| EVALUATION
OF NOVEL BIOCHEMICAL MARKERS FOR PROSTATE CANCER PROGRESSION:
SERUM OSTEOPROTEGERIN, MARKERS OF BONE TURNOVER AND CIRCULATING
PSAmRNA.
Dr Joshua G. Phillips, Professor F. C. Hamdy Academic Urology Unit, Royal Hallamshire Hospital, University of Sheffield |
OBJECTIVE
This project has two aims; firstly it is proposed to verify the performance of several of the latest markers to emerge in prostate cancer; particularly those indicating bony involvement. Preliminary studies have shown that these markers can predict bony metastases before they become established. If such a marker can be verified it will be of the utmost benefit in helping clinical management.
Secondly the the researchers will use a new(ish) molecular biological technique RT-PCR to determine the number of metastatic prostate cancer cells in the circulation.
Collaboration with a group in Finland will happen and it is hoped the new technique will significantly improve treatment timing and decision making for men with prostate cancer.
SUMMARY OF FINAL REPORT - 18 March 2007
A number of biochemical markers have been suggested as possible early indicators of disease progression in prostate cancer. Measuring levels of these markers may provide important information to help in the early diagnosis and management of metastatic disease in men with prostate cancer. Recent small studies have indicated that PSAmRNA, serum osteoprotegerin (OPG) and bone turnover markers may all have value in this respect. This project investigated whether these markers were indeed good indicators of disease progression in a large number of men with prostate cancer over a 3.5-year period.
High levels of PSAmRNA in the blood may indicate that prostate cancer cells have entered the circulation. PSAmRNA levels were measured using a state-of-the-art technique developed by the University of Turku, Finland, in 291 men.
High levels of OPG and other bone markers in the circulation may indicate that the bone is being affected by metastases. Serum OPG levels were measured in 389 men, to find out whether this is sufficiently accurate to be considered a useful marker of prostate cancer progression.
The study found that the value of PSAmRNA as a marker remains inconclusive. Although PSAmRNA was detected more frequently in the blood from men with metastatic disease compared with non-metastatic patients, the variability between samples was too high for this marker to be used with confidence in the clinic.
However, exciting results were found for serum OPG, where higher levels were indeed found in patients whose cancer had begun to metastasise. Higher levels were also seen in patients on hormone therapy whose PSA had started to rise, indicating relapse. Interestingly, patients who had low levels of serum OPG on entering the study were less likely to relapse than those with high levels.
In conclusion, elevated levels of serum OPG before or during treatment are associated with a propensity to relapse, and may forecast failure of therapy even earlier than PSA measurement. Serum OPG may well have value as a marker for metastatic disease.
Summary of final report dated 18 March 2007
Project 2003/05