ORIGINAL ARTICLE
Diagnostic Performance of Initial Transperineal Templateguided Mapping Biopsy of the Prostate Gland Nathan Bittner, MD, MS,* Gregory S. Merrick, MD,wz Abbey Bennett, BS,w Wayne M. Butler, PhD,w Hugo J. Andreini, MD,z Walter Taubenslag, MD,z and Edward Adamovich, MDy
Objectives: To evaluate the utility of transperineal template-guided mapping biopsy (TTMB) of the prostate as an initial means of establishing tissue diagnosis. Materials and Methods: A total of 191 consecutive patients underwent TTMB of the prostate using an anatomic-based technique with sampling of 24 regions. All patients had elevated prostate-specific antigen on routine screening which was followed by a confirmatory prostate-specific antigen and none had undergone previous biopsy of the prostate. The locations of cancer involvement were recorded for each patient in an effort to approximate the percentage of men whose cancer would have been missed or Gleason score underestimated on a standard 12-core biopsy. The median number of submitted biopsy cores was 54.0. Results: Of the 191 study patients, 140 (73.3%) were diagnosed with cancer on TTMB. Among these biopsy-positive patients, 124 (88.6%) had clinically significant cancer. Eighty-nine of the biopsy-positive patients (64.6%) had a Gleason score of Z7. A total of 34 of the 140 diagnosed cancers were identified exclusively in regions that fell outside of the theoretical 12-core biopsy scheme, suggesting that 24.3% of these cancers would have gone undiagnosed in the absence of TTMB. Among the 107 cancers that would have been diagnosed using a 12-core biopsy approach, 18 (16.8%) were upgraded to a Gleason score of Z7 with mapping biopsy. Conclusions: TTMB appears to provide more detailed information about prostate cancer grade and location compared with standard 12core biopsy scheme. This information may serve as a baseline reference for image-guided biopsy (ie, magnetic resonance imaging) regimens, may facilitate clinical decision making and aid in the appropriate selection of patients for active surveillance. Key Words: prostate, cancer, transperineal mapping biopsy
(Am J Clin Oncol 2015;38:300–303)
MATERIALS AND METHODS
S
aturation biopsy (SB) has been utilized as a tool to improve prostate cancer detection in patients with persistently elevated prostate-specific antigen (PSA) despite history of negative transrectal ultrasound-guided (TRUS) biopsy.1 In this context, SB has consistently been shown to increase cancer detection rates.2 Even so, a significant proportion of these SBdetected cancers are clinically insignificant making the role of SB somewhat nebulous.3 From the *Tacoma/Valley Radiation Oncology Centers, Tacoma, WA; wSchiffler Cancer Center, Wheeling Hospital, Wheeling Jesuit University; Departments of zUrology; and yPathology, Wheeling Hospital, Wheeling, WV. The authors declare no conflicts of interest. Reprints: Gregory S. Merrick, MD, Schiffler Cancer Center, Wheeling Hospital, Wheeling Jesuit University, 1 Medical Park, Wheeling, WV 26003. E-mail:
[email protected]. Copyright r 2013 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0277-3732/15/3803-0300 DOI: 10.1097/COC.0b013e31829a2954
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Although SB has been extensively studied in the setting of repeat biopsy, the role of this procedure in obtaining a de novo tissue diagnosis has not been firmly established. The high incidence of Gleason score underestimation with a standard 12-core biopsy provides 1 rationale for more extensive sampling of the prostate.4 A detailed assessment of prostate cancer grade and geography will become increasingly important as more patients are selected for active surveillance and many clinicians begin to direct their efforts toward focal therapy.5–7 Previous studies comparing 10-core biopsy to transrectal SB have not demonstrated any significant differences in cancer detection when SB is performed as an initial biopsy strategy.8 Nevertheless, there are technical limitations to the transrectal approach that may be mitigated by an alternative biopsy technique. One such technique is transperineal templateguided mapping biopsy (TTMB). Compared to TRUS biopsy, TTMB has been shown to provide better access to the anterior/ apical regions of the prostate and the transition zone (TZ).9–11 The transperineal approach also offers superior precision because of its ability to provide stereotactic needle guidance on an immobilized prostate gland. Importantly, TTMB provides valuable information, may serve as the optimal baseline reference for what may be expected with image-guided (ie, magnetic resonance imaging [MRI]) biopsy regimens, and aid in the appropriate selection of patients for active surveillance and focal therapy.5,11 Along these lines, there is interest in the use of TTMB as a means of establishing initial tissue diagnosis in select patient populations.12 Herein, we report our results of upfront TTMB for patients with elevated screening PSA.
From July 2005 through January 2012, 191 consecutive men underwent TTMB of the prostate using an anatomic-based technique with sampling of 24 regions. Previously, our TTMB technique has been described.9 All patients in this study had an elevated age-adjusted PSA on routine screening which was followed by a confirmatory PSA determination. None of the patients in this analysis had an abnormal digital rectal examination and none had undergone previous biopsy. The majority of patients in the study population were self-referred for TTMB and the remainder were receiving anticoagulation, in which case upfront mapping biopsy was requested as a way of minimizing time off of anticoagulation. The TTMB procedure was performed in the operating room under general anesthesia. Biopsy patients were placed in the dorsal lithotomy position. Transrectal ultrasound was used to visualize the prostate in the axial and sagittal dimensions. Images were collected from the level of the proximal seminal vesicles/ base of the prostate to the apex using a 5.0-7.5 transducer (Sonoline; Seimens Inc., Issaquah, WA). Prostate volume was calculated by a volumetric evaluation. In addition, the prostate
American Journal of Clinical Oncology
Volume 38, Number 3, June 2015
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American Journal of Clinical Oncology
Diagnostic Performance of Initial TTMB of the Prostate Gland
Volume 38, Number 3, June 2015
and TZ volumes were estimated as an ellipsoid using the following formula: Length WidthHeight 0.5236. Transperineal biopsies were obtained through template apertures corresponding to the 24 regional biopsy locations (Fig. 1). For each of the 24 regions, 1 to 3 biopsy cores were obtained using an 18-G, 25-cm-long Max-Core biopsy needle (C.R. Bard Inc., Covington, GA). A stabilizing needle was placed before the procedure to immobilize the prostate gland. With each biopsy core, the template coordinate and the offset from base were recorded thus preventing duplicate sampling of the same prostatic regions. Biopsy regions included posterior prostate (3, 4, 12, 13, 21, 22), posterior lateral (2, 5, 11, 14, 20, 23), anterior lateral (1, 6, 9, 10, 15, 16), anterior apex (19, 24), and TZ (7, 8, 17, 18). The TTMB procedure was performed on an outpatient basis. Tamsulosin (0.8 mg daily) was initiated 2 days before the procedure and was continued for an additional 2 weeks afterward. All patients received perioperative antibiotic therapy. For each patient, the location, number, and percentage of positive biopsy cores were recorded. All biopsy specimens were reviewed by a single pathologist (E.A.) with expertise in
urologic pathology. Cancer was classified as clinically insignificant when all of the following criteria were met: no core with Gleason score >6, no core with >50% involvement, PSA density 1 day. No patient required a urinary catheter for >4 days.
DISCUSSION Transrectal SB has customarily been reserved for patients with high-grade prostatic intraepithelial neoplasia, atypical small acinar proliferation, or those with persistently elevated PSA despite history of negative biopsy.1,14 Under these circumstances, SB has routinely been shown to increase diagnostic yield, although a significant proportion of these detected cancers are clinically insignificant.2–4 The role of upfront SB is less studied, but there is reason to believe that it may provide useful information in an era where more patients are opting for active surveillance and clinicians are beginning to explore partial gland therapies.5 With this being said, most clinical studies indicate that transrectal SB offers no additional information compared to the standard 10- to 12-core scheme in the setting of initial biopsy.6 These findings may reflect the limitations inherent to a transrectal biopsy approach rather than the shortcomings of an extended biopsy strategy. In this study, we evaluated a group of men who underwent initial TTMB of the prostate for elevated PSA. Approximately three quarters of these patients were ultimately diagnosed with prostate cancer. Among those patients with biopsy-positive disease, 64.6% had a maximum composite Gleason score of Z7. Our analysis indicates that nearly one quarter of these cancers would have gone unrecognized and 16.8% would have erroneously been assigned a Gleason score of 6, when in reality there was Gleason 7 or higher disease identified in other regions of the gland. These findings may actually underestimate the true falsenegative rate and Gleason score accuracy because with TTMB 2 to 3 cores are obtained for each of the biopsy sites, the gland is
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immobilized and each 3-dimensional coordinate is recorded minimizing chances of rebiopsy of the same area. Currently, there is no prospective comparison of TRUS and transperineal biopsy, but the available retrospective data seem to be concordant with the findings of our study. Barzell et al11 recently reported a group of 124 men with favorable risk prostate cancer who were considering active surveillance. Study patients underwent repeat TRUS biopsy and template-guided mapping biopsy as a confirmatory strategy. In this analysis, repeat TRUS biopsy failed to detect 80% of clinically important cancers. Higher cancer detection rates and improved reliability in Gleason scoring with TTMB may be attributed in part to its ability to better access the anterior portions of the prostate gland. Previous studies have shown that compared to a transrectal approach, transperineal biopsy detects proportionally more anterior tumors and is able to identify these cancers at a smaller size threshold.15 Moreover, the mapping biopsy technique is performed on an immobilized gland with systematic sampling guided by a coordinate system. This is in contrast to TRUS biopsies, which are performed using a free-hand methodology. Our findings indicate that TTMB can be accomplished with a minimal level of morbidity. The most common side effect in this study was transient urinary catheterization. In a previous publication, we showed that TTMB had no measurable impact on long-term urinary or erectile function using patient validated metrics and urodynamic studies.16 In this study, we did not observe any cases of postbiopsy sepsis. This is noteworthy given the accrual of data demonstrating a growing incidence of flouroquinolone-resistant Escherichia coli bacteremia following TRUS biopsy.17,18 In light of this emerging pathogenic risk, the transperineal approach may provide a more sterile route of access to the prostate. Although the results of this analysis provide a compelling argument for transperineal mapping biopsy, the data should be interpreted with a degree of caution. First, this was a small, single-institution study where selection for the TTMB procedure was largely patient driven. This introduces a degree of selection bias and raises some uncertainty about whether these findings can be extrapolated to the general population of patients referred for prostate biopsy. Second, the designation of clinically significant versus insignificant prostate cancer was assigned on the basis of the Epstein criteria, which is a classification system that was intended specifically for use in patients undergoing TRUS.13 Using that definition, only a small number of patients were noted to have clinically insignificant disease. However, this definition may not be appropriate in the context of transperineal mapping biopsy. The Epstein criteria have not been validated for TTMB and it is likely that the criteria of
