Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of death globally. Despite the prevalence and high mortality associated with prostate cancer, its pathophysiology is not well understood. This is because prostate cancer arises out of a complex interplay of risk factors, such as genetics, environment, diet, lifestyle, and hormones. However, while further research is needed, a solid theoretical explanatory framework does exist for understanding prostate cancer’s etiology (McChance & Huether, 2019, p. 849).
Figure 4. The location of the prostate. (CDC, 2019)
In order to understand the carcinogenesis of prostate cancer, a basic understanding of its normal physiology is helpful. The prostate is a walnut-sized gland located in the male pelvis. It is situated directly beneath the bladder, where it surrounds the urethra and is enmeshed in the muscles of the pelvic floor. The growth and development of the prostate is regulated by androgenic hormones, and it plays an important role in the creation of seminal fluid. During ejaculation, the prostate secretes prostatic fluid through rhythmic contractions as semen passes through the prostatic portion of the urethra. The prostatic fluid helps sperm to survive by reducing the pH of the seminal fluid to counteract the acidic environment in the female reproductive tract. The prostate also secretes other substances, such as prostate specific antigen (PSA), which can be used as a biomarker for prostate cancer (McChance & Huether, 2019, p. 744).
There are a number of factors that contribute to the development of prostate cancer. For example, family history and genetics play an important role in explaining roughly 5% to 10% of prostate cancer. Men who have one first degree blood relative with prostate cancer are five times more likely to develop it themselves. Also, certain genetic mutations are associated with an increased risk of prostate cancer. The most notable being the BRCA2 gene which confers the highest known genetic risk of developing prostate cancer. However, these changes and associations account for only a small percent of men who are diagnosed with prostate cancer. So what other factors contribute? (McChance & Huether, 2019, p. 849-851, 854)
Many studies have examined the relationship between lifestyle factors like exercise, diet, and alcohol consumption and the incidence of prostate cancer. The results of these studies have been inconsistent. Surprisingly, unlike many other cancers, exercise does not seem to be a factor in the development of prostate cancer. High dietary intake of animal fats, (especially red meats and dairy) are associated with an increased risk of prostate cancer. Obesity likewise is associated with an increased risk. Some foods like monounsaturated fats appear to be associated with a decreased risk of prostate cancer, but there is no definitive evidence that prostate cancer can be prevented with diet McChance & Huether, 2019, p. 849-851).
Hormones and inflammation seem to be the two most important contributing factors. The vast majority of prostate cancers are similar in appearance to adenocarcinomas and are androgen dependent for their development and progression. The prostate is a hormonally active androgenic gland. The most important hormonal process taking place is called intraprostatic conversion. This is the process by which the prostate creates dihydrotestosterone (DHT) from testosterone. Since the prostate is involved in the synthesis of androgenic hormones, it is very sensitive to the levels of androgens in the blood. One androgen in particular, estrogen, has been show to lead to the development of premalignant lesions in the prostate. This is especially evident when in the presence of relatively low testosterone levels (McChance & Huether, 2019, p. 851-855).
As men age, the prostate’s ability to produce DHT is reduced. Testosterone levels likewise decrease over time. Estrogen concentration, on the other hand, has an age-dependent increase. This means that as men age the ratio of testosterone to estrogen decreases. It is this combination of relatively high estrogen and low testosterone that seems to play the most significant role in the development of precancerous lesions in the prostate. This is due to its interactions with the prostatic receptor ER-alpha. The mechanism for this interaction is poorly understood, but it is believed that ER-alpha functions as an oncogene (McChance & Huether, 2019, p. 854-855).
Figure 5. Prostatic Intraepithelial Neoplasia. (Nelson, W. G., 2003)
Alongside the importance of hormones in the development of prostatic precancerous lesions is the carcinogenic effects of chronic inflammation in the prostate. The inflammatory damage done to the prostate can be the result of oxidative stress, infections, autoimmune diseases, circulating toxins, urinary reflux, or the dietary factors previously mentioned. As damage is done over time to the epithelium of the prostate, a lesion called prostatic intraepithelial neoplasia (PIN) appears. PIN can be viewed as the beginning of a series of progressive stages resulting in invasive carcinoma. As the prostate is damaged and healed repeatedly, the stroma of the prostate changes. These changes promote an immune response that leads to the proliferation of cells in the prostate (McChance & Huether, 2019, p. 856-857).
The concomitant effects of hormonal changes in the prostate related to estrogen and the proliferative response in the stroma of the prostate to chronic inflammation lead to the development of prostatic tumor cells. The aggressiveness of the cancer is largely dependent on how poorly differentiated the cancerous prostatic cells are and the presence of oncogenes, such as ER alpha and BRCA2. Other environmental factors, like diet, play a part in modulating the prognosis of prostate cancer. It is this complex interplay between several factors that lead to the carcinogenesis of prostate cancer (McChance & Huether, 2019, p. 856-857).
Like many other cancers, the only way to diagnose prostate cancer definitively is through tissue biopsy. The decision to biopsy is based on clinical presentation and the results of screening tools. For example, finding a suspicious nodule during digital rectal examination (DRE) or having an increased prostate specific antigen (PSA) level are helpful in determining whether or not to biopsy. However, screening methods have also caused controversy due to their low specificity and sensitivity. Clinical signs and symptoms are subtle to interpret as prostate cancer is often asymptomatic until it has advanced significantly. In cases where a patient presents with signs and symptoms of prostate cancer they are often similar to benign prostatic hypertrophy (BPH) but differ in that they are unremitting and do not respond to treatment. It takes a skilled clinician to accurately assess for the need of biopsy in regards to this disease (McChance & Huether, 2019, p. 857).