Elsevier

European Urology

Volume 61, Issue 5, May 2012, Pages 1019-1024
European Urology

Prostate Cancer
Upgrading and Downgrading of Prostate Cancer from Biopsy to Radical Prostatectomy: Incidence and Predictive Factors Using the Modified Gleason Grading System and Factoring in Tertiary Grades

https://doi.org/10.1016/j.eururo.2012.01.050Get rights and content

Abstract

Background

Prior studies assessing the correlation of Gleason score (GS) at needle biopsy and corresponding radical prostatectomy (RP) predated the use of the modified Gleason scoring system and did not factor in tertiary grade patterns.

Objective

To assess the relation of biopsy and RP grade in the largest study to date.

Design, setting, and participants

A total of 7643 totally embedded RP and corresponding needle biopsies (2004–2010) were analyzed according to the updated Gleason system.

Interventions

All patients underwent prostate biopsy prior to RP.

Measurements

The relation of upgrading or downgrading to patient and cancer characteristics was compared using the chi-square test, Student t test, and multivariable logistic regression.

Results and limitations

A total of 36.3% of cases were upgraded from a needle biopsy GS 5–6 to a higher grade at RP (11.2% with GS 6 plus tertiary). Half of the cases had matching GS 3 + 4 = 7 at biopsy and RP with an approximately equal number of cases downgraded and upgraded at RP. With biopsy GS 4 + 3 = 7, RP GS was almost equally 3 + 4 = 7 and 4 + 3 = 7. Biopsy GS 8 led to an almost equal distribution between RP GS 4 + 3 = 7, 8, and 9–10. A total of 58% of the cases had matching GS 9–10 at biopsy and RP. In multivariable analysis, increasing age (p < 0.0001), increasing serum prostate-specific antigen level (p < 0.0001), decreasing RP weight (p < 0.0001), and increasing maximum percentage cancer/core (p < 0.0001) predicted the upgrade from biopsy GS 5–6 to higher at RP. Despite factoring in multiple variables including the number of positive cores and the maximum percentage of cancer per core, the concordance indexes were not sufficiently high to justify the use of nomograms for predicting upgrading and downgrading for the individual patient.

Conclusions

Almost 20% of RP cases have tertiary patterns. A needle biopsy can sample a tertiary higher Gleason pattern in the RP, which is then not recorded in the standard GS reporting, resulting in an apparent overgrading on the needle biopsy.

Introduction

Numerous studies have assessed the correlation of Gleason score (GS) at needle biopsy with that of the corresponding radical prostatectomy (RP) [1]. In 2004 one of the authors of the current article led a consensus on updating the Gleason grading system, published in 2005 [2]. From this update and subsequent modifications, the major changes are that cribriform, glomeruloid, and poorly formed glands are now considered Gleason pattern 4 as opposed to pattern 3 in the old system. The GS is now derived by adding the most common and highest Gleason pattern on biopsy, as opposed to the original GS that added the most common and second most common pattern. There was also consensus on the prognostic importance of tertiary grade patterns in RP specimens.

Biopsy grade has assumed greater importance in recent years with a relative increase in men undergoing therapy other than RP, such as radiation therapy or active surveillance where the only tissue sampled is on the needle biopsy. Not only is there a potential for undertreatment resulting from undergrading on needle biopsy, but overtreatment (ie, additional radiotherapy) remains a concern for men whose biopsies are overgraded. The issue of accounting for tertiary grade patterns is significant as can be seen in almost 20% of RP specimens [3]. The current evaluation of a large number of cases analyzing the relationship between needle biopsy and RP GS improves on prior works by (1) accounting for the updated Gleason system in both the needle biopsy and RP, (2) reporting RP higher tertiary grade patterns, (3) including only cases with extended needle biopsy sampling, and (4) including RPs that were examined histologically in their entirety.

Section snippets

Patients and methods

The Institutional Urology Prostate Cancer Database was searched for cases of RP specimens removed between January 1, 2002, and December 21, 2010. Institutional review board approval was received. Cases were included only if the corresponding needle biopsy had at least a 10-core sampling. Cases with neoadjuvant therapy were excluded. Treatment with 5α-reductase inhibitors was not an exclusion criterion for the present analysis. A total of 7643 RPs and corresponding needle biopsies formed the

Relation of needle biopsy to radical prostatectomy Gleason score

Table 2 details the corresponding RP GS for each of the five needle biopsy GS groups. Of note, 36.3% of cases were upgraded from a needle biopsy GS 5–6 to a higher grade at RP; nearly 20% of the cohort had a tertiary Gleason pattern, and if one ignored the tertiary patterns, 25.1% were upgraded. Approximately 50% of the cases had matching GS 3 + 4 = 7 at biopsy and RP with an approximately equal smaller number of cases downgraded or upgraded. When the biopsy was 4 + 3 = 7, there was an almost equal

Discussion

The needle biopsy and corresponding RP GS may not be the same for several reasons: pathology error, borderline grades, and sampling error. Some of the more common pathology errors in grading limited needle biopsy specimens include (1) overcalling Gleason pattern 4 on tangentially sectioned small glands of pattern 3 that mimic poorly formed glands, (2) undercalling cribriform Gleason pattern 4 as pattern 3, and (3) undercalling GS 9–10. Because the differences between different Gleason patterns

Conclusions

GS upgrading and downgrading remain an important issue using the updated Gleason system, even when accounting for tertiary Gleason patterns in the RP. Even in the setting of grading prostate cancer in a center with extensive prostate cancer pathology expertise, approximately a quarter of GS 5–6 tumors on biopsy will be GS 7 or higher at RP. Additional tools are needed to better predict upgrading and downgrading because the currently available standard clinical and pathologic variables are

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