Sonographic and Pathological Staging of Patients with Clinically Localized Prostate Cancer

0022-534 7/8S /1425-1259$02"00 /0 THE JOURNAL OF UROLOGY

Vol. 142, November Printed in U.S.A.

Copyright© 1989 by AMERICAN UROLOGICAL ASSOCIATION) INC.

SONOGRAPHIC AND PATHOLOGICAL STAGING OF PATIENTS WITH CLINICALLY LOCALIZED PROSTATE CANCER GERALD L. ANDRIOLE,* DOUGLAS E. COPLEN, DAVID J. MIKKELSEN WILLIAM J. CATALONA

AND

From the Division of Urologic Surgery, Washington University School of Medicine, St. Louis, Missouri

ABSTRACT

We evaluated 64 patients with clinically localized prostate cancer (on the basis of rectal examination, serum acid phosphatase, bone scan and pelvic computerized tomography scan) by transrectal sonography before radical prostatectomy. Of the 48 patients with histologically proved localized prostate cancer sonography overstaged the disease in 5 (10%) and correctly staged it in 43 (90% ). All overstaged cancer patients were scanned after either prostatic biopsy (4) or transurethral prostatectomy (1) established the diagnosis of prostate cancer. Of the 16 patients with histologically proved, locally advanced prostate cancer (that is extracapsular extension and/or seminal vesicle invasion) sonography understaged the disease in 10 (62%) and correctly staged the disease in 6 (38%). These data suggest that sonography is associated with considerable staging errors when used to evaluate men with clinically localized prostate cancer. (J. Ural., 142: 1259-1261, 1989) Since the introduction of transrectal ultrasound of the prostate in the mid 1970s1 multiple studies 2 - 7 have assessed various possible roles for this modality in the diagnosis, staging and management of patients with prostate cancer. Although considerable data have been accumulated, the exact role of sonography remains enigmatic. The sensitivity and specificity of transrectal ultrasound in the detection of early prostate cancer do not presently appear to be sufficiently high to warrant widespread sonographic screening of men for prostate cancer. 7• 8 Transrectal ultrasound of the prostate, however, may be of considerably more benefit in the staging of presumed localized prostate cancer. Fujino and Scardino reported that in 9 of 18 men who were evaluated by rectal examination and transrectal ultrasound before prostate exploration (and placement of radioactive gold) the disease was understaged by digital rectal examination, while ultrasound understaged the cancer in only 1.9 Kadow and associates supported this view and believed that ultrasound was unsurpassed as a method for accurate T category staging of proved prostate carcinomas. 10 Salo and associates reported that sonography identified 12 of 14 patients with extracapsular extension and 16 of 17 without extracapsular extension before radical prostatectomy. 11 However, the ability of sonography to identify seminal vesicle invasion was less certain, since only 2 of the 7 patients with seminal vesicle invasion were identified sonography. Pontes and associates noted that transrectal ultrasound identified 15 of 22 patients with extracapsular extension and 2 of 7 with seminal vesicle invasion. 12 Our prospective study was done to shed further light on the exact accuracy of sonography in T staging of prostate cancer. PATIENTS AND METHODS

Between July 1987 and October 1988 transrectal ultrasonography of the prostate was performed on 68 patients with clinically localized prostate cancer (on the basis of digital rectal examination, serum prostatic acid phosphatase, bone scan and computerized tomography scan of the pelvis). All patients were believed to be suitable surgical candidates for bilateral pelvic lymphadenectomy and nerve-sparing radical retropubic prostatectomy. Of these patients 4 did not subsequently undergo radical prostatectomy: 3 because of microscopic nodal metasAccepted for publication May 17, 1989. *Requests for reprints: Division of Urologic Surgery, 4960 Audubon Ave., St. Louis, Missouri 63110.

tasis found on pelvic lymphadenectomy and 1, who had undergone 2 prior transurethral resections of the prostate, because of difficulty developing a dissection plane between the prostatic capsule and levator muscles. The remaining 64 patients underwent nerve-sparing radical retropubic prostatectomy. The ultrasonographic and histopathological findings of these patients form the basis of this report. All sonographic examinations were performed with a Bruel and Kjaer model 1846 scanner equipped with the 8538 and 1850 (7 MHz.) transrectal transducers. All patients were placed in the left lateral decubitus position and the prostate was scanned transversely from the seminal vesicles to the apex of the gland and sagittally from the right to left sides. Multiple transverse and sagittal images were recorded on either film or tape. These recordings were interpreted with specific attention to the size and symmetry of the seminal vesicles and prostate, the echographic appearance of the peripheral zone of the prostate, and prostatic capsular symmetry and integrity. Eight sonograms were performed before the histological diagnosis of prostate cancer; 14 patients with stage A disease were scanned 1 to 4 weeks after transurethral prostatectomy and 42 patients with clinical stage B disease were scanned 2 to 8 weeks after core needle biopsy. The sonographic criteria of extracapsular extension included capsular asymmetry or capsular bulging in a region adjacent to a hypoechoic focus. Seminal vesicle invasion was diagnosed on sonography if asymmetry or marked enlargement of 1 or both seminal vesicles was noted. For purposes of this study all sonograms were reviewed blindly without knowledge of history or physical examination findings. Patients then underwent modified bilateral pelvic lymphadenectomy and nerve-sparing radical retropubic prostatectomy. The surgical specimens were examined grossly by the pathologist in the operating room. All margins were stained with india ink, and carefully sectioned to determine tumor grade, location and extent within the prostate, as well as the presence of seminal vesicle invasion or extracapsular extension. Comparison was then made between the sonographic and pathological findings. Calculations of sensitivity, specificity and predictive values were made as described by Wasson and associates. 13 RESULTS

Of the 64 patients who underwent radical retropubic prostatectomy 5 had clinical stage Al, 9 stage A2, 22 stage Bl and 28

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ANDRIOLE AND ASSOCIATES

stage B2 disease. Twelve patients (19%) had histological evidence of extracapsular extension. Preoperative transrectal ultrasound correctly predicted this condition in 6 patients. Therefore, the sensitivity of transrectal ultrasound to detect extracapsular extension was 50%. Transrectal ultrasound correctly identified 47 of the 52 patients without histological evidence of extracapsular extension. Therefore, the specificity of transrectal ultrasonography in the detection of extracapsular extension was 90%. Over-all, the predictive values of a sonogram interpreted as positive and negative for extracapsular extension were 55 and 89%, respectively (table 1). Preoperative transrectal ultrasound identified seminal vesicle invasion in 1 of the 5 patients shown histologically to have seminal vesicle involvement. All other sonograms were negative for seminal vesicle invasion. Therefore, the sensitivity and specificity of transrectal ultrasound in identifying seminal vesicle invasion were 20 and 100%, respectively. The predictive values of a scan interpreted as positive and negative for seminal vesicle invasion were 100 and 94%, respectively (table 1). Over-all, 16 of the 64 patients (25%) had extraprostatic disease (extracapsular extension and/or seminal vesicle invasion). Transrectal ultrasound correctly identified this condition in 6 of the 16 patients (38%) and understaged the disease in 11 (62%). Of the patients 48 had truly localized prostate cancer; sonography correctly staged 43 cases (90%) and overstaged 5 (10%) (table 2). The influence of prior needle biopsy or transurethral resection of the prostate on the accuracy of sonographic staging is

1. The ability of transrectal ultrasound to detect extracapsular extension of and seminal vesicle invasion by carcinoma of the prostate

TABLE

Extracapsular Extension

Seminal Vesicle Invasion

6

1 59

True pos. True neg. False pos. False neg. Totals Sensitivity(%) Specificity (%) Pos. predictive value (%) Neg. predictive value(%)

47 5 6

0 4

64

64

50 90 55* 89+

20 100

lOOt 94§

* Transrectal ultrasound with extracapsular extension.

t Transrectal ultrasound with seminal vesicle invasion.

:j: Transrectal ultrasound without extracapsular extension. § Transrectal ultrasound without seminal vesicle invasion.

TABLE 2.

Sonographic staging errors No.

Transrectal Sonographic Staging No.(%)

In men with clinically localized prostate Ca Prostate Ca: Overstaged 5 (10) Histologically localized 48 Histologically advanced Understaged 10 (62) 16 Staging error 15 (23) Total 64 In pts. with clinically localized prostate Ca scanned before or after histological diagnosis of prostate Ca Sonography before histological 8 Correct 7/8 (88) diagnosis Understaging error 1/8 (12) 14 Sonography after transurethral Correct 12/14 (86) U nderstaging error prostatectomy 1/14 (7) Overstaging error 1/14 (7) Sonography after needle biopsy 42 Correct 30/42 (71) U nderstaging error 8/42 (19) Overstaging error 4/42 (10)

shown in table 2. Sonography performed before biopsy correctly staged the disease in 7 of 8 patients (88%), sonography performed after transurethral prostatectomy correctly staged the disease in 12 of 14 (80%) and sonography performed after core needle biopsy of the prostate correctly staged the disease in only 30 of 42 (71 %). All overstaging errors occurred in patients scanned after either transurethral prostatectomy or needle biopsy: 1 of 14 (7%) transurethral prostatectomy patients had overstaging, compared to 4 of 42 (10%) needle biopsy patients. Sonography understaged the cancer in some patients from all groups: 1 of 8 (12%) before biopsy, 1 of 14 (7%) after transurethral prostatectomy and 8 of 42 (19%) after needle biopsy. There was no relationship in the interval between biopsy (or transurethral prostatectomy) and sonography with accuracy of the sonogram. In estimating the intraprostatic extent of carcinoma, sonography identified tumor within 1 lobe only in 36 patients; 18 of the patients (50%) actually had bilateral tumor involvement. Of 16 patients with sonographic evidence of bilateral tumor 5 (31%) had only unilateral disease on histological study. The correlation of intraprostatic tumor extent with pathological stage is shown in table 3. DISCUSSION

This study was designed to assess the ability of sonography to stage locally prostate cancer. It was anticipated that sonography would be superior to digital rectal examination. Since all of our patients were believed to have localized prostate cancer on the basis of rectal examination and since most patients were scanned after prostatic biopsy or transurethral prostatectomy established the diagnosis of prostate cancer, no direct statistical comparison between the sensitivity and specificity of sonography and rectal examination in the staging of prostate cancer is possible. The over-all staging error of rectal examination was 25% (16 of 64 cases of advanced local disease were understaged). Sonography was associated with a staging error in 15 of 64 patients (23%)-5 cases of localized disease were overstaged and 10 of advanced disease were understaged. It is important to consider that all 5 of the overstaged cases were scanned after the histological diagnosis of prostate cancer was made and in at least 1 instance biopsy-induced artifact could be implicated retrospectively as the cause of the falsely positive capsular bulge (see figure). In the 8 patients scanned before transurethral prostatectomy or prostate biopsy, sonography was associated with a 12% staging error (1 of 8 cases understaged). As more patients are scanned before prostatic biopsy or transurethral prostatectomy the impact of these procedures on sonographic staging errors will become more apparent. The ability of each modality (sonography and rectal examination) to estimate the intraprostatic extent of prostate cancer also was comparable. Sonography underestimated the intraprostatic extent of 18 of 52 evaluable tumors (35%, 12 of the 64 tumors were not seen sonographically) and overestimated the extent of 5 (10%). Rectal examination underestimated the intraprostatic extent of 9 of 50 evaluable patients (18%, 14 stage A tumors were impalpable) and overestimated the extent of 9 (18%). However, direct comparison of these modalities is TABLE 3.

Intraprostatic extent and pathological stage of carcinoma of the prostate

Extent of Intraprostatic Tumor Sonography Unilat., 36 Bilat., 16 Tumor not clearly seen, 12

Histology Unilat. 18 Bilat. 18 Unilat. 5 Bilat. 11 Unilat. 4 Bilat. 8

Pathological Stage Al

A2

Bl

B2

C

13

3 4 1

15 1 4 2

4 0 7

7

2 1

SONOGRAPHIC AND PATHOLOGICAL STAGING 00' PATmNTS WITH PROSTATE CANCER

3.

4.

5.

6.

7. Preoperative sonogram obtained after needle biopsy of prostate in patient with clinical stage B2 prostate cancer. At operation organized hematoma was found intimately associated with prostate capsule. Sonogram was interpreted prospectively as positive for capsular penetration.

not possible given the fact that most sonog:rams were performed after the histological diagnosis of prostate cancer. These data suggest that as p:resently practiced there are considerable staging errors associated with transrectal sonography, particularly if performed after the histological diagnosis of prostate cancer. The magnitude of these staging errors may preclude the use of sonography to guide management in individual patients with clinically localized prostate cancer. REFERENCES

8.

9.

10.

11.

12.

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