Prostate cancer is the most common non-skin cancer and the second leading cause of cancer mortality in American men. Despite the fact that this cancer will be diagnosed in an estimated 186,320 American men in the year 2008 and will lead to the death of approximately 28,660 men, there is no universally agreed-upon strategic plan for its diagnosis and management.

Epidemiology

Age The risk of developing prostate cancer begins to increase at age 50 years in white men who have no family history of the disease and at age 40 years in black men and those who have a first-degree relative (father, brother) with prostate cancer. Risk increases with age, but, unlike other cancers, prostate cancer has no “peak” age or modal distribution. There has been a downward “age migration” in the PSA (prostate-specific antigen) era such that the median age at diagnosis is now approximately 60 years old.

Race The highest incidence of prostate cancer in the world is found in American black men, who have approximately a 9.8% lifetime risk of developing this cancer. This rate is slightly higher than the 8% lifetime risk for American white men. Black men have an incidence of prostate cancer that is 1.6 times that of white men.

The Japanese and mainland Chinese populations have the lowest rates of prostate cancer. Interestingly, although Japanese immigrants to the United States have a higher incidence of prostate cancer than Japanese people living in Japan, their rate is still about half that of American whites.

Socioeconomic status appears to be unrelated to the risk of prostate cancer, and the explanation for racial variability is unknown. However, an interplay of diet, hormonal factors, and genetics likely accounts for the variability.

Geography The incidence of prostate cancer is highest in Scandinavian countries (22 cases per 100,000 population) and lowest in Asia (5 per 100,000). Risk may be inversely related to ultraviolet light exposure, as the incidence increases the farther one lives from the equator. However, recent studies show extremely high rates in populations of African heritage, such as Jamaicans.

Etiology and risk factors

Family history Men who have a first-degree relative with prostate cancer have approximately a twofold increased risk of developing prostate cancer during their lifetime. An individual who has two first-degree relatives with prostate cancer has a ninefold increase in lifetime risk.

True hereditary prostate cancer occurs in a small number of men and tends to develop at an early age (< 55 years old).

Dietary fat Studies have suggested that dietary fat may increase the risk of prostate cancer. However, no definitive proof of its role has yet been found.

These studies indicate that progression of prostate cancer, which is likely to be more clinically relevant, has different risk factors than those associated with its initiation/incidence and that some of these risk factors are likely modifiable. Recent findings from the Health Professionals Follow-up study have, however, demonstrated different dietary risk factors for the incidence compared with progression of prostate cancer. For example, African-American race, a positive family history, low consumption of tomato products, and high consumption of alpha-linolenic acid have been associated with higher risks of incident prostate cancer. However, height, body mass index, low physical activity, smoking, low consumption of tomato sauce, high calcium and alpha-linolenic acid intake, African-American race, and positive family history have all been associated with fatal cancer.

In addition, recent findings suggest that cruciferous or brassica family vegetables may reduce the risk of advanced prostate cancer. This family includes broccoli, cauliflower, cole slaw, and sauerkraut. Interestingly, the intake of brussels sprouts, spinach, and mustard greens did not appear to be protective, and the consumption of fruit was not associated with the incidence or progression of prostate cancer.

Vasectomy Several large epidemiologic studies suggest that vasectomy may increase the relative risk of prostate cancer by as much as 1.85. However, these same studies do not report an increased risk of dying from prostate cancer associated with vasectomy but do indicate a statistically increased risk of dying from lung cancer. These findings argue against an association between vasectomy and prostate cancer. Currently, this association is unproven and does not constitute grounds for fundamental changes in the use of vasectomy.

Sexual activity/sexually transmitted disease A large prospective study of more than 29,000 men demonstrated an association between high ejaculatory frequency (more than 21 ejaculations/month) and a decreased risk of prostate cancer, with a lifetime relative risk of 0.67. However, there may be several confounding factors associated with high sexual activity, such as differences in prostate cancer screening or lifestyle. There was no associated increased risk for men in the lowest ejaculatory frequency category.

Inflammation may underlie the findings associated with a relatively higher risk of prostate cancer in men seen in STD (sexually transmitted disease) clinics, but it may also be related to screening bias. Several cohort studies and one meta-analysis have demonstrated a protective role for the daily intake of aspirin and the risk of prostate cancer. In addition, the lipid-lowering and anti-inflammatory statin compounds have been associated with a reduction in the risk of high-grade tumors. These findings require prospective validation in randomized trials.

Prevention Active research on the chemoprevention of prostate cancer is ongoing. The only prospective randomized trial to demonstrate an effect was the Prostate Cancer Prevention Trial (PCPT), which showed a 24.8% reduction in the risk of prostate cancer among men randomized to receive finasteride (Proscar) daily versus those men on the placebo arm. Finasteride as a chemopreventive agent has not been universally accepted, however, because patients in the treatment arm were possibly more likely to exhibit higher-grade prostate cancer. Recent follow-up studies of the PCPT suggest that finasteride probably does not induce high-grade disease, and the observation may be a detection artifact. Other agents under study include vitamin E and selenium, both of which have been associated with a decreased risk of prostate cancer. A large prospective randomized trial to evaluate the effects of these agents in healthy men is currently under way.

Signs and symptoms

Early-stage disease Men with organ-confined prostate cancer often are completely asymptomatic. Men with a large component of benign prostatic hyperplasia often present with bladder outlet obstruction unrelated to prostate cancer.

Locally advanced disease Bladder outlet obstruction is the most common sign of locally advanced prostate cancer. A few men with locally advanced disease present with hematuria, urinary tract infections, and irritative voiding symptoms secondary to bladder outlet obstruction.

Advanced disease Rarely, men with bulky lymph node metastasis may present with bilateral lower-extremity edema. Men with bony metastasis often present with bone pain and, uncommonly, with lower-extremity weakness or paralysis from spinal cord compression.

Screening and diagnosis

Prostate cancer screening with PSA and digital rectal examination (DRE) has resulted in not only an increase in prostate cancer detection but also a stage shift. More cancers are now being detected at earlier stages, when they are potentially curable. Prior to screening efforts, most prostate cancers were detected when they produced local symptoms or distant metastases, at which point treatment for cure often was impossible.