The Gleason score is based on the level of differentiation and growth pattern of prostate cancer cells. Cancer cells that closely resemble the normal prostate cells when viewed under low-power magnification are well differentiated. Cancer cells that do not retain the structure of the surrounding normal cells are poorly differentiated. Scores range from 1 to 5.
In examining histologic samples of a patient’s prostate tissue, the pathologist will identify the 2 most commonly occurring patterns (types of differentiation) among the cancer cells and assign a numerical value to each pattern. The 2 numbers are then added to yield the final Gleason score. If a single pattern dominates, the pathologist will simply double the corresponding value.
Total scores range from 2 to 10. Scores in the range of 2–4 are considered well-differentiated, 5–7 are moderately differentiated, and 8–10 are poorly differentiated. In general, the higher the score, the worse the prognosis. Men with well-differentiated tumors that are treated conservatively have minimal risk of dying from prostate cancer.
Is declining mortality a sign of screening success?
Prostate cancer mortality has been declining since the mid-1990s in numerous parts of the world; the US,6,34 Canada,35 Australia,36 and the United Kingdom37 have all reported a reduction in the rate of prostate cancer deaths. Advocates of PSA screening point to this trend as evidence of the effectiveness of screening. But such ecological data are difficult to interpret. For instance, although much less PSA screening is performed in the UK, mortality trends are similar to those in the US where PSA testing has been used more widely.38
Aggressive screening not necessarily the reason. In the US, 2 geographic areas—Seattle, Washington and Connecticut—provided a natural experiment to compare the effect of aggressive screening on prostate cancer mortality (LOE: 2c).39 Although more aggressive screening and treatment took place in the Seattle area, prostate cancer mortality rates were similar to those in Connecticut over 11 years of follow-up. Similarly, in a study in British Columbia, prostate cancer mortality from 1985 to 1999 was not associated with the intensity of PSA screening (LOE: 2c).40
Other possible explanations. If the mortality decrease is not related to PSA screening, what could cause it? One explanation is “attribution bias.” Death certificate misattribution of cause of death from prostate cancer may partially explain the pattern of increasing, then decreasing mortality rates (LOE: 2c).41 Improvement in prostate cancer treatment, especially for advanced stage, and in particular hormone therapy, is another possible explanation for the decreasing prostate cancer mortality (LOE: 2c).14,42
Benefits of screening
The benefit of any effective screening test is a decrease in the risk of the screened-disease mortality. The best way to demonstrate decreased risk is through a randomized controlled study of the screening test, and 2 such trials are underway for prostate cancer. In the meantime, a decision model estimates that aggressive treatment of organ-confined disease potentially adds 3 years of life for men in their fifties, 1.5 years for men in their sixties, and 0.4 years for men in their seventies (LOE: 2c).3
Others have concluded that 25 men with clinically detected prostate cancer would need to be treated with surgery to prevent 1 prostate cancer death during a 6-year period, without evidence that quality of life is improved (LOE: 2c).43
Consider quality of life. With uncertainty surrounding improvement in the quantity of life as a result of prostate cancer screening, improved quality of life may be an issue for patients. Focus group research has demonstrated that some patients believe it is better to know if a cancer is present than to wonder if it will be diagnosed when it is too late for cure.44
General quality of life has been found to be similar among men treated for prostate cancer and age-matched controls without prostate cancer; however, urinary, sexual, and bowel function vary substantially between treated and untreated men and by treatment type (LOE: 3b) (TABLE 2).45,46 In general, men treated with radical prostatectomy and brachytherapy often report better general quality of life than men who undergo radiation treatment, despite having more urinary and sexual problems (LOE: 2b).47,48
Estimates of risk associated with specific prostate cancer treatments 12 months or more after treatment
|TREATMENT OUTCOMES||RADICAL PROSTATECTOMY (%)||EXTERNAL BEAM RADIATION (%)||BRACHY-THERAPY* (%)||ANDROGEN DEPRIVATION THERAPY (%)||UNTREATED (%)|
|Death within 2 months of treatment||0.5–0.7||0.2–0.5||0.2–0.5|
|Other symptoms||Breast swelling: 5–25|
|Hot flashes: 50–60|
|* Fewer studies on brachytherapy are available, especially those with long-term follow-up; therefore, these findings are less certain than other entries.|
|‡ Includes nerve-sparing prostatectomy.|
|† EBRT and brachytherapy patients are more likely to experience irritative voiding symptoms (i.e. dysuria, urgency and hesitancy and noctoria), while RP patients are more likely to experience incontinence.|
|** Impotence risk gradually increases with time after treatment.|
|§ Includes symptoms such as painful bowel movement and urgency|
|Sources:references 14, 50–53, 65–71.|