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.