Understanding the Epidemiology, Natural History, and Key Pathways Involved in Prostate Cancer
Section snippets
Prevalence and Incidence
Globally, prostate cancer (PCa) is highly prevalent. It is the most common noncutaneous cancer in men.1, 2 An estimated 782 600 new cases and 254 000 deaths caused by the disease occurred in 2007.3 The mortality rates for PCa have been decreasing in many developed countries (eg, the United States, the United Kingdom, and Canada), which has been attributed to improved treatment and early detection.3, 4 In contrast, PCa mortality has been increasing in some Asian countries (eg, Japan, Singapore).
Natural History
Our understanding and narrative of PCa's natural history is far from complete. This is partly because the disease is heterogeneous in both morphology and clinical behavior.15 About one third of all American men >50 years old have histologic evidence of PCa; however, most of these cases remain clinically “silent.” Multiple genetic changes appear to be necessary for clinically aggressive PCa to develop.16
How the disease develops when localized varies. Lower grade tumors (ie, highly or moderately
Current Understanding of Prostate Growth: Role of Dihydrotestosterone
Testosterone is the main circulating androgen in men.24 In the prostate and other organs, testosterone functions as a prohormone; it is converted to dihydrotestosterone (DHT) in the prostatic stromal and basal cells by 5α-reductase (5AR), an intracellular enzyme present in the prostate, skin, and liver.24, 25 In serum, the ratio of testosterone to DHT is approximately 10:1. This ratio is reversed in the prostate.26
DHT is the primary prostatic androgen and plays an essential role in prostate
Conclusions
PCa is a highly prevalent disease that imposes a significant burden on patients and the public healthcare system. The incidence of PCa is expected to increase as the U.S. population continues to age. Black men appear to be disproportionately affected; white men are significantly less likely to develop the disease; and Hispanic and Asian-American men have lower rates than white men. The natural history of PCa is far from completely understood, but our picture of the development and progression
References (55)
- et al.
The epidemiology of prostate cancer
Urol Clin North Am
(2003) - et al.
Prevalence of incidental prostate cancer in the general population: a study of healthy organ donors
J Urol
(2008) - et al.
The epidemiology of sex steroid hormones and their signaling and metabolic pathways in the etiology of prostate cancer
J Steroid Biochem Mol Biol
(2004) - et al.
Clinical evidence for and implications of the multistep development of prostate cancer
J Urol
(1990) - et al.
Morphology of prostate cancer: the effects of multifocality on histological grade, tumor volume and capsule penetration
J Urol
(1994) - et al.
Androgens and male physiology the syndrome of 5α-reductase-2 deficiency
Mol Cell Endocrinol
(2002) - et al.
Differences in steroid 5alpha-reductase iso-enzymes expression between normal and pathological human prostate tissue
J Steroid Biochem Mol Biol
(1999) - et al.
Localization by in situ hybridization of steroid 5alpha-reductase isozyme gene expression in the human prostate and preputial skin
J Urol
(1998) - et al.
The rationale for inhibiting 5α-reductase isoenzymes in the prevention and treatment of prostate cancer
J Urol
(2008) - et al.
5-Alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males
Lancet
(1992)
5α-reductase type 1 immunostaining is enhanced in some prostate cancers compared with benign prostatic hyperplasia epithelium
J Urol
Levels of 5α-reductase type 1 and type 2 are increased in localized high grade compared to low grade prostate cancer
J Urol
The effects of 5α-reductase inhibitors on the natural history, detection and grading of prostate cancer: current state of knowledge
J Urol
5α-Reductase inhibitors in benign prostatic hyperplasia and prostate cancer risk reduction
Best Pract Res Clin Endocrinol Metab
Chemoprevention of prostate cancer in men at high risk: rationale and design of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial
J Urol
Cancer statistics, 2008
CA Cancer J Clin
SEER cancer statistics review (based on November 2007 SEER data submission, posted to the SEER Web site, 2008)
Global cancer facts and figures 2007
International trends in prostate-cancer mortality: the decrease is continuing and spreading
Cancer Causes Control
Human prostate cancer risk factors
Cancer
Racial variation in prostate cancer incidence and in hormonal system markers among male health professionals
J Natl Cancer Inst
Prostate cancer among African-American males: understanding the current issues
J Natl Black Nurses Assoc
Ethnic and racial differences in prostate stromal estrogen receptor α
Prostate
Cancer epidemiology in populations of the United States—with emphasis on Hawaii and California—and Japan
Cancer Res
Meat consumption among black and white men and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort
Cancer Epidemiol Biomarkers Prev
Fat and meat intake and prostate cancer risk: the multiethnic cohort study
Int J Cancer
The Gordon Wilson lecture: natural history and treatment of early stage prostate cancer
Trans Am Clin Climatol Assoc
Cited by (0)
E. D. Crawford serves as a consultant and speaker for GlaxoSmithKline, Sanofi-Aventis, and AstraZeneca and receives grant support from the National Institutes of Health and Endocare.