patient care perspectives

Analyzing Diagnostic and Assessment Tools in Advanced Prostate Cancer

by Peter R. Carroll, MD, MPH


Although men with elevated prostate-specific antigen (PSA) levels may proceed directly to biopsy, the use of magnetic resonance imaging (MRI) and biomarkers to aid in the decision-making process is on the rise. Likewise, genomic signatures and molecular and/or imaging biomarkers are increasingly being used to assess the disease, once detected.

Expert Commentary

Peter R. Carroll, MD, MPH

Ken and Donna Derr – Chevron Distinguished Professor
Taube Family Distinguished Professor in Urology
Department of Urology
UCSF - Helen Diller Comprehensive Cancer Center
University of California, San Francisco
San Francisco, CA

“Both imaging and genomics are being integrated into the workup, with a move toward the development of predictive biomarkers.”

Peter R. Carroll, MD, MPH

There has been a gradual evolution over the last several years with the introduction of advanced imaging and molecular techniques for the diagnosis and assessment of prostate cancer. Both imaging and genomics are being integrated into the workup, with a move toward the development of predictive biomarkers. There are therapeutic implications as well, with interest in theranostics and genomic signatures to individualize treatment. 

These newer tools complement those that are already in use. PSA-based screening is here to stay. This screening involves an informed discussion between patients and physicians about the risks and benefits of PSA testing. Once the patient has been adequately counseled and it is determined that they want to proceed with testing, we start with the PSA, a useful screening tool but an imperfect biomarker. Men with PSA levels between 4 ng/mL and 10 ng/mL have about a 25% chance of having prostate cancer. Of those with cancer, some 25% to 40% have low-grade tumors that may not require treatment. Although you could proceed to a biopsy based on an elevated PSA level alone, secondary screening techniques, including urine- and serum-based techniques (eg, the 4Kscore or the Prostate Health Index), as well as MRI, are available. Both biomarker tests indicate the likelihood that a man with an elevated PSA will have clinically significant disease. By using such tools, perhaps in combination, you can avoid significant percentages of unnecessary biopsies with a very low chance of missing clinically significant disease. 

There is some controversy regarding whether to use a biomarker alone, an MRI, or a combination of the two. In Europe, they often turn to MRIs right off the bat. Here in the United States, however, there is a lot of focus on biomarkers. Many patients might be screened with a biomarker first, such as the 4Kscore or the Prostate Health Index, and then the focus shifts to an MRI if there is an elevated risk of the patient having clinically significant disease. Once you decide to perform a biopsy, I think that MRI targeting reduces the chance of missing clinically significant disease. If one proceeds to an MRI in the absence of another biomarker, the decision to avoid a biopsy cannot be based on a negative MRI, as you will miss approximately 15% of clinically significant tumors in those with a normal MRI. In such cases, the negative predictive value of testing can be improved by adding a biomarker, one as simple as PSA density (PSAD <0.15), which is readily available on the MRI report.

Fusion-guided biopsy is a technique that will perhaps allow providers to perform a better biopsy (ie, miss fewer high-grade cancers). In “cognitive fusion,” the provider will review the MRI report and will perform the biopsy using ultrasound alone. However, there are several software packages that enable you to actually integrate the MRI results with the ultrasound image in real time, allowing you to overlay the MRI to the ultrasound image. These techniques are recommended in a patient who has had a negative biopsy and who may still be at risk of having disease, but it is rapidly becoming an initial biopsy technique. Insurance companies do not always reimburse for this, but I think that you will see that there is a worldwide movement incorporating MRI before all biopsies. A new technique called high-resolution micro-ultrasound has the capability of imaging prostate cancer based on alterations in ductal anatomy. This technology has potential advantages over MRI in that it is associated with lower costs and may be more accessible.


Fridhammar A, Axelsson U, Persson U, Bjartell A, Borrebaeck CAK. The value of a new diagnostic test for prostate cancer: a cost-utility analysis in early stage of development. Pharmacoecon Open. 2021;5(1):77-88. doi:10.1007/s41669-020-00226-7

Hofman MS, Lawrentschuk N, Francis RJ, et al; proPSMA Study Group Collaborators. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet. 2020;395(10231):1208-1216. doi:10.1016/S0140-6736(20)30314-7

Kouspou MM, Fong JE, Brew N, et al. The Movember prostate cancer landscape analysis: an assessment of unmet research needs. Nat Rev Urol. 2020;17(9):499-512. doi:10.1038/s41585-020-0349-1

Rouvière O. Choosing the right diagnostic pathway in biopsy-naive patients with suspected prostate cancer. JAMA Oncol. 2021;7(4):542-543. doi:10.1001/jamaoncol.2020.7578

Schoots IG, Padhani AR. Risk-adapted biopsy decision based on prostate magnetic resonance imaging and prostate-specific antigen density for enhanced biopsy avoidance in first prostate cancer diagnostic evaluation. BJU Int. 2021;127(2):175-178. doi:10.1111/bju.15277

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