E. David Crawford, MD
Researchers are making progress in identifying biomarkers and developing assays that will help clinicians improve the management of patients with prostate cancer from screening strategies to making therapy choices, according to E. David Crawford, MD.
“Biomarkers are a game changer in prostate cancer—something new and exciting and not that difficult,” said Crawford, a professor of Surgery, Urology and Radiation Oncology at the University of Colorado in Denver speaking at the 7th Annual Interdisciplinary Prostate Cancer Congress™, which Physicians’ Education Resources, LLC (PER®) hosted March 15 in New York City.
There is a need for better biomarkers to increase the rate of positive biopsies and to minimize the number of unnecessary biopsies by finding ways to distinguish between malignant and benign disease, said Crawford. Biomarkers also are needed for stratifying low-risk from high-risk tumors once a patient is diagnosed, more accurately staging and classifying disease, and monitoring and predicting clinical responses during therapy.
Crawford outlined the current biomarkers in use in the clinic including tissue, blood, and urine biomarkers as well as imaging modalities. He categorized promising indicators in development into three “biomarker buckets” based upon their potential utility: when to biopsy, when to rebiopsy, whom to treat or not treat (Table). Some of the markers have been introduced in commercially available tests while others remain in the process of clinical validation.
“There are a lot of biomarkers out there but there are only a few that are in use and it is not that difficult to understand which to use and when,” said Crawford.
Prostate-specific antigen (PSA) screening can double the risk of a prostate cancer diagnosis for a man aged 50 to 70 years from 10% to about 20%, but this screening also decreases the risk of prostate cancer death by 20%, from 3% to 2.4%. “The urologist’s dilemma is that the PSA test is not perfect and not specific to prostate cancer,” said Crawford.
In a 2011 study, using a retrospective cohort, Crawford and colleagues identified a PSA of 1.5 ng/ mL as a safe cut-off for prostate cancer risk: prostate cancer rates for men with PSA levels of 1.5 ng/mL or higher were 15-fold greater compared with men whose PSA levels were lower than 1.5 ng/mL.1
The study also showed that both Caucasian and African American men with baseline PSA values between 1.5 ng/mL and 4.0 ng/mL are at increased risk for future prostate cancer compared with those who have an initial PSA value below 1.5 ng/mL.
A higher PSA level is also a surrogate for an enlarged prostate, said Crawford. “Our way forward is to treat PSA as any other test ordered for patients, including lipid, cholesterol levels, and liver enzyme levels.” For the 70% who have normal PSA outcomes, a discussion about prostate cancer risk is not necessary and for the 30% who do have an elevated PSA level, the discussion with the patient should be done not by a general practitioner, but with a urologist or specialized internist.
The goal for diagnostic biomarkers is to improve sensitivity and specificity and to potentially identify an aggressive cancer early. About 1.3 million biopsies are performed in the United States each year yet only 241,000 (18.5%) of these result in a prostate cancer diagnosis, leaving 1 million men having undergone a negative biopsy. Moreover, about 25% of biopsies result in a false negative. “We biopsy patients because we worry about cancer and that worry does not completely go away even once the biopsy is negative,” said Crawford. Biopsies not only cause potentially unnecessary worry but are linked to morbidity. Up to 6.9% of men are hospitalized for complications that include bleeding, infection, sepsis, endocarditis, sexual dysfunction, and urinary symptoms.2
Although much research into genomic markers is under way, validating new markers is a long-term process, Crawford noted. “Almost every week there is a new signature that can identify a subgroup of prostate cancer patients,” he said. But, these are not relevant to clinical practice until validated, and currently, only a few diagnostic biomarkers are in use in the clinic.