Determining Prostate Cancer Risk When a Prostate Biopsy is Negative

Men who have in the past had an elevated prostate-specific antigen (PSA) level, followed by a negative prostate biopsy, are regularly monitored by their urologists with follow-up PSA tests. If these men continue to have elevated PSA levels, show increasing PSA levels, or have abnormal results following a digital rectal examination (DRE), it presents a unique challenge for urologists and patients. Traditionally, these patients would automatically be scheduled for a repeat prostate biopsy or a magnetic resonance imaging (MRI) scan, but biomarker tests provide an intermediary step in prostate cancer screening and help doctor and patient assess whether a patient’s prostate cancer risk warrants one of these additional procedures. Screening for specific biomarkers can determine the likelihood that a subsequent biopsy would be negative, potentially avoiding a procedure that can be a negative experience for a patient.

Pathways of care

For patients with an initial biopsy that was negative, the standard care pathway has traditionally been:

• 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 procedure
• Patient and urologist review biopsy results and determine next steps

The additional information a biomarker test provides alters this care pathway and prevents unnecessary procedures. 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 challenges of going from high PSA straight to repeat biopsy or MRI

Biopsies can provide valuable information about prostate health. The procedure, usually a transrectal biopsy or transperineal biopsy, is uncomfortable, 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 often tends to be older and contains more comorbidities. Patients with comorbidities–such as diabetes or heart disease–are also at increased risk for biopsy side effects. Also, biopsies can potentially miss cancer that might be present, if the biopsy cores do not penetrate the area with cancerous tissue.

MRI scans are daunting for many patients and may induce claustrophobia. They tend to be more costly and more lengthy, with the procedure itself lasting 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 in the care pathway

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 can be less costly, less time-consuming, and less invasive than repeat biopsy or MRI procedures. Some patients may be reluctant to enter the MRI “tube” or may be hesitant to repeat the discomfort of a prostate biopsy, and a 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 to inform a urologist’s and patient’s clinical care decisions and next steps.