Understanding Prostate Cancer: Pathogenesis, Risk Factors, and Early Detection

Prostate cancer (PC) is one of the main causes of cancer-related mortality among men and the second most common malignancy afflicting men worldwide (Yu et al., Front Oncol 13:1165732, 2023). According to recent GLOBOCAN data, in 2020, PC was responsible for 6.8% (375,304) and 14.1% (1,414,259) of all male cancer deaths and cases, respectively (Huang et al., Clin Genitourin Cancer 21:e261–e270.e50, 2023). This is a disease that mainly affects older men over 65 years of age, although in high-risk individuals, including those with a strong family history, it can start in their 40s. It seems to be significantly influenced by environmental factors over and above the genetic predisposition, for example, African-American males demonstrated 40 times higher incidence rates when compared to indigenous African males in Africa (Rawla, World J Oncol 10:63–89, 2019). In South Africa, incidence rates nearly doubled in 10 years, rising from 29.4 case/100,000 men in 2007 to 49.4/100,000 in 2017 (Ramaliba et al., Front Public Health 10:882586, 2022). PC is a heterogenous cancer exhibiting extensive variations that range from patient-to-patient differences, intertumoral variation within the same patient, to intratumoral variations occurring at genomic, epigenetic, phenotypic, and morphological levels (Haffner et al., Nat Rev Urol 18:79–92, 2021). It is an androgen-dependent cancer that relies on testosterone and/or dihydrotestosterone interactions with androgen receptors (AR) for pathogenesis and progression, but as the cancer continues to grow, it sheds its dependence on the androgens, becoming refractory to the hormones (Girling et al., Indian J Urol 23:35–42, 2007). Advanced age, race, and family history are the recognized, verified risk factors for prostate cancer. The Gleason Score System, which constitutes the sum of the two most prevalent histological patterns found in a PC, is used to express the histological grade of the disease. For example, a tumor can be classified as GSS 3 + 3 = 6 or 4 + 3 = 7 where the first number represents the most dominant histology (Epstein, Mod Pathol 31:47–63, 2018; Tagai et al., J Cancer Educ 34:441–445, 2019). This chapter delves into the understanding of prostate cancer, including its pathogenesis, risk factors, and the importance of early detection. We discuss the various genetic and environmental factors that contribute to the development of prostate cancer. Additionally, we explore the role of genetic testing and screening methods in identifying individuals at high risk and enabling early detection. By enhancing our understanding of the disease and identifying those at risk, we can effectively transform prostate cancer care.