Evolution of prostate biopsy
Katsuto Shinohara, M.D.
University of California, San Francisco

Historical change of prostate biopsy procedure

Prostate biopsy has been a common urologist’s office procedure for a number of years. However, this procedure has changed significantly in recent years due to advances in equipment and efforts to improve the sensitivity of the procedure. About 15 years ago, this procedure was commonly done by a large caliber needle, such as Vim-Silberman or True-cut needle under anesthesia. The biopsy was performed either transrectally or transperineally and was done only on prostates with a palpable abnormality. Only a few biopsy samples were obtained from the abnormal region using finger guidance. Although transrectal ultrasonography was already available at that time, the technology was rarely used to guide the biopsy needle. In the late 1980’s transrectal ultrasound guided prostate biopsy using an 18 G needle loaded in a spring action automated device was introduced.¹ Since then, prostate biopsy under ultrasound guidance has been a standard procedure among urologists and radiologists.

Systematic random biopsy

Initially prostate biopsy was mainly carried out only on lesions discovered on TRUS imaging. Therefore, only a few biopsy samplings were done even with using these instruments. Meanwhile, prostate specific antigen (PSA) became clinically available, and more and more patients with elevated PSA without having abnormality on digital rectal examination (DRE) or TRUS were discovered. A significant number of these patients were subsequently diagnosed with prostate cancer. In order to improve the sensitivity of prostate biopsy, Hodge et al proposed systematic multiple random prostate biopsy.² With this procedure, the prostate was divided into six regions, apex, mid and base bilaterally, and one representative sample was obtained from each sextant. Selzer et al compared accuracy of sextant biopsy with lesion directed biopsy. This revealed that sextant random biopsy essentially eliminated the necessity of lesion directed biopsy.³ TRUS is known to be an operator dependent diagnostic procedure which requires expertise to obtain good sensitivity and specificity. Sextant multiple random biopsy, therefore, was quickly accepted by urologists and became the gold standard for the procedure.

Issues with the number of biopsy specimens

Even with sextant random biopsy, a number of men require multiple biopsy sessions to diagnose cancer. Radical prostatectomy specimens often showed prostate cancer to be located in the peripheral zone of the gland, especially at the posterior lateral aspects. In order to improve the sensitivity of the biopsy, Stamey et al suggested that the sextant biopsy be performed slightly more laterally.⁴ By doing so, more peripheral zone tissue is sampled. Chang et al added four lateral regions (lateral mid and lateral base) in addition to the sextant biopsy. This revealed that lateral region biopsies found an additional 14% of positive cancer biopsies not diagnosed with regular sextant biopsy.⁵ This study also revealed that lateral biopsy often showed higher Gleason’s grade tumor. Eskew et al reported five region random biopsy.⁶ With this technique the prostate is divided into five regions (mid-line area and mid-lobe and lateral areas bilaterally), and samples are obtained from each region totaling 13 biopsies. The chance of hitting a small prostate cancer lesion by sextant biopsy will be significantly different between a small gland and a very large gland. Vashi et al calculated the number of the biopsy specimen necessary to hit a certain size lesion by random sampling in various sizes of glands.⁷

Transition zone biopsy

McNeal reported that about 68% of prostate cancer originates from the peripheral zone. However, 24% originate from the transition zone.⁸ In regular transrectal prostate biopsy, biopsy specimens are obtained from the posterior part of the gland only. In a large prostate gland, the anterior part of the gland is completely untouched by sextant or other biopsy techniques stated above. Lui et al proposed adding transition zone biopsy to the sextant biopsy in order to improve sensitivity of the procedure.⁹ Chang studied the yield of prostate cancer by adding six transition zone biopsy in a large prostate gland (more than 50 cc in volume).¹⁰ This revealed that transition zone biopsy in a large gland added about 13% of prostate cancers. They concluded that transition zone biopsy should be considered routinely if the gland is more than 50 cc.

Persistent elevation of PSA

Despite these efforts to improve sensitivity of prostate cancer diagnosis, there are still a significant number of patients who continue to have an elevation of PSA even after multiple sessions of negative prostate biopsy. When and how often the biopsy should be repeated are unanswered questions. Often PSA density, velocity and free PSA are used to select patients at increased risk and to decide on the timing of repeat biopsy. Recently 168 patients who underwent at least three sessions of multiple random biopsy at UCSF were reviewed.¹¹ The positive biopsy rate at repeat biopsy among this population was high at 38%. The prostate gland size (less than 50 cc), PSA density (more than 0.2) and PSA velocity (more than 0.74 ng/ml/year) were significant risk factors for positive biopsy. Since previous biopsies are often performed only at posterior part of the gland, careful TRUS often revealed visible lesions in the anterior part of the gland. These lesions probably originate in the anterior horn of the peripheral zone and are commonly located along the prostate capsule anteriorly. Therefore, anterior prostatic capsule has to be included in the anterior biopsy of the gland.

PIN and atypia

PIN and atypia are often discovered in the prostate without actual cancer. High-grade PIN has been known to be frequently associated with true invasive carcinoma. Aboseif et al reported that about 87 % of high-grade PIN cases were subsequently found have be carcinoma.12 Park et al reported that PIN and atypia were both significant factors to predict cancer in subsequent biopsy. They also reported the area found to have atypia or PIN had a significantly higher risk of harboring cancer than other parts of the gland.¹² However, about 25% of cancer was discovered in the area unrelated to PIN or atypia on the subsequent biopsy. It is suggested that if PIN is found in one sextant, three specimens from that sextant and two specimens from the adjacent sextant should be obtained in addition to the regular sextant biopsies.¹³

References:

1. Lee F, Torp-Pedersen ST, Sider DB: Use of transrectal ultrasound in diagnosis, guided biopsy, staging, and screening of prostate cancer. Urology, 33(suppl):7, 1989.

2. Hodge KK, McNeal JE, and Stamey TA: Random systematic versus directed ultrasound guided transrectal core biopsies of the prostate. J of Urol. 142:71, 1989.

3. Seltzer MA, Shinohara K, Bhargava V, et al: Comparison of systematic sextant and lesion directed biopsies in prostate cancer detection. Urol Oncol, 2: 136, 1996.

4. Stamey TA: Making the most out of six systematic sextant biopsies. Urology, 45:2, 1995.

5. Chang JJ, Shinohara K, Bhargava V et al: Prospective evaluation of lateral biopsies of the peripheral zone for prostate cancer detection. J of Urol, 160:2111, 1998.

6. Eskew LA, Woodruff RD, Bare RL et al :Prostate cancer diagnosed by 5 region biopsy method is significant disease. J of Urol, 160:794, 1998.

7. Vashi AR, Wojno K, Gillespie B et al: A model for the number of cores per prostate biopsy base on patient age and prostate gland volume. J of Urol, 159:920, 1998.

8. McNeal JE, Redwine EA, Freiha FS, et al:Zonal distribution of prostatic adenocarcinoma correlation with histologic pattern and direction of spread. Am J Surg Pathol, 12:897, 1988.

9. Lui PD, Terris MK, McNeal JE, et al: Indication for ultrasound guided transition zone biopsies in the detection of prostate cancer. J of Urol, 153:1000, 1995.

10. Chang JJ, Shinohara K, Hovey RM et al:Prospective evaluation of systematic sextant transition zone biopsies in large prostate for cancer detection. Urology 52:89, 1998.

11. Shinohara K : Significant risk of cancer in patient with a history of multiple negative prostate biopsies. J of Urol 163(suppl):273 # 1213, 2000.

12. Aboseif S, Shinohara K, Weidner N et al: The significance of prostatic intra-epithelial neoplasia. Br J of Urol, 76:355, 1995.

13. Park S, Shinohara K, Grossfeld G et al: Prostate cancer on repeat biopsy in men with an initial biopsy of atypical adenomatous hyperplasia or high grade intraepithelial neoplasia. J of Urology, 161(suppl):322 #1243, 1999.