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 was diagnosed in an estimated 217,730 American men in the year 2010 and led to the death of approximately 32,030 men, there is no universally agreed-upon strategic plan for its diagnosis and management. The estimated number of deaths increased from last year. However, the death rate per 100,000 people declined 2.4% per year from 2000 to 2006, and the denominator (the older population) grew, so the overall rate of death is lower.
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 prostate-specific antigen (PSA) era such that the median age at diagnosis is now approximately 60 years.
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, studies show extremely high rates of prostate cancer 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
Although early studies suggested a link between dietary fat and prostate cancer risk, more recent studies have failed to confirm these observations. Thus, the relationship between dietary fat and prostate cancer risk remains unclear. Using animal models, one study pointed to high levels of simple carbohydrates being a culprit in promoting prostate cancer growth.
Studies indicate that progression of prostate cancer, which is likely to be more clinically relevant, has different risk factors from those associated with its initiation/incidence and that some of these risk factors are likely modifiable. 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 more advanced cancer.
In addition, 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 unproved 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 sexually transmitted disease (STD) 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(Drug information on 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. Two prospective randomized trials have demonstrated a 20% to 25% reduction in the risk of prostate cancer among men who were randomized to receive either finasteride(Drug information on finasteride) or dutasteride (Avodart) daily vs those men on the placebo arm. Finasteride or dutasteride chemopreventive agents have not been universally accepted, however, because of concerns over the relative merits of prevention of low-grade disease, with little effect on high-grade tumors. In addition, concerns over side effects such as impotence, as well as reductions in PSA levels with these therapies that may make cancer detection more challenging, have limited the generalized use of these drugs and thus an individualized risk/benefit discussion about use of these agents as preventive measures is recommended. Finally, randomized trials using selenium(Drug information on selenium) and vitamin E(Drug information on vitamin e) have failed to demonstrate a benefit of these agents to reduce prostate cancer risk. Ongoing studies will examine vitamin D and omega-3 fatty acid supplementation as preventive strategies in cancer, including prostate cancer.
Signs and symptoms
Early-stage disease
Men with organ-confined prostate cancer often are completely asymptomatic, given the predominant posterior peripheral zone location of prostate adenocarcinomas. 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.
Initial results of a multicenter trial show that 2 biomarkers, PCA3 and T2-ERG, are found at high levels in prostate cancer compared to noncancerous prostate cells and correlate well with 2 indicators of aggressive prostate cancer, tumor volume and Gleason score.
It is still difficult to gauge the probability that a low-risk prostate cancer patient may be upgraded to a higher prostate cancer stage. Researchers at Vanderbilt University Medical Center have now determined that smaller prostates were more likely to evolve into more serious, aggressive disease.
We have entered a period of accelerated drug development and optimism in the care of advanced prostate cancer. The treatment paradigm for these patients is rapidly evolving, with future study needed to define the optimal sequencing and potential combinations of these new agents.