REPLY BY AUTHORS
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frozen section is performed, 2 locations are typically evaluated, in- cluding the apex and posterolaterally in the neurovascular bundle region. I have always opposed frozen section at either the apex or the base. If the urologist, while performing radical prostatectomy, ex- tends the surgery distally and proximally as far as possible without compromising continence, there will be a reluctance to remove addi- tional tissue even in the presence of a positive frozen section. The study by Shah et al provides objective data to address this issue as it relates to apical frozen section during radical prostatectomy. This study illustrates several points that argue against performing apical frozen section. Frozen section missed a significant number of positive margins at this site. In their study 3 of 7 positive margins at the apex, as seen on permanent sections, were not detected by frozen section. This discrepancy could relate to frozen sections not covering as broad an area as that of permanent sections. Also, as the authors describe, it may be difficult to assess for the presence of prostate cancer on frozen section. The diagnosis of prostate cancer may be difficult even on permanent section, as frozen section analysis of prostatic margins is fraught with difficulty and has the risk of false-positive and false-negative diagnoses. Another reason that ar- gues against the use of frozen section analysis of the apical margin is that it helped to achieve a negative margin status in only 2 of 95 (2.1%) cases. This low incidence reflects the infrequent occurrence of positive frozen sections at the apex and that some men with positive frozen sections at the apex, who were eventually rendered disease- free by frozen sections, had positive margins elsewhere. Although I concur with the authors not to perform frozen section at the apex, I disagree with their recommendations to excise a 2 to 3 mm. circum- ferential urethral margin during radical prostatectomy to be submit- ted separately as permanent sections. Rather, while performing rad- ical prostatectomy, urologists should extend the surgery as far apically as possible without compromising continence. While per- forming a separate circumferential shave margin, there is an in- creased risk of having a false-positive margin in contrast to removing the entire radical prostatectomy specimen intact, whereby the pa- thologist can perform perpendicular margins at the apex. Shah et al report a high incidence (54%) of benign prostate tissue at the apical margin. Although data from The Johns Hopkins Hos- pital has not been published, this incidence is much higher than I would expect based on our own material. As Shah et al demonstrate, there is no difference in continence between those patients with and those without benign prostate tissue at the apex. This data seem to indicate that radical prostatectomy performed in this series could have been modified to remove additional apical benign prostate tissue without worsening continence. The other anatomical site in which urologists will sometimes per- form frozen section is posterolaterally in the neurovascular bundle region. In contrast to the apical or basal regions, a higher amount of tissue can be removed here while attempting to render a positive frozen section margin negative. However, removing this extra neu- rovascular bundle tissue negatively impacts on postoperative po- tency. Several years ago, numerous urologists at The Johns Hopkins Hospital sporadically performed frozen section in the neurovascular bundle region. Initially, the prostate was removed with preservation of the neurovascular bundles. The specimen was then sent to pathol- ogy where we performed perpendicular frozen section on the area of induration posterolaterally. Invariably, we reported the frozen sec- tion as “tumor closely approaching the inked margin yet negative.” Verbally, we communicated to the urologists that we could not, due to sampling issues, guarantee that there would not be a positive margin elsewhere in the neurovascular bundle region when the permanent sections were analyzed. Consequently, the final decision as to whether to resect the neurovascular bundle was deferred back to the urologists, leaving him or her with no better information than had the frozen sections not been performed. The problem is that prostate cancers occurring in the peripheral zone almost always begins up against the edge of the prostate and extends extremely close to the edge of the gland. However, even when tumor extends to less than 1 mm. from the edge of the prostate, patients have a low risk of recurrence. 1 Consequently, a close posterolateral margin dur- ing frozen section is common and should not be used when deciding whether to resect the neurovascular bundle. Is there a situation when frozen section is appropriate during radical prostatectomy to assess resection margins? Occasionally, a urologist has difficulty ascertaining what plane of tissue they are in, possibly due to fibrosis resulting from prior biopsy. Frozen section in this situation is appropriate to make sure that an intraprostatic plane of sectioning has not developed, resulting in capsular incision. In summary, routine frozen section of radical prostatectomy spec- imens to assess margins of resection is not recommended. Perform- ing such frozen section has the risk of false-negative margins at the apex and false-positive margins in the neurovascular bundle region. Jonathan I. Epstein Department of Pathology The Johns Hopkins Hospital Baltimore, Maryland 1. Epstein, J. I. and Sauvageot, J.: Do close but negative margins in radical prostatectomy specimens increase the risk of postop- erative progression? J Urol, 157: 241, 1997 REPLY BY AUTHORS Epstein concludes, based on his experience and our data, that it is unnecessary to perform a frozen section of the apical soft tissue margin at the time of radical prostatectomy because frozen sections miss a significant number of positive margins at the site and frozen section analysis of the apical margin rarely helps to achieve an overall negative margin. He recommends extending the surgery as far apically as possible without compromising continence. Herein lies the surgical challenge. In many cases, especially when the prostate is small or if there is excessive anterior apical tissue, the plane between the prostate and urethra is difficult to discriminate visually. In many cases when we were confident, based on visual inspection, that prostate tissue was left at the apical margin, the frozen section failed to show any prostatic elements. In other cases when we were abso- lutely certain no prostate tissue was left at the apical margin, the frozen section showed significant prostatic tissue. While we totally agree with Epstein that one should leave as much of the urethra intact as possible, this often cannot be accomplished reliably by visual inspection. This information is most reliably provided by an apical margin soft tissue biopsy. Alsikafi and Brendler recommend (without validation) including 3 additional mm. of the urethra with the surgical specimen to decrease positive surgical margins (reference 10 in article). We generally attempt to divide precisely at the prostato-urethral junction to max- imize urethral length since we rely on the frozen section of the apical soft tissue margin to indicate when additional apical tissue needs to be excised. This procedure may explain why a relatively high per- centage of our cases have minimal benign elements in the apical soft tissue margin biopsy. We do not appear to be alone in this practice since the only other report to our knowledge of routinely biopsying the apical soft tissue margin also had a high proportion of benign prostatic elements at the apical margin (reference 25 in article). Based on our findings, the literature and Epstein’s comment, we recommend either precisely dividing the apex at the prostato- urethral junction and submitting a permanent section of the apical soft tissue margin or simply extending the apical margin 2 or 3 mm. beyond the presumed prostato-urethral junction to maximize nega- tive margin status at the apex. We do not believe that either ap- proach will have an advantage as far as post-prostatectomy conti- nence. Both approaches would likely achieve the same apical soft tissue margin status. The only advantage of frozen section analysis of the apical soft tissue margin is that it gives the surgeon the opportunity to excise additional tissue. In this report, none of the re-excised urethral soft tissue margins contained prostate cancer. Since submission of this manuscript, we have encountered 4 cases (less than 2%) in which the re-excised tissue specimen contained minimal elements of cancer which likely contributed to achieving negative margin. The individual surgeon must determine if this low rate justifies a frozen section analysis of the apical soft tissue mar- gin. Obviously, the rare individual who benefits will applaud frozen section analysis of the apical soft tissue margin. ANALYSIS OF APICAL SOFT TISSUE MARGINS DURING RADICAL RETROPUBIC PROSTATECTOMY 1949
Transcript of REPLY BY AUTHORS
frozen section is performed, 2 locations are typically evaluated, in-cluding the apex and posterolaterally in the neurovascular bundleregion. I have always opposed frozen section at either the apex or thebase. If the urologist, while performing radical prostatectomy, ex-tends the surgery distally and proximally as far as possible withoutcompromising continence, there will be a reluctance to remove addi-tional tissue even in the presence of a positive frozen section. Thestudy by Shah et al provides objective data to address this issue as itrelates to apical frozen section during radical prostatectomy. Thisstudy illustrates several points that argue against performing apicalfrozen section. Frozen section missed a significant number of positivemargins at this site. In their study 3 of 7 positive margins at theapex, as seen on permanent sections, were not detected by frozensection. This discrepancy could relate to frozen sections not coveringas broad an area as that of permanent sections. Also, as the authorsdescribe, it may be difficult to assess for the presence of prostatecancer on frozen section. The diagnosis of prostate cancer may bedifficult even on permanent section, as frozen section analysis ofprostatic margins is fraught with difficulty and has the risk offalse-positive and false-negative diagnoses. Another reason that ar-gues against the use of frozen section analysis of the apical margin isthat it helped to achieve a negative margin status in only 2 of 95(2.1%) cases. This low incidence reflects the infrequent occurrence ofpositive frozen sections at the apex and that some men with positivefrozen sections at the apex, who were eventually rendered disease-free by frozen sections, had positive margins elsewhere. Although Iconcur with the authors not to perform frozen section at the apex, Idisagree with their recommendations to excise a 2 to 3 mm. circum-ferential urethral margin during radical prostatectomy to be submit-ted separately as permanent sections. Rather, while performing rad-ical prostatectomy, urologists should extend the surgery as farapically as possible without compromising continence. While per-forming a separate circumferential shave margin, there is an in-creased risk of having a false-positive margin in contrast to removingthe entire radical prostatectomy specimen intact, whereby the pa-thologist can perform perpendicular margins at the apex.
Shah et al report a high incidence (54%) of benign prostate tissueat the apical margin. Although data from The Johns Hopkins Hos-pital has not been published, this incidence is much higher than Iwould expect based on our own material. As Shah et al demonstrate,there is no difference in continence between those patients with andthose without benign prostate tissue at the apex. This data seem toindicate that radical prostatectomy performed in this series couldhave been modified to remove additional apical benign prostatetissue without worsening continence.
The other anatomical site in which urologists will sometimes per-form frozen section is posterolaterally in the neurovascular bundleregion. In contrast to the apical or basal regions, a higher amount oftissue can be removed here while attempting to render a positivefrozen section margin negative. However, removing this extra neu-rovascular bundle tissue negatively impacts on postoperative po-tency. Several years ago, numerous urologists at The Johns HopkinsHospital sporadically performed frozen section in the neurovascularbundle region. Initially, the prostate was removed with preservationof the neurovascular bundles. The specimen was then sent to pathol-ogy where we performed perpendicular frozen section on the area ofinduration posterolaterally. Invariably, we reported the frozen sec-tion as “tumor closely approaching the inked margin yet negative.”Verbally, we communicated to the urologists that we could not, dueto sampling issues, guarantee that there would not be a positivemargin elsewhere in the neurovascular bundle region when thepermanent sections were analyzed. Consequently, the final decisionas to whether to resect the neurovascular bundle was deferred backto the urologists, leaving him or her with no better information thanhad the frozen sections not been performed. The problem is thatprostate cancers occurring in the peripheral zone almost alwaysbegins up against the edge of the prostate and extends extremelyclose to the edge of the gland. However, even when tumor extends toless than 1 mm. from the edge of the prostate, patients have a lowrisk of recurrence.1 Consequently, a close posterolateral margin dur-ing frozen section is common and should not be used when decidingwhether to resect the neurovascular bundle.
Is there a situation when frozen section is appropriate duringradical prostatectomy to assess resection margins? Occasionally, aurologist has difficulty ascertaining what plane of tissue they are in,possibly due to fibrosis resulting from prior biopsy. Frozen section inthis situation is appropriate to make sure that an intraprostaticplane of sectioning has not developed, resulting in capsular incision.
In summary, routine frozen section of radical prostatectomy spec-imens to assess margins of resection is not recommended. Perform-ing such frozen section has the risk of false-negative margins at theapex and false-positive margins in the neurovascular bundle region.
Jonathan I. EpsteinDepartment of PathologyThe Johns Hopkins HospitalBaltimore, Maryland
1. Epstein, J. I. and Sauvageot, J.: Do close but negative margins inradical prostatectomy specimens increase the risk of postop-erative progression? J Urol, 157: 241, 1997
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Epstein concludes, based on his experience and our data, that it isunnecessary to perform a frozen section of the apical soft tissuemargin at the time of radical prostatectomy because frozen sectionsmiss a significant number of positive margins at the site and frozensection analysis of the apical margin rarely helps to achieve anoverall negative margin. He recommends extending the surgery asfar apically as possible without compromising continence. Herein liesthe surgical challenge. In many cases, especially when the prostate issmall or if there is excessive anterior apical tissue, the plane betweenthe prostate and urethra is difficult to discriminate visually. In manycases when we were confident, based on visual inspection, thatprostate tissue was left at the apical margin, the frozen section failedto show any prostatic elements. In other cases when we were abso-lutely certain no prostate tissue was left at the apical margin, thefrozen section showed significant prostatic tissue. While we totallyagree with Epstein that one should leave as much of the urethraintact as possible, this often cannot be accomplished reliably byvisual inspection. This information is most reliably provided by anapical margin soft tissue biopsy.
Alsikafi and Brendler recommend (without validation) including 3additional mm. of the urethra with the surgical specimen to decreasepositive surgical margins (reference 10 in article). We generallyattempt to divide precisely at the prostato-urethral junction to max-imize urethral length since we rely on the frozen section of the apicalsoft tissue margin to indicate when additional apical tissue needs tobe excised. This procedure may explain why a relatively high per-centage of our cases have minimal benign elements in the apical softtissue margin biopsy. We do not appear to be alone in this practicesince the only other report to our knowledge of routinely biopsyingthe apical soft tissue margin also had a high proportion of benignprostatic elements at the apical margin (reference 25 in article).
Based on our findings, the literature and Epstein’s comment, werecommend either precisely dividing the apex at the prostato-urethral junction and submitting a permanent section of the apicalsoft tissue margin or simply extending the apical margin 2 or 3 mm.beyond the presumed prostato-urethral junction to maximize nega-tive margin status at the apex. We do not believe that either ap-proach will have an advantage as far as post-prostatectomy conti-nence. Both approaches would likely achieve the same apical softtissue margin status. The only advantage of frozen section analysisof the apical soft tissue margin is that it gives the surgeon theopportunity to excise additional tissue. In this report, none of there-excised urethral soft tissue margins contained prostate cancer.Since submission of this manuscript, we have encountered 4 cases(less than 2%) in which the re-excised tissue specimen containedminimal elements of cancer which likely contributed to achievingnegative margin. The individual surgeon must determine if this lowrate justifies a frozen section analysis of the apical soft tissue mar-gin. Obviously, the rare individual who benefits will applaud frozensection analysis of the apical soft tissue margin.
ANALYSIS OF APICAL SOFT TISSUE MARGINS DURING RADICAL RETROPUBIC PROSTATECTOMY 1949
