Limited additional lateral biopsies improve the diagnostic accuracy of transrectal ultrasound guided sextant prostate biopsy

KC Balaji; I Arnautovic; A Arnautovic; Durwood Neal

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RESEARCH ARTICLE

Year : 2003 \| Volume : 19 \| Issue : 2 \| Page : 125-128

Limited additional lateral biopsies improve the diagnostic accuracy of transrectal ultrasound guided sextant prostate biopsy

KC Balaji¹, I Arnautovic¹, A Arnautovic¹, Durwood Neal²
¹ Department of Surgery, University of Nebraska Medical Centre, Omaha, Nebraska, USA
² Department of Surgery, University of Missouri, Columbia, Missouri, USA

Correspondence Address:
K C Balaji
Director of Urological Oncology Research, Associate Professor, Urological Surgery, 982360, University of Nebraska Medical Center, Omaha. Nebraska 68198-2360
USA

Source of Support: None, Conflict of Interest: None

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Abstract

We prospectively evaluated the need for routine use of additional lateral biopsies at the time of standard sextant prostatic biopsy to reduce the false negative rates. A total of 23 consecutive patients underwent 24 TRUS guided prostatic biopsies resulting in 246 biopsy cores. Prostate cancer was diagnosed in 8/24 (33.3%) biopsies. Although the age and prostate volume did not significantly differ between patients with or without cancer (p>O. 05), the prebiopsy PSA and PSAD were significantly higher in patients diagnosed with prostate cancer (p<0.05). Of the 8 patients diagnosed with prostate cancer 2/8 (25%) had cancer in the biopsies lateral to but not in the standard sextant biopsy sites. The additional lateral biopsies improved the sensitivity and negative predictive value of TRUS guided biopsy by 33.3% and 13% respectively. In conclusion, in spite of the small sample size in this study, prostate cancer detection is increased by 25% because of additional lateral biopsies at time of standard sextant prostatic biopsy.

Keywords: Prostate, biopsy, ultrasound, sextant, PSA, additional.

How to cite this article:
Balaji K C, Arnautovic I, Arnautovic A, Neal D. Limited additional lateral biopsies improve the diagnostic accuracy of transrectal ultrasound guided sextant prostate biopsy. Indian J Urol 2003;19:125-8

How to cite this URL:
Balaji K C, Arnautovic I, Arnautovic A, Neal D. Limited additional lateral biopsies improve the diagnostic accuracy of transrectal ultrasound guided sextant prostate biopsy. Indian J Urol [serial online] 2003 [cited 2022 May 22];19:125-8. Available from: https://www.indianjurol.com/text.asp?2003/19/2/125/37143

Introduction

Prostate cancer is the most commonly diagnosed noncutaneous cancer in American men.^[1] In a large study of 132, 246 men undergoing prostate biopsy for the first time, 38.2% of patients were diagnosed with prostate cancer.^[2] A repeat biopsy within a year in 6350 of the remaining men, prostate cancer was diagnosed in 25.2%, suggesting a significant false negative rate at the initial biopsy. Although major complications are infrequent following TRUS guided prostate biopsy, about 2/3rds of patients undergoing biopsy suffer from at least I minor complication such as transient hematuria or fever.^[3] However, in most studies patient's discomfort or complications following TRUS guided prostatic biopsy is not significantly associated with number of biopsies.^[3],[4]

In order to reduce the false negative rates and the need for repeat TRUS guided prostate biopsy, we initiated a prospective study that included 2 additional biopsies on each side lateral to the standard sextant biopsy sites. Although additional biopsies have not been shown to be significantly associated with increased complications or patient's perception of pain and discomfort, additional biopsies increase time and expense.^[5] Therefore, we carried out an interim analysis and report our results on the need for routine use of additional lateral biopsies at the time of standard sextant prostatic biopsy.

Patients and Methods

Between September 1999 and June 2000, a total of 23 consecutive men underwent 24 TRUS guided ultrasound biopsies in a community based medical school setting for evaluation of prostate cancer. The indication for prostate biopsy was either abnormal prostate specific antigen (PSA) and/or digital rectal examination (DRE). All men received a Fleet's® enema the night prior to the procedure and received 24 hours of peri-procedure oral quinolones or similar antibiotics. Prior to beginning of the biopsy, pre-biopsy PSA and findings on DRE were noted. The serum PSA values were determined using the Hybritech Tandem-E assay (Hybritech Inc., San Diego, CA., normal < 4.0 ng/ ml). After obtaining informed consent, the patients were placed in left lateral position and real time TRUS imaging was done using a Bruel & Kjaer 2002 ADI ultrasound machine (B-K Medical systems Inc., N Billerica, MA) with a biplanar 7 MHz ultrasound 8508 transducer. Initially, the probe was advanced into the rectum until the seminal vesicles were visualized in the transverse plane and then the probe was gradually withdrawn until past the apex of the prostate and suspicious regions, if any, were identified for lesion directed biopsy.

The size of the prostate was determined by measuring the transverse and sagittal dimensions at the point of maximum transverse diameter. The length of the prostate was measured from the bladder neck to the prostatic apex in the midline in the longitudinal plane. The prostate volume was calculated by automatic planimetry and the PSAD by methods previously described.^[6],[7] The probe was fitted with a biopsy guide and biopsy was performed in the sagittal plane using an 18 gauge Bard Monopty biopsy instrument (CR Bard Inc., Covington, GA). At least 10 biopsies were taken from each patient (standard sextant + 2 biopsies lateral to the standard sextant sites on each side, [Figure - 1]) and any other suspicious regions either on TRUS imaging or DRE were biopsied as well.

The proximal margins of the biopsy cores were inked in different colors to identify the sites and were sent for pathological review in a single container. The cores were fixed in a single cassette, paraffinized, stained with eosin and hematoxylin and reviewed by different pathologists in a community setting. If prostate cancer was present, Gleason grade of the cancer, length of core in millimeters (mm) and percentage fraction of the entire core involved by cancer and the exact location of cancer from the proximal margin of the core were reported. The data were prospectively entered and analyzed in a computerized prostate biopsy database.

Statistical Analysis

The data for analysis were confirmed to have a near normal distribution by exploratory analysis and means were compared by independent samples T-test. P value <0.05 was considered statistically significant in all tests. SPSS 10.0 (SPSS Inc., Chicago, IL) statistical software was used for analysis.

Results

A total of 23 patients underwent 24 TRUS guided prostatic biopsy in this study resulting in 246 biopsy cores. The mean age of the entire cohort was 62.2 years (range 41-74). The mean pre-biopsy PSA, PSAD and prostate volume (PV) ± standard error for the entire cohort were 8.1 ± 1.6 ng/ml, 0.19 ± 0.01 and 40 ± 3.6 cc respectively. Prostate cancer was diagnosed in 8/24 (33.3%) biopsies. The comparative characteristics between patients with or without cancer on prostate biopsy are shown in [Table - 1]. The pre-biopsy PSA and PSAD were significantly higher in patients diagnosed with prostate cancer, 14 ± 3.5 ng/ml and 0.38 ± 0.1 compared to rest of the group, 5.2 ± 1.2 ng/ ml and <0.1 respectively (p<0.05). The age and prostate volume did not significantly differ between the two groups (p>0.05).

Of the 8 patients diagnosed with prostate cancer, 6 patients had prostate cancer in their sextant biopsy specimens and 2 patients had negative sextant biopsies but cancers present in the lateral biopsies. One of these 2 patients had associated high grade prostatic intraepithelial neoplasia (PIN) in 1 of the sextant biopsy sites and would have undergone a repeat biopsy to rule out associated prostate cancer, if additional biopsies were not done initially. In the other patient, detection of prostate cancer may have been missed or delayed without the additional biopsies because the sextant biopsy sites showed benign prostatic hyperplasia. There were no significant differences in the parameters studied in patients with cancer in standard sextant biopsy compared to patients with cancer in the biopsies lateral to but not in the standard sextant biopsy sites [Table - 2]. This lack of difference between these 2 groups may be related to the small sample size and inadequate power in the current study to identify small differences.

We did not specifically address the issue of complications associated with the biopsy in this study. However, none of the men were admitted to the hospital for a biopsy-related complication. Of the 8 patients diagnosed with prostate cancer, 2 chose continued observation, 2 underwent radiation treatment, 2 underwent radical prostatectomy and 2 were followed up elsewhere. 5 patients had high grade PIN in their prostate biopsies and 3 were associated with cancer. 2 patients with PIN without associated cancer underwent repeat biopsies; 1 showed persistent PIN and the other showed benign prostatic hyperplasia. Because the sample sizes are small, further statistical analysis of these subsets was not done.

Discussion

It is estimated that 198,100 American men will be diagnosed with prostate cancer in the year 2001.^[8] Since only 1/ 3 men undergoing prostate biopsy will be diagnosed with cancer,^[9] it can be estimated that over half million prostate biopsies will be done in the United States this year. Although the standard sextant biopsy is the gold standard for diagnosing prostate cancer, false negative rates up to 39% have been reported.^[2],[10] This translates to thousands of prostate cancers missed by standard sextant biopsy and these patients may need to undergo repeat biopsy or risk delayed or missed prostate cancer diagnosis.

Several methods have been described to improve the prostate cancer detection rate at the time of standard sextant biopsy such as improved ultrasound imaging, increasing the number of cores, directing biopsies at the most suspicious areas and other methods.^{[11],[12],[13]} While rapid advances are being made in prostate imaging technologies and non-invasive methods of diagnosing prostate cancer, these are not in common clinical use yet.^[14] Therefore, an immediate option to improve prostate cancer detection rate is to increase the number of cores of biopsy, thereby, limiting sampling errors. While several studies have shown that additional cores of biopsy at the time of standard sextant biopsy can improve prostate cancer detection rate by about 30%,^[13],[15] other randomized studies have failed to demonstrate significant improvement in prostate cancer detection with biopsies in addition to standard sextant.^[4],[16] Interestingly in 1 of these large randomized trials involving 244 patients, which, failed to demonstrate a >15% difference between a 6 and 12 core biopsies, 7/33 (21 %) of cancers were identified on a 12 core biopsy that were missed on the sextant biopsy.^[4]

Several of the above studies were done in major teaching institutions and 12 or more biopsy cores were taken from each patient. Our study was done in a community medical school setting and was limited to 10 biopsies per patient except for lesion directed biopsies. We limited the number of biopsies in this study to 10 because of better patient acceptability and limiting costs. Community pathologists reviewed all biopsy cores and therefore our analysis would closely match the experience in the community rather than a major teaching institution. The additional lateral biopsies detected cancer in 2/8 (25%) of patients that were missed on standard sextant biopsy, thereby improving the sensitivity and negative predictive value of TRUS guided prostate biopsy by 33% and 13% respectively.

Our data suggest that sensitivity of TRUS guided prostate biopsy in detecting prostate cancer can be significantly increased by the addition of 2 lateral biopsies from each side. This is associated with excellent patient acceptability, minimal additional patient discomfort and complications. If confirmed in a larger cohort of patients, the biopsy scheme evaluated in this study may become a reasonable substitute for the more extensive biopsies involving 12 or more cores because it increases prostate cancer detection by 25%, which, is at least comparable to the results (6.625.2%) reported in other studies involving extensive biopsy schedule.^[2],[13] Furthermore, because the study was done in a community setting it is more likely to be reflective of the practice pattern in the community.

The pre-biopsy PSA and PSAD were significantly increased in patients diagnosed with prostate cancer compared to rest of the group [Table - 1]. However, there were no significant differences in the parameters studied in patients with cancer in standard sextant biopsy compared to patients with cancer in the biopsies lateral to but not in the standard sextant biopsy sites. Although this is a prospective study designed to evaluate the need for additional lateral biopsies, the current study has several limitations. The sample size being small, we did not include free PSA or costs in our analysis and did not specifically address the complications associated with TRUS guided prostate biopsy. The lack of difference in the pre-biopsy PSA and PSAD in patients with cancer in standard sextant biopsy compared to patients with cancer in the biopsies lateral to but not in the standard sextant biopsy sites in this study may be related to the sample size. In addition, we do not know the true number of cancers that were missed in this study because we did not do extensive 12 core or more biopsies. However, because the cancer detection rate of 33% for the entire cohort and 25% additional detection rate from the additional lateral biopsies closely match the data in the literature, the number of missed biopsies in this study is likely to be very small.

In conclusion, in spite of the small sample size, our study demonstrates a 25% increase in prostate cancer detection by routine use of 2 biopsies on both sides lateral to the sextant biopsy sites. Furthermore, the biopsy scheme was evaluated in a community setting, had excellent patient acceptability, detected as many additional cancers as reported in the more extensive biopsy studies published in the literature and had no apparent increase in complications. If these findings are confirmed in a larger cohort of patients, our relatively simple biopsy scheme can be easily adapted for day to day clinical practice to improve prostate cancer detection.

References

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