Prostate Cancer

Prostate cancer is the most common type of cancer in men, excluding skin cancer, and is the second leading cause of cancer death. Risk factors include age (incidence increases in men over the age of 65 years). It is more prevalent in the western world and 10% of cases can be linked to family history.Prostate cancer is a continuum, progressing through localised, locally advanced, advanced and hormone-refractory stages. In general it is a slow growing cancer which is primarily under hormonal control i.e. testosterone. Choice of treatments which include watchful waiting, surgery (prostatectomy), radiotherapy, hormonal therapy and chemotherapy are dependent on the stage of disease.If detected early, using PSA determination, DRE examination and biopsies, and treated appropriately, survival rates are excellent.

Pathology of Prostate Cancer

Carcinogenesis is a multi-step accumulation of genetic lesions that may eventually result in uncontrolled cellular proliferation, and/or a decrease in cell death or apoptosis. When a normal prostate cancer cell loses the ability to respond to the usual controls that regulate cell division, it proliferates out of control. As the cancer growth progresses, the cells become less specialised, or less well differentiated, and the cancer becomes more dangerous.

The tumour can spread through invasion of local tissues, or through cells breaking away from the primary tumour and travelling through the lymphatic or circulatory systems to infect other parts of the body – a process called metastatic spread.The causes of prostate cancer are not clear, but androgens, mainly testosterone, are thought to play a part in initiating and promoting prostate cancer. Various growth factors, such as epidermal growth factor and insulin growth factor, may also play a role. Mutations in the androgen receptor are also believed to contribute to the development and/or progression of prostate cancer and are known to play a role in the progression of hormone-sensitive cancers to hormone insensitivity.

At least 95% of prostate cancers are adenocarcinomas, meaning that they arise in the glandular tissue derived from the epithelial cells of the prostate gland rather than the supporting, connective structures. Most prostate cancers (60–70%) arise in the peripheral zone of the prostate gland, with 5–15% arising in the central zone and the remainder developing in the transition zone.Prostate cancers are usually slow-growing. Microscopic foci (groups) of ‘latent’ prostate cancer cells have been detected in almost one-third of men over 50 years of age.

However, in many cases the disease does not reach a stage where it becomes clinically significant. This means that though many older men may die with prostate cancer, they do not necessarily die from prostate cancer.Attempts have been made to identify the ‘premalignant’ cells that progress to invasive cancer. The most likely candidate identified thus far is prostatic intraepithelial neoplasia (PIN). PIN appears to be associated with a higher risk of developing cancer:
- autopsy studies reveal that PIN precedes the development of cancer by 10 years
- in a controlled study of 100 patients with high-grade PIN, 36% developed prostate cancer within 24 months, compared with only 13% of patients without PIN.