EDITORIAL: TRANSRECTAL ULTRASOUND GUIDED PROSTATEBIOPSY—DEFINING A NEW STANDARD

KEY WORDS: prostate, biopsy, ultrasound

Transrectal ultrasound guided prostate biopsy has hadan interesting history since its introduction in the early1980s. Issues such as patient discomfort because of theneed to sit on a fixed probe attached to a chair, urologistinexperience with interpreting ultrasound images, the factthat most prostate cancers were palpable and easily biop-sied by digital guidance, and a poor understanding of pros-tate anatomy and tumor location all contributed to a tepidresponse to this new technology. Many advances duringthe ensuing 15 years have changed this view, and thistechnique is now a mainstay of prostate cancer diagnosis.These advances include technological developments, suchas handheld high resolution probes with multi-axial pla-nar imaging capabilities and spring-loaded needles thatallow multiple cores of tissue to be easily obtained, wholemount anatomic studies of prostatectomy specimens thatdefined the zonal anatomy of the prostate and permitteddetailed mapping of tumor location, large-scale clinicalexperience demonstrating feasibility and clinical use,1 anda profound stage migration induced by prostate specificantigen (PSA) based screening that resulted in most tu-mors being nonpalpable at diagnosis, thereby necessitat-ing a method for sampling the entire prostate for diagno-sis.

Despite these advances, transrectal ultrasound has alimited capacity to identify prostate cancer because of vari-ability in the ultrasonic appearance of tumors and lack ofspecificity, as while most cancers appear hypoechoic, mosthypoechoic lesions are not cancer. In addition, most earlystage tumors are isoechoic and not readily distinguishedfrom surrounding benign tissue. Thus, in the PSA erawhen most tumors are of early stage, not palpable andultrasonographically indistinguishable from normal pros-tate, the true utility of transrectal ultrasound is to enablesampling of all relevant areas of the prostate includingthose that appear ultrasonically normal.

Cooner1 and Hodge2 et al were the first to report thatsystematic sampling of the prostate guided by transrectalultrasound improved the detection rate of prostate cancerover merely sampling hypoechoic or other lesions. Hodge et aldefined the current standard of sextant biopsies, with di-rected biopsies of the base, mid, and apical portions of thegland from each side in the parasagittal plane.2 Keetch et aldemonstrated that the likelihood of finding prostate cancer inmen with a normal digital rectal examination and serumPSA between 4 and 20 ng./ml. was approximately 25%.3However, of interest, was the observation that the positivebiopsy rate for a second set of sextant biopsies was 20% inthose with initially negative biopsies. This observation im-plied that the sextant technique may under sample the pros-tate and that more biopsies initially would improve the di-agnostic yield. This concept was held back in practice by theperception that additional biopsies would be too painful forpatients to tolerate and concern that more biopsies wouldincrease the detection of insignificant cancers. Subsequently,several groups demonstrated that the sextant technique isinadequate for thorough sampling of larger prostates andadvocated additional samples in glands greater than 50 cc involume.4, 5 Most recently, Eskew et al described an extendedsystematic technique that includes the far lateral and moremedial portions of the peripheral zone, in addition to biopsies

in the mid parasagittal plane, which improves the diagnosticyield.6 The 4 articles in this issue of the Journal addressthese concepts in more detail and we believe establish a newstandard for transrectal ultrasound guided prostate biopsyfor the diagnosis and staging of prostate cancer.

Presti et al (page 163) demonstrate convincingly that add-ing 2 to 4 laterally placed peripheral zone biopsies to thetraditional sextant technique improves the detection rate to42% in men with a normal digital rectal examination andPSA greater than 4 ng./ml., which is remarkably similar towhat Keetch et al suggested would be detected with a secondsextant set in men with initially negative biopsies. Presti etal report that the most important additional biopsies includethose more laterally directed at the base and mid gland, andthey suggest that 8 to 10 biopsies, including these areas,should be the new standard. Importantly, they also indicatethat these additional biopsies are not likely to increase thenumber of potentially insignificant cancers, estimating thatonly 8.4% of the tumors could be potentially latent based ongrade and core length involvement.

Naughton et al (page 168), and Soloway and Obek (page172) directly address the issue of patient discomfort with anextended biopsy scheme. Naughton et al describe patientreported discomfort associated with prostate biopsy as part ofa randomized trial of 6 versus 12 biopsies as assessed byanonymous questionnaire. They demonstrated that therewere no statistically significant differences in abdominal orrectal pain scores between groups, although the incidence ofhematochezia and hematospermia was higher in the 12 bi-opsy group. Soloway and Obek provide anecdotal evidencethat pre-biopsy injection of lidocaine into the neurovascularbundles markedly diminishes the discomfort associated withtransrectal biopsy and, thus, may improve patient toleranceof additional biopsies. Presti et al used a similar techniquebut did not report on patient discomfort. Together, thesereports suggest that the additional biopsies needed for im-proved sampling can be tolerated by most patients with mi-nor discomfort. Although no complications of lidocaine injec-tion were reported by any of these authors, it is important toremember that direct intravascular injection of lidocaine cancause seizures, and one must wonder whether injection intothe neurovascular bundles causes fibrosis which might com-plicate nerve sparing during radical prostatectomy or inhibitthe return of potency.

Another early criticism of transrectal ultrasound guidedsystematic biopsy was that little additional information wasgained beyond making a diagnosis of prostate cancer. In hiseditorial comment following the initial description of sextantbiopsies by Hodge et al,2 Paulson wrote “. . . the authors havefailed to provide sufficient information to confirm their posi-tion that random systematic ultrasound guided transrectalcore biopsies have the potential to provide quantitative use-ful information in the preoperative evaluation of men withprostatic malignancy. The concept of sampling of the prostatein a sequential and orderly manner is of value but it may notnecessarily require ultrasound guidance to establish such anorderly pattern of biopsy.”7 The observations of Sebo et al(page 174) lay to rest even this criticism. They describe amultivariate model which suggests that useful informationbeyond the simple detection of prostate cancer can be pro-vided by additional biopsy cores. They demonstrate in a large

0022-5347/00/1631-0179/0THE JOURNAL OF UROLOGY® Vol. 163, 179–180, January 2000Copyright © 2000 by AMERICAN UROLOGICAL ASSOCIATION, INC.® Printed in U.S.A.

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cohort of patients who underwent radical prostatectomy thatthe number of positive cores (along with PSA and grade) hasindependent value for predicting extracapsular extensionand tumor volume. This information may be incorporatedinto existing nomograms and/or neural network based pre-dictive models, and holds promise for improving our ability toselect patients likely to be cured by a single modality versusthose who will require more aggressive approaches.

Along with the extended clinical experience of many clini-cians, these studies solidify and further refine transrectalultrasound guided biopsy as an essential tool for the diagno-sis and staging of prostate cancer. The accumulated evidencesuggests that sextant biopsies alone may miss half of existingcancers in men with a normal digital rectal examination andPSA greater than 4 ng./ml., and that an extended biopsytechnique, including more laterally placed biopsies, is neces-sary for complete detection. Additional biopsies do not seemto increase the rate of potentially insignificant cancers, andmost patients tolerate extra biopsies with acceptable discom-fort, which may be ameliorated with local anesthesia. Fur-thermore, information derived from extended biopsy proto-cols, such as the number of cores which contain cancer,should be incorporated into prognostic models that predictpathological stage and ultimately could alter therapeutic ap-proaches, making transrectal ultrasound guided biopsy not

only essential for diagnosis, but a standard clinical diagnos-tic tool necessary for planning therapy.

Eric A. Klein and Craig D. ZippeSection of Urologic Oncology, Department of UrologyCleveland Clinic FoundationCleveland, Ohio

REFERENCES

1. Cooner, W. H., Mosley, B. R., Rutherford, C. L., Jr. et al: Prostatecancer detection in a clinical urological practice by ultrasonog-raphy, digital rectal examination and prostate specific anti-gen. J Urol, 143: 1146, 1990.

2. Hodge, K. K., McNeal, J. E., Terris, M. K. et al.: Random sys-tematic versus directed ultrasound guided transrectal corebiopsies of the prostate. J Urol, 142: 71, 1989.

3. Keetch, D. W., Catalona, W. J. and Smith, D. S.: Serial prostatebiopsies in men with persistently elevated serum prostatespecific antigen values. J Urol, 151: 1571, 1994.

4. Uzzo, R. G., Wei, J. T., Waldbaum, R. S. et al: The influence ofprostatic size on cancer detection. Urology, 46: 831, 1995.

5. Karakiewicz, P. I., Bazinet, M., Aprikian, A. G. et al: Outcome ofsextant biopsy according to gland volume. Urology, 49: 55,1997.

6. Eskew, L. A., Bare, R. L. and McCullough, D. L.: Systematic 5region prostate biopsy is superior to sextant method for diag-nosing carcinoma of the prostate. J Urol, 157: 199, 1997.

7. Paulson, D. F.: Editorial comment. J Urol, 142: 75, 1989.

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