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

There is some controversy as to whether screening techniques for PC reliably promote detection at an earlier stage.

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Equal uncertainty surrounds the benefits and risks of radical prostatectomy (RP) as opposed to watchful waiting (WW) for patients with early, organ-confined PC.

Appropriate management, therefore, mandates reconsideration of benefits and harms of screening, preferred treatment options, and issues governing quality of life and overall survival.3 Primary-care providers occupy influential positions in assisting patients with data review and decision making within an evolving menu of often confusing methodologies.

Would you recommend annual prostate cancer screening for a healthy man aged 55 years?

Epidemiology

According to the CDC, 206,640 U.S. men in the were diagnosed with PC in 2009.2 Of these, 28,088 died from the disease. Peak age at diagnosis is 66 years. More than 80% were classified as having low-risk, clinically localized disease.

Although the lifetime risk of PC disease is 15% (one man in seven), the risk of dying from PC is far less at 3% (one man in 33). Of six newly diagnosed cases of PC per year, only one death occurs.4,5

These discrepancies suggest that PC often behaves as a biologically indolent neoplasm and indicate that conservative management is appropriate in many cases.4

Indeed, five- and 10-year survival rates are 100% and 92%, respectively, for all PC stages combined, reflecting the known tendency toward latency for most PC lesions.PC is twice as common in black men than in white men, followed by men of Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native origin.2,6

Death rates from PC are highest among black men, and white men rank second.6 Autopsy data reveals that 50% of men at age 50 years, and 75% of men at age 85 years, harbored histologic evidence of PC but died of other causes.7

The implication is that PC in large numbers of asymptomatic men tends to be biologically insignificant, unlikely to metastasize or kill, and compatible with long life.

Etiology

A number of risk factors exist for PC. Cumulative exposure of the prostate gland to androgen influence correlates strongly with PC incidence, a reflection of the advanced age of most men with PC. Other factors include black ethnicity, high-fat diet, obesity, smoking, and elevated levels of testosterone and dihydrotestosterone.8

Although the disease is rarely documented in men younger than age 40 years, among black men, PC is diagnosed at an earlier age and more advanced stage than in white men. Incremental mortality in blacks may be related to genetics, diet, socioeconomic status, higher serum values of prostate specific antigen (PSA), and underutilization of medical care.8-11

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.2,8

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.12

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 U.S. Preventive Services Task Force currently recommends against PSA-based screening.13

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.2,12
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 <4 mg/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. The benefits of lab work
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.14 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.14

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