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NY Prostate Cancer Conference - V.E. Reuter - Session 2: Upgrading/downgrading of prostate cancer from biopsy to radical prostatectomy: Incidence and predictive factors
 

NY Prostate Cancer Conference - V.E. Reuter - Session 2: Upgrading/downgrading of prostate cancer from biopsy to radical prostatectomy: Incidence and predictive factors

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    NY Prostate Cancer Conference - V.E. Reuter - Session 2: Upgrading/downgrading of prostate cancer from biopsy to radical prostatectomy: Incidence and predictive factors NY Prostate Cancer Conference - V.E. Reuter - Session 2: Upgrading/downgrading of prostate cancer from biopsy to radical prostatectomy: Incidence and predictive factors Presentation Transcript

    • PROSTATE CANCER:PREDICTING PATHOLOGIC STAGE
      Victor E. Reuter, M.D.
      Memorial Sloan-Kettering Cancer Center
      2nd Interdisciplinary Conference on Prostate Cancer
      New York, April 2011
    • OUTLINE
      A Pathologist’s perspective:
      • Preoperative factors associated with pathologic stage
      • New and controversial issues
      • The role of repeat biopsy in selecting patients for further management
      • Prostate cancer in the context of zonal anatomy
      • Notes on including markers to improve predictive models
    • PROSTATIC ADENOCARCINOMARoutine Diagnostic/Prognostic Armament
      • Digital rectal examination (DRE)
      • Transrectal ultrasound (TRUS)
      • Magnetic Resonance Imaging/Spectroscopy
      • Serum prostatic specific antigen (PSA)
      • Pathology
      - transrectal biopsy / TURP
      - prostatectomy
      • Markers
    • NOMOGRAM FOR PREDICTINGPATHOLOGIC STAGE
      Johns Hopkins, Baylor, U. Michigan SPOREs
      PSA 4.1-10 PSA 10.1-20
      Gleason Sum Clinical Stage Clinical Stage
      T1c T2b T3a T1c T2b T3a
      Organ-Confined
      5 69 38 23 57 28 16
      (63-74) (32-45) (13-38) (50-64) (22-34) (8-28)
      7 48 21 11 36 14 7.2
      (42-53) (17-25) (5.8-20) (30-42) (11-18) (4-14)
      Modified from Partin AW, Kattan MW, Subong ENP, Walsh PC, Wojno KJ, Oesterling JE, Scardino PT, Pearson JD. JAMA 1997; 277:1445.
    • Shifts in pathological diagnosis and grading N = 1,148 (TURP and NBx)
      20
      15
      10
      Proportion of cohort
      5
      0
      2
      4
      6
      8
      10
      Gleason score at diagnosis
      Berney D et al, BJU Int 2007;100:1240
    • Reviewed Pathology - Gleason Score distribution: N = 1,724
      40
      30
      20
      Proportion of cohort
      10
      0
      4
      6
      8
      10
      Reviewed Gleason score
      133 patients (7%) were reassigned a nonmalignant diagnosis
    • DSS: Reviewed Gleason score
      Multivariate analysis (adjusted for clinical stage, PSA, specimen type):
      • Original GS was not associated with DSS (HR=1.03), p=0.65
      • Revised GS was associated with DSS (HR=1.71), p=0.001
      Berney D et al, BJU Int 2007;100:1240
    • 0
      10
      20
      30
      40
      50
      60
      70
      80
      90
      100
      Preoperative Nomogram for Prostate Cancer Recurrence
      Points
      PSA
      4
      20
      0.1
      1
      2
      3
      6
      8
      9
      10
      12
      16
      30
      45
      70
      110
      7
      T2a
      T2c
      T3a
      ClinicalStage
      T1c
      T1ab
      T2b
       2+3
      3+  2
       4+4
      Biopsy Gleason Grade
       2+  2
      3+3
       3+ 4
      Total Points
      0
      20
      40
      60
      80
      100
      120
      140
      160
      180
      200
      60MonthRec. Free Prob.
      .96
      .93
      .9
      .85
      .8
      .7
      .6
      .5
      .4
      .3
      .2
      .1
      .05
      Instructions for Physician: Locate the patient’s PSA on the PSA axis. Draw a line straight upwards to the Points axis to determine how many points towards recurrence the patient receives for his PSA. Repeat this process for the Clinical Stage and Biopsy Gleason Sum axes, each time drawing straight upward to the Points axis. Sum the points achieved for each predictor and locate this sum on the Total Points axis. Draw a line straight down to find the patient’s probability of remaining recurrence free for 60 months assuming he does not die of another cause first.
      Note: This nomogram is not applicable to a man who is not otherwise a candidate for radical prostatectomy. You can use this only on a man who has already selected radical prostatectomy as treatment for his prostate cancer.
      Instruction to Patient: “Mr. X, if we had 100 men exactly like you, we would expect between <predicted percentage from nomogram - 10%> and <predicted percentage + 10%> to remain free of their disease at 5 years following radical prostatectomy, and recurrence after 5 years is very rare.”
      • 1997 Michael W. Kattan and Peter T. Scardino
      Kattan MW et al: JNCI 1998; 90:766-771.
    • Gleason 6 (3+3)
      1 core / 14 cores
      Tot. Ca. Length 0.2 mm
      Tot. Core Length 136 mm
      % Cancer 0.15 %
      % G4/5 0 %
      Lat
      Lat
      Med
      Med
      NEG
      HG PIN
      NEG
      NEG
      Base
      Base
      Base
      TZ
      TZ
      NEG
      NEG
      NEG
      NEG
      NEG
      G6 (3+3)
      1.6 %
      Mid
      Mid
      Mid
      ASAP
      NEG
      ASAP
      NEG
      Apex
      Apex
      Apex
      Rt.
      Lt.
    • Gleason 7 (3+4)
      4 core / 14 cores
      Tot. Ca. Length 17.3 mm
      Tot. Core Length 130 mm
      % Cancer 13.3 %
      % G4/5 8.4 %
      Lat
      Lat
      Med
      Med
      G7 (3+4)
      40%
      G7 (3+4
      30%
      NEG
      G6 (3+3)
      20%
      Base
      Base
      Base
      TZ
      TZ
      NEG
      NEG
      NEG
      NEG
      NEG
      G6 (3+3)
      15 %
      Mid
      Mid
      Mid
      NEG
      NEG
      NEG
      NEG
      Apex
      Apex
      Apex
      Rt.
      Lt.
    • Variables Individually Correlated with Pathologic Stage
      Variablep value
      Biopsy Gleason score <0.0001
      No. of involved cores <0.0001
      Total percent of cancer <0.0001
      Total millimeters of cancer <0.0001
      Maximum millimeter of cancer on one core 0.0001
      Serum PSA density 0.001
      Maximum percent of cancer on one core 0.01
      Bilateral cancer 0.01
      Serum PSA value 0.028
      Epstein. Urol 1998; 51:759-764.
    • Contemporary Preoperative Nomogram
    • Gleason 7 (4+3)
      pT2c (02’AJCC)
      ECE negative
      SVI negative
      LNI negative
      SM negative
      TTV 3.02 cm3
      %G4/5 55 %
      MaxCaDiam 2.90 cm
      Prostate V 33.30 cm3
      TTV/Prostate V 9.06 %
      Significant
      Gleason 6 (3+3)
      pT2c (02’AJCC)
      ECE none
      SVI negative
      LNI negative
      SM negative
      TTV 0.24 cm3
      %G4/5 0 %
      MaxCaDiam 0.71 cm
      Prostate V 35.24 cm3
      TTV/Prostate V 0.67 %
      Indolent
      Gl. 3
      Gl. 4
    • Predicting the presence of an “indolent” cancer
      from clinical factors and systematic biopsy resultsEstimation of accuracy by ROC analysis
      1.00
      B
      0.75
      A
      Sensitivity
      0.50
      0.25
      AUC
      A. PSA, cT stg, biopsy grade 0.781
      B. A + PSAD, mm Ca, %Bx+0.881
      0.00
      0.00
      0.25
      0.50
      0.75
      1.00
      1 - Specificity
      Ohori, Kattan et al, MSKCC, 2001
    • Nomogram to Predict an Indolent Cancer:<0.5 cc, confined, no Gleason patterns 4 or 5
    • Clinical and Biopsy Factors
      Associated with the Frequency of “Indolent” Cancer
    • PATHOLOGICAL FEATURES OF THE INITIAL AND REPEAT BIOPSIES
      Biopsy # of cores # of Pos. cores Length of Cores Length of Cancer
      Session mean mean mean (mm) mean (mm)
      Initial Bx. 8.33 2.0 71.2 7.14
      n=59 (3-17) (1-7) (16-140) (0.5-55)
      Repeat Bx. 11.05 3.03 95.7 11.3
      n=59* (7-19) (0-13)* (33.5-192) (0-67)*
      p-value .0001 .0107 .0001 .046
      * 14 pts. had no cancer on repeat biopsy
      Sircar K, et al
    • CLINICAL AND BIOPSY FEATURES IN 59 PATIENTS ACCORDING TO RESULT OF REPEAT BIOPSY
      Repeat biopsy Pre-operative PSA % Free PSA Prostate Volume PSA density
      ng/ml, median median cm3, median ng/ml/cm3, median
      Negative 3.725 18 34.05 0.083
      n=14 (1.38-13.8) (5-31.8) (15.5-204.5) (.05-.241)
      Positive 6.605 11 37.15 0.191
      n=45 (.29-27.91) (2.5-71.5) (12.6-78.27) (.007-.754)
      p-value 0.0279 0.0126 0.7992 0.0476
      Sircar K, et al
    • CLINICAL AND BIOPSY FEATURES IN 59 PATIENTS ACCORDING TO RESULT OF REPEAT BIOPSY
      Repeat biopsy % cancer in % positive cores Gleason 4/5 in Previous negative first + biopsy in first + biopsy first + biopsy biopsy sessions(%)
      Negative 1.86 11.8 0 11 (79)
      (n=14) (0.4-6.1) (8.33-16.6)
      Positive 7.69 25 20 (44%) 2 (5)
      (n=45) (1.05-86.6) (9.1-100)
      p-value 0.0089 0.0017 0.002 <.0005
      Sircar K, et al
    • PATHOLOGIC FEATURES OF CANCER IN RADICAL PROSTATECTOMY SPECIMENS BASED THE RESULT OF THE REPEAT BIOPSY
      Pathologic Stage (%)
      Repeat Indolent Tumor Volume % Gleason 4/5 Confined ECE SVI LN mets
      Biopsy cancer cm3 cancer pT2 pT3a pT3b pN+
      Negative 10 .202 0 14 0 0 0
      n=14 (71%) (.016-4.53) (100%)
      Positive 3 2.52 4.96 29 12* 4 0
      n=45 (7%) (.145-23.84) (0-100%) (67) (27) (4)
      p-value <.0005 <.0005 .0031 .0012 .017 .417 --
      * 8 pts. had established ECE
      Subsequent study (Berglund RK et al J Urol 2008;180:1964) on 104 eligible patients**:
      - Repeat Bx negative in 26%. - 27% cases upgraded or upstaged
      - Upgraded/upstaged cases were associated with higher grade (0.001) and pT (0.003) at RRP.
    • REPEAT BIOPSY FINDINGS IN A COHORT OF PATIENTS UNDERGOING PROSTATECTOMY
      Among 3296 patients who had radical prostatectomy between 2000-2005, 285 (9%) had both a positive > 12 core NB and RP
      51/285 patients with low risk pathologic features on first diagnostic biopsy and who subsequently underwent early repeat NB and radical prostatectomy
      46 patients remain in cohort:
      Clinical stage: 37 cT1c, 9 cT2a
      PSA: mean 5.3, median 4.7
      Time between NB: mean 4.9 mos, median 3.3 mos
      # of cores in initial biopsy: mean 10.9, median 12
      Fine SW et al, USCAP 2010
    • Results – Repeat NB
      Group 1 [n=10; 22%]: still had low risk features
      All GS 3+3=6
      # cores positive: one (7/10), two (3/10)
      % core involvement: 1-20%
      At prostatectomy: all cases organ-confined
      Group 2 [n=36; 78%]: exceeded low risk features
      Exceeded one criterion: 15 patients
      Exceeded two criteria: 13 patients
      Exceeded three criteria: 8 patients
      At prostatectomy: pT2 = 27 (75%), pT2+ = 3 (8%), pT3a = 6 (17%), and large anterior tumors
      Fine SW et al, USCAP 2010
    • Anterior Dominant Tumors: Zone of Origin (n=197)
      • 197 tumors
      Peripheral Zone: 97
      Transition Zone: 70
      PZ+TZ: 14
      IND: 16
      Al-Ahmadie HA et al AJSP 2008;32:229
    • TRANSITION ZONE-DIRECTED BIOPSY: DETECTION OF TZ CANCER
      61 cases with TZ-directed NB-detected cancer and corresponding RP
      Prostate cancer was detected in:
      Left TZ-directed Nbx: 25/61 (41%)
      Right TZ-directed Nbx: 23/61 (38%)
      Bilateral TZ-directed Nbx: 13/61 (21%)
      On RP:
      24/61 (39.5%) cases had no tumor in the TZ
      24/61 (39.5%) cases showed non-dominant TZ cancer
      13/61 (21%) displayed a dominant TZ lesion
      Haarer C, et al J Urol 2009:182:1340
    • Preoperative Prediction of Pathologic Stage: Summary of Multivariate Analysis Findings in 349 Cases
      Outcome VariablePreoperative Variablep
      Extraprostatic extension (yes/no) PSA 0.0001
      % of biopsy involved 0.0001
      Gleason score 0.0103
      Clinical stage 0.1853 NS
      Perineural invasion 0.8178 NS
      Seminal vesicle invasion % of biopsy involved 0.0006
      PSA 0.0033
      Gleason score 0.0108
      Clinical stage 0.2893 NS
      Perineural invasion 0.9797 NS
      Pathologic stage PSA 0.0001
      % of biopsy involved 0.0001
      Gleason score 0.0003
      Clinical stage 0.2107 NS
      Perineural invasion 0.4189 NS
      Egan et al. 1997; 21:1496-1500
    • PERINEURAL INVASION
      Morphologic criteria are important
      Importance in predicting extracapsular extension (NB) or biochemical recurrence is controversial
      Am J Surg Pathol. 1993;17:336
      J Urol. 1999;162:103
      Importance of the diameter of the nerve involved in predicting failure has not been confirmed
      Unanswered questions on NBx: amount, location, size
    • INTRADUCTALCARCINOMA
      Cohen et al, Arch Pathol Lab Med 2007;131
    • INTRADUCTAL CARCINOMA ON NEEDLE BIOPSY
      Associations at prostatectomy:
      • High Gleason grade
      • High tumor volume
      • Extracapsular extension (pT3)
      • Disease progression
      Guo et al Mod Pathol 2006;19:1528
      Robinson BD , et al J Urol 2010;184:1328
    • HOW ABOUT TISSUE BASED MARKERS?
      • Ploidy: Anticancer Res 2011;30:719
      • Ki67: BJ Cancer 2009;100:888 (and others)
      • Myc: Mod Pathol 2002;15:35
      • Systems Path (Aureon): Cancer 2009;115:303
      J Urol 2009;182:125
      • CNA (MSK): Cancer Cell 2010;18:11
      • Gene signature (Myriad): Lancet Oncol 2011;11:245
      p = 0.01
      p = 0.86
      Postoperative Model
      Gene Expression Model
      Combined Model
      Stephenson AJ et al. Cancer 2005;104:290