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

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

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