Prognostic Implications of Important Genetic Alterations in Prostate Cancer

The prostate is a walnut-sized gland that is located caudally from the urinary bladder. It excretes fluid as a part of the semen of men. Prostatic neoplasia is common; in Western developed countries prostate cancer is the most common non-cutaneous malignancy in men and it is the second leading cause of all male cancer deaths. The detection of prostate cancer has markedly increased since the introduction of the serum prostatespecifi c antigen (PSA) in the late eighties. Although familial and hereditary prostate cancer occurs, sporadic cancers account for at least 85% of all prostate cancers. Age is the strongest risk factor for developing prostate cancer. From autopsy studies it is known that in the 6th decade already 55% of the male population has the disease, and more than 75% of men older than 85 years have cancer foci in their prostate. Prostate cancer is a very heterogeneous disease that can range from indolent, asymptomatic tumours in many patients to a rapidly fatal malignancy in some. At diagnosis, the majority of tumours are confined to the prostatic gland, named clinical stage cT1 and cT2 (see Table 1 for the Tumour, Node, Metastasis (TNM) classifi cation). Some tumours, however, already grow outside the prostatic capsule (cT3) or even invade the surrounding organs (cT4). Dissemination of the disease usually occurs to the regional pelvic lymph nodes and the axial skeleton. The latter will mainly cause pain, although neurological deficit due to compression of the myelum is also possible in severe cases. Diagnostic modalities to detect prostate cancer are digital rectal examination (DRE), measurement of the serum prostate-specific antigen (PSA), transrectal ultrasound of the prostate (TRUS) with subsequent ultrasound-guided prostate biopsies, and magnetic resonance imaging (MRI). Computerized tomography (CT) of the pelvis is reserved for detection of enlarged lymph nodes, whereas bone metastases can be detected by nuclear scintigraphy, CT, MRI or conventional X-ray of the skeleton. The serum PSA is a marker for prostate cancer. Although PSA lacks specificity, it is currently the most valid biomarker available, not only for diagnostic purposes but also for disease monitoring after treatment with curative intent. Since its introduction, PSA has been widely used as a screening tool to detect prostate cancer in asymptomatic men. Recent findings showed that PSA-based screening for prostate cancer resulted in a relative risk reduction of 20% to die from the disease. It must be noted, however, that at the time of the first statistical relevant difference between the intervention and control arm, it was shown that 48 patients had to be treated to prevent one death from prostate cancer. The findings by Schroder et al. show the difficulties that remain to correctly identify the indolent prostate tumours from the ones that need curative treatment. Therefore, prognostic markers that facilitate a risk stratification of prostate cancer patients and that are helpful for optimizing treatment decisions are still very much needed.

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