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PATHOLOGY
The Epstein criteria predict for organ-confined but not insignificant
disease and a high likelihood of cure at radical prostatectomy
Lee MC, Dong F, Stephenson AJ, Jones JS, Magi-Galluzzi C, Klein EA
Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland,
OH, USA
Eur Urol. 2010; 58: 90-5
- Background:
Few reports attempt to validate the role of Epstein criteria in selecting
patients for an active surveillance protocol.
Objective: To determine the performance of the Epstein biopsy criteria
for predicting pathologic end points and biochemical relapse-free survival
(bRFS) in men with early stage prostate cancer (PCa) treated by radical
prostatectomy (RP).
Design, Setting and Participants: Between October 1999 and January 2007,
746 consecutive patients were biopsied, and then underwent RP at our
tertiary care institution. Two hundred sixty-eight patients met the
entry criteria of Gleason 6 disease only on initial biopsy with complete
pathologic information.
Measurements: Primary end point was insignificant disease. Insignificant
disease was defined using a classical (organ-confined, Gleason score
< 6, and tumor volume < 0.5 cm(3)) and more liberal (organ-confined,
Gleason < 6 tumor of any volume) formulation. Secondary end points
included organ-confined disease and bRFS.
Results and Limitations: One hundred thirty-six men (51%) met the Epstein
biopsy criteria, and 167 (62%) had organ-confined cancer. Insignificant
disease by the classical and liberal definitions was present in 68 (25%)
and 92 (34%) patients, respectively. Cases meeting Epstein biopsy criteria
were more likely to have insignificant disease by either definition
(p < 0.001) and more likely to have organ-confined tumors (p <
0.001). Sensitivity, specificity, positive predictive value (PPV), and
negative predictive value (NPV) varied widely among the end points,
with sensitivity (74%) and NPV (86%) best for the classical definition
of insignificant disease and specificity (74%) and PPV (92%) best for
organ-confined disease. The estimated 5-yr bRFS was 100% for those meeting
Epstein biopsy criteria compared to 83% for those not meeting these
criteria.
Conclusions: The Epstein biopsy criteria predict for a high likelihood
of organ-confined disease and the absence of biochemical failure up
to 5 years after RP. These criteria are insufficiently robust to predict
the presence of biologically insignificant disease.
- Editorial
Comment
The conclusion of Lee’s et al. study from Cleveland Clinic is
that Epstein biopsy criteria predict for a high likelihood of organ-confined
disease but are insufficiently robust to predict the presence of insignificant
disease defined as organ-confined, Gleason low-grade, and minimal volume
(= 0.5 cc).
The findings are supported by other studies (1-3). Epstein’s criteria
are highly predictive for organ-confined prostate cancer. The frequency
varies from 91% to 97%. However, the predictive value for insignificant
cancer varies from 37% to 84%. Jeldre’s et al. concluded that
Epstein’s criteria might underestimate the true nature of prostate
cancer in as many as 24% of European patients (1). Approximately 31%
Korean patients who meet all the conditions of the contemporary Epstein’s
criteria for prediction of clinically insignificant prostate cancer
may actually harbor prostate cancer with unfavorable pathological features
(2). In the Middle East (Egypt), 46% of patients may present unfavorable
cancer (3).
There are several causes for the discrepancies. Prostate cancers diagnosed
in Asian, American, and European men may have innate differences associated
with racial and/or environmental factors. However, methodological factors
seem to be more important: among others, number of patients studied,
number of cores of the biopsy, and criteria for volume evaluation. The
last one was considered by Lee’s et al. study from the Cleveland
Clinic.
According to volume, the authors defined prostate cancer by two ways:
classical and liberal. The classical definition considered a tumor volume
< 0.5 cc; and the liberal definition any grade of volume. Using the
liberal definition, the predictive value of Epstein’s criteria
for insignificant cancer was 58%; using the classical definition was
37%. In a similar study at our Institution (data not published), the
frequency was 55% and 46%, respectively.
References
- Jeldres
C, Suardi N, Walz J, Hutterer GC, Ahyai S, Lattouf JB, et al.: Validation
of the contemporary epstein criteria for insignificant prostate cancer
in European men. Eur Urol. 2008; 54: 1306-13.
- Lee SE,
Kim DS, Lee WK, Park HZ, Lee CJ, Doo SH, et al.: Application of the
Epstein criteria for prediction of clinically insignificant prostate
cancer in Korean men. BJU Int. 2010; 105: 1526-30.
- Hekal
IA, El-Tabey NA, Nabeeh MA, El-Assmy A, Abd El-Hameed M, Nabeeh A, et
al.: Validation of Epstein criteria of insignificant prostate cancer
in Middle East patients. Int Urol Nephrol. 2010; 42: 667-71.
Dr.
Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil
E-mail: athanase@fcm.unicamp.br
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