Prevalence Of A Tertiary Gleason Grade And Its Impact On Adverse Histopathologic Parameters In A Contemporary Radical Prostatectomy Series

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology
Article Date: 15 Nov 2008 - 6:00 PST

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UroToday.com - Almost 40 years ago, Donald F. Gleason pioneered his well acknowledged grading system of prostate adenocarcinoma. In the ensuing years, the reliability of the Gleason system in predicting the outcomes of patients with prostate cancer (PCa) undergoing surgery, radiation therapy or surveillance has been proven in several single and multi-institutional studies. In its original version, the Gleason system considered only the two most predominant Gleason patterns.

Although it has been acknowledged that a substantial number of radical prostatectomy (RP) specimens contain more than two different Gleason grades, a third or fourth potentially present Gleason pattern did not contribute to the Gleason-score, regardless of its magnitude or state of aggressiveness. Recently, a handful of studies have been published, which uniformly demonstrated that the presence of a tertiary Gleason grade is significantly associated with adverse disease at the time of RP. Moreover, a tertiary Gleason grade was a statistically significant predictor of biochemical failure after RP in some of the studies.

Limitations, however, arise in consideration of these study designs, which were nearly all retrospective and were often limited by low statistical power due to small study populations. Furthermore, the data were derived from time intervals when pathological reporting of a tertiary Gleason grade might not have been mandatory. Consequently, prevalence and definition of the reported TGG differed substantially in the above-mentioned studies, ranging from 13 to 50%, which might hamper the assessment of their clinical impact.

Due to the paucity of available contemporary data addressing this issue, we decided to conduct the presented study.

Results and future aspects

As shown in the abstract, we found that the presence of a tertiary Gleason grade in RP-specimen was statistically significantly associated with all the addressed adverse pathological features, namely presence of extracapsular extension, seminal vesicle invasion, positive surgical margins, and presence of lymph node metastases (p<0.001). However, the amount of the tertiary Gleason grade had to be at least 5% of the overall cancer volume. Conversely, the presence of a tertiary Gleason grade containing <5% of the overall tumor amount did not show a statistically significant association to any of the addressed end-points. This indicates that the tertiary Gleason grade must exceed a certain amount of the overall tumor volume to have a significant impact on the pathological stage.

Due to the lack of a clinically meaningful follow-up period, so far, our study does not answer the question which is of major importance: is a tertiary Gleason grade an independent predictor of treatment failure after therapy with curative intent? As indicated above, some authors already indicated that the presence of a (worse differentiated) tertiary Gleason grade is a significant predictor of biochemical recurrence after RP. However, the statistical power of most of these studies is limited by a relatively small sample size. Moreover, differences in the design of the various studies (e.g. different definition of a tertiary Gleason grade, differences in the histopathological evaluation of the RP-specimen) make it difficult to compare the results unequivocally. In consequence, additional large-scale studies with prospective assessment of the tertiary Gleason grade are warranted to determine its effect on biochemical failure after therapy with curative intent.

Written by Hendrik Isbarn, Guido Sauter, Markus Graefen, Hartwig Huland, and Thomas Steuber as part of Beyond the Abstract on UroToday.com

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