Prostate Cancer Pathologic Parameters and Clinical Outcome : Results from the Cooperative Prostate Cancer Tissue Resource
Jonathan Melamed1, Milton W. Datta2, Mike Becich3, Maarten Bosland1, Rajiv Dhir3, Andre Kajdacsy-Balla2, Jan Orenstein4, Sylvia Silver4, Jules Berman5, and the Co-Operative Prostate Cancer Tissue Resource.
Departments of Pathology, 1New York University School of Medicine, New York, NY, 2Medical College of Wisconsin, Milwaukee, WI, 3University of Pittsburgh, Pittsburgh, PA, 4George Washington University, Washington D.C., and 5National Cancer Institute, Bethesda, MD.
The NCI-funded Cooperative Prostate Cancer Tissue Resource (http://www.prostatetissues.org ) contains over 3300 prostate cancer cases, including 2892 prostatectomy specimens, 954 with associated prostate needle biopsies, from 12 hospitals representing four separate academic institutions. In each case the pathologic specimens were reviewed by academic pathologists using defined criteria as established by the AFIP Prostate Fascicle (Third Series) and the Gleason grading web site at Johns Hopkins University (http://22.214.171.124/prostate/ ). These pathologic parameters have been correlated with clinical outcome, patient demographics, and PSA recurrence. The average duration of follow-up is 4.4 years (range 0 to 13 years). The mean patient age is 62.7 years (range 35 to 85 years). The dataset includes people of the following defined ethnicity/race; 1883 Caucasians, 420 African-Americans, 57 Hispanic, 25 Asians/pacific islanders. Pathologic review identified the following number of cases with specific Gleason scores; 1 Gleason 2, 10 Gleason 4, 120 Gleason 5, 1089 Gleason 6, 1362 Gleason 7, 181 Gleason 8, 117 Gleason 9, and 4 Gleason 10. Pathologic staging included 386 pT2a, 1545 pT2b, 553 pT3a, 241 pT3b,12 pT4 cases. 230 patients have had subsequent radiation therapy, 239 have had hormonal therapy, and 259 have had chemotherapy. PSA recurrence data was calculated on 909 patients with a minimum of 3 follow-up PSA values and a mean follow-up period of 36 months. Of these 340 (37.4%) had post-prostatectomy residual tumor as defined by post-surgical PSA values greater than 0.2 that did not follow a subsequent downward slope. Of the patients who underwent PSA nadir, 175 (19.2%) have undergone a PSA recurrence, with the average time to recurrence of 21.1 months (range 1 to 107 months). 394 (43.3%) are without evidence of recurrence with a mean follow-up period of 43.1 months (range 4-148 months). In addition, 42 patients have clinical evidence of recurrence, and 252 (8.7 %) have died. Significant associations were noted between post-prostatectomy residual tumor and percent gland involved (p<0.05), extracapsular extension (p<0.04), margin positivity (p<0.0001), and African-American ethnicity (p<0.001), In addition, significant associations were noted between PSA recurrence and percent gland involved (p<0.002), margin positivity (p<0.001), and African-American Ethnicity (p<0.001). When Gleason Score 6 or 7 tumors were compared, a significant difference was seen wrt PSA recurrence (p<0.005), but not Post-prostatectomy residual tumor. Within Gleason score 7 tumors, pattern 4+3 tumors were more likely to have post-prostatectomy tumor (p<0.005) and a trend was seen between the higher percentage of Gleason pattern 4/5 tumor and post-prostatectomy tumor. No such relationship was seen for PSA recurrence. No significant association was identified between PSA recurrence and initial PSA value, size of the largest tumor nodule, perineural invasion, family history of prostate cancer, or smoking history. The results of this study, the largest multiple institution study of its kind, represent the level of pathologic evaluation obtained in current academic institutions, and can serve as a general guide for expected clinical outcomes based on current pathologic standards. In addition, as a component of an NCI-funded Cooperative Prostate Cancer Tissue Resource, the described findings represent an available patient dataset that may be used for tissue based prostate cancer studies through such technologies such as tissue microarrays.