Prostate Cancer

CHAPTER 1

Prostate Cancer Epidemiology

Annie Darves-Bornoz1, Joe Park1, and Aaron Katz2

1Stony Brook University and Winthrop University Hospital, New York

2Department of Urology, Winthrop University Hospital, New York

United States—recent trends in incidence and mortality

Incidence

Prostate cancer is the most common non-skin cancer diagnosed among American males, affecting roughly one in six men (16.15%) over the course of their lifetime. Prostate cancer is also the second leading cause of cancer-related deaths in American men. According to the most recent data from the Surveillance Epidemiology and End Results (SEER) database, an estimated 241 740 men were diagnosed with prostate cancer and over 28 000 died of it in the United States in 2012 [1]. The incidence of prostate cancer spiked in the United States in the early 1990s because of the advent of more aggressive prostate-specific antigen (PSA) screening [2]. This was followed by a sharp decline from 1992 to 1995 during which incidence rates returned to a new baseline which remained approximately two and a half times the pre-PSA era rate, likely due to the fact that increased screening in prior years had successfully diagnosed much of the previously undetected prostate cancer patients in the population.

Mortality and survival

Most recent data show that mortality rates due to prostate cancer have been declining, with a 3.5% decrease between 2000 and 2009 [3]. In addition, 5-year survival rates have also been increasing, jumping from 76% between 1983 and 1985 to 98% between 1992 and 1998 [4]. While this staggering rise in survival and decline in mortality can in part be attributed to the recent trend in earlier detection and more aggressive treatment [5], screening overdiagnosis of preclinical prostate cancers which may never progress clinically is likely a major contributor as well. Overall, 5-year relative survival is nearly 100%, relative 10-year survival is 98%, and relative 15-year survival is 93%.

The stage of the prostate cancer is a major contributor to survival, as patients with local and regional disease had relative 5-year survival rates nearing 100%, while patients with distant metastasis had a relative 5-year survival of only 28% [6]. As screening is advancing, there has been an increase in incidence of organ-confined and regional diseases and a decrease in incidence of metastatic diseases [7].

International trends

Prostate cancer is the second most common cancer among men in the United States and fifth most common cancer worldwide [8]. However, incidence and mortality of this disease differ greatly depending on the geographical area. Incidence is highest in Scandinavia and North America (especially among African-Americans, with an annual rate of 236.0 per 100 000 men) and lowest in Asia (1.9 cases per 100 000 annually) [1, 8]. With respect to mortality rates, the highest rates are found in the Caribbean (at 26.3 deaths per 100 000 annually) and the lowest rates are found in Asia (<3 deaths per 100 000 annually). There are numerous explanations for these drastically different mortality rates among countries. Two major factors are differences in treatment and misattribution of cause of death. Environment is likely to play a role as well. One study comparing Japanese men living in the United States with Japanese men living abroad found that Japanese men living in the United States had more similar rates of prostate cancer to persons of similar ancestry living in the United States than to the Japanese men living in Japan [9].

Advancing age

Advancing age is the principal risk factor for acquiring prostate cancer. From 2005 to 2009, the median age of diagnosis was 67 years, with approximately 90% of diagnoses occurring at the age of 55 years and above. In addition, older men are more likely to be diagnosed with high-risk prostate cancer leading to lower overall and cancer-specific survival [1].

Race/ethnicity

Race is a major risk factor for prostate cancer, both with respect to incidence and mortality; however, the reasons as to why are less clear. African-Americans have the highest incidence of prostate cancer than any other race or ethnicity in the United States (between 2005 and 2009, 236.0 per 100 000 men annually). This is in contrast to other groups living in the United States, including white American males (146.9 per 100 000 men annually), Asian/Pacific Islanders (85.4 per 100 000 men annually), American Indian/Alaska Natives (78.4 per 100 000 men annually), and Hispanics (125.9 per 100 000 men annually). African-Americans also have the highest mortality rate (between 2005 and 2009, 53.1 per 100 000 men annually) once diagnosed with prostate cancer. Again, white American males (21.7 per 100 000 men annually), Asian/Pacific Islanders (10.0 per 100 000 men annually), American Indian/Alaska Natives (19.7 per 100 000 men annually), and Hispanics (17.8 per 100 000 men annually) all had significantly lower mortality rates in comparison [1].

There are numerous explanations for this disparity in outcomes among races. Higher mortality in African-Americans has been attributed to lower socioeconomic status [10–12], less frequent PSA screening [13], less aggressive treatment [14], and a lack of access to advanced treatment facilities [15]. However, even in studies which seemingly control for economic status, PSA screening, diagnostic approaches, and treatment barriers worse outcomes are still found in African-American males [16, 17]. Further research is warranted to elucidate both biologic and societal causes of such disparate outcomes among races.

Family history

Family history is one of the strongest risk factors when considering who will develop prostate cancer. Having an affected relative, the number of affected relatives, and the age of onset of prostate cancer in the affected relative are all risk factors for developing prostate cancer. Risk of prostate cancer doubles for a male who has one affected first-degree relative [18–22]. For males with more than one affected relatives, the risk is further increased [20]. Age of onset in affected first-degree relatives is also important, as younger age of onset correlates with increased risk as well [20, 23]. Another study from Sweden found prognostic correlation in families where both the father and son had prostate cancer. When comparing fathers who survived for 5 or more years versus fathers who survived less than 2 years, sons of fathers who survived for 5 or more years had a hazard ratio of 0.62 (95% CI) [24].

These familial factors point to a possible hereditary component in the development of prostate cancer. This notion is corroborated by a study of 45 000 twin pairs from Sweden, Denmark, and Finland which found that there was a higher concordance for prostate cancer diagnosis in monozygotic twins (18%) versus dizygotic twins (3%). This study estimated that potentially 42% of the risk of developing prostate cancer could be due to heritable causes [25]. Inheritance patterns of prostate cancer are not yet well understood, although segregation analyses of prostate cancer families point to an autosomal dominant [26], X-linked, or recessive inheritance [27].

Hormonal factors

Androgens

Androgens are important for the normal development of the prostate gland and are likely important in the carcinogenesis of the prostate as well. The results of the Prostate Cancer Prevention Trial demonstrated that inhibition of the conversion of testosterone to dihydrotestosterone by finasteride, a 5α-reductase inhibitor, significantly decreased incidence of prostate cancer, thus confirming the role of androgens in the development of prostate cancer [28]. However, a meta-analysis of 18 studies showed that normal variations in serum androgen levels were not correlated with an increased risk of developing prostate cancer [29].

Insulin-like growth factor-1

Higher concentrations of insulin-like growth factor-1 (IGF-1), which normally promotes proliferation and apoptotic inhibition of normal prostate cells [30], have been associated with an increased risk of prostate cancer [31]. A pooled analysis of 12 studies also found that IGF binding protein 3 was weakly associated with increased risk of prostate cancer as well [31]. IGF-1 levels are both genetically and nutritionally dependent, which may be a reason why certain countries and populations have higher or lower rates of prostate cancer.

Lifestyle decisions

Smoking cigarettes

A meta-analysis determined that smoking was not associated with increased risk of developing prostate cancer, but was associated with fatal prostate cancer [32]. Smokers had a 24–30% increased risk of death due to prostate cancer compared with nonsmokers. A large study also found that smokers actually had an 18% decreased risk of developing prostate cancer, but a 67% increased risk of mortality due to prostate cancer [33].

Alcohol

Most studies have shown that there is no effect of alcohol consumption on the incidence or mortality of prostate cancer [34–36]. Additionally, red wine has not been shown to have any protective effect on prostate cancer [35]. These studies suggest that alcohol consumption does not play a major role in the development of prostate cancer.

Diet

Obesity

The role of obesity, as defined by high body mass index (BMI), in the pathogenesis of prostate cancer is not well defined. Many studies show that excess body weight does not lead to increased cases of prostate cancer [37–39],...