"INTERNAL MEDICINE"

CARCINOMA PROSTATE

INCIDEDNCE

Prostate cancer is the leading cancer diagnosis and the second most common cause of cancer-related death in men in the United States. Worldwide, prostate cancer is the fourth most common cancer in men, with incidence and mortality rates that vary markedly among and within different countries. African-American men have the highest incidence of prostate cancer in the United States

RISK FACTORS

Although the specific causes of prostate cancer initiation and progression are not yet known, considerable evidence suggests that both genetics and environment play a role in the evolution of this disease. Classic and molecular epidemiology studies have identified a number of potential risk factors associated with the development of prostate cancer.

Hereditary Prostate Cancer

A number of case-control studies have demonstrated familial clustering of prostate cancer, suggesting that some prostate cancers may be inherited. Men with one first-degree relative with prostate cancer had a twofold risk of developing prostate cancer, while men with two or three affected first-degree relatives had a 5- to 11-fold risk, respectively.

Androgen

the degree to which androgen or androgen metabolites contribute to prostate cancer risk remains a contentious issue

VITAMIN D

Vitamin D (i.e., 1,25(OH)2 D) is a steroid hormone that can inhibit proliferation and induce differentiation of prostate cancer cell lines.

FAT

Giovannucci and colleagues (1993) prospectively studied the relationship between diet and prostate cancer in men enrolled in the Health Professionals Follow-Up Study. Men who consumed a high-fat diet had an increased risk of developing advanced prostate cancer. In summary, although many epidemiologic and biologic studies support the hypothesis that high dietary fat intake is a risk factor for prostate cancer, additional epidemiologic studies are needed to prove this definitively.

VITAMIN E

. A prospective Finnish trial designed to test the effect of vitamin E supplements on lung cancer incidence in smokers showed a 32% decrease in prostate cancer incidence and a 41% decrease in prostate cancer mortality compared with placebo

Sexual Activity, Smoking, Height and Weight, and Alcohol Consumption

A number of genetic (height and weight) and environmental (sexual activity, smoking, and alcohol consumption) exposures have been hypothesized to modulate prostate cancer risk. In general, no consistent relationship between these factors and prostate cancer has been established. Sexual activity, for example, is hypothesized to expose the prostate to infectious agents, which may increase the risk of prostate cancer, akin to the causal relationship between human papillomavirus (HPV) and cervical cancer in women. Although some studies have found a link among early sexual intercourse, number of sexual partners, and prostate cancer ([103] Honda et al, 1988), these results have not been consistent ([53] Ewings & Bowie, 1996). Studies have also not consistently identified HPV or other pathogens (i.e., chlamydia) in prostate cancer tissue ([236] Wideroff et al, 1996).

Cigarette smoking is a common risk factor for lung, bladder, and other epithelial cancers. There is little agreement over the role of cigarette smoking in prostate cancer risk. Both positive ([106] Hsing et al, 1990b; [101] Hiatt et al, 1994) and negative ([1] Adami et al, 1996; [50] Engeland et al, 1996) prospective studies have been reported. One study suggested that smokers have a worse prognosis than nonsmokers, perhaps related to an increase in androgens associated with smoking ([43] Daniell, 1995; [71] Giovannucci et al, 1999).

Heavy alcohol use is known to increase estrogen production and decrease testosterone levels and might be predicted to lower prostate cancer risk ([19] Breslow et al, 1999). Despite this hypothesis, no relationship between alcohol use and prostate cancer has been established ([173] Pollack et al,

Prevention

Screening For High-Risk Individuals

Ten percent of prostate cancers are inherited. In addition, inherited polymorphisms may contribute to prostate cancer risk in many individuals with sporadic tumors. Elevated levels of IGF may also indicate an increased risk of prostate cancer. These findings suggest that genetic or serum testing may play a role in prostate cancer prevention strategies.

Dietary Intervention

There is strong evidence that diet contributes to prostate cancer risk. It is reasonable to infer that dietary interventions might prevent prostate cancer initiation or alter the natural history of prostate cancer once established.

Fat

High-fat diets are linked to an increased risk of prostate cancer. Reducing dietary fat can slow the growth of human prostate cancer xenografts

Soy Isoflavones

One of the major differences between Asian and Western diets is the consumption of soy products. Soy contains a number of constituents that have weak estrogenic activity. These phytoestrogens, or isoflavones, are hypothesized to have anticarcinogenic properties. Genistein, the most abundant isoflavone in soy products, is of particular interest because it is a natural inhibitor of tyrosine kinase receptors such as EGFR and her-2/neu, both implicated in prostate carcinogenesis ([42] Dalu et al, 1998). Genistein has been shown to inhibit the proliferation of cancer cells, including prostate cancer, both in vitro and in vivo ([153] Messina et al, 1994; [9] Barnes, 1995).

Vitamin E

Long-term dietary supplementation with -tocopherol (vitamin E) reduced prostate cancer incidence in male smokers ([96] Heinonen et al, 1998).

Green Tea

Another difference between Western and Asian diets is the consumption of green tea. Green tea contains polyphenols, particularly epigallocatechin-3-gallate (EGCG), that are known to possess strong antioxidant activity. EGCG induces apoptosis in both androgen-dependent and androgen-independent prostate cancer cell lines ([2] Ahmad et al, 1997; [167] Paschka et al, 1998). EGCG has also been shown to inhibit activity of ornithine decarboxylase, an enzyme associated with prostate cancer proliferation ([89] Gupta et al, 1999). These results suggest that green tea may have potential as a preventive agent in prostate cancer.

Vitamin D Analogues

Vitamin D has potent growth-inhibiting and differentiating effects on various normal and malignant tissues and cells ([16] Bouillon et al, 1995).

TREATMENT

Treatment options for men with organ-confined prostate cancer include radical prostatectomy, external-beam radiation therapy, and interstitial radiotherapy (brachytherapy).

1.For radical prostatectomy, the overall 5-year freedom from PSA progression is 61–87% in several published series (Urol Clin North Am 20:713, 1993). Overall, 10-year disease-specific survival following radical prostatectomy for clinically localized prostate cancer is 85% (81–87%, 95% confidence interval) (JAMA 276: 615, 1996).

2.External-beam radiotherapy achieves disease-free rates of 45–85% for localized disease (N Engl J Med 331:996, 1994).

3.Technical improvements in dosimetry and implantation combined with reports of low morbidity have led to a renewed interest in brachytherapy. Some authors have suggested that brachytherapy alone may have a higher rate of PSA progression than other treatment modalities (Urology 51:884, 1998). The optimal form of treatment for clinically localized prostate cancer has not been conclusively determined.

4.Hormonal therapy with either bilateral orchiectomy or luteinizing hormone–releasing hormone agonists usually is reserved for men with locally advanced or metastatic disease.

5.Watchful waiting is appropriate for men with a life expectancy of fewer than 10 years and low-stage, low-grade prostate cancer (J Urol 159:1431, 1998).