Aggressiveness of Prostate Tumors May Not Change as Cancer Evolves

Prostate tumors may not readily evolve from low to high grade, according to a research study published in Cancer Research. Kathryn Penney, ScD, epidemiologist at the Harvard School of Public Health and the Channing Division of Network Medicine at Brigham and Women’s Hospital in Boston, and colleagues show that the aggressiveness of a prostate tumor could be established at the time of tumor formation.

The results have important clinical implications for prostate cancer patients and clinicians when deciding on whether to choose active surveillance or treatment. If the aggressiveness of a tumor does not change drastically in the course of the disease, patients diagnosed with early-stage and low-grade prostate tumors may be more likely to avoid overtreatment and choose surveillance.

Men diagnosed with prostate cancer receive a Gleason score that indicates the potential aggressiveness of their disease. Together with the stage of disease at diagnosis, these factors indicate the likelihood of the progression of the prostate cancer. But whether the aggressiveness of a tumor remains static throughout the course of the disease or whether it changes, as reflected by the Gleason score, has not been clear.

Taking advantage of the shift in the proportions of men diagnosed with early- and advanced-stage prostate cancer over the course of the last 30 years, the researchers used a population approach rather than tracking individual patients through serial biopsies.

As a result of the use of prostate-specific antigen (PSA) screening, the proportion of men diagnosed with late-stage disease has decreased by more than 60-fold in the last 22 years. This has resulted in men being diagnosed 10 to 12 years earlier in the course of their disease, according to the study authors. If the aggressiveness, as measured by the Gleason score, also progresses with the disease over time, Penney and colleagues reasoned that, along with a decrease in diagnosis of advanced prostate cancer, a similar reduction in high-grade tumors should be seen in the prostate cancer population over the last few decades.

To study this, the researchers tracked the biology of the disease among 1,207 participants diagnosed between 1982 and 2004, both before and after the introduction of PSA testing. All study participants were part of either the Physicians’ Health Study or the ongoing Health Professionals Follow-Up Study. Data on PSA testing was captured in these studies starting in 1994. In 1994, 42% of participants had a PSA test within 2 years compared with 81% in 2000. Because of the change in the way the Gleason score is characterized, the researchers reassessed the Gleason score of prostate tissue collected during radical prostatectomy rather than tissue biopsy.

The proportion of men diagnosed with late-stage tumors decreased drastically, and the proportion of those with high-grade disease also decreased. From 1983 to 1994, the proportion of men with a Gleason score of 8 or higher was 25% compared with 18% between 2000 and 2004. For those men with early-stage disease (T1–T2 stage), the proportions of Gleason score 8–10 prostate cancer were 19.5% from 1983 to 1993, and 16% from 2000 to 2004. The decrease in proportion of high Gleason score cancers, however, was due to higher rates of low-grade disease diagnosis as a result of PSA screening.

The researchers show that the shift in Gleason score proportions over time is not likely due to changes in the age at diagnosis.

“We were surprised by just how constant the incidence of high-grade disease has been over time,” said Penney in a statement.

“Although we cannot rule out the possibility that Gleason grade progresses within an individual, we conclude that it is not a major feature of prostate cancer,” state the authors in their discussion of the results.

Further studies to confirm these results are needed. The authors of the current study acknowledge that the biopsy data used for this analysis may have missed additional tumors in patients with a higher Gleason score. This highlights the problem of biopsy sampling from heterogeneous tumors, as the biopsy sample may not always capture representative cells of a tumor, which can result in an underestimation of the Gleason score.

The results also have implications for the biology of prostate cancer-both environmental and genetic risk factors may influence the development of either more or less aggressive disease, according to the study authors.

If these results are indeed supported, “the knowledge that Gleason score largely does not progress may make the choice of active surveillance more appealing for patients with low-grade disease,” stated the authors.