Prostate Cancer Bệnh lý nền

Introduction

Prostate cancer is the second most common cancer in men and one of the most common cancers in men >50 years of age. 

Epidemiology

Prostate cancer is one of the most common cancers in the world, accounting for as many as 1,467,854 new cases just in 2022. It is the fourth most common cancer in the world. Among the different continents, Europe has the highest incidence, with 473,011 new cases in 2022. This is followed by Asia with 386,424 cases, Northern America with 255,782 cases, Latin America and the Caribbean with 225,985 cases, Africa with 103,050 cases, and Oceania with 23,602 cases The incidence of prostate cancer is strongly correlated with age and would disproportionately affect older males. Its incidence rapidly rises with increasing age, with the highest rates seen in males aged 70-80 years. In terms of mortality, it is the eight most common cause of cancer death worldwide, accounting for 397,430 deaths in 2022 It is one of most common causes of cancer death in males.  

In Asia, prostate cancer is one of the most diagnosed cancers, leading to as many as 120,485 deaths in 2022, the highest among the different continents.

Pathophysiology

The prostate is a male sex glandular structure located in the pelvis at the base of the penis. Prostate cancer arises from the epithelium, normally in the peripheral glandular portion of the prostate. Key to the pathogenesis of prostate cancer is its heavy reliance on androgenic reliance, that is why hormonal therapy has been so effective. However, castrate-resistant tumors are thought to have mutations that improve the functional activity of the androgen receptor, sometimes even generating intracellular androgens. Malignant transformation involves what is called prostatic intraepithelial neoplasia (PIN) as precursor in the peripheral basal cells. Progressive accumulation of genetic alterations (eg androgen receptor bypass, tumor suppressor gene inactivation, etc.) is postulated to facilitate cellular transformation from normal epithelium to PIN, invasive neoplasia, and then castration resistance. 

Risk Factors

The risk of developing prostate cancer increases with age, particularly among men >50 years old. A positive family history, either first- or second-degree relatives diagnosed with metastatic prostate, ovarian, breast (female ≤45 years old), colorectal, endometrial (≤50 years old) or pancreatic cancer, and those with ≥2 first- or second-degree relatives diagnosed with prostate, breast, colorectal, or endometrial cancer at any age are also at risk.  

Genetic mutations such as breast cancer gene 1 (BRCA1), breast cancer gene 2 (BRCA2) mutations, ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (CHEK2), homeobox B13 (HOXB13), epithelial cellular adhesion molecule (EPCAM), nibrin (NBN), tumor protein 53 (TP53), partner and localizer of BRCA2 (PALB2), deoxyribonucleic acid (DNA) mismatch repair genes (mutS homolog 2 [MSH2], mutL homolog 1 [MLH1], Lynch syndrome, mutS homolog 6 [MSH6], post-meiotic segregation increased 2 [PMS2]), and insulin-like growth factor-1 (IGF-1) are all implicated in the development of prostate cancer.  

Ethnicity, especially those of African ancestry and Ashkenazi Jewish descent, and chemical exposures (eg toxic combustion products) are also risk factors for the development of the disease. Other risk factors under research include a positive medical history of inflammation of the prostate gland (eg prostatitis, sexually transmitted diseases [STDs], proliferative inflammatory atrophy [PIN]) and vasectomy.