News Release

Recent improvements in prostate cancer outcomes may be result of shift in classification

Peer-Reviewed Publication

Journal of the National Cancer Institute

Some of the improvement in prostate cancer survival rates over the past decade may be due to a shift in the classification of prostate tumors rather than to an actual improvement in outcomes, according to an article in the September 7 issue of the Journal of the National Cancer Institute.

Prostate cancers are assigned a score called a Gleason score that ranges from 2 to 10, based on the pathologist's estimation of the likelihood that the cancer cells will spread. Twenty years ago, doctors routinely labeled newly diagnosed prostate tumors with relatively low Gleason scores of 2 to 5, indicating a less dangerous cancer. Today, scores this low are rarely encountered, even though there has been no change in the Gleason scoring system itself in the last decade. In addition, there have been several reports of improvements in 5-year and 10-year survival in prostate cancer based on Gleason score.

To determine whether these improvements in survival are true improvements or the result of a changes in the way cancers are assigned Gleason scores, Peter C. Albertsen, M.D., of the University of Connecticut Health Center in Farmington, and colleagues collected medical records from 1,858 men diagnosed with prostate cancer between 1990 and 1992. They retrieved slides of the prostate tissue taken from these men at the time of their diagnosis, as well as the original Gleason score assignments. An experienced pathologist, blinded to the original numbers, examined the slides and assigned Gleason scores according to contemporary standards.

The study found that about 55% of the 1,858 specimens received higher scores than the original assignments. The scores increased from an average of 5.95 for the original readings to an average of 6.8 by contemporary standards. In addition, two other pathologists reviewed samples of the slides and also arrived at higher scores than the original readings.

The authors suggest that perhaps "pathologists are more hesitant to assign low Gleason scores to contemporary prostate needle biopsy specimens because these scores are frequently upgraded" after reviewing the whole tumor after it has been surgically removed.

The authors also suggest that with more tumors labeled with higher Gleason scores than a decade ago, many low-grade tumors are being labeled as more dangerous than they actually are. This re-labeling could skew mortality and survival rates for prostate cancer patients because those higher score categories would include patients with less aggressive forms of the disease. This statistical artifact is known as the Will Rogers phenomenon, based on a Will Rogers joke: "When the Okies moved to California, the IQ of both states went up." In research, this refers to situations in which reclassifying groups of patients changes the outcomes of both groups without changing the outcomes of all patients combined.

For example, the study found that contemporary prostate cancer mortality rates for the men in the study appeared to be 28% lower than Gleason score-standardized historical rates, even though the overall number of deaths remained the same. Such "statistical artifacts may be producing a false sense of therapeutic accomplishment," the authors write. "Unless researchers are careful, some or all of an apparent improvement in clinical outcomes that is observed when contemporary series are compared with historical series may reflect a statistical artifact--Will Rogers would probably not be amused," they conclude.

The Will Rogers phenomenon of prostate cancer presents a situation "where all the biopsies are necessary and all cancers require treatment, as all have Gleason scores above 5," write Ian M. Thompson, M.D., of the University of Texas Health Science Center in San Antonio, and colleagues in an accompanying editorial. Referring to the phenomenon as "grade inflation," they express concern that score inflation "is a component of the more insidious phenomena of overdetection and overtreatment of prostate cancer." They point out that about 75% of U.S. men have had a PSA test, and more than 17% will be diagnosed with prostate cancer during their lifetime. However, there is only a 3% to 4% lifetime risk of prostate cancer death. As many as 5 of every 6 men diagnosed with the disease may not require treatment--treatment that may negatively affect quality of life, they add.

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Contacts:
Article: Jim Walker, Communications Department, University of Connecticut Health Center, walker@nso1.uchc.edu.
Editorial: Will Sansom, University of Texas Health Science Center, 210-567-2579, sansom@uthscsa.edu.

Citations:
Article: Albertsen PC, Hanley JA, Barrows GH, Penson DF, Kowalczyk PDH, Sanders MM. Prostate Cancer and the Will Rogers Phenomenon. J Natl Cancer Inst 2005;97:1248–53.
Citation: Thompson IM, Canby-Hagino E, Lucia MS. Stage Migration and Grade Inflation in Prostate Cancer: Will Rogers Meets Garrison Keillor. J Natl Cancer Inst 2005;97:1236–37.

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.


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