Global Lab Testing / January 14, 2019 / by beaconlbs
Making Sense of Prostate-Specific Antigen (PSA) Testing
Confusion exists the role of routine PSA testing in screening for prostate cancer. BeaconLBS answers your questions below in our blog about the history, role and evidence regarding routine PSA testing.
In 2015, there were about 180,000 new cases of prostate cancer in the United States, according to the Centers for Disease Control and Prevention (CDC). Prostate specific antigen (PSA) testing was first approved in the mid-nineties by the Food and Drug Administration (FDA) as a screening tool for prostate cancer. However, an elevated PSA may have other causes (false-positives) and may not be able to differentiate between slow-growing and aggressive forms of the disease. Although the literature reports a decline in prostate cancer mortality since screening has been employed in the United States, screening by measuring PSA may have risks for harm, including unnecessary prostate biopsies with associated side effects, over diagnosis (diagnosis of malignancy that would have not been known during the life of the patient without screening), and overtreatment.
Contributing to the confusion is some of the published data regarding PSA screening. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was designed to provide data for evidence-based guidelines; it followed about 76,000 men aged 55 to 74 from 1993 to 2001. The study population was split in half with one group receiving routine screening by digital rectal exam and the other group having PSA screening with digital rectal exam. Cancer diagnoses were higher in the PSA group when compared to the control (routine screening) group. Conversely, there was no statistically significant change in mortality between the two groups. It was reported that 40%-52% of those in the control group underwent PSA screening during the trial. Also, 44% of patients had at least one PSA test prior to random group assignment, which should have excluded them from the study. Finally, there was no standardization of a PSA threshold that would constitute a positive test. Therefore, the study was not informative for the original purpose for which it was designed.
There are numerous guidelines by multiple professional societies regarding PSA screening, such as the American Cancer Society, American College of Physicians, National Comprehensive Cancer Network, European Society for Medical Oncology, US Preventive Services Task Force, and Canadian Urological Association, among others. These societies have varying guidelines depending on what evidence is cited in the literature. Specific recommendations such as individual baseline PSA values, age to screen (or not to screen), method and timing of screening, and follow-up options for a positive test differ among professional societies.
Even with this lack of concordance, the literature presents some evidence that may be agreed upon among some (but not all) professional societies:
- PSA screening must be individualized to the patient. All screening options including benefits, risks, and limitations should be reviewed with the patient by the clinician.
- PSA screening should be offered to men with a “reasonable life expectancy”. Some would say less than 70 years of age, or with at least 10 years of life expectancy.
- “High-risk” and “average-risk” patients have different screening guidelines, although there is some disagreement about screening protocols for each group.
There is an age limit for PSA screening because of the risk of overtreatment due to over diagnosis. Many elderly patients diagnosed with prostate cancer are at a higher risk of experiencing the harms of screening, diagnosis, and treatment. They may die from other causes, making prostate cancer treatment unnecessary. The median age of prostate cancer presentation is 68 years. Younger men with prostate cancer are at a higher risk of having cancer in other tissues. It has also been observed that men who are diagnosed with advanced prostate cancer between ages 35 and 44 have a higher risk for death when compared to those diagnosed at an older age. Younger patients with high-grade, poorly differentiated adenocarcinoma of the prostate typically have a lower PSA level that may not be detected on a PSA screen.
Randomized control trials are engineered to produce robust data for care providers that are clinically actionable. On the other hand, these trials may be limited to a single population, or may be improperly executed, as seen in the previous example. Given the lack of consensus among professional societies regarding PSA screening, some physicians are taking a comprehensive, individualized approach.
This method may recognize that PSA screening is not a stand-alone test. It is one of many tools available to physicians. Much effort has been put into developing new tests and measurements to assess for prostate cancer and PSA screening is evolving as new data is published. For example, the Prostate Health Index and the 4Kscore® are two more recent tools clinicians may use when deciding how to manage an elevated PSA test. They measure additional biomarkers to help physicians determine if a prostate biopsy is needed, thus lowering the risk for adverse procedure-related side effects.
An individualized approach views professional guidelines as what they are meant to be – a guide. They are not meant to be restrictive or to cause harm to a patient. Additionally, most guidelines are not static. If there are new data in the published literature, they may be re-visited periodically. This gives a chance for edits and fine-tuning as the body of knowledge expands. Physicians using a personalized approach may assess that guidelines are a starting point for the provider and patient to formulate a plan for management and preventative care. Professional guidelines should be applied and modified while taking the patient’s personal and family health history into account, in addition to other clinical factors. As stated earlier, PSA screening should be individualized after a thorough discussion between the patient and physician. Physicians who screen for prostate cancer must be vigilant in their ability to research new screening technology and familiarize themselves with new guidelines in order to facilitate optimum care for their patients.
- https://gis.cdc.gov/Cancer/USCS/DataViz.html – accessed 11/11/2018
- Carter HB. Prostate-Specific Antigen (PSA) Screening for Prostate Cancer: Revisiting the Evidence. 2018 May 8;319(18):1866-186.
- Loeb S. Evidence-Based Versus Personalized Prostate Cancer Screening: Using Baseline Prostate-Specific Antigen Measurements to Individualize Screening. 2016 Aug 10;34(23):2684-6.
- Kim EH, Andriole GL. Prostate-specific antigen-based screening: controversy and guidelines. BMC Med. 2015 Mar 24;13:61
- Andriole GL, Crawford ED, et. al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009 Mar 26;360(13):1310-9.
- Araujo FAGDR, Oliveira U Jr. Current guidelines for prostate cancer screening: A systematic review and minimal core proposal. Rev Assoc Med Bras. 2018 Mar;64(3):290-296.
- Rendon RA, Ross MJ et. al. Canadian Urological Association recommendations on prostate cancer screening and early diagnosis. Can Urol Assoc J. 2017 Oct;11(10):298-309.
- Gupta S, Gupta A, Saini AK, Majumder K, Sinha K, Chahal A. Prostate Cancer: How Young is too Young?. Curr Urol. 2016;9(4):212-215.
- Lin DW, Porter M, Montgomery B. Treatment and survival outcomes in young men diagnosed with prostate cancer: a Population-based Cohort Study. Cancer. 2009;115(13):2863-71.
- Prensner JR, Rubin MA, Wei JT, Chinnaiyan AM. Beyond PSA: the next generation of prostate cancer biomarkers. Sci Transl Med. 2012;4(127):127rv3.
- Loeb S, Catalona WJ. The Prostate Health Index: a new test for the detection of prostate cancer. Ther Adv Urol. 2014;6(2):74-7.
Insights / February 20, 2019 / by beaconlbs
BeaconLBS works with our health plan, employer and accountable care organization (ACO) partners to use evidence-based policies and guide lab test benefit management. Read about our four steps below.