Of the primary tools currently available to clinicians for determining which patients should have a prostate biopsy—prostate specific antigen (PSA) testing and digital rectal examination (DRE)—neither have a high degree of accuracy. After examining the benefits and risks of PSA screening, the United States Preventive Services Task Force (USPSTF) concluded that the test is associated with little potential benefit and significant potential harm, and recommended against its use.1
While acknowledging that PSA screening identifies many asymptomatic cancers, the USPSTF report found that many of these tumors would act in one of two ways: the tumor would not progress or would progress so slowly that they would remain asymptomatic for the balance of the patient’s life. The USPSTF recommendation remains controversial and many patients continue to request PSA screening, despite its known limitations.
The Holy Grail for researchers studying prostate cancer screening technologies is to develop a test that distinguishes between slow-growing tumors, which can be managed with nothing more than regular monitoring, and faster-growing tumors for which surgery is justified. According to a recent article in The New York Times, more than a dozen companies have introduced new tests for prostate cancer screening or have tests in development.2
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A test that measures the expression level of 31 genes to determine the cell cycle progression (CCP) score, a potential predictor of prostate cancer recurrence, has been investigated in two studies using tumor samples. The first study, which used samples from men who had undergone radical prostatectomy or were managed conservatively, found that the CCP score, when combined with PSA testing, was highly predictive of time to death from prostate cancer.3 The second study, which used tumor samples from needle biopsies of men with localized cancer that had been conservatively managed, found that each 1 unit increase in the CCP score was associated with a doubling of the hazard ratio for death from prostate cancer. Further validation of the clinical utility of the CCP score will be required.4
A study of 2,914 men undergoing prostate biopsy investigated whether measuring blood levels of 4 kallikrein forms—total, free, and intact PSA and kallikrein-related peptidase 2—would predict biopsy results.5 The researchers found that use of the test in men with elevated PSA would substantially reduce the number of biopsies; however, it would miss 12% of high-grade cancers and 31% of low-grade cancers.
Despite being less sensitive than PSA, DRE retains a role in prostate cancer screening, according to a recent investigation from the Pennsylvania State College of Medicine. In this retrospective study, researchers examined the medical charts of 806 men who underwent prostate needle biopsy, 306 of whom were diagnosed with prostate cancer. Of the patients with prostate cancer, 136 had an abnormal DRE and of these, 43 had a normal PSA. Thus, 14% of cases of prostate cancer were diagnosed by DRE, and would have been missed if treating physicians had relied on PSA alone.
Although screening for prostate cancer remains an uncertain and frustrating endeavor, new technologies and regular use of an old standby may increase its specificity, therefore offering patients a more reliable means of testing for the disease.
References
1. Moyer VA et al. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157:120-34.
2. Pollack A. New prostate cancer tests could reduce false alarms. New York Times. March 26, 2013. http://www.nytimes.com/2013/03/27/business/new-prostate-cancer-tests-may-supplement-psa-testing.html?ref=health&_r=0. Accessed March 29, 2013.
3. Cuzick J et al. Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study. Lancet Oncol. 2011;12:245-55.
4. Cuzick J et al. Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer. 2012;106:1095-9.
5. Vickers A et al. Reducing unnecessary biopsy during prostate cancer screening using a four-kallikrein panel: an independent replication. J Clin Oncol. 2010;28:2493-2498.
