Prostate cancer

Prostate cancer is predominantly a tumor of elderly men. Almost 99% of patients with clinically evident disease are older than 50 years. It is the third most common cancer in men, especially in Northern Europe and USA. Age as the main risk factor for the development of prostate cancer. Positive family history of prostate cancer and inherited cancer syndromes caused by mutations in BRCA1, BRCA2 genes, mismatch repair, and other genes contribute to risk.

Symptoms range from frequent urination with weak or interrupted urine flow, and blood in urine to erectile dysfunction and discomfort or pain when sitting. It can be associated with prostate enlargement which can be detected by digital rectal exam and transurethral or transrectal ultrasound. Prostate cancer often causes elevated levels of prostatic specific antigen (PSA) in blood, which is used as a screening method. Diagnosis of prostate cancer is often made on fine needle biopsy samples taken during an ultrasound examination.

Adenocarcinoma is the most common type of prostate cancer. Most of the adenocarcinomas are of acinar type (95%), followed by ductal type, while other types are rare. Typically, tumors consist of well-formed and delineated glands with columnar cells but without basal cells. Other growth patterns include poorly formed or fused glands, glomeruloid, and cribriform architecture, as well as solid islands with or without necrosis. Near carcinoma, glands with atypical cells and preserved basal cells can be found. Such glands represent prostatic intraepithelial neoplasia, a precursor of prostatic adenocarcinoma.

All adenocarcinomas are classified using the Gleason grade (Modified Gleason Grading System). The Gleason grade is a system of characterizing prostate cancer tissue based on the microscopical patterns of growth. The Gleason grade ranges from 1 to 5, and in principle, the two most dominant patterns are scored and combined to provide the Gleason score. The score is the sum of these grades (e.g. 3+4). Both the Gleason score and grades of each of the dominant patterns are used to generate grade groups (ranging from 1-5). Gleason grade groups much better reflect prognosis compared to the Gleason scores alone.

Diagnosis of prostate carcinoma is often based on morphological features on microscopy. Immunohistochemistry can be used to distinguish prostate adenocarcinoma from prostatic intraepithelial neoplasia and other forms of cancer, including neuroendocrine carcinomas. The presence of basal cells, which are present in prostatic intraepithelial neoplasia but not adenocarcinoma, can be confirmed with antibodies against p63 and high-molecular-weight keratins. Malignant prostatic acini do not display basal cells and are identified using other immunohistochemistry markers such as antibodies towards alpha-methylacyl-CoA racemase (AMACR) and NKX3.1. Immunopositivity for androgen receptors, prostate-specific antigen (PSA), and prostate-specific acid phosphatase (PAP), can be useful for the diagnosis of metastatic prostate carcinoma.

Therapy of prostate carcinoma includes surgical removal of prostate, radiotherapy, and chemotherapy in advanced disease. Hormonal therapy with antiandrogens is also an option, as most of the tumors are androgen-sensitive. The rate of tumor growth varies from slow to moderately rapid, and certain patients may have prolonged survival even after cancer has metastasized to distant sites such as bone. Since the median age at diagnosis is high, most patients - especially those with localized tumors - may die of other illnesses without ever having suffered significant disability from cancer.