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The Biopsy Gleason
Score: Only An Estimate Of The Final Pathological Gleason Score, But The
Best Estimate We Can Get (Sept 2004)
It is not a new finding
that the Gleason score based on core biopsies may differ significantly
from the Gleason score based on whole mount analysis of the
prostatectomy specimen. A recent report is a useful reminder of this
fact: "Limitations of biopsy gleason grade: implications for counseling
patients with biopsy Gleason score 6 prostate cancer", J Urol July 2004,
by a group from University of Miami School of Medicine. They evaluated
531 cases in which the core biopsies were assigned 3 + 3 = 6 followed by
a full analysis of the whole mount prostatectomy specimen. Concordence
was found in only 51%. The RP Gleason score was higher in 41% and lower
in 8%. Among the upgraded scores 36% were raised to Gleason score of 7,
4% to 8 and 1% to 9. They summarized their review of this subject and
stated, "Concentrating on the most common Gleason score of 6, 30% to 70%
of cases are undergraded with the majority having a Gleason 7 tumor on
analysis of the entire prostate". In the upgraded specimens as compared
to those that remained Gleason 6, extraprostatic tumor extenseion was
found in 22% vs. 4% and seminal vesicle involvement in 9% vs. 2%.
At the median follow-up
55.1 months, the outcome showed that "The risk of biochemcial recurrence
was three times higher in patients upgraded following radical
prostatectomy, 6% vs. 18%. There was no improvement of prediction
accuracy when the cores were analyzed in terms of number of cores
positive nor maximum percent of tumor on biopsy.
Unfortunately the
extent of tumor heterogeneity and the random distribution of multiple
foci understandably escape complete detection by random core biopsies.
The underlying prostate pathology that confounds the sampling process is
nicely described in the article "Heterogeneneity of Gleason Grade in
Mulitfocal Adenocarcinoma of the Prostate", R. Arora et. al, Indiana
School of Medicine, CANCER, June 1, 2004. Not unlike findings of other
researchers, this group found that among 115 RP specimens multiple foci
of cancer were found in 100 (87%); 2 foci were found in 20 specimens; 3
foci in 33; 4 in 17; 5 in 13; and >5 in 17. Just as with the reporting
policy of the Dynacare pathologists, the reported global Geason score
was based on the largest ("index") tumor. Arora found that "The primary
grade of the index tumor was the same as the overall primary grade [of
the multiple foci] in 97% of specimens whereas the secondary grade of
the index tumor the same as the overall grade in only 68% of specimens.
Gleason grade 4 or 5 pathology was found in 19 specimens whose overall
Gleason scores of < 6, and in these instances could be reported
as "tertiary". However, only in 3 these instances was the "tertiary"
high grade patterns found in the non-index tumors. Although this study
had only a small number of "tertiary" high grade elements, their
importance of tertiary elements is emphasized by Arora by noting that
"the existence of a high-grade component, even if it accounts for a
small percentage of a tumor, had a marked adverse influence on the
biologic behavior of the tumor."
Bottom Line:
The full extent of tumor heterogeneity and multifocality that can only
be appreciated by examination of the entire prostate specimen, and the
limitation of random biopsies in fully reflecting this complexity points
up the challenge faced by physicians in counseling patients about
treatment choices and outcome based on core biopsy information.
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