Interobserver Variability in Histologic Evaluation of Radical Prostatectomy Between Central and Local Pathologists: Findings of TAX 3501 Multinational Clinical Trial

ObjectivesTo determine the agreement between the local pathologist findings and central pathologist findings using data from the TAX 3501 trial. TAX 3501 was a randomized, multinational trial comparing the outcomes of patients with high-risk prostate cancer treated with androgen deprivation with or without docetaxel after radical prostatectomy (RP). Patient eligibility was determined by a minimal 5-year progression-free survival estimate of 60% using Kattan's nomogram.MethodsThe pathologic findings were reassessed in 257 consecutive RP specimens by 2 central pathologists and compared with the local pathologist data.ResultsFor the Gleason score, agreement was found in 181 (70%) of 257 cases, upgrading in 57 (75%), and downgrading in 25% of the RP specimens The most frequent upgrade was from Gleason score 7 to 8 or 9 and downgrading from Gleason score 8 to 7. Of the upgrades and downgrades, 37% and 21% were of 2 Gleason score points, respectively. For the tumor extent, agreement was found in 179 (70%) of 256 specimens, with upstaging in 70 (91%) and downstaging in 9%. The most frequent upstage was from focal to extensive extraprostatic extension (45%). For seminal vesicle invasion, agreement was found for 238 (93%) of 256 RP specimens Almost equal rates of underdiagnosing and overdiagnosing seminal vesicle invasion was observed. For margin status, agreement was present for 229 (89%) of 256 cases. The central pathologist review led to reclassification as a positive margin in 17 cases and a negative margin in 10. For lymph node status, 2 (1%) of 210 RP specimens had positive nodes identified only by the central pathologist. Agreement was observed in 154 negative and 54 positive cases.ConclusionsSignificant interobserver variations were found between the central and local pathologists. From the central pathologist review, the progression-free survival estimates were altered in 31 patients (13%), including 22 who were reassigned a greater risk estimate, rendering them study eligible. Thus, interobserver variability affected prognostication and trial accrual.