BERKELEY, CA (UroToday.com) - A systematic review and meta-analysis by Dr. Harnden and associates suggests that a tertiary Gleason grade is associated with worse oncologic prostate cancer (CaP) outcomes and warrants greater prospective analysis and consideration for inclusion in the Gleason grading system. This report appears in the May 2007 issue of the Lancet Oncology.

The standard prostate pathology report includes a primary and secondary Gleason grade. On some occasions, a tertiary grade is reported. In 2005 an International Consensus Conference of uro-pathologists suggested that the Gleason system for prostatic biopsy reports should be modified to account for the presence of a poorly differentiated or undifferentiated tertiary component. The modified approach would sum the most prevalent primary grade and the highest grade. Thus, in the situation with a primary grade 3 and a secondary grade 4, cancers with a tertiary grade of 5 would be classified as high grade (3+5). This proposal has not been implemented, as the existing system is well rooted in clinical practice.

A systematic review of the literature was performed to identify all studies that assessed the prognostic value of a tertiary Gleason pattern. The risk ratio was calculated for PSA recurrence in the presence of a tertiary pattern. In one study of 101 completely sectioned whole-mount radical prostatectomy specimens, the number of different grades was 2.7. In total, 7 papers addressed this topic. Two studies reported on the prognostic significance of a high-grade tertiary component and pathological outcome.

The presence of a tertiary Gleason grade was more common in patients with extraprostatic extension (77%) compare to organ-confined disease (32%). For Gleason 5-6, a high-grade tertiary component was more commonly seen in patients with focal or extensive extraprostatic extension than in those with organ-confined disease. This was significant for extensive, but not focal tumor extension.

There was a significantly higher frequency of a tertiary grade in the presence of seminal vesicle invasion for all Gleason scores combined, compared with that when SV invasion was not present. A difference was not discernable regarding lymph node involvement. Studies demonstrated that a tertiary grade was more than twice as likely to be associated with a positive rather than a negative margin (57% vs. 27%). Also, cancers with a Gleason score of 3+4 had a significantly higher frequency of positive surgical margins when a tertiary grade was present than when no tertiary grade was present (28% vs. 8%). Patients with a Gleason score of 4+3 had twice the frequency of positive surgical margins if a tertiary component was present than if absent (28% vs. 8%). Patients with a Gleason score of 7 and a tertiary grade 5 had similar outcomes to those with a score of 8. However, equivalence was not found between patients with Gleason score 4+3 and tertiary grade 5 and those with Gleason 4+5, as the latter group is more likely to have SV invasion or lymph node metastasis.

Harnden P, Shelley MD, Coles B, Staffurth J, Mason MD

Lancet Oncology 2007; 8(5):411-419

UroToday.com Prostate Cancer Section

Written by Christopher P. Evans, MD, a Contributing Editor with UroToday.

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