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Survival
As a result of national screening programmes, 58% of all prostate cancers diagnosed in the USA in 1997 were discovered while still localised within the prostatic capsule. The 5-year relative survival rate for patients diagnosed with prostate cancer at this stage is 100%. In Europe, where there is no standardised early screening, 25–30% of prostate cancers are diagnosed at the advanced stage and overall 5-year survival rates are between 50% and 60%.
Survival rates for patients diagnosed with a prostate cancer that has breached the prostatic capsule is poor and patients with metastatic disease have the lowest predicted survival rates of all. One estimate shows that, on average, 46% of patients with metastatic disease die about 22 months after diagnosis, and approximately 70% of all patients diagnosed with metastatic disease die within 5 years.
Assessing prognostic outcome is especially critical for patients with early, localised disease, whose cancer is still manageable and potentially curable. Prognostic factors can give an indication of how likely the disease is to recur following treatment and the subsequent survival probability of the patient. Some variables can be used to predict or eliminate certain courses of treatment.
Clinical prognostic factors
The most important clinical prognostic indicators of disease outcome in prostate cancer are pre-therapy PSA level and Gleason score. Patients with localised prostate cancer who have pre-therapy PSA levels of less than 4ng/ml and pre-therapy Gleason scores of less than 4 have an excellent post-treatment prognosis, with a disease–free survival of greater than 90% following either radical prostatectomy or radiation therapy. In contrast, patients with pre-therapy PSA levels of greater than 20ng/ml and Gleason scores of more than 8 have a poor prognosis (less than 50% disease-free survival). For the 50% of patients with intermediate values of PSA and Gleason scores, additional prognostic strategies are required to give an accurate prediction of disease outcome.
Related information: Risk of recurrence
Pathological prognostic factors
Tumour stage and Gleason score are the most important pathological prognostic markers following surgery. The pathological stage of the tumour is a strong predictor of outcome. In patients who have undergone radical prostatectomy, examination of excised tissue can determine whether there is involvement of the lymph nodes and/or seminal vesicles, a finding that is associated with a poor prognosis and a high rate of relapse (53–85% relapse within 5 years). In patients with disease that is still confined to the prostate, there is a very low recurrence rate, less than 10%.
In the absence of tissue from radical prostatectomy, systematic prostate biopsies can provide more accurate staging of the tumour than can be achieved by DRE and/or PSA alone.
Gleason score is also an important predictor of outcome in patients who do not have lymph node or seminal vesicle involvement. Localised cancer with a Gleason score of 2–4 carries with it an excellent, post-surgery prognosis (5-year freedom from relapse of more than 90%), while a Gleason score of 8–10 is uniformly poor (10-year disease-free survival rate of 35%). For patients with intermediate Gleason scores (5–7), the surgical margin status, whether or not cancerous cells are found at the edges of excised tissue, is a useful prognostic marker.
Related information: Risk of recurrence
Molecular and cellular prognostic markers
For individuals where both PSA levels and Gleason scores are intermediate, accurate prognosis can be difficult. However, new prognostic markers are being introduced and evaluated continuously. Perhaps the most promising results will be found through investigation of the genetic mutations responsible for cancer. It is now possible to detect the gene products (proteins) associated with cancer progression and metastasis, and so predict with greater accuracy the likely outcome for these patients.
Most of these potential markers are still under investigation to determine their robustness and overall prognostic value; a brief overview of some of the most promising is presented here:
- p53 tumour suppressor gene. The p53 gene is involved in cell-cycle control, inhibiting its progression to allow time for DNA repair before cell division. Mutations in this gene allow cells to undergo division before they can repair their DNA, leading to a higher risk of genetic instability and the possibility of transformation to malignancy. Several studies investigating the mutated p53 gene in prostate cancer have shown that its presence in prostate tissue is an indicator of a poor prognosis, even in patients with low or intermediate Gleason scores. The potential of this gene as a prognostic marker is being investigated
- bcl-2 proto-oncogene. The bcl-2 proto-oncogene is involved in regulating programmed cell death, or apoptosis. Like p53, bcl-2 is expressed in 27–68% of prostate cancer tissue samples. Increasing expression of bcl-2 is associated with increasing Gleason score and tumour stage and appears to be an independent predictor of a poor prognosis
- proliferation (Ki-67). Ki-67 is present in dividing cells but not in stationary cells, and therefore has the potential for use as a marker for cellular proliferation. Ki-67 expression has been correlated with recurrence of disease following prostatectomy, with increased expression of the antigen associated with a lower disease-free survival rate
- apoptotic index. There is some evidence that the apoptotic index may be a better predictor of 5-year disease-free survival than tumour volume, mitotic index or status of organ confinement
- angiogenesis. The ability of tumours to grow is dependent upon their ability to form new blood supplies (angiogenesis). The proliferation of blood vessels within a tumour can be measured by tissue staining and quantified. Microvessel density (MVD) has been shown to increase with the worsening pathological stage of the tumour and can predict the likelihood of extracapsular extension.
