Recent improvements in prostate cancer outcomes may be result of shift
in classification
07 Sep 2005

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.

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.

The Journal of the National Cancer Institute is published by Oxford
University Press and is not affiliated with the National Cancer
Institute. Visit the Journal online at
jncicancerspectrum.oxfordjournals.org.

Steve U