Emerging issues

 

There are many other controversies on how to report the grade of prostate cancer on needle biopsies and radical prostatectomy specimens. This tutorial is not a textbook and only aims to give a brief introduction to practical grading. It is not necessary to read the comments below before you finish Test 2.

 

Here is a brief list of issues:

 

 

Global vs. highest GS in needle biopsies

 

Global GS means that the GS in the bottomline diagnosis is based on all cancer present in the cores. This is used by a majority of pathologists in Europe. A disadvantage is that we do not know if all cancer in the cores comes from the same tumor focus.

 

Highest GS means that the GS in the bottomline diagnosis is the highest GS of an individual core. This is more commonly used in North America. A disadvantage is that a core with a small amount of cancer of higher grade (e.g. 4+4 in a case that is otherwise 3+4) may lead to an overgrading of the case.

 

 

Grading of multifocal cancer in RP specimens

 

The ISUP 2005 recommendation was to grade each of the dominant nodules separately. However, there is no consensus as to the definition of dominant or index tumor. In most cases the largest focus also has the highest grade but occasionally a smaller tumor has a higher grade. Furthermore, it may sometimes be difficult to determine which foci are separate tumors. In large cancers, it may appear as if separate tumors have merged into one focus when expanding. Some have argued to use global GS on RP specimens too, which would be a way to get around these difficulties.

 

 

Reporting of tertiary patterns of higher grade

 

Inclusion of a small focus of GP5 in a GS 4+3=7 cancer on needle biopsy would move the GS from 7 to 9 and the ISUP grade from 3 to 5. Whether this is justified has been questionned.

 

It is also controversional when smaller foci of e.g. GP5 should be included in the GS of RP specimens. Is there a percentage threshold when GP5 needs to be included even when it is the tertiary grade?

 

 

Reporting of <5% components of higher grade in RP specimens

 

The ISUP 2005 consensus conference decided to include small foci (<5%) of higher grade in the GS of needle biopsies but not in RP specimens. It has been suggested to do the same in RPs. The problem with this is, however, that when the entire tumor is available for analysis there will very often be minute areas of at least GP4. If they are included in the GS, then GS 6 will more or less disappear, the Gleason inflation will be further fueled and the Gleason system will lose some of its predictive value if compressed to fewer scores.

 

 

Reporting of % Gleason pattern 4

 

It was shown already in the late 1990s that the percentage of Gleason grades 4/5 correlates with outcome. At the ISUP 2014 it was proposed to re-introduce this in a slightly modified form as % Gleason grade 4. The purpose would be to better communicate to the clinicians the amount of the GP4 component of a GS 7 tumor. With the ISUP 2005 decision to include minute amounts of high-grade cancer in the GS and the Gleason inflation that followed there may be a need to for example tell that a GS 7 cancer has such a small amount of GP4 that it may still be suitable for active surveillance.

 

However, several issues remain to resolve. It has been recommended that it is unnecessary to report this measure in each core of needle biopsies as this would be too cumbersome for the pathologist and the amount of provided information too confusing for the clinician. It has been suggested that we estimate the % GP4 of all cancer present in a set of biopsies. This would indeed facilitate the reporting but could also cause some confusion if the highest GS is given in the bottomline diagnosis. With a highest GS 4+4=8 and an overall % GP4 of 10% it is understandable if the clinician would find the information conflicting. This would be less contradictory is global GS was used in the bottomline diagnosis as this would be congruent with the reporting of % GP4.

 

Another problem with % GP4 is whether it should be based on the percentage of linear extent of cancer that is GP 4 or the amount of cancer cells.