Prostate cancer grade usually does not progress over time

The proportion of men with advanced-stage prostate tumors at diagnosis has dropped dramatically since the widespread implementation of prostate-specific antigen (PSA) screening, but the proportion of men with high-Gleason-grade, or aggressive, cancers at diagnosis has not changed substantially, researchers found.

Epidemiologist Kathryn L. Penney, ScD, of Brigham and Women's Hospital in Boston, Massachusetts, and colleagues analyzed data from 420 participants from the Physicians' Health Study and 787 from the Health Professionals Follow-up Study. All the men had received a diagnosis of prostate cancer between 1982 and 2004 and had undergone prostatectomy.

The proportion of participants who had undergone PSA screening increased from 42% in 1994 to 81% in 2000. A comparison of the distribution of tumor grade and clinical stage across the pre-PSA and PSA screening eras revealed that the proportion of advanced-stage tumors dropped by more than six-fold from the earliest period (December 1982 to January 1993) to the latest (May 2000 to December 2004): from 19.9% (stage T3 or stage T4) to 3% (stage T3 and no stage T4), respectively. This represented an 85% drop in stage at diagnosis.

A second review of grade, however, showed that the corresponding proportions of Gleason scores of 8 or higher decreased substantially less, from 25.3% in the earliest period to 17.6% in the latest, translating to a decline of 30%. Penney's team further discovered that the moderate drop in high-Gleason-grade cancers was due to an increased diagnosis of low-grade disease that would not have been detected without PSA screening, and not due to the prevention of progression to more aggressive disease as a result of screening.

“Over time, because of PSA screening, men have been more likely to be diagnosed with prostate cancer at an earlier stage, before the disease has had an opportunity to grow and spread,” explained Penney in a statement from the American Association of Cancer Research (AACR); the study was published in the AACR journal Cancer Research (2013;73[16]:5163-5168). “If Gleason grade also progressed over time, we would expect a similar decrease in high Gleason grade disease over time. We were surprised by just how constant the incidence of high-grade disease has been over time.

The authors noted in their report that the findings suggest tumor grade may be established early in tumor pathogenesis. This has implications for the understanding of tumor progression and prognosis, and may help patients who receive a diagnosis of lower-grade prostate cancer feel more comfortable choosing active surveillance.
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