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NY Prostate Cancer Conference - J.I. Epstein - Session 2: Predicting grade
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  • 1. UPGRADING/DOWNGRADING OF PROSTATE CANCER FROM BIOPSY TO RADICAL PROSTATECOMY: INCIDENCE AND PREDICTIVE FACTORS Jonathan I. Epstein, M.D.   Professor of Pathology, Urology, Oncology The Johns Hopkins Hospital, Baltimore, MD
  • 2. Incidence – Problems with Methodology
    • Various Grade Grouping
    • 2-4; 5-6; 7; 8-10
    • 2-6; 7; 8-10
    • 6; 347; 437; 8-10
    • 6; 347; 437; 8; 9; 10
    • 2; 3; 4; 5; 6; 347; 437; 8; 9
    • 3; 4; 5; 6; 7; 8; 9; 10
  • 3. Upgrading Incidence < 6 vs. > 7
    • Problems with Older Studies
    • 1. Different Gleason grading
    • 2. Different biopsy sampling
    • 3. Different patient populations with worse disease
  • 4. Upgrading Incidence < 6 to > 7
    • 21 Studies with Cases from 1992 to Present
    • (minimum 100 cases)
    • Upgrading in 3975/11,472 (35%)
    • Mean 36%
    • Median 35.5%
    • Range: 14%-51%
  • 5. JHH Data
    • Since 2004 (accounts for Modified Gleason grading)
    • At least 10 cores sampled
    • No neoadjuvant therapy
    • No tertiary grades in RP (19.6% of cases)
    • 6,308 cases
  • 6. Upgrading Incidence < 6 to > 7
    • RP
    • 3+4=7 21.6%
    • 4+3=7 3.5%
    • 8 0.6%
    • 9-10 0.5%
    • Total 26.2%
  • 7. Downgrading Incidence
    • 4 Studies with Cases from 1992 to Present
    • (minimum 100 cases)
    • Imamoto et al.: 57/107 (56%) 8-10 to < 7
    • Moussa et al.: 68/169 (40%) 8-10 to < 7
    • Ruijter et al.: 31/106 (29%) 8-10 to < 7
    • Moussa et al.: 54/735 (7.3%) 3+4 to 3+3
  • 8. Biopsy 3+4=7
      • RP
      • 3+3=6 15.6%
      • 3+4=7 64.3%
      • 4+3=7 16.5%
      • 8 2.0%
      • 9-10 1.6%
  • 9. Biopsy 4+3=7
      • RP
      • 3+3=6 7.6%
      • 3+4=7 39.4%
      • 4+3=7 39.8%
      • 8 5.7%
      • 9-10 7.5%
  • 10. Biopsy 4+4=8
      • RP
      • 3+3=6 1.6%
      • 3+4=7 17.1%
      • 4+3=7 26.2%
      • 8 30.0%
      • 9-10 25.1%
  • 11. Causes of Up or Downgrading
    • Pathology error
      • Overcalling pattern 4 with focal poorly formed glands
      • Undercalling cribriform gland pattern 4 as pattern 3
      • Undercalling Gleason 9-10
    • Borderline cases
      • Poorly formed glands of pattern 4 vs small glands of pattern 3
      • Very poorly formed glands of pattern 4 vs pattern 5
  • 12. Causes of Up or Downgrading
    • Sampling error
      • Miss high grade component (undergrade)
        • ie. Gleason 6 on bx miss pattern 4 in RP: RP 3+4 or 4+3
      • Sample RP tertiary component on bx (overgrade)
        • ie. Gleason 3+4=7 on bx hit tertiary pattern 4 in RP: RP 3+3 with tertiary pattern 4 (gets recorded in study as 3+3=6)
  • 13. Prior Studies Not Predictors of Upgrading
    • Age: Not predictive
    • Clinical stage: Almost all studies not significant with the few significant studies showing only weak correlations
  • 14. JHH Data
    • Age: 58.8 upgrading vs. 57.0 no upgrading p<0.0001
    • Clinical Stage p=0.001
    • T1c 914/3598 (25.4%) T2a 164/400 (41.0%)
    • > T2b 42/64 (65.6%)
  • 15. Prior Studies Major Predictors of Upgrading
    • Sampling (number of cores)
    • PSA
    • Prostate volume
    • Extent of cancer on biopsy
  • 16. Sampling
    • Sextant vs. Extended
    • King et al.: 78 men with 10 core extended biopsy vs. if had done only 6 biopsies in the same patient
    • Upgrading
    • 6 cores 25%
    • 10 cores 13%
  • 17. Sampling
    • Sextant vs. Extended
    • Emiliozzi et al.: 79 cases 6-8 cores vs. 46 cases 12 cores
    • Upgrading Downgrading
    • 6-8 cores 39% 11%
    • 12 cores 24% 6%
  • 18. Sampling
    • Sextant vs. Extended
    • Mian et al.: 221 cases 6 cores vs. 205 cases > 10 cores
    • Upgrading
    • 6-8 cores 41%
    • > 10 cores 17%
  • 19. Sampling in Saturation Biopsies
    • Capitanio at al.: D’Amico Low Risk Cohort
    • Upgrading bxGS6
    • 10-12 (n=71) 47.9%
    • 13-18 (n=98) 31.6%
    • 19-24 (n=132) 23.5%
  • 20. Serum PSA Levels
    • 17/22 studies PSA correlates with upgrading
    • In several, correlation was weak
    • Most correlated in MVA
  • 21. PSA (ng/ml)
    • Hong et al.:
    • No Upgrade Upgrade
    • Median (range) 4.8 5.7
    • <4 37 (30.3%) 19 (23.5%)
    • 4–10 85 (69.7%) 62 (76.5%)
    • p=0.041
  • 22.
    • Pinthus et al.
    • No Upgrade Upgrade
    • Mean PSA 6.21 10.52 p=0.0004
    • PSA levels
    • <5 61 (44.9%) 53 (26.4%) p=0.0001
    • 5-10 54 (39.7%) 90 (44.8%)
    • 10-20 20 (14.7%) 38 (18.9%)
    • > 20 1 (0.74%) 20 (9.9%)
  • 23. %Free PSA & PSAV
    • Visapaa et al.:
    • Krane et al.:
    • No Upgrade Upgrade
    • %free PSA 16 12.1 p=0.0002
    • PSAV .78 1.01 p=0.1
    • PSAV>0.75 42% 48% p=0.05
  • 24. Prostate Size
    • 10/14 studies increased upgrading with smaller size
    • Budäus et al.: < 30, 31-40, 41-50
    • Dong et al.: <60
    • Turley et al.: <30, 30-50, >50
    • Kassouf et al.: <25, 25-50, >50
    • Tilkil et al.: <31 vs. >45
  • 25.
    • Serkin et al.: bxGS6
    • No Upgrade Upgrade
    • < 20 gms 43.8% 33.7% p=0.0007
    • 21–40 gms 45.4% 29.2%
    • 41–60 gms 56.6% 23.1%
    • >60 63.3% 17.4%
  • 26.
    • Hopkins:
    • < 25 gms 26-50 gms 51-75 gms >75 gms.
    • Upgrading 29% 26% 24% 17%
    • Downgrading 7% 8% 8% 8%
  • 27. PSAD (PSA/Volume)
    • Magheli et al.: GS6 on bx
    • Krane et al.: GS6 on bx
    • No Upgrade Upgrade
    • PSAD 0.22 0.28 p<0.001
    • PSAD 0.13 0.17 p=0.004
  • 28. Extent of Cancer on Bx
    • 9/16 increased cancer correlates with upgrading
    • Increase with number of positive cores, maximum percent of cancer per core, overall percent of cancer, fraction of positive cores
  • 29.
    • Hong et al. No Upgrade
    • Upgrade
    • No. positive cores
    • 1 54.1% 29.6% <0.001
    • > 2 45.9% 70.4%
    • Median % total 1.1 1.5 <0.001
    • tumor length
    • Median maximum % 12.1 22.2 <0.001
    • tumor in any core
  • 30. Perineural Invasion (PNI)
    • Moussa et al.
    • Lee et al.
    • Ayman et al.
    • PNI correlate with upgrading
  • 31. Imaging
    • Hong et al. TRUS Hypoechoic lesion NS
    • Fradet et al. If suggestive of cancer on MR, increased risk of upgrading 6 to 7. TRUS NS and MR spectroscopy NS.
    • Apostolos et al. 3-6 core sampling with TRUS guided by endorectal MRI: 8.5% upgrade, 1.4% downgrade
  • 32. JHH Univariate Analysis – Upgrade From Biopsy GS6 to Higher
    • Age p<0.0001
    • Clinical stage p=0.001
    • PSA p<0.00001
    • Pathology weight p<0.00001
    • Number of positive cores p<0.00001
    • Maximum %cancer per core p<0.00001
  • 33. JHH MVA Predict Upgrade from 6 to >6
    • Age p<0.0001
    • PSA p<0.0001
    • Maximum % cancer per core p<0.0001
    • Lower pathology weight p<0.0001
  • 34. JHH MVA Predict Upgrade from 347 to >347
    • Age p<0.0001
    • PSA p<0.0001
  • 35. JHH MVA Predict Downgrade from 347 to 6
    • Lower maximum % cancer p=0.0001
    • Lower PSA p=0.02
    • Higher pathology weight p=0.03
  • 36.  
  • 37.  
  • 38. Validating Chun Nomogram
    • Imamoto et al.
    • Correspondence between actual and ideal nomogram not always within the 10% margin of error.
    • Capitanio et al.
    • Overall accuracy of the nomogram was 74.9%. Model tended to underestimate the observed rate of upgrading; discordance between the predicted and observed rate of upgrading ranged from -7 to +10%.
  • 39. Prognosis
    • Numerous studies upgrading correlates with increased EPE, positive margins, SVI, LN, BCR
    • Conflicting studies upgrading 6 bx to 7 rp
    • worse prognosis than 7 bx = 7 rp.
    • Pinthus et al. No
    • Müntener et al. Yes
  • 40. Summary
    • Considering prostate cancer heterogeneity and the minute fraction of the prostate that is sampled by prostate needle biopsy, biopsy grade is still predictive of RP grade.
    • However, significant upgrading and downgrading between bx and RP exists.
    • Various clinical and pathological predictors can help identify which biopsy grades may be less accurate, which can aid in determining optimal therapy.
  • 41.