According to two recent articles published in the Journal of the American Medical Association, factors associated with an increased risk of death from prostate cancer have been identified. Patients with factors that place them at a higher risk of a cancer recurrence or death may wish to proceed with more aggressive therapy than patients with a lower risk.

The prostate is a gland of the male reproductive system that is responsible for producing some of the fluid that transports the sperm during male ejaculation. In prostate cancer, cancer cells form in the tissues of the prostate. After skin cancer, prostate cancer is the most common form of cancer diagnosed in men. Localized, or early-stage prostate cancer, refers to cancer that has not spread beyond the prostate or surrounding tissues. Standard treatment approaches for early-stage prostate cancer include radiation therapy, surgery, delay of treatment until signs of cancer progression (“watchful waiting”) and/or hormone therapy. Some patients respond well to a specific type of treatment, while others soon relapse or their cancer spreads. Researchers are now realizing that specific factors or variables can help identify patients who are at a higher or lower risk of a cancer recurrence following their diagnosis. Those who are at a higher risk may benefit from more aggressive therapeutic approaches than those who are at a lower risk of a recurrence.

Following initial therapy, patients are often monitored for signs of cancer progression or recurrence with a prostate-specific antigen (PSA) test. Prostate-specific antigens are small proteins that are normally shed by the prostate; PSA levels often become elevated when prostate cancer develops or recurs. Levels of PSA can be determined through a blood sample, and if they continue to rise following treatment, patients are considered to have a “biochemical relapse”. Tests other than PSA levels may also be performed in an attempt to determine where the cancer has spread and to what extent. The time interval it takes for PSA levels to double is referred to as PSA doubling time (PSADT). Recently, studies have indicated PSADT either prior to diagnosis or following therapy may be an important predictor of the course of prostate cancer. Further research is evaluating the role of PSADT in the clinical setting.

The first study, an analysis of data that included 379 men who had been treated with surgery between 1982 and 2000.[1], was conducted by researchers from the John Hopkins Hospital in Maryland . All patients had experienced a biochemical relapse, followed by two subsequent increases in PSA values at least 3 months apart. The average follow-up time was approximately 10 years. Overall, PSADT, Gleason score (measure of aggressiveness of cancer determined from tissues samples) and the time from surgery to biochemical failure were the only risk factors that predicted the risk death from prostate cancer. The categories of PSADT that indicated predictive value were: less than 3 months (highest risk of death from prostate cancer), 3 to 8.9 months, 9 to14.9 months, and 15 months or greater (lowest risk of death from prostate cancer). Gleason score values that indicated predictive value were 8 to10 (most aggressive and highest risk of death from prostate cancer) and 7 or less (lowest risk of death from prostate cancer). Time from surgery to biochemical failure that indicated predictive value was 3 years or less (highest risk of death from prostate cancer), and greater than 3 years (lowest risk of death from prostate cancer). A statistical model that evaluated these three variables (PSADT, Gleason score, and time from surgery to biochemical relapse) together resulted in prediction of risk of death from prostate cancer 15 years following biochemical relapse. For example, patients at the highest risk of death from prostate cancer according to these variables (Gleason score 8 or greater, PSADT less than 3 months, and biochemical relapse three years or less following surgery) had a survival rate or less than 1 percent at 15 years; conversely, patients placed in the lowest risk of death from prostate cancer according to these variables (Gleason score 7 or less, PSADT 15 months or greater, and biochemical relapse greater than three years following surgery) had a survival rate of 94 percent at 15 years.

The second study, an analysis of data that included 358 men with localized prostate cancer who were treated with radiation therapy between 1989 and 2002.[2], was conducted by researchers from Brigham and Women’s Hospital and Dana Farber Cancer Institute in Boston. Of these men, 125 had earlier stage disease and 243 had more advanced disease. The researchers evaluated PSA velocity (the speed at which PSA levels rise) during the year prior to diagnosis of prostate cancer in these men and its value in predicting the risk of death from prostate cancer. Overall, a PSA level increase of less than 2.0 ng/mL per year was associated with a significant increased survival, compared to a PSA level increase of greater than 2.0 ng/mL. At 7 years, men with the earliest stage disease had a 19 percent risk of death from prostate cancer if their PSA levels increased greater than 2.0 ng/mL the year prior to diagnosis, compared with a 0 percent risk of death from prostate cancer if PSA levels rose less than 2.0 ng/mL during the year. Furthermore, at 7 years, men with more advanced disease had a 24 percent risk of death from prostate cancer if their PSA level rose greater than 2.0 ng/mL during the year prior to diagnosis, compared with a 4 percent risk of death from prostate cancer in men whose PSA level rose less than 2.0 ng/mL within that year.

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The researchers from both studies concluded that risk factors such as PSADT, time from surgery to biochemical relapse, Gleason score and a rise in PSA levels greater to or less than 2.0 ng/ml during the year prior to diagnosis of prostate cancer all are associated with a risk of death from prostate cancer. Patients with localized prostate cancer may wish to speak with their physician regarding their individual risks of death from prostate cancer according to these variables, as well as individual variables that may affect outcomes. Patients at a higher risk of cancer progression or death from cancer may wish to undergo more aggressive therapy than their counterparts considered to be at a lower risk.

References:[1] 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

[2] D’Amico An, 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.

Related Article:Risk Factors May Predict the Development of Prostate Cancer

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