Definition

 • a malignant epithelial tumour arising in the prostate.

Epidemiology

 • The most common malignant tumour in men, accounting for about 25% of all male cancers.

• about 1 in 8 men will develop prostate cancer in their lifetime.

• Prevalence rising due to longer life expectancy and increased detection rates.

• a less prominent cause of cancer- related deaths, as many cases behave in a relatively indolent fashion.

Aetiology

 • Racial background and genetic factors are important, with a 5- to 10- fold increased risk in men with two or more affected first- degree relatives.

• Dietary association with animal products, particularly red meat.

Carcinogenesis

• arises from a precursor lesion known as prostatic intraepithelial neoplasia (PIN), characterized by neoplastic transformation of the epithelium lining of the prostatic ducts and acini.

• Harbour mutations in a number of genes, including GST-pi, PTEN, AMACR, p27, and E-cadherin (note these are not classical tumour suppressor genes or oncogenes).

Presentation

• The vast majority of prostate cancers are diagnosed early following investigation of a raised serum prostate- specific antigen (PSA) level.

• More advanced localized disease may be present with a suspicious- feeling prostate on digital rectal examination or lower urinary tract symptoms.

• Rarely, patients present with symptoms of metastatic disease.

 Diagnosis

• Patients with raised PSA are usually referred for MRI of the prostate to identify suspicious areas that may be targeted for biopsy.

 • Prostate biopsy may be performed via a transperineal or transrectal route. The transperineal route carries a much lower risk of introducing infection into the prostate gland.

 Histopathology

 • The most common type of prostate cancer is acinar adenocarcinoma, in which the malignant epithelial cells form glandular structures.

• One of the key diagnostic features of prostate cancer is the abnormal architecture of the malignant glands which are crowded and show infiltration between benign glands and ducts.

• Malignant epithelial cells have enlarged nuclei with prominent nucleoli and denser amphophilic cytoplasm.

• Malignant glands often have intraluminal crystalloids (dense crystal- like structures), amorphous pink secretions, or blue- tinged mucin.

Gleason scoring

 • Prostate cancers are graded using the Gleason scoring system.

• Gleason scores are expressed in the format x +y =z and are based on the two most common Gleason patterns present in the tumour.

• Gleason patterns range from 1 to 5 and are based on the architectural growth of the tumour.

 • in practice, patterns 1 and 2 are never diagnosed, and so all prostate cancers have a Gleason score of between 6 and 10.

 • Gleason pattern 3 is composed of well- formed discrete glandular units (Fig. 1).

• Gleason pattern 4 is composed of poorly formed, fused, or cribriform glands (Fig. 2).

 • Gleason pattern 5 is composed of solid sheets, cords, or single cells showing no glandular differentiation.

 Immunohistochemistry

 • Prostate cancer cells are typically positive for PSA and CK7 whilst being negative for CK20.

• Basal cell markers (e.g. p63 or cytokeratin 5, are often used to confirm a morphological diagnosis of prostate cancer by demonstrating absence of basal cells around the cancer glands).

Fig1. Gleason pattern 3 prostate adenocarcinoma composed of individual well- formed glandular acini (see Plate 33).

Fug2. Gleason pattern 4 prostate adenocarcinoma composed of fused poorly formed glands (see Plate 34).

Prognosis

 • The Gleason score is a powerful prognostic indicator, with a higher score associated with a worse outcome.

• Other important factors include the serum PSA level and the stage of the disease.

Prostate cancer screening

• Screening using serum PSA is a controversial subject.

• at present, most countries do not operate an organized prostate screening programme.

• Current evidence suggests that screening would result in overdiagnosis and overtreatment of many men with prostate cancers that are unlikely to behave in an aggressive manner.