The precise histologic assessment of RP specimens in patients with prostate cancer is of paramount importance for achieving an accurate risk assessment of disease recurrence and hence implementation of proper additional management.3,4,7–9
TAX 3501 was uniquely designed to use a postoperative monogram to calculate the risk estimates to define patient eligibility. The pathologic data used in the nomogram was determined using the RP findings from the CP and not the LP to ensure consistency. Therefore, the TAX 3501 trial presented us with an opportunity to evaluate the effect of central pathology review on the risk assessment and assess interobserver variability between the CPs and LPs in RP Gleason grading, tumor extent (OC vs EPE), margin status, seminal vesicle, and lymph node involvement.
Several studies have previously assessed interobserver variability in Gleason grading in both the setting of needle biopsy and RP specimens.10–15
In contrast, the studies evaluating interobserver variation of the histologic elements of RP staging and margin status have been limited to only 4 previous analyses.15–18
The 70% Gleason score agreement rate found in the present study is within the 36%–73% range cited by previous studies11
and is almost identical to the rates encountered in more recent studies.12,19
Similar to previous reports, our study showed that most disagreements in GSc were within 1 point.
Among the 4 previous studies evaluating interobserver variability in pathologic staging and margin status in RP,15–17
the study by van der Kwast et al17
shares the closest design similarities with our present study. It involved a single CP review of 552 RP specimens obtained as a part of the European Organization for Research and Treatment of Cancer 22911 trial. Our 70% rate of agreement between the CP and LP in evaluating organ confinement versus EPE is virtually identical to the 69% rate found by van der Kwast et al.17
In contrast to that study, however, we found the greater proportion of the differences resulted from CP upstaging, rather than downstaging (27% and 3%), and van der Kwast et al17
encountered 4% CP upstaging and 27% downstaging in their European Organization for Research and Treatment of Cancer 22911 cohort. The study by Ekici et al,15
similar to ours, found a relatively greater likelihood of upstaging from OC to EPE (13%) compared with their 3% rate of downstaging on expert review.
Of the reasons we found responsible for understaging of EEPE by LPs, ambiguity of the prostate confines at the apex deserves further discussion. Variation in interpreting EPE at this location continues to exist among expert urologic pathologists, which was highlighted recently at the latest International Society of Urologic Pathologist Consensus Conference in 2009. Some of the cases in which tumor involved the apex and extended to the margin of resection were designated as organ confined by the LP and, at RP analysis, were designated as EEPE by the CP. Currently, the recommendation is to stage these cases as pT2+ (ie, uncertain whether the cases are OC or EPE) owing to the ambiguity of the boundaries of the prostate at this region, although disagreement among expert urologic pathologists continues to exist on the nuances of how to interpret EPE at the apical region. Additional studies to address the true biologic effect of tumor presence beyond the level of benign glands and tumor extension to the ink at the apical margin are needed and could help pathologists in the future reach a better consensus regarding EPE versus OC staging at the apex.
As with the previous 2 studies by Ekici et al15
and van der Kwast et al,17
we found a very high rate of concordance in the evaluation of SV and lymph node involvement (93% and 99%, respectively) corresponding to 95% and 99% in the study by Ekici et al15
and a 94% concordance rate of SV status assessment in the study by van der Kwast et al.17
Compared with the results from the present study, the recent study by Kuroiwa et al.18
found a slightly lower rate of SV evaluation concordance (83%) but a similarly high rate of agreement in the lymph node assessment.
Our finding of an 11% rate of margin status disagreement between the CP and LP was almost identical to the 12% rate found by Kuroiwa et al,18
was lower than the 26% rate found by van der Kwast et al,17
and was slightly greater than the 8% rate found by Ekici et al.15
Most discrepancies in our study resulted from undercalls. Attention to the presence of tumor cells at the inked areas of cautery and crush artifact will help improve the margin status interobserver variability.
From the CP review, 31 (13%) of our initially consented patients who underwent RP had their disease reclassified in terms of their PFS risk estimate and TAX 3501 study eligibility. More than two thirds of the reclassified patients were reassigned to a greater PFS risk estimate, placing them within the eligibility criteria for the study using Kattan’s nomogram (predicted 5-year PFS of ≤60%). The latter further illustrates the value of CP review in ensuring accuracy in adherence to multi-institutional clinical trials’ eligibility criteria and providing consistency in the initial PFS estimates that might ultimately affect the trial outcomes and jeopardize the validity of final results.