Early prostate cancer refers to cancer that has not spread to distant sites in the body; it remains in or near the prostate. Most men who have undergone screening for prostate cancer are familiar with the term PSA—prostate specific antigens. Prostate specific antigens are proteins that are normally shed by the prostate into the bloodstream. Measuring PSA from a blood sample has become a routine screening method for prostate cancer, as the presence of cancer is often associated with a rise in PSA levels. Furthermore, men undergoing treatment for prostate cancer often undergo routing PSA testing to monitor response to therapy or disease progression.

Men diagnosed with early prostate cancer have several treatment options; they include surgical removal of the prostate and surrounding tissues (prostatectomy), radiation therapy, cryotherapy, or a “watch and wait” approach (no treatment is initiated until the cancer progresses). Treatment for this disease largely depends upon the aggressiveness of the cancer, the extent of spread, side effects of treatment, and/or age of the patient.

To add to the mix of variables, research has now demonstrated that PSA velocity (the time it takes for PSA to rise to a certain level) or PSA doubling-time (the time it takes for PSA levels to double [PSADT]), either before treatment or following surgery, may predict the aggressiveness of the cancer.

Four Studies Linking Rate of PSA Rise with Worse Outcomes

I. Results recently published in the Journal of Urology included a study in which researchers evaluated data from 2,290 men who underwent a prostatectomy between 1990 and 1999. Each patient had multiple PSA measurements prior to surgery. At a median follow-up of 7.1 years, researchers found that a rapid rise in PSA levels was associated with worse outcomes.

Men with a PSA doubling time of 18 months or less prior to surgery had over a 6-fold increased risk of death from prostate cancer compared with men whose PSA doubling time was greater than 18 months.

Men whose PSA rose more than 3.4 ng/ml per year also had over a 6-fold increased risk of death from prostate cancer compared to men whose PSA rose less than 3.4 ng/ml per year.

II. Results recently published in the New England Journal of Medicine included a study in which researchers from Harvard University evaluated 1,095 men with early prostate cancer; all men had undergone a prostatectomy. Variables including PSA level at diagnosis, Gleason score (measurement of the aggressiveness of the cancer), stage of the cancer (extent of spread), and the PSA velocity during the year prior to diagnosis were evaluated to determine whether these variables were associated with long-term outcomes for these patients.

At a follow-up of over 5 years, men with a PSA velocity of more than 2.0 ng/ml in the year prior to diagnosis had a risk of death from prostate cancer that was approximately 10-time higher than men whose PSA velocity was equal to or less than 2.0 ng/ml in the year prior to diagnosis. Men whose PSA velocity was greater than 2.0 ng/ml in the year prior to diagnosis also had a shorter time before cancer recurred and reduced overall survival than men with less rapid PSA velocity. A PSA velocity of 2.0 ng/ml or greater was associated with a higher Gleason score, lymph node metastasis, and a higher stage than a PSA velocity of 2.0ng/ml or less in the year prior to diagnosis.

III. Results presented at the 2004 annual meeting of the American Urologic Association included a study in which researchers from Baltimore , Maryland , evaluated different cancer characteristics and associated outcomes in patients with prostate cancer. This study included nearly 6,000 men who had been diagnosed with early prostate cancer and had been treated with a radical prostatectomy since 1982.

Following a prostatectomy, patients who had a PSA doubling time of less than 10 months were significantly more likely to develop advanced cancer compared to those whose PSA doubling time was less than 10 months. At over 8 years of follow-up, the researchers discovered that PSA doubling time also effected survival in these patients. In the group of patients with a PSA doubling time of less than 10 months following a prostatectomy, 42% of patients died from prostate cancer. Conversely, in the group of patients who had a PSA doubling time of greater than 10 months, only 7% of patients died from prostate cancer.

IV. Results published in two studies in the Journal of the American Medical Association included over 700 men to determine which variables were associated with an increased risk from prostate cancer death. Overall results from both of the studies indicated that a short PSADT and a rise in PSA levels equal to or less than 2.0 ng/ml during the year prior to diagnosis of prostate cancer were significantly associated with a risk of death from prostate cancer.

In Conclusion

These results taken together provide evidence that PSA velocity or PSA doubling-time, either prior to diagnosis of prostate cancer, or following treatment for prostate cancer, are indicative of the aggressiveness of a patient’s cancer. Patients may wish to keep track of their PSA levels, noticing the rate at which the levels rise, as well as determining the time interval it takes for PSA levels to double. These results should be discussed with a physician and taken into consideration when deciding upon treatment options; this may allow patients to make the most informed choices regarding their own therapy.

References:

Sengupta S, Myers R, Slezak J, et al. Preoperative Prostate Specific Antigen Doubling Time and Velocity are Strong and Independent Predictors of Outcomes Following Radical Prostatectomy. Journal of Urology. 2005;174:2191-2196.

D’Amico A, Chen M-H, Roehl K, Catalona W. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. The New England Journal of Medicine. 2004;351:125-135.

Partin A, Humphreys E, Mangold L, et al. Prostate specific antigen doubling time after radical prostatectomy as a predictor of cause specific survival. Proceedings from the 99th annual meeting of the American Urological Association. 2004;171:Abstract #1451.

Freedland S, Humphreys E, Mangold L, et al. Risk of Prostate Cancer-Specific Mortality Following Biochemical Recurrence After Radical Prostatectomy. Journal of the American Medical Association. 2005; 294:433-439.

D’Amico A, Renshaw A, Sussman B, Chen M-H. Pretreatment PSA Velocity and Risk of Death From Prostate Cancer Following External Beam Radiation Therapy. Journal of the American Medical Association. 2005; 294:440-447.