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Stacy Loeb, MD

Role of Biomarker Assays in Prostate Cancer Detection and Management
Stacy Loeb, MD

Practice Community

New York, New York


Hospital and Institutional Affiliations

Assistant Professor of Urology and Population Health, New York University Langone Medical Center, New York

Number of Patients Seen in a Week

Approximately 35


Practice Niche

Prostate cancer, men's health

Question 1. Should biomarker assays be an integral part of prostate cancer patient management? Do they have a role in every step along the continuum of care?

I believe that biomarkers should be an integral part of prostate cancer management and have a potential role at every step in the pathway. Now that we have better tests available, why wouldn't we use them? For screening, historically, we used total prostate-specific antigen (PSA) alone to make decisions about who should undergo prostate biopsy, but we know that total PSA has limited specificity. Due to confounding and variability in PSA, we recommend repeating the measurement for confirmation prior to proceeding with biopsy. However, we now have several other blood tests that are more specific than total PSA, so why not use one of those tests to help with the decision? The 2016 NCCN [National Comprehensive Cancer Network] guidelines recommend 3 different second-line testing options for men with elevated PSA to help decide on an initial biopsy: free PSA, the Prostate Health Index (phi), and the 4Kscore. For men who have already had a negative biopsy, they offer these same 3 second-line testing options as well as prostate cancer antigen 3 (PCA3), ConfirmMDx, and multiparametric magnetic resonance imaging (MRI). Several other new tests have come out as well, such as SelectMDx, so this is a rapidly evolving space, and it is encouraging that we finally have new tools to help with prostate biopsy decisions. There are also marker tests available for men who already have a diagnosis of localized prostate cancer that can provide additional information on risk stratification for initial treatment selection or decisions about secondary therapy.

Question 2. Which biomarker assays have you found to be the most useful in clinical decision-making?

Overall, multiparametric MRI is probably the most transformative development in the context of prostate cancer detection.  Not only does it show which patients are at greater risk of harboring clinically significant prostate cancer, but it can also be used to target the biopsy itself and increase diagnostic yield. In terms of markers, in my opinion, phi and the 4Kscore are the most useful second-line tests in screening since they are like new and improved versions of PSA itself. Both of these tests are consistently shown across many prospective, international studies to be more specific for clinically significant prostate cancer. By contrast, PCA3 is worse at identifying aggressive cancer, so I do not use that test in my practice.


For men with newly diagnosed prostate cancer, Prolaris®, Oncotype DX®, or Decipher® can be used for men with borderline features to help discuss the pros and cons of active surveillance vs upfront treatment.  There are no data on the superiority of any one of these tests over the other, and they report different end points, so at this time which one to obtain is a matter of physician and/or patient preference. For men with high-risk disease at prostatectomy, there is good evidence that Decipher can help predict who will actually develop metastatic disease. Traditionally, I have favored early salvage over adjuvant radiation therapy, but there may be a subset of men with high Decipher scores who would benefit from earlier radiation therapy. Prospective studies are needed to determine the long-term impact of using these markers to alter management decisions.

Question 3. Do the results of biomarker tests help in patient counseling?

The results of MRI and marker tests can definitely help in patient counseling. One particular scenario is a patient who has undergone multiple repeat prostate biopsies with persistently elevated PSA. We will usually start with an MRI for this type of patient to identify any suspicious lesions in the prostate that may not have been sampled previously. However, if the MRI is negative and PSA is rising, other marker tests may be used to help determine the urgency of repeating a biopsy.  Another patient population where markers may be helpful are individuals with newly diagnosed prostate cancer who are borderline candidates for active surveillance (eg, very low volume of Gleason 3+4 disease or high-volume Gleason 3+3=6 disease) or where there is a discrepancy between the MRI findings and biopsy features. In such cases, genomic tests can be useful to help patients make a more informed decision about whether to do surveillance vs treatment.

Question 4. Is there a benefit to using biomarker assays in combination? Have you found any combinations to be especially helpful?

Some of the markers like phi and 4Kscore are very similar, so I would only get one or the other on a particular patient at a given time, not both. However, markers can be useful in combination with MRI in the context of detection and management decisions. MRI is extremely helpful but is not perfect, so markers may be especially useful for MRI-negative cases or when the MRI results are discordant with other clinical data. Finally, different markers may be useful at different points during the course of care; for example, a patient who had one marker used during detection may benefit later from a different marker for therapeutic decisions.  

During active surveillance, both phi and MRI have been shown to predict disease reclassification longitudinally, so this combination may be used to help inform the ideal interval for performing repeat biopsy. This is a setting where noninvasive testing options are particularly important, since there are significant risks associated with multiple repeat biopsies and most patients would like to space out the biopsies as much as possible without compromising their opportunity to detect progressive disease in time for cure.

Question 5. Are there any biomarkers now in the early stages of development that have the potential to be a game changer with respect to risk stratification?

The initial results for SelectMDx were impressive, so it will be interesting to see additional studies comparing this test to other markers like phi and the 4Kscore. Certainly, detection is an area where there is always significant room for improvement, and more data are needed on how to best integrate these markers with MRI. In terms of men already diagnosed with prostate cancer that is very low risk, the prognosis with active surveillance is excellent even without additional complex testing options, so I think that biomarkers are unlikely to be game changing in this scenario. If we continue to try to push the envelope in expanding enrollment for active surveillance, genomic tests may play a much greater role to help confirm eligibility for borderline cases at the higher end of the low-risk group or at the low end of the intermediate-risk group. Finally, there are many new tests being studied for patients with advanced prostate cancer that could potentially lead to significant changes in their management.


Suggested Readings

1. Tilki D, Evans CP. The Decipher genomic classifier independently improves prognostication for patients after prostatectomy [published online April 26, 2017]. Eur Urol.  doi: org/10.1016/j.eururo.2017.04.020


2. Gore JL, du Plessis M, Santiago-Jiménez M, et al. Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: interim results from the Multicenter Prospective PRO-IMPACT study [published April 19, 2017]. Cancer. doi: 10.1002/cncr.30665


3. Russo GI, Regis F, Castelli T, et al. A systematic review and meta-analysis of the diagnostic accuracy of Prostate Health Index and 4-kallikrein panel score in predicting overall and high-grade prostate cancer [published online December 30, 2016]. Clin Genitourin Cancer. doi: 10.1016/j.clgc.2016.12.022

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