Prostate cancer (PC) is the most common male-related malignancy in the United States, the second most common cause of cancer-related death among US men, and the fourth most prevalent male malignancy worldwide.1,2

Clinical Presentation

Clinical aspects of PC vary widely, and two men with similar PC stage and PSA values may develop sharply different outcomes. The fact that most men are asymptomatic at diagnosis is a reflection of the tendency of PC to arise in the peripheral aspect of the prostate, distant from the urethra.

Obstructive and irritative urinary symptoms are consistent with larger-volume tumors involving the central tissue zone. Such symptoms are by no means restricted to PC and may be mimicked by such conditions as benign prostatic hyperplasia (BPH), urinary tract infection, and prostatitis. Progressive bone pain involving the spine, pelvis, or hips may herald the presence of metastases.

Currently, the most typical initial scenario is an older asymptomatic man with an elevated PSA who is found at subsequent biopsy to have an unanticipated histologic surprise in the form of PC. Fortunately, 90% of PC cases detected today are at a clinically localized stage.2,4 

Assessment and Differential Diagnosis

PC screening tools include the PSA blood test and the digital rectal examination (DRE).2 Since the introduction of PSA testing in 1987, PC incidence has increased sharply, and mortality rates have trended downward.5

Yet the cumulative risk/benefit comparisons for screening are not consistently persuasive due to the disturbing lack of randomized controlled trials (RCTs) demonstrating reduced mortality in screened populations. In fact, the US Preventive Services Task Force currently recommends against PSA-based screening.6

In 1995, the Office of Technology Assessment concluded that available evidence indicated that PSA testing was of no proven mortality benefit. The CDC, American Cancer Society, and American Urological Association endorse testing with PSA and DRE annually in men reaching age 50 years, with earlier screening at age 40 years for black men or those with a family history of PC.

Since 90% of men with elevated PSA and normal DRE will be proven at biopsy to have disease confined to the prostate, most men can anticipate a favorable prognosis and a wide array of treatment options.2,5

PSA is a serine protease that functions to liquefy the ejaculate. The prostate gland is the predominant source of PSA in serum. Elevations of PSA occur with architectural disruption of the gland as in PC, BPH, prostatitis, prostate biopsy or massage, transurethral resection of prostate, and (transiently) ejaculation.

PSA levels increase with advancing years of life, such that age-specific normal values have been established (Table 1). Healthy men typically have PSA values <4mg/mL.2 Refinements capable of enhancing sensitivity and specificity include PSA density, PSA velocity, PSA doubling time, and free-PSA vs. bound-PSA.

Table 1. Age-Specific Normal PSA Values
Age (years) Normal PSA range ng/mL
<40 0 to 2.0
45 0 to 2.4
50 0 to 2.8
55 0 to 3.3
60 0 to 3.8
65 0 to 4.5
70 0 to 5.3
75 0 to 6.2
>80 0 to 7.2
Source: Cornett PA, Dea TO. Cancer. In: McPhee SJ, Papadakis MA, Rabow MW, eds. CURRENT Medical Diagnosis & Treatment 2011. New York, N.Y.: McGraw-Hill; 2011:1564-1569.

DRE allows estimation of prostate size and detection of nodules, induration, asymmetry, or tenderness.2 The palpating finger examines only the peripheral zone, where the majority of PC lesions arise.

Taken together, PSA and DRE in combination are slightly more effective in early detection of PC than either procedure alone.7 PSA exceeding age-specific normal values, or abnormal DRE, usually leads to prostate ultrasound and biopsy to confirm the presence of PC or to document such benign conditions as BPH or prostatitis. Biopsy-proven PC is then graded according to the 10-point Gleason score and staged by the Tumor-Node-Metastasis system.

Such radiologic imaging studies as CT, PET, and bone scan may be necessary if metastases are suspected.7

This article originally appeared on Clinical Advisor