Value of Systematic Transition Zone Biopsies in the Early Detection of Prostate Cancer

0022-5347/96/1552-0605$03.00/0 THEJOURNAL OF UROLCGY Copyright 0 1996 by AMERICAN UROLOCICAL ASS~CUTION.INC.

Vol. 155.606606, February 1996 Printed in U S A

VALUE OF SYSTEMATIC TRANSITION ZONE BIOPSIES IN THE EARLY DETECTION OF PROSTATE CANCER MICHEL BAZINET,* PIERRE I. KARAKIEWICZ, ARMEN G. APRIKIAN, CLAUDE TRUDEL, SAMUEL ARONSON, MAHMOUD NACHABfi, FRANCOIS PfiLOQUIN, JEAN DESSUREAULT, MICHELLE GOYAL, WE1 ZHENG, LOUIS R. BfiGIN AND MOSTAFA M. ELHILALI From t h UROMED plnstate Cancer Detection Center and Departments of Urdqs,and , -P

MCGill Vnivemity, M o d , Q u e k conada

ABSTRACT

Purpose: A prospective study was done to determine the value of performing 2 systematic transition zone biopsies in addition to systematic sextant peripheral zone biopsies for early detection of prostate cancer. Materials and Methods: From January 1to August 31, 1994 we evaluated 847 consecutive patients referred to us for a suspicious lesion on digital rectal examination or an elevated serum prostate specific antigen level. All patients underwent 2 systematic transition zone biopsies in addition to systematic sextant biopsies of the peripheral zone. Results: Of the transition zone biopsies 68 (24.4%)contained malignancy, including only 8 (2.9%) with cancer found exclusively in the transition zone. The remaining271 cases (97.1%)had 1 or more positive peripheral zone biopsies and would have been detected with or without additional systematic transition zone biopsies. The same analysis of 552 patients with a negative digital redalexamination yielded 6 (4.1%)exclusively transition zone tumors among 145 cancers detected in this group. Conclusions: The low additional yield of transition zone biopsies (2.9 to 4.1%) does not warrant their systematic use for the early detection of prostate cancer. KEYWORDS: biopsy; prostate; prostatic neoplasms; antigem, neoplasm The recommended prostatic evaluation of patients with unremarkable findings on digital rectal examination and an elevated serum prostate specific antigen (PSA) level consists of transrectal ultrasound with systematic biopsies of the peripheral zone. In select cases when a lesion is noted on ultrasound directed biopsies are usually performed. Recently, in addition to systematic sextant biopsies of the peripheral zone the use of 2 systematic biopsies of the transition zone has been proposed among patients with an unremarkable digital rectal examhation but with serum PSA greater than the age-specrfic reference range.' The few studies on this diagnostic approach prompted US to evaluate prospectivelythe usefulness of 2 systematic transition zone biopsies in addition to the systematic sextant peripheral zone biopsies among consecutive patients referred to our prostate cancer detection center. MATERIALS AND METHODS

Between January 1 and August 31,1994 we prospectively evaluated 847 consecutive men referred by urologists to o u r Prostate cancer detection center because of suspicious digital rectal examination and/or elevated serum PSA levels determined by Hybritech or Abbott IMx assays. Digital rectal examination was systematically performed by the attending urologist just before transrectal ultrasound with the patient in the left lateral decubitus position, and the results were classified as either normal or suspicious for cancer. The Prostate was considered to be suspicious for disease if it was diffusely hard, contained a discrete firm area, or showed irregular contours or prominent lobe asymmetry. All transrectal ultrasound examinations were performed in real time using a Bruel& Kjaer model 1846 scanner with an 8551 multiplane probe (7 MHz. transducer). Each gland was examined in the axial and sagittal projections. Patients with Palpable abnormalities were carefully screened for corre9 p t e d for publication August 18,1995. Montreal General %uests for re rink De artment of Urol Hospital, 1650 c& A;., bf~~~treal, Quebec%h H3G lA4.

sponding lesions by transrectal ultrasound. Prostate volume was calculated as 0.52 x (length X width x height) with length being measured in the longitudinal view, and width and height in the transaxial views. PSA density was calculated by dividing serum PSA by prostatic volume (expressed in cubic centimeters). Final transrectal ultrasound impressions were classified as benign or suspicious for cancer. Findings were considered suspicious if a hypoechoic lesion noted in the prostate could not be explained by other factors, such as vascular structures, cysts or artifacts. All patients with either a suspicious digital rectal examination or serum PSA greater than 4.0 ng./ml. underwent systematic sextant biopsies of the peripheral zone as described previously2 as well as 2 systematic transition zone biopsies. To obtain transition zone tissue the needle was inserted in the mid portion of each half of the prostate and was manually pushed through the peripheral zone. The biopsy gun was fired when the tip of the needle reached the peripheral zone-transition zone junction. The transition zone biopsies contained tissue from the left and right sides of the anterior prostate as defined by McNeal.3 In select cases additional biopsies were directed towards suspicious areas noted on the ultrasound image or on digital rectal examination with geographic coordination. All biopsies were performed under ultrasound guidance via the transrectal route on an outpatient basis. Biopsy material was obtained with a spring driven biopsy gun using 18 gauge Tru-Cutt biopsy needles. The same pathologist (L.R. B.) examined all biopsies. Each biopsy specimen was categorized histologically (normal, atrophic changes, acute or chronic inflammation, prostatic intraepithelial neoplasia or cancer) and all cancers were graded by Gleason scores. The cancer present in each core was quantified as a percentage of the total core. One patient with an unremarkable digital rectal examination and a serum PSA of 3.1 nglml. (within the normal range) underwent transrectal ultrasound guided biopsies because of

605

t naveno1 Laboratories, Deerfield, Illinois.

606

SYSTEMATIC TRANSITION ZONE BIOPSIES IN EARLY DETECTION OF PROSTATE CANCER

Descrtpttce statrstics on patient serum PSA, PSA density, age-specific reference range of PSA, Gleason score, number of positive cores and tumor percentage per biopsy core Median (range from 25th to 75th percentile I

No Pts Serum PSA All pts.: Ca Transition zone pos Ca Exclusive transition zone Ca Neg. digital rectal examination findings: Ca Transition zone pos Ca transition zone Ca . Exclusive .

847 279 132.91 68 (24.41 8 12.91 552 145 I26 31 30120.71 6 14.11

7 915 a 1 1 41 9 2i6%14 41 9 8 i 8 0-157, 9 5 18 5-13 8) 7 8 t5 9-10 81 8 9 I6 %12 21 10 4 18 4-16 2 ) 9 5 i 8 0 - 1 1 41 _.

PSA Density

0 19 ( 0 12-0 291 0 26 I0 17-0 481 0 35 ( 0 23-0 701 0 37 I0 28-0 481 0 18 10 12-0 271 0 23 10 15-0 341 0 31 10 21-0 80) 0 37 1023-0 501

ck F'ts With

Median (range) Age-Specific Reference

Rapgof Gleason Score 87 0 93 2 95 1 100 91 3 93 9 94 3 100

AV Q Tumor per Core lrangei

No Pos Cores

-

-

-

-

7 (2-101 7 14-101 7 17-81

3 11-81 4 11-8) l(1-21

4.5 2 15-93)

-

6 12-10) 6 13-10) 7 (7-81

38 2 15-98) 51 6 15-93)

-

-

2 (141 2 11-81 111-21

30 9 15-93) 31 3 15-93) 52 5 15-93]

study population of 847 consecutive patients we would have missed only 8 of 279 cancers (2.94) and we would have spared these 847 patients h m undergoing transition zone biopsies. Similarly, if systematic transition zone biopsies were omitted among the 552 patients with negative digital rectal examination findings we would have missed only 6 of 145 tumors (4.1%) and we would have spared these 552 patients from undergoing transition zone biopsies. Therefore, we detected only 1 exclusive transition zone cancer for every 106 systematic transition zone biopsies performed in the entire study population. Similarly, we RESULTS deteded only 1 exclusive transition zone cancer for every 92 A total of 847 patients 38 to 83 years old (average age 64) systematic transition zone biopsies performed in t h e group witk. underwent transrectal ultrasound guided biopsies based on a negative digital rectal examination findings. suspicious digital rectal examination and/or serum PSA greater The use of 2 systematic transition zone biopsies did not imthan 4.0 ngJml. The transrectal ultrasound guided biopsies prove the cancer detection rate among the 58 patients with included 2 systematic transition zone biopsies in addition to systematic sextant peripheral zone biopsies. Of 279 cancers prior negative biopsies of the peripheral zone. The lack of pos(positive biopsy rate 32.9%)68 (24.44,)were detected on the itive transition zone findings among those men may be partly basis of positive transition zone and peripheral zone biopsies. explained by the small sample size, low ratio of transition zone Only 8 of these 279 cancers (2.9%1 were detected exclusively by biopsy core-to-total transition zone volumes, as well as the pathological transition zone findings. Among the remaining 60 presence of an intermediate elevation of serum PSA among tumors with positive transition zone biopsies disease was also those men (median 10.5). However, transition zone biopsies 1 present in the peripheral zone and would have been detected by may prove to be more beneficial among patients with extremely elevated serum PSA levels as reported previously.4 peripheral zone biopsy findings alone. We repeated our analysis on a subgroup of 552 patients with CONCLUSIONS negative digital rectal examination findings. In this category We believe that the low additional yield of routine systematic biopsies were performed based solely on serum PSA greater than 4.0 ngJml. Of 145 cancers (26.34) only 6 (4.1%)were transition zone biopsies does not warrant their use in early detected exclusively by transition zone biopsies. The remaining prostate cancer detection. Therefore, we do not recommend 139 cancers were diagnosed by positive peripheral zone findings routine systematic transition zone biopsies in addition to sysand would not have been missed if transition zone biopsies were tematic sextant biopsies of the peripheral zone. However, omitted. The table shows descriptive statistics on patient serum systematic transition zone biopsies may be recommended in F'SA, PSA density, age-specific reference range of PSA, Gleason select cases, including patients with negative digital rectal exscore, number of positive cores and tumor percentage per biopsy amination and transrectal ultrasound findings, and a high index of suspicion for cancer. Similarly, among patients in whom core. We detected 17 cancers in the 58 patients with a prior no cancer was found on routine peripheral zone studies, despite negative biopsy of the peripheral zone. These tumors were elevated or persistently increasing serum PSA, 2 or more biop detected exclusively in patients with unremarkable digital sies of the transition zone may be indicated since the risk of rectal examination findings accompanied by persistently el- missing a transition zone cancer with exclusive peripheral zone evated or increasing serum PSA. No transition zone biopsy biopsies may be increased. core contained cancer. Ms. Barbara Vyncke assisted with data entry.

a history of finasteride therapy up to the time of investigation. Of 58 patients (6.8%)in whom previous transrectal ultrasound guided biopsies showed benign results 5 had suspicious digital rectal examination findings t h a t prompted repeat biopsy, 3 had a suspicious digital rectal examination and a persistently elevated serum PSA level, and 50 had unremarkable digital rectal examination findings accompanied by persistently elevated or increasing serum PSA.

~

DISCUSSION

We examined prospectively the usefulness of transition zone biopsies for early detection of prostate cancer. A substantial proportion of patients (24.4%) harbor cancer in the transition zone. However, the majority of these patients will have coexistent detectable cancer in the peripheral zone. Only a small percentage (2.9to 4.1% of cancers will be detected exclusively in the transition zone. Therefore. the yield of transition zone biopsies is minimal in a urological referral population. Consequently, routine systematic transition zone biopsies probably can be omitted safely in early prostate cancer detection. If we had omitted systematic transition zone biopsies in our

REFERENCES

1. Oesterling, J. E., Cooner, W. H., Jacobsen, S. J.,Guess, H. A. and Lieber, M. M.: Influence of patient age on the serum PSA concentration. An important clinical observation. Urol. Clin. N. h e r . , 2 0 671, 1993. 2. Bazinet, M., Meshref, A. W., Trudel, C., Aronson, S., Pelcquin, F., Nachabe, M., %gin, L. R. and Elhilali, M. M.: Pmspective evaluation of prostate-specificantigen density and systematic biopsies for early detection of prostatic carcinoma. Urology, 43:44.1994. 3. McNeal, J. E.: The zonal anatomy ofthe prostate. hstate, 2: 35,1981. 4. Lui, P. D., Terris, M. K, McNeal, J . E. and Stamey, T. A.: Indications for ultrasound guided transition zone biopsies in the d e w tion of prostate cancer. J. Urol., part 2, 153: 1000. 1995.