The Gleason Grade Grouping System for Consulting fees: Genomic - - PDF document

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UCSF

The Gleason Grade Grouping System for Prostate Cancer: What does it Mean? How to Use It.

UCSF Current Issues in Pathology, 2016 Jeffry P. Simko, PhD, MD Professor of Clinical Pathology UCSF Departments of Urology, Radiation Oncology and Anatomic Pathology UCSF

Disclosures: All Paid to UCSF

• Consulting fees: Genomic Health,

GenomeDx, 3Scan, 3D Biopsy

• Advisor Board / Speakers honoraria:

Genomic Health, Maximum Medical, 3Scan, 3D Biopsy

• Research support: Genomic Health, Myriad

Genetics

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Grade Groups:

• No formal name yet.

– Endorsed by WHO: WHO Grade Groups ? – Gleason Grade Groups (GGG).

• Based on using modified Gleason grades.

– ISUP 2005 and ISUP 2014 consenus conferences

• Why this system was developed.
• How this system relates to Gleason grades

and patient outcomes.

• How to apply this reporting system to practice

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Original Gleason

• Architecture alone (not cytology)
• Accounted for Tumor heterogeneity
• Grades 1 -5 based on gland growth patterns
• Socre (sum): Gleason score X + Y = Z

X = Most common tumor growth pattern (primary grade) Y = Second most common pattern (Secondary grade) If Y < 5% of total tumor, then repeat X. UCSF

Problems with original Gleason

• Some patterns are extremely rare / not cancer

– Grade 1 likely adenosis. – Grade 2 cant be diagnosed on small needle Bx

• Not all possible growth patterns represented
• Some descriptions vague

– Cribriform 3 vs. Cribriform 4 – Inter-observer variability; degraded prognostics

• No rules for when more than two patterns

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Gleason Modifications: ISUP

• International Society of Urologic Pathologists

Consensus Meetings: 2005, 2014

– Dozens of prostate pathologists at the meetings

• Treating clinicians also attended the 2014 meeting

– Identify common areas: Consensus statements – Identify areas of confusion: Experiments to clarify – Criticized at the time for no outcome data

• Outcome studies have now validated most
• Increased consistency in grading

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Gleason Modifications: ISUP

• Do not use Grades 1 or 2 (or use very sparingly)
• All carcinomas with cribriform growth = 4

– Glomerulations = 4 but outcome data not in yet.

• Certain patterns (grades) better classified:

Gleason growth pattern actually better than specific grades for some tumor morphologies.

– Tumor glands floating in mucin (mucinous carcinoma not all 4) – Tumor with columnar cells (Ductal Ca) not always 4 – Tumor cells with vacuoles seen in Gleason patterns 3, 4 or 5.

• Scoring rules changed to better represent biology

– In Bx, primary grade + worst = score, not secondary – In Bx, if secondary lower grade and < 5%, ignore it.

• Prostatectomy, score discreet tumors of different

grades separately.

• Recommend reporting percent tumor > pattern 3.

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Clinical Problems:

• ”BEST” score now 3+3=6 on scale 2-10.

– Confusing to patients – Difficult to explain – Patient anxiety precluding conservative management

• (patient and clinician frustration)
• 3+4=7 and 4+3=7 same score, but very different outcome!!!

UCSF Pierorazio, et al. Br J Urol Int 111: 753-60 (2013). UCSF Pierorazio, et al. Br J Urol Int 111: 753-60 (2013).

PROSTATECTOMY

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UCSF

Grade Groups (Epstein):

• Grade Group 1 = Gleason score < 7
• Grade Group 2 = Gleason score 3+4 = 7
• Grade Group 3 = Gleason score 4+3 = 7
• Grade Group 4 = Gleason score 8 (4+4, 3+5, 5+3)
• Grade Group 5 = Gleason score > 8 (4+5, 5+4, 5+5)
• Validated in numerous f/u studies
• Endorsed by WHO
• UCSF Data: 4+4, 4+5, 5+4 same, 5+5 worse (unpubl)

UCSF

How to apply Grade Groups:

• Use ISUP modified Gleason Grades works best
• Use Biopsy with highest score

– Subsequent study showed that using overall Bx grade group or highest Bx grade group gave similar prognosis (Berney et al., Br J Cancer Apr 21, 2016 epub)

• Prostatectomy: If Grade 5 > 5%, then secondary

– Does not strictly follow ISUP, but makes biologic sense – Probably works either way.

• Simple translation from Gleason score to GGG

– Clinicians can easliy translate to grade groups – Keeps report cleaner / less confusion UCSF

Future Directions:

• Simple system to report meaningful grade info.

– Independent validations done – Improve communication with patients – Grade compression not compromising prognostics

• Some tumor growth patterns still need improved

correlation with outcome data

– Glomeruations – Discriminating some patterns of 4 from 5 difficult – Stromal changes as a prognostic factor UCSF That’s all Folks!!!!!