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369
International Consultation
on Prostatic
lntraepithelial Neoplasia
and Pathologic Staging
- - of
Prostatic Caicinoma
Workgroup 3
Current Prognostic Factors and Their Relevance
to Staging
Robert v. P. Hutter, M.D. (Chairperson$
James E. Montie, M.D.(Rapporteur)'
Christer Busch, M.D.3
David J. Grignon, M.D!
Michael Lieber, M .D .~
Christopher Logothetis, M.D."
Haakon Ragde, M . D . ~
Victor E. Reuter, M . D . ~
'
Chairman, Department of Pathology, St. Barnabas Medical Center, Livingston, New
Jersey.
Division of Urology, University of Michigan, Ann Arbor, Michigan.
Department of Pathology, University of Uppsala, Uppsala, Swederi.
Department of Pathology, Wayne State University, Detroit, Michigan.
Department of Urology, Mayo Clinic, Rochester, Minnesota.
GU Medical Oncology Department, M. D. Anderson Cancer Center, Houston, Texas.
Pacific Northwest Cancer Foundation, Seattle, Washington.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York.
T
Presented at the International Consultation on
Prostatic lntraepithelial Neoplasia and Pathologic Staging of Prostatic Carcinoma, Mayo
Clinic, Rochester, MN, November 3-4, 1995.
Address for reprints: Robert V. P. Hutter, M.D.,
St. Barnabas Medical Center, Department of Pathology, 94 Old Short Hills Road, Livingston,
NJ 07039.
Received December 7, 1995; revision received
March 21, 1996; accepted March 21, 1996.
0 1996 American Cancer Society
he workgroup identified putative prognostic facttors and then assessed the utility of each at two separate times: (1) prior to primary therapy; and ( 2 ) after radical prostatectomy. These categories
were selected because the first relates to the capability to predict
the extent of disease and thereby aids in the selection of appropriate
therapy. The second includes additional pathologic factors obtained
from radical prostatectomy specimens such as the pT and pN classification. The assessment includes four categories of potential prognostication for each putative factor prior to primary therapy, including their value in predicting the following: pathologic stage, biochemical relapse, cancer related (cause specific) survival, and
survival (death from any cause). After review and discussion of each
putative prognostic factor, the conclusion of the workgroup was
categorized in Table 1 as follows: +: a prognostic factor for the
category; -: not a prognostic factor for the category; I: insufficient or
inconclusive evidence; and NA: factor not applicable for that specific
category. Prognostic factors assessed after radical prostatectomy
were categorized similarly in Table 2 .
There was considerable discussion regarding the status of ploidy as
a prognostic factor. The workgroup concluded that singe institution multivariate analysis suggests that ploidy is an important and independent
370
CANCER July 15,1996 / Volume 78 / Number 2
TABLE 1
Prognostic Markers: Before Primary Therapy
Factor
Age
Comorbidityh
African-American race
Serum total PSA
T classification'
Gleason scored
DNA ploidy
Tumor volume
Number of cores involved'
Anatomic location, transition zone'
Anatomic location, other
PAP
Histologic we, small cell
Histologic type, other
Predict
pathologic
stage
Predict
biochemical
relapse
Predict survival
(cause specific)
Predict survival
(all causes)
I
Independent
indicator"
t
1
t
t
t
t
t
t
t
t
I
NA
t
t
t
I
NA
I
I
I
I
NA
I
I
I
I
NA
I
I
t
t
I
I
t
t
I
I
1
t
t
t
I
NA
I
I
I
I
I
I
-: the factor is prognostic; -: the factor is not prognostic; I: insufficient or inconclusive data; NA not applicable; PSA prostate specific antigen; PAP: prostatic
acid phosphatase by enzymatic assay.
"Independent prognostic indicator based on multivariate analysis.
"Serious health conditions in addition to prostate carcinoma.
' Anatomic extent of the primaq cancer as described in 1992 American Joint Committee on Cancerhternational Union Against Cancer manuals for staging of cancer.
Sum of the Gleason primary and secondary grades (e.g., Gleason score 7 equals Gleason primary Grade 4 plus secondary Grade 3).
"Based on a totai of six cores sampled by needle biopsy.
'Includes location in aoex, base, or oerioheral zone.
TABLE 2
Prognostic Markers: After Radical Prostatectomy
Factor
Age
Comorbidity"
African American race
T classification'
Gleason scored
Serum total PSA
DNA ploidy
Tumor volume
No. cores involved'
Anatomic location, transition zone'
Anatomic location, other
PAP
Histologic type, small cell
Histologic type, other
Predict biochemical
relapse
Predict survival
(cause specific)
Predict survival
(all causes)
Independent
indieatof
-
-
t
I
I
I
I
t
t
t
I
I
t
t
t
t
t
t
t
t
t
t
I
I
t
t
t
I
I
NA
I
I
I
I
NA
NA
I
I
NA
I
I
t
t
t
t
I
I
1
I
I
I
-
I
I
I
1
t:'The factor is prognostic; -: The factor is not prognostic; I: Insufficient or inconclusive data; N A Not applicable; PSA prostate specific antigen; PAP prostatic
acid phosphatase by enzymatic assay.
Independent prognostic indicator based on multivariate analysis.
Serious health conditions in addition to prostate carcinoma.
'Anatomic extent of the primary cancer as described in 1992 American Joint Committee on Cancerilnternational Union Mainst Cancer manuals for staging of cancer.
Suni of the Gleason primary and secondary grades [e.g., Gleason score 7 equals Gleason primary Grade 4 plus secondary Grade 3)
'Based on a total of six cores sampled by needle biopsy.
'Includes location in apex, base, or peripheral zone.
PIN Workgroup 3/Hutter et al.
TABLE 3
Prognostic Markers: Metastatic Disease
Factor
to lymph node(s) only
DNA ploidy
Extent bone metastasis"
Minimal ( ~ 3 )
Extensive (>3)
Visceral
Serum testosterone
Performance status
Hemoglobin
PSA
Small cell histolow
Survival (cause specific)
Survival (overall)
t
t
+
+
t
t
t
t
t
I
t:'The factor is prognostic (An elevatpd serum PAP is a prognostic factor; however, PAP is rarely elevated
during the clinical course ofpatlents with prostate Carcinoma and, therefore, it is used infrequently.); I:
Insufficient or inconclusive data; PSA: prostate specific antigen.
"Metastases may be to multiple sites (5 1-3, or > 3) in a single bone or multiple bones.
371
prognosticator following prostatectomly. However, the
value of ploidy determined on core needle biopsies
has not been established. Multiple studies suggest that
ploidy determined on needle aspiration biopsies predicts for response to hormones and hormone therapy.
Existing data strongly suggest that ploidy may be an
important prognosticator for patients with prostate
carcinoma but Phase I11 studies are required to assess
its clinical contribution more definitively.
Members of the workgroup expressed the need
to identify prognostic factors for patients with metastatic carcinoma of the prostate. Therefore, putative
prognostications for these patients are assessed in
Table 3 .
The workgroup emphasized the olbvious, that this
assessment is a consensus of the state of the art at this
time. Periodic reassessment may identify data that
would require recategorization of a prognostic indicator.
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