Gleason Grade Progression Is 'Uncommon'

Nick Mulcahy

August 14, 2013

The phenomenon of Gleason grade progression "is not a major feature of prostate cancer," according to the authors of a new study published August 14 in Cancer Research.

The news may provide some reassurance to men with prostate cancer with lower Gleason grades who are considering active surveillance as an initial management approach, say the study authors, led by Kathryn Penney, ScD, instructor in medicine at Harvard Medical School and associate epidemiologist at the Channing Division of Network Medicine at Brigham and Women's Hospital in Boston, Massachusetts.

"If a patient is diagnosed with a lower Gleason grade, then it is unlikely that the tumor will progress to a higher grade," Dr. Penney told Medscape Medical News during a telephone interview.

She explained that Gleason grade, which is a measure of a tumor's aggressiveness, is one of the best-established indicators of prostate cancer long-term outcome — the lower the grade, the better the outcome, typically. However, it has not been known whether the grade commonly changes and worsens over time.

In that regard, Gleason grade is a strong contrast to tumor stage, which is an indicator of the extent of the spread of the disease, and is also a predictor of disease outcomes. "It is well established that stage will progress in some proportion of patients over time," said Dr. Penney.

Gleason grade has been a different story. "It is unknown if grade is a set feature or it can increase over time," she added.

Any attempt to study grade over time is tricky, said Dr. Penney, because grade is determined via biopsy, which is an inexact method. Thus, it is difficult to determine whether tissue taken from the gland at any point in time is from the original tumor or a new tumor or a tumor that was missed by the needles the first time around, she said.

So Dr. Penney and her colleagues did not look at Gleason grade within a set of individuals to learn whether it changed over time. Instead, they looked at grade on a population level.

They hypothesized that if grade was indeed like stage and subject to worsening over time, then grade would also behave like stage at the population level. Since the onset of widespread prostate-specific antigen (PSA) testing, the proportion of advanced-stage prostate cancers has dropped dramatically at the population level as more and more cancers are caught early. The authors wanted to see whether the same held true for grade.

What the Findings Mean for Patients

The team retrospectively looked at 1207 men who were diagnosed with prostate cancer from 1982 to 2004 and subsequently treated with surgery while enrolled in large, longitudinal health professional studies.

They found that the proportion of advanced-stage tumors (≥T3) dropped from 19.9% during the earliest period of the study (1982–1993, when PSA screening was not well established) to 3% during the latest period of the study (2000–2004).

On the other hand, the proportion of high Gleason scores (≥8) decreased substantially less, from 25.3% to 17.6%, during the earliest and latest study periods.

Dr. Kathryn Penney

Thus, there was a "dramatic shift" in stage since the introduction of PSA screening but only a "more modest shift" in Gleason grade, say the authors. "This suggests that Gleason grade is not behaving like stage," summarized Dr. Penney. "You would expect similar reductions."

What does that mean? The authors say the "moderate decrease in the proportion of high-grade cases may be due to the increased diagnosis of low-volume, nonprogressing disease — cases that would otherwise never have been detected if not for PSA screening."

"These additional cases are more likely to be indolent and therefore low-grade disease," they also state.

"These findings suggest that grade may be established early in tumor pathogenesis," conclude the authors.

However, Dr. Penney acknowledged that it cannot be ruled out that Gleason grade can progress in an individual. But it is "uncommon," say she and her coauthors.

The new study and its conclusion are supported by other population-level studies of grade, say the authors.

For instance, a 2011 study found that upon Gleason score rereview, there was no difference in Gleason distribution between the early PSA and late PSA eras (Adv Anat Pathol 2011;18:159-164).

The study findings have implications for clinical practice in patients with low-grade disease upon diagnosis, say the authors.

"Gleason score is a strong predictor of prostate cancer-specific death, and seems set early in the disease process; this suggests that later influences, such as diet, lifestyle, or environmental factors, might be important to trigger disease progression among men with low grade disease," they write.

The authors have disclosed no relevant financial relationships.

Cancer Res. Published August 14, 2013. Abstract

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