determination on Medicare coverage, we believe this publication further supports our efforts to secure reimbursement for the Oncotype DX prostate cancer test."

While the company is also working on developing a similar test for Colon cancer, their Oncotype DX breast cancer test is already included in all major cancer treatment guidelines to promote active surveillance for breast cancer.



1. Knezevic D, Goddard AD, Natraj N, et al. Analytical validation of the Oncotype DX prostate cancer assay—a clinical RT-PCR assay optimized for prostate needle biopsies.BMC Genomics. 2013;14:690.

2. Falzarano SM, Ferro M, Bollito E, et al. Novel biomarkers and genomic tests in prostate cancer: a critical analysis.Minerva Urol Nefrol. 2015;67(3):211-31.

3. Yuh L, Dall’Era MA, Penson DF et al. Active Surveillance for Prostate Cancer under the Patient Protection and Affordable Care Act. Urology Practice. 2015;2(4):154-159.

4. Badani KK, Kemeter MJ, Febbo PG, et al. The impact of a biopsy based 17-gene genomic prostate score on treatment recommendations in men with newly diagnosed clinical prostate cancer who are candidates for active surveillance.Urology Practice. 2015;2(4):181-189.

5. Heidenreich A, Bastian PJ, Bellmunt J et al: EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update 2013.Eur Urol. 2014; 65: 124.

6. Mohler JL and NCCN Prostate Cancer Guidelines Panel: Joint statement by members of the NCCN Prostate Cancer Guidelines Panel.J Natl Compr Canc Network.2013; 11:1310.

7. Carter HB, Albertsen PC, Barry MJ et al: Early detection of prostate cancer: AUA Guideline.J Urol. 2013; 190: 419.

8. NCCN guidelines for prostate cancer.20thAnnual Edition; Accessed August 4, 2015.

9. Eric A. Klein. Medicare considers coverage of genetic prostate cancer test. 2015; Accessed August 4, 2015.