Prostate Cancer

The prostate gland is a male accessory sex gland that stores and secretes an alkaline fluid that makes up part of the semen.  Females have an equivalent (the paraurethral gland) but this is located near the lower end of the urethra and prostate cancer cannot occur in women.  The gland secretes prostate-specific antigen (PSA), the level of which tends to rise in advanced prostate cancer: the decline in PSA level on treatment is a good prognostic indicator.

The most common non-skin cancer in men, one in six American men will be diagnosed with prostate cancer although more than 65% of them will be over the age of 65.  However, about one third of men over the age of 50 would show histological evidence of the disease if their prostates were examined.  The fact that in most cases the disease does not become life-threatening indicates the complexity of its development.  Over 1000 genes have been shown to be abnormally expressed in prostate cancers and of these 20 were associated with pathological grade.  Perhaps unsurprisingly most of these play a role in controlling progression round the cell cycle.

New cases/year

World 2008: 899,000;

USA 2011 (est): 240,890; UK 2008: 37,051

Deaths/year World 2008: 258,000;USA 2011 (est): 33,720; UK 2008: 10,168
Risk factors

Age (rare before age 40), heredity (a father, brother or son with the disease confers double the risk for an individual, race (more common in North America, northwestern Europe, Australia and the Caribbean than in Asia, Africa and Central and South America).  The geographical distribution suggests that diet may affect the risk but there is no unequivocal evidence.

Benign prostatic hyperplasia (non-cancerous enlargement of the prostate) or prostatitis (infection in the prostate) does not increase the risk of developing prostate cancer.

Symptoms

Urinary difficulties, blood in urine or semen, pelvic, back or hip pain, weight loss.

Staging TNM system is used (see Tumour staging).
Classification

Conventional methods for identifying prostate tumours are unreliable and may miss up to 30% of significant cancers. A gene signature of over 100 genes has now been identified that predicts tumour status with very high accuracy.

Major gene mutations

Inherited (germline) mutations that drive prostate cancer can occur in a number of genes (e.g., BRCA1, BRCA2, ELAC2, MSR1 and RNASEL).

Many other genes can become mutated including AR, P53, PTEN, RAS and in mitochondria DNA. The combination of alterations in ERBB2 and PTEN is associated with poor survival. Chromosome-wide analysis shows widespread loss and some amplification. The extent of disruption reflects the risk of recurrence and suggests that 20% of patients could be nominated for ‘watchful waiting’.

Treatment

Surgery. Radiotherapy. Chemotherapy (mitozantrone, doxorubicin, vinblastine, paclitaxel, docetaxel, estramustine phosphate, etoposide).  Systemic ablation of testosterone by castration and/or hormone therapy (LHRH agonists, LHRH antagonists or anti-androgens, e.g., abiraterone).

Side effects

Nausea, hair loss, general suppression of the immune system and increased infection risk.

Prognosis

For localised cancer (stages 1 and 2, i.e. T1 or T2) 5-year survival rate is 99%. For stage 3 (locally advanced cancer) rate is 70-80%; for stage 4 5-year survival rate is ~30%.

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