How a Biomarker Test Can Help When a Prostate Biopsy is Negative

Men who have had an elevated prostate-specific antigen or PSA level, followed by a negative biopsy, are regularly monitored by their urologists with follow-up PSA testing. Men who continue to have elevated PSA, show increasing PSA levels, or have abnormal results following a digital rectal examination (DRE) present a unique challenge for urologists.

Traditionally, a physician would schedule these patients for a repeat prostate biopsy or a magnetic resonance imaging (MRI) scan. Now, biomarker tests provide an intermediary step in prostate cancer screening by shedding light on whether the risk of clinically significant prostate cancer warrants one of these additional procedures.

Screening for specific urinary genetic biomarkers, such as PCA3 or TMPRSS2:ERG, can determine the likelihood that a subsequent biopsy would be negative, potentially avoiding a procedure that can be an unpleasant experience for a patient.

Options after a negative biopsy

For patients whose initial biopsy was negative, the standard care pathway has traditionally been as follows:

• Patient schedules a follow-up PSA/DRE appointment
• Urologist reviews results and, if PSA levels are elevated or DRE is abnormal, schedules a repeat biopsy or MRI
• Patient undergoes repeat biopsy or MRI scan
• Patient and urologist review biopsy results and determine next steps

The additional information a biomarker test provides alters this treatment regimen and prevents unnecessary biopsies. For patients with a prior negative biopsy, an updated care pathway is available:

• Patient schedules a follow-up PSA/DRE appointment
• Urologist reviews results, and, if PSA levels are elevated or DRE is abnormal, schedules a biomarker test
• Patient’s blood or urine is screened for specific biomarkers
• Patient and urologist review biomarker test results and determine whether a repeat biopsy or MRI is advisable

The problems with a repeat prostate biopsy or MRI

Biopsies can provide valuable information about prostate health. The procedure, usually either a transrectal or transperineal biopsy, is uncomfortable for the patient, however, and potential side effects include blood in the urine or semen, anal bleeding, or infection. With advancing age, the likelihood of these side effects increases, as does risk of infection or complications with each subsequent biopsy.

The prior-negative biopsy population tends to be older, with more comorbidities such as diabetes or heart disease, putting them at increased risk for biopsy side effects. Also, biopsies may miss high-grade prostate cancer if the biopsy cores do not penetrate the area with a cancerous tumor.

Meanwhile, MRI scans are daunting for many patients and may induce claustrophobia. They’re also expensive, and the procedure can last up to an hour. In addition, magnetic resonance imaging machines are less accessible to those living in rural or sparsely populated areas.

Biomarker tests as a new step

Blood, urine, and tissue-based biomarker tests are increasingly becoming a viable prostate cancer screening option for urologists and their patients who have a prior negative biopsy and high PSA or abnormal DRE. These tests are less costly, less time-consuming, and less invasive than repeat biopsies or MRI scans.

Some patients may be reluctant to enter the MRI “tube” or hesitant to repeat the discomfort of a prostate biopsy. A blood or urinary biomarker screening test can help these patients decide whether to undergo one of these procedures or opt for active surveillance.

There are a number of biomarkers that provide insight into an individual’s prostate cancer risk. In addition to the most widely known biomarker, the protein PSA, and its variants (“isoforms”), different biomarkers can also be molecules or genes that have been altered through mutation, rearrangement, or fusion; or certain enzymes. Using biomarker tests to gather more information about an individual’s clinically significant prostate cancer risk can save patients and their urologists time, money, discomfort, and anxiety and prevent uncomfortable repeat biopsies or costly MRIs.

Biomarker tests provide next-generation accuracy about the likelihood of aggressive prostate cancer to inform decisions about next steps.