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NY Prostate Cancer Conference - J.I. Epstein - Session 2: Predicting grade
 

NY Prostate Cancer Conference - J.I. Epstein - Session 2: Predicting grade

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    NY Prostate Cancer Conference - J.I. Epstein - Session 2: Predicting grade NY Prostate Cancer Conference - J.I. Epstein - Session 2: Predicting grade Presentation Transcript

    • 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
    • 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
    • Upgrading Incidence < 6 vs. > 7
      • Problems with Older Studies
      • 1. Different Gleason grading
      • 2. Different biopsy sampling
      • 3. Different patient populations with worse disease
    • 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%
    • 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
    • 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%
    • 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
    • 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%
    • 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%
    • 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%
    • 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
    • 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)
    • 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
    • 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%)
    • Prior Studies Major Predictors of Upgrading
      • Sampling (number of cores)
      • PSA
      • Prostate volume
      • Extent of cancer on biopsy
    • 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%
    • 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%
    • Sampling
      • Sextant vs. Extended
      • Mian et al.: 221 cases 6 cores vs. 205 cases > 10 cores
      • Upgrading
      • 6-8 cores 41%
      • > 10 cores 17%
    • 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%
    • Serum PSA Levels
      • 17/22 studies PSA correlates with upgrading
      • In several, correlation was weak
      • Most correlated in MVA
    • 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
      • 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%)
    • %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
    • 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
      • 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%
      • Hopkins:
      • < 25 gms 26-50 gms 51-75 gms >75 gms.
      • Upgrading 29% 26% 24% 17%
      • Downgrading 7% 8% 8% 8%
    • 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
    • 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
      • 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
    • Perineural Invasion (PNI)
      • Moussa et al.
      • Lee et al.
      • Ayman et al.
      • PNI correlate with upgrading
    • 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
    • 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
    • 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
    • JHH MVA Predict Upgrade from 347 to >347
      • Age p<0.0001
      • PSA p<0.0001
    • 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
    •  
    •  
    • 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%.
    • 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
    • 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.
    •