Higher tertiary grade linked with quicker PSA failure

Gleason score 7 and high tertiary grade similar to higher Gleason scores.

Issue: November 1, 2007

Men with a large pattern of moderately aggressive disease found on prostate biopsy, who also have a small area of highly aggressive cancer, have a worse prognosis than men without the small pattern of disease.

Among men with initial Gleason score 7 for localized prostate cancer, those with tertiary grade 5 pattern progressed to PSA failure nearly two years earlier than those with Gleason score 7 but no tertiary grade 5 pattern.

The study, published in a recent Journal of the American Medical Association, suggests that men with Gleason score 7 but tertiary grade 5 could perhaps be better suited for treatment typically given to patients with a higher Gleason score, according to Abhijit A. Patel, MD, PhD, a radiation oncologist at Brigham and Women’s Hospital.

“We were surprised that the recurrence rates for these men were similar to rates seen for men with highly aggressive disease,” Patel said. “It was surprising that even a very small pattern of highly aggressive cancer seems to dominate the behavior of the overall disease in terms of the likelihood of recurrence.”

Histology slide showing prostate cancer. On the right is a somewhat normal Gleason score of 3 with moderately differentiated cancer. On the left is less normal tissue with a Gleason score of 4 that is highly undifferentiated.

Source: Otis Brawley

Time to PSA failure

Researchers observed 2,370 men with clinical tumor category 1c to 3b. The patients underwent surgery or radiation therapy with or without hormonal therapy. A pathologist with expertise in genitourinary cancers assigned Gleason scores to the prostate needle biopsy specimens.

The main outcome measure was time to PSA failure. Researchers found that the median time to PSA failure for men with Gleason score 7 and tertiary grade 5 disease was five years compared with 6.7 years for men with Gleason score 7, but without tertiary grade 5 (P<.001). Men with Gleason score 7 and tertiary grade 5 had similar median time to PSA failure as men with Gleason score 8 to 10.

“Because the results of this study show that this finding is of prognostic significance, and can affect treatment decisions for these patients, a tertiary grade of 5 should always be reported if it is seen in a biopsy specimen,” Patel said.

Validating the results

The results of the study are in line with the 2005 recommendations of the International Society of Urologic Pathology consensus conference, which stated that men with Gleason score 7 and tertiary score 5 should have their cancer classified as Gleason score 8 or 9.

Donald L. Trump, MD, president and CEO of the Roswell Park Cancer Institute and editor of Hem/Onc Today’s Genitourinary Cancer section, said that the results of this study need validation, and immediate application of the findings is problematic. A tertiary pattern is not routinely read. Also, all of the biopsies in this study were read by a single pathologist experienced in genitourinary pathology. According to Trump, the direct extrapolation to a practice wherein multiple pathologists, who may vary in their experience in genitourinary pathology, is an issue.

“There is no doubt that experienced pathologists can do this evaluation and if the evaluation is validated such data may aid in developing treatment plans for men with localized prostate cancer,” said Trump. “But until that learning curve is negotiated and this work is validated, the direct application to day to day care is limited.” – by Angelo Milone

For more information:

Patel AA, Chen MH, Renshaw AA, et al. PSA failure following definitive treatment of prostate cancer having biopsy Gleason score 7 with tertiary grade 5. JAMA. 2007;298:1533-38.