Systematic Transrectal Ultrasound Guided Prostate Biopsy After Negative Digitally Directed Prostate Biopsy

0022-5347 /92/14 73-0827$03.00/0 Vol. 147, 827-829, March 1992

THE JOURNAL OF UROLOGY Copyright© 1992 by AMERICAN UROLOGICAL ASSOCIATION, INC.

Printed in U.S.A.

SYSTEMATIC TRANSRECTAL ULTRASOUND GUIDED PROSTATE BIOPSY AFTER NEGATIVE DIGITALLY DIRECTED PROSTATE BIOPSY HOWARD R. LIPPMAN, ABRAHAM A. GHIATAS

AND

MICHAEL F. SAROSDY*

From the Division of Urology and Department of Radiology, University of Texas Health Science Center, San Antonio, Texas

ABSTRACT

The diagnostic accuracy of digitally directed prostate biopsies was evaluated by performing systematic ultrasound guided biopsies on 44 patients who had previously had a negative prostate biopsy by systematic digitally directed technique. All 44 patients still had palpable abnormalities. Core biopsies (2 to 4) were obtained from each lateral lobe of the prostate with 2 additional cores directed at hypoechoic lesions. Only 4 of the 44 ultrasound directed biopsies (9.1%) were positive for cancer. These results confirm the postulate that random systematic digitally directed biopsy is highly accurate in making the diagnosis of prostate cancer. They also suggest that performing biopsies in a systematic pattern is more important than the method used to guide the biopsy needle. KEY WORDS:

prostate, biopsy, ultrasonic diagnosis

Transrectal ultrasound of the prostate has become a routine imaging technique in the evaluation of prostate glands in which cancer is suspected based upon digital rectal examination or an elevated prostate specific antigen. Although the use of ultrasound to screen for prostate cancer remains controversial, the use of ultrasound for directing prostate biopsy needles has gained considerable acceptance. 1- 5 Hodge et al have prompted the concept of "random systematic biopsies" to increase the diagnostic accuracy of the biopsy procedure. 6 While this concept has been defined simultaneously with the advent of ultrasonography, its value may falsely lend support to ultrasound imaging as being responsible for any perceived heightened diagnostic accuracy of transrectal ultrasound guided biopsies. We attempt to determine whether ultrasound is responsible for diagnostic accuracy or if systematic biopsy alone might be responsible for the perceived heightened accuracy oftransrectal ultrasound guided biopsies reported by others. MATERIALS AND METHODS

Between August 1987 and October 1988, 136 patients with palpable prostatic abnormalities at the Audie Murphy Veterans Administration Hospital underwent digitally directed transrectal core biopsies. All biopsies were performed by 4 resident physicians using the 14 gauge Tru-Cutt biopsy needle and identical technique. With patients in the dorsolithotomy position and under diazepam sedation 2 to 4 core biopsies were obtained from each lateral lobe of the prostate (base, middle and apex) and an additional 2 to 3 cores were obtained from the palpable lesion. The second phase of the study was conducted between January and April 1989 during which time 44 of the 96 men with negative digitally directed biopsy consented to return for repeat biopsy under ultrasound guidance. All 44 patients still had palpable abnormalities at the time of repeat biopsy. Of the remaining 52 patients who did not participate in the study 4 died, 16 moved, 14 refused to participate, 3 had urinary tract infections, 11 had debilitating medical illnesses and 4 had undergone transurethral prostatectomy in the interim. Biopsies were performed by 1 investigator (H. L.) with patients in the right decubitus position with knees pulled to chest. Prostates were imaged with the Diasonics 400 ultrasound machine using a 7.5 biplaner endorectal probe in the transverse and sagittal Accepted for publication August 2, 1991. * Requests for reprints: Division of Urology, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7845. t Travenol Laboratories, Deerfield, Illinois.

planes. Biopsies were obtained using the automated Biopty:j: gun and an 18 gauge needle with sagittal ultrasound guidance. Two to 4 cores were obtained from each lateral lobe (base, middle and apex) with additional cores obtained from hypoechoic regions. All specimens were considered adequate for pathological diagnosis. Patients were treated for 3 days after the procedure with 500 mg. ciprofloxacin twice a day. RESULTS

Using the systematic digitally directed biopsy technique 40 of the original 136 cases (30%) were positive for cancer. In this group 28 had discrete nodules and 12 had diffuse areas of induration on digital rectal examination. Of the 28 patients with discrete nodules biopsies were positive from the nodule in 21 (75%), and from the nodule and contralateral lobe in 7 (25 %) . Of the 12 patients with diffuse areas of induration biopsies were positive from the abnormal area in 6 (50% ), from the abnormal area and contralateral lobe in 5 (42%), and from the contralateral lobe only in 1 (8%). The remaining 96 cases (70%) were negative for cancer, of which 4 7 had discrete nodules and 49 had areas of diffuse induration by digital rectal examination (table 1). The pathological findings reported in 47 patients with discrete nodules revealed that 45 had benign prostatic hypertrophy and 2 had inflammation. Of the 49 patients with diffuse induration 43 had benign prostatic hypertrophy and 6 had inflammation. Among the 44 patients who returned for repeat biopsy using transrectal ultrasound guidance 28 (63%) had discrete nodules and 16 had areas of induration. Of the 44 patients 4 (9.1 %) had prostate biopsies positive for adenocarcinoma, including 2 with discrete nodules that sonographically appeared as hypoechoic lesions and 2 with diffuse induration that appeared isoechoic :j: Bard Urological, Covington, Georgia. TABLE

1. Results of digitally directed and transrectal ultrasound

biopsies of palpable prostate abnormalities Cancer

Totals

Digitally directed biopsy

Nodule Induration Totals(%)

28 12

40 (30)

47 49

96 (70)

75 61 136

Transrectal ultrasound directed biopsy after neg. digitally directed biopsy

Nodule Induration Totals(%)

827

Benign

2 2 4(9)

26 14

40 (91)

28 16

44

828

LIPPMAN, GHIATAS AND SAROSDY

(table 1). In all 4 patients the positive biopsy came from the area of the palpable abnormality. The sonographic characteristics of the 40 negative biopsies was also of interest. Of those who had discrete nodules 9 had hypoechoic, 7 had hyperechoic and 10 had isoechoic lesions. Of those who had areas of induration 3 had hypoechoic, 1 had hyperechoic and 10 had isoechoic lesions (table 2). Transrectal ultrasound directed biopsies were well tolerated, with most patients denying discomfort and several describing no more than a mild sensation of burning during the biopsies. All patients were discharged from the hospital within several hours of the procedure. One patient who did not take the postbiopsy antibiotics returned with epididymitis and fever requiring hospitalization and intravenous antibiotics. In another patient mild epididymitis develop_ed without fever, which wa_s treated with oral antibiotics. DISCUSSION

The finding of 9.1 % positive transrectal ultrasound guided prostate biopsies after a previous negative digitally directed biopsy is significantly less than reports from other centers (table 3). Hodge et al performed systematic transrectal ultrasound directed biopsies in 53 patients with negative digitally directed biopsy and reported a 53% incidence of cancer with biopsies using transrectal ultrasound guidance. 1 They did not specify how many cores were obtained at the first biopsy nor whether a systematic pattern was used. Similarly, Brawer and Nagle reported on 22 patients with negative digitally directed biopsies and found a 50% positive rate for cancer when they were re-biopsied using transrectal ultrasound guidance. 7 Likewise, they did not specify the number or pattern of digital biopsies. Resnick reported on 33 patients who underwent transrectal ultrasound and digitally directed biopsy. 8 Transrectal ultrasound directed biopsy detected cancer in only 6% of the cases that were negative by digitally directed biopsy. No random biopsies were obtained. In a separate study Hodge et al demonstrated the importance of using a systematic biopsy pattern to diagnose cancer of the prostate. 6 They reported that with this technique 50% of the patients were found to have cancer in areas of the prostate other than the area of palpable abnormality. This incidence is similar to the 42% rate of unsuspected cancers in the contralateral lobe of prostatectomy specimens from patients with unilateral malignant nodules. 9 Our approach to prostate biopsies has always been based on the belief that a systematic patterning of cores is optimal, which was practiced previously under digital direction and is now continued under ultrasound guidance. It is unclear from the other reports cited what technique was used to obtain the digitally directed biopsies. If biopsy cores were obtained only from the palpable lesion, then it is certain that many cancers may have been missed. This may explain the discrepancy between our lower yield compared to the high positive rate reported by Hodge et al6, and Brawer and Nagle. 7 TABLE

Dr. Thomas P. Ball reviewed the manuscript. REFERENCES

1. Hodge, K. K., McNeal, J. E. and Stamey, T. A.: Ultrasound guided

2. Ultrasound characteristics of palpable prostate abnormalities

after negative digitally directed prostate biopsy Hyperechoic Hypoechoic Isoechoic Totals

TABLE

Ultrasound imaging provided no guide to the prediction of cancer after previously negative digitally directed biopsy. In this study most cases of prostate cancer had been previously selected by digitally directed methods. Of the 14 hypoechoic lesions seen in our study 2 were identified as cancer and 12 were benign. Therefore, when performing a repeat biopsy under transrectal ultrasound guidance, the echogenic pattern is an even less reliable indicator of cancer than in initial biopsies. Clearly, cancer may be present in prostate tissue regardless of the echogenicity. Ultrasound does offer the advantage of allowing "visual" guidance of a biopsy needle into a specific lesion. Ultrasound guidance provides a more accurate means of systematically placing the biopsy needle throughout the prostate and assures a representative _£1:!mplin.g_from the base, middl!l f[_ndape_X c>f each lobe. When a discrete sonographic lesion is present, such as one most often seen in the peripheral zone, it is much easier to place accurately the biopsy needle tip directly into the lesion using ultrasound guidance. Ultrasound also provides information that might be helpful in evaluating the local extent of disease with clear images of the seminal vesicles and prostatic capsule. However, a recent report indicates that prediction of pathological stage might be no higher than 50%. 10 Nonetheless, we recommend that sonography be used for guiding prostate biopsies and for evaluation of the extent of spread within the limits of accuracy. One might conjecture that our study was biased towards the group that underwent Tru-Cut needle biopsies because the 14 gauge Tru-Cut needle is twice the diameter of the 18 gauge needles used with ultrasound probes. The volume of the 14 gauge Tru-Cut biopsy core is 0.047 cc and that of the 18 gauge needle is 0.018 cc. Thus, the Tru-Cut needle core has a volume 2.5 times greater than the 18 gauge needle core. However, the difference is relatively insignificant when compared to the total volume of the prostate. For example, 6 core biopsies with the 14 gauge needle would sample 0.94% of a 30 gm. prostate with a volume of 30 cc compared to 6 core biopsies with the 18 gauge needle, which would sample 0.36% of the prostate. It seems unlikely that the larger volume of 14 gauge biopsy would be more responsible for the results of the biopsy than the accuracy of the needle placement under ultrasound guidance. In clinical situations when transrectal ultrasonography is unavailable or not practical digitally directed prostate biopsy is still a valuable and reliable diagnostic tool for the urologist. We have shown that systematic digitally directed prostate biopsies provide a high level of diagnostic accuracy. Which technique is more accurate for guidance of systematic biopsies may not be the important question. The most important question may be whether the prostate is adequately sampled.

Cancer

Benign

0 2

2

8 12 20

4

40

2.

3. 4.

3. Results of studies performing transrectal ultrasound guided

biopsy after negative digitally directed prostate biopsy Reference

No. Pts.

Hodge et al' Brawer and Nagle' Resnick8

53

22 33

Cancer No.(%)

Benign No.(%)

23 (53) 11 (50) 2 (6)

20 (47) 11 (50)

31 (94)

5.

6.

transrectal core biopsies of the palpably abnormal prostate. J. Urol., 142: 66, 1989. Coplen, D. E., Andriole, G. L. and Catalona, W. J.: Transrectal prostatic ultrasonography (TRUS) as a means of guiding prostatic biopsy in patients with palpable prostatic abnormalities. J. Urol., part 2, 141: 277A, abstract 430, 1989. Scardino, P. T.: Transrectal ultrasound in management of prostate cancer. Urology, suppl. 6, 33: 27, 1989. Lee, F., Torp-Pedersen, S. T. and Siders, D. B.: Use of transrectal ultrasound in diagnosis, guided biopsy, staging, and screening of prostate cancer. Urology, suppl. 6, 33: 7, 1989. Torp-Pedersen, S., Lee, F., Littrup, P. J., Siders, D. B., Kumasaka, G. H., Solomon, M. H. and McLeary, R. D.: Transrectal biopsy of the prostate guided with transrectal US: longitudinal and multiplanar scanning. Radiology, 1 70: 23, 1989. Hodge, K. K., McNeal, J. E., Terris, M. K. and Stamey, T. A.: Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J. Urol., 142: 71, 1989.

SYSTEMATIC PROSTATE BIOPSY UNDER DIGITAL OR ULTRASOUND GUIDANCE

7. Brawer, M. K and Nagle, R. B.: Transrectal ultrasound guided prostate needle biopsy following negative digitally guided biopsy. J. Urol., part 2, 141: 278A, abstract 433, 1989. 8. Resnick, M. I.: Transrectal ultrasound guided versus digitally directed prostatic biopsy: a comparative study. J. Urol., 139: 754, 1988. 9. Carter, H.B., Hamper, U. M., Sheth, S., Sanders, R. C., Epstein, J. I. and Walsh, P. C.: Evaluation of transrectal ultrasound in the early detection of prostate cancer. J. Urol., 142: 1008, 1989. 10. Rifkin, M. D., Zerhouni, E. A., Gatsonis, C. A., Quint, L. E., Paushter, D. M., Epstein, J. I., Hamper, U., Walsh, P. C. and McNeil, B. J.: Comparison of magnetic resonance imaging and ultrasonography in staging early prostate cancer. Results of a multi-institutional cooperative trial. New Engl. J. Med., 323: 621, 1990.

EDITORIAL COMMENTS The authors are correct that we did not know the precise digital technique used in our 53 patients who had a negative digitally directed biopsy (reference 1 in article). These patients were unlikely to have had the "systematic patterning of cores" used in this article. We also agree that it is important to sample adequately the whole prostate. However, we do not believe that this can be done nearly as accurately with digital guidance as by ultrasound guidance. For example, we have many impalpable cancers whose depth is no more than 2 to 3 mm. from the capsule, which itself is usually only 0.2 or 0.3 mm. thick. It is almost impossible to guide consistently a needle in such a way as to include the peripheral zone capsule of the prostate. Transrectal ultrasound placement of the needle not only allows consistent inclusion of the capsule but at least with the Bri.iel and Kjaer equipment, it also allows a consistent 45-degree angle of the biopsy at equally spaced intervals (apex, middle and base of the prostate). Thomas A. Stamey Division of Urology Stanford University Medical Center Stanford, California This report is interesting and supports my own bias that the more the prostate is biopsied, by whatever method, the greater the likelihood of finding cancer. As noted by the authors, the detection rate on repeat ultrasound guided biopsy was relatively low, presumably due to the

829

higher positivity associated with the multiple systematic biopsies that were digitally directed. It is of interest that the rate of positivity of the initial digitally guided biopsies was not dissimilar to the rate of positivity of systematic biopsies performed under ultrasound guidance as reported by Hodge et al (reference 6 in article). In this study 75% of the cases with discrete nodules and 50% of those with areas of induration were positive on the initial biopsy. These data emphasize the importance of taking multiple biopsies and sampling other portions of the prostate, which demonstrate neither an ultrasound nor a palpable abnormality. As indicated by the authors the performance of systematic biopsies may be more important than the method used to guide the biopsy needle. The concept of the rate of positivity being related to the number of biopsies performed applies to the use of biopsy in detecting prostate cancer. For instance, Lee et al biopsied 9.8% of their patients and reported a cancer detection rate of 2.4%, 1 and Cooner et al biopsied 46.2% of their patients and found a detection rate of 14.6%. 2 In a recent report all patients in a specifically defined group underwent prostate biopsy and the detection rate was 24%. 3 Prostate biopsy as performed today is a much safer and easier technique than it was a decade ago. Because we are performing biopsy more frequently and taking a greater number of specimens at the time of biopsy, it only seems reasonable that the detection rate of cancer of the prostate will increase. This is particularly true if we select our population correctly, that is symptomatic patients, those with suspicion of cancer (for example abnormal rectal examination, elevated prostate specific antigen), those with a positive family history and so forth. Martin I. Resnick Division of Urology University Hospitals of Cleveland Cleveland, Ohio 1. Lee, F., Littrup, P. J., Torp-Pedersen, S. T., Mettlin, C., McHugh, T. A., Gray, J. M., Kumasaka, G. H. and McLeary, R. D.: Prostate cancer: comparison of transrectal US and digital rectal examination for screening. Radiology, 168: 389, 1988. 2. Cooner, W. H., Mosley, B. R., Rutherford, C. L., Jr., Beard, J. H., Pond, H. S., Terry, W. J., Igel, T. C. and Kidd, D. D.: Prostate cancer detection in a clinical urological practice by ultrasonography, digital rectal examination and prostate specific antigen. J. Urol., 143: 1146, 1990. 3. Catalona, W. J., Smith, D.S., Ratliff, T. L., Dodds, K. M., Coplen, D. E., Yuan, J. J. J., Petros, J. A. and Andriole, G. L.: Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. New Engl. J. Med., 324: 1156, 1991.