| CONTINUATION OF THE PROJECT ON MOLECULAR
GENETIC CHANGES IN PROSTATE CANCER: GUIDES TO CLINICAL
MANAGEMENT Mark R Feneley, Senior Lecturer in Urological Oncology, UCL |
Background to the project
Early prostate cancer restricted to the prostate can be cured with radical prostatectomy or radical radiotherapy. However, most early cancers, such as those detected by screening, will not cause symptoms and the man will die of some other cause. Conversely up to 40% of early cancers treated by radical prostatectomy have already spread outside the prostate, and these individuals are much more likely to be killed by the disease. So the doctor and the patient have a dilemma - should they wait and see whether the cancer is aggressive and perhaps miss the opportunity to cure it, or should they opt for radical treatment with all its side-effects when it may not be necessary. The uncertainty for both the patient and his doctor could be removed if we could accurately predict the outcome before embarking on treatment.
Cancer develops as a result of genetic changes in cells. Early changes impart a growth advantage and allow the cancer cells to invade and spread through prostate tissue. Eventually the cancer cell acquires the genetic changes needed to spread outside the prostate. Although we have discovered lots of genetic changes in prostate cancer, we do not yet know which genetic change controls each step in the progression of prostate cancer. When we have achieved this goal, we might be able to predict the outcome of radical therapy.
The long term aim of this study is to identify genetic changes that we can use to help men select the best treatment for their prostate cancer.
Progress to date
The strategy is to compare cancers from men that have a good outcome with cancers from men that have a bad outcome following radical prostatectomy. The first task was to select suitable men from the PRCUK radical prostatectomy database. Two groups were identified: firstly men who developed a biochemical relapse within 2 years of radical prostatectomy and secondly men with no clinical or biochemical evidence of prostate cancer recurrence for at least 3 years after surgery. In order to exclude the influence of factors already known to influence outcome, the two groups were matched for stage, Gleason score and pre-operative PSA.
The next stage is to extract DNA from these cancers and use allelic imbalance and comparative genomic hybridisation (CGH) to measures loss and gain of genetic material. In this way we hope to identify tumour suppressor genes and oncogenes that are consistently altered in prostate cancer.
Reference
Bott SRJ, Masters JMW, Kirby RS, Parkinson MC, Hooper J, Feneley MR, Williamson MW. Allelic imbalance and outcome after radical prostatectomy. European Urology, submitted.
This research work is continued in project 2003/11 where later information will be found.
Research summary dated 15 October 2004
Project 2002/17