New Prognostic Signature for Prostate Cancer May Help in Treatment Decisions

Researchers at the Queen Mary University of London and a team of collaborators have identified a genetic signature among prostate tumors that may help determine the best course of treatment for patients. The results of the study will be published in the March 2011 issue of Lancet Oncology.

Scientists tested the hypothesis that genes whose expression fluctuates depending on the stage of the cell cycle, also called “cell cycle progression” (CCP) genes, may have a prognostic value in prostate cancer as has been previously demonstrated for breast and lung cancers. CCP gene expression goes up when cells, including tumor cells, are dividing. Therefore, the level of these CCP genes are an indication of how fast tumors are growing, and may be useful in differentiating more aggressive tumors from ones that can be safely managed using non-surgical conservative treatment approaches. The higher the CCP score, the more likely a prostate tumor is aggressive.

The researchers used tumor samples from two cohorts of prostate cancer patients: those treated with radical prostatectomy and those who were conservatively treated. They found that the CCP score, consisting of a signature expression profile of 31 CCP genes, was the most robust single way of predicting reoccurrence of disease. Combining CCP score with prostate-specific antigen (PSA) concentration turned out to be the best predictor of outcome.

Accurate diagnosis of the stage and potential outcome of prostate cancer is very important, but identifying whether a prostate tumor is relatively harmless and requires minimal treatment and watchfulness or an aggressive one that necessitates fast treatment is still relatively difficult. There are few tools available to accurately differentiate between the different tumor types. Currently, clinical variables such as tumor stage, PSA concentration, and Gleason score are used to predict disease outcome. While these markers are about 80% effective in predicting an outcome for patients who undergo surgery, they are less accurate for conservatively treated patients.

The new data from the Lancet Oncology paper suggest that the CCP score and PSA concentration are independent readouts of the aggressiveness of the prostate cancer and both are required for an accurate assessment of outcome. The combined CCP score and PSA concentration would be particularly helpful for those patients with early-stage disease, of which 10% still die of prostate cancer. Identifying early but potentially high-risk tumors would mean identifying those patients that would most benefit from early aggressive treatmen.

The study used tumor samples and patient data from a total of 706 men from both the US and Great Britain. Study follow-ups are needed, however, to validate the method. If confirmed, men with non-aggressive slow-growing tumors could be spared unnecessary surgery and its adverse effects, while those with fast-acting tumors would receive the necessary treatment faster.

This type of patient tumor analysis is progress toward personalized cancer treatment. A molecular diagnostics company, Myriad Genetics, based in Salt Lake City, Utah already has a commercial diagnostics test that tests the level of 46 CCP genes that was utilized in the University of London study. If these published results are confirmed in other trials such as adjuvant radiation, androgen deprivation, and novel systemic treatments, the test could soon be commonly used to estimate the risk of prostate cancer outcome and reoccurrence.