Prostate Cancer Review

Ekaterina Kachur, PharmD


US Pharmacist. 2018;43(8):HS7-13. 

In This Article

Screening and Diagnosis

The primary modality for prostate cancer screening is the evaluation of PSA with or without digital rectal examination (DRE) in asymptomatic men.[3,4] PSA is a glycoprotein produced by prostate epithelial cells. In prostate cancer, an increase in PSA levels is caused by increased PSA production as well as disruption of tissue between the prostate and capillaries, thereby allowing for more PSA in the serum.[3] However, although PSA is specific to prostate tissue, it is not specific to cancer. Other factors that may increase PSA levels include prostate manipulations (DRE, biopsy), prostatitis, benign prostatic hyperplasia (BPH), and ejaculation.[4] Use of 5 alpha-reductase inhibitors leads to about a 50% decrease in PSA levels after 1 year of therapy.[4,5] Some experts suggest doubling the PSA results for patients on chronic 5 alpha-reductase inhibitors to correctly interpret them.[5]

Traditionally, a PSA >4 ng/mL is considered abnormal.[4,6] However, PSA values between 4 and 10 ng/mL have poor discriminating ability between BPH and prostate cancer.[3,4] Several methods can be used to increase the specificity of PSA results and decrease unnecessary biopsies.[4] For men with PSA values between 4 and 10 ng/mL, measurement of the percentage of free PSA should be considered. Free PSA values >25% most likely indicate BPH; these patients do not require a biopsy.[7] The rate of change in PSA over time, PSA velocity, is another tool that can be used with a PSA level between 2 ng/mL and 10 ng/mL to improve specificity. Most experts agree that for men with PSA velocity value of more than 0.35 ng/mL per year, a further workup, including biopsy, should be strongly considered.[4]

Prostate cancer antigen 3 (PCA3) is an FDA-approved test to help determine if repeat biopsy is necessary in men aged more than 50 years who had negative prostate biopsies in the past. In a prospective, multicenter trial, men with a PCA3 score more than 25 were 4.6 times more likely to have a positive biopsy compared with men with scores under 25.[4] In the era of PSA-testing, the role of DRE in prostate cancer screening is controversial. Most organizations recommend DRE as a complementary test for men with elevated serum PSA rather than a standalone screening tool.[4,8,9] In men with suspected cancer, microscopic evaluation of prostate tissue acquired via needle biopsy remains the gold standard for diagnosis.[4]

Screening recommendations aim to balance the benefit of prostate cancer detection to prevent mortality versus the harm of overdiagnosis and overtreatment of this often slow-growing disease. Table 1 summarizes screening recommendations from several national medical organizations. While there are some differences, all organizations underscore the importance of shared decision-making that involves patient education regarding the pros and cons of screening and open discussion between the provider and the patient.[4,8–11] Screening recommendations are often based on a patient's life expectancy, with most organizations suggesting avoiding or discontinuing screening in patients with less than 10 years of life expectancy.[8,9]