Mona Norberg

THE SEXTANT PROTOCOL FOR ULTRASOUND-GUIDED CORE BIOPSIES OF THE PROSTATE UNDERESTIMATES THE PRESENCE OF CANCER

OBJECTIVES The aim of this prospective study was to evaluate the sensitivity of the sextant biopsy protocol compared with a more extensive procedure for the detection of prostate cancer and to define a biopsy model with the minimal number of biopsies necessary to maintain diagnostic accuracy. METHODS A total of 512 consecutive patients with suspected prostate cancer were examined with transrectal ultrasound (TRUS) and underwent TRUS-guided core biopsy. All patients had 8 or 10 standardized biopsy samples taken, with the number depending on the size of the gland. Additional biopsy samples were taken from hypoechoic or hyperechoic lesions located outside the predetermined location for the standardized biopsies (ie, target biopsies). The sensitivity of the detection of cancer for different combinations of biopsy samples was analyzed and compared with that of our model with 8 to 10 biopsies. RESULTS In all, 276 cancers were detected, of which 88 (32%) had an isoechoic appearance. Sensitivity was 59% for focal lesions detected by TRUS, 85% to 97% for different combinations of systematic biopsy samples, and 93% to 98% for a combination of systematic and target biopsy samples. The sensitivity for the standard sextant protocol was 85%. By adding target biopsies, the sensitivity increased to 93%. CONCLUSIONS The standard sextant protocol leaves 15% of cancers undetected compared with results obtained from a more extensive biopsy procedure. By combining systematic and target sampling, the sensitivity increases; however, a major concern is that the clinical importance of cancers detected by multiple biopsies needs to be evaluated.

Determinants of complications after multiple transrectal core biopsies of the prostate

Transrectal ultrasound-guided biopsies of the prostate were performed on 347 consecutive men. All patients were given prophylactic antibiotics. The first 199 patients received 400 mg norfloxacin immediately after the biopsies were performed and 400 mg the same evening. The second group of 148 patients received 400 mg of norfloxacin 1 h before the examination followed by five doses administered twice daily. A total of 15 major complications were noted. In the first group the complication rate was 6.5% and in the second group 1.4%. The different regimes of prophylactic antibiotic treatment were the only parameters shown to have a statistically significant impact on the complication rate. The number of complications decreased, but were not eliminated, when prophylactic treatment with norfloxacin was given before the biopsies were taken and continued for a total of 3 days.

Estimation of prostate cancer volume by multiple core biopsies before radical prostatectomy

OBJECTIVES To investigate whether tumor volume, an important prognostic factor in prostate cancer, could be estimated from the amount of cancer in multiple core biopsies. METHODS In 80 men, transrectal ultrasound-guided biopsies were taken from focal lesions detected by ultrasound and 8 to 10 standardized positions, including sextant biopsies (apex, midmedial, base) and midlateral and transition zone biopsies. The cancer length in the biopsies was measured. After radical prostatectomy, the prostates were totally embedded, whole-mounted, and tumor volume was measured planimetrically. RESULTS The tumor volume correlated significantly with the total cancer length of all biopsies (r = 0.56) and of the sextant biopsies (r = 0.39). It was found that midlateral and transition zone biopsies provided independent information when included in a multiple regression model with tumor volume as the dependent variable and the sextant biopsies as explanatory variables. All men (n = 6) with less than 3 mm cancer length in only one positive biopsy and a Gleason score less than 7 had a tumor volume less than 1 mL. Nine of 10 men with less than 7 mm of cancer in one positive biopsy and Gleason score less than 7 had tumors smaller than 1 mL. Sextant biopsies did not reliably predict cancer volumes less than 1 mL. CONCLUSIONS The cancer yield of 8 to 10 biopsies correlated better with the volume of prostate cancer than sextant biopsies. This extended biopsy protocol could be used to predict cancers of less than 1 mL in volume.

The value of multiple core biopsies for predicting the Gleason score of prostate cancer

Objective To evaluate the accuracy of Gleason grading of prostate cancer in multiple core biopsies, compared with the final Gleason score of total prostatectomy specimens, and to investigate whether the prediction of the correct Gleason score is improved by increasing the number of biopsies.

Three-dimensional computer reconstruction of prostate cancer from radical prostatectomy specimens: evaluation of the model by core biopsy simulation

OBJECTIVES A technique was developed for three-dimensional (3D) modeling of prostate cancer and transrectal biopsies. To test the model, the cancer yield of a simulated 10-biopsy protocol was compared with a simulated sextant protocol and with preoperative biopsies regarding cancer detection and correlation with tumor volume. METHODS Transrectal ultrasound-guided core biopsies were taken from 81 men according to a standardized 10-biopsy protocol that included sextant biopsies. The patients underwent radical prostatectomy and specimens were step-sectioned and whole-mounted. Cancer and the prostate capsule were outlined on the slides and the regions transferred to a computer software program developed by our group. A 3D volume of each prostate was reconstructed from the sections. Virtual core biopsy needles imitating the positions of the real biopsies were inserted into the prostate and the cancer yield was calculated. Only the standardized positions were considered in this study (ie, additional biopsies from hypoechoic foci were not accounted for). RESULTS Of the cancers detected with 10 standardized virtual biopsies, 24% would have remained undetected with sextant biopsies. The cancer yield of 10 virtual biopsies correlated with the preoperative biopsies (r = 0.64) and with the tumor volume (r = 0.56). A multiple regression analysis showed that the cancer yield of a simulation of 10 biopsies correlated better with tumor volume than did a simulation of sextant biopsies (P = 0.02). CONCLUSIONS We conclude that computer-assisted 3D reconstruction of prostate cancer can be used as a model for evaluation and optimization of biopsy protocols.

Five Year Follow-up after Radical Prostatectomy for Localized Prostate Cancer—a Study of the Impact of Different Tumor Variables on Progression

Fifty-one patients with clinically localized prostate cancer stages A and B, who underwent radical prostatectomy have been followed for a minimum of 5 years. The impact of age, stage, capsular penetration, total tumor volume, Gleason score, seminal vesicle invasion and lymph node metastases on progression has been evaluated. Progression free survival was calculated according to the Kaplan-Meier method. Uni- and multivariate analyses were performed according to the Cox proportional hazards model. During the observation period 16 patients (31%) experienced progression. Tumor volume, grade and seminal vesicle invasion emerged as statistically significant predictors of tumor progression in the survival analyses while age at surgery, preoperative stage and different levels of capsular penetration were not statistically significant. The findings in the Cox models were in accordance with those at actuarial survival analyses though tumor volume was the only variable proven to have an independent statistically significant influence on progression.

Characterization of localized prostatic cancer: distribution, grading and pT-staging in radical prostatectomy specimens.

Ninety-one patients underwent radical retropubic prostatectomy. Forty-three specimens were examined after limited sectioning (series 1) and 48 underwent whole organ serial step-sectioning at 5 mm intervals (series 2) of the removed prostate gland. The latter allowed a more extensive assessment of tumour localization, multicentricity, extension, pT-stage and grade. Eighty-eight percent of specimens in series 1 had free surgical margins compared with only 41% in series 2 (p = 0.00001). Preoperative tumour grading by fine-needle aspiration biopsy, TUR-chips or 1.2 mm core biopsies was in agreement with postoperative grading in the prostatectomy specimens in 48% of the cases in series 1 and 67% in series 2, respectively. In series 2, preoperative localization of the tumours by palpation was accurately assessed in 75% of cases when compared to the findings at step-sectioning. Sixty-eight percent of 40 eligible glands in series 2 contained multiple tumours. 12/13 cases of unifocal tumours (92%) were classified as large single tumours. The sections were divided into four peripheral and four central parts/octants, and the tumour localization was marked within these octants. The apical and middle third of the prostate contained tumour in all cases, whereas the basal (cranial part) was engaged in 35%. Small tumours were localized mainly in the periphery of the gland, with no significant difference between dorsal and ventral octants. However, large tumours were situated mainly in the dorsal peripheral octants, concomitant with an increased involvement of the ventral and central octants.(ABSTRACT TRUNCATED AT 250 WORDS)

Three-dimensional modeling of biopsy protocols for localized prostate cancer

Prostate cancer is the most common malignant tumor in American men, yet only a small percentage of men will develop clinically significant disease. Needle core biopsies are used to confirm the presence of cancer prior to surgery. While needle core biopsies have shown some ability to predict tumor volume and grade in prostatectomy specimens, for the individual patient they are neither sensitive nor specific enough to guide therapy. In this paper, we describe a system for simulating needle biopsies on three-dimensional models of cancerous prostates reconstructed from serial sections. First we segment the serial sections, delineating tumors and landmarks. Next, we register the sections using a color-merging scheme, and reconstruct the three-dimensional model using modified-shape-based interpolation. The resulting volume can be rendered, and simulated needle core biopsies can be taken from the reconstructed model. We use our system to simulate two different biopsy protocols on a reconstructed prostate specimen.

The significance of tumor heterogeneity for prediction of DNA ploidy of prostate cancer

Objective. In a previous study, we mapped the ploidy heterogeneity of prostate cancer using flow cytometry in 676 tumor samples from 50 radical prostatectomy specimens. Ploidy heterogeneity was common (42% of tumors) and was found in all non-diploid tumors. The volume of non-diploid tumor was estimated and found to predict extra-prostatic extension and seminal vesicle invasion. The aim of this study was to evaluate the impact of tumor heterogeneity on preoperative ploidy assessment. Material and methods. In 50 men at least six core biopsies were taken before prostatectomy. Sections from biopsies with cancer were Feulgen-stained for image cytometry. After exclusion of biopsies with insufficient material, 123 histograms from 48 men (mean 2.6; range 1–7) remained for analysis. Results. In 32 men, biopsies were diploid. In 16 men, at least one biopsy was non-diploid (14 tetraploid, two aneuploid) and 10 of them also had diploid biopsies. In 34 men (71%), the prostatectomy specimens were correctly predicted as being either diploid (48%) or non-diploid (23%). The sensitivity and specificity of biopsies for predicting non-diploid cancer were 55% and 82%, respectively, and the positive and negative predictive values were 69% and 72%, respectively. The ploidy status of tumors with and without ploidy heterogeneity was correctly predicted in 55% and 82% of cases, respectively (p=0.04). Biopsies underestimated ploidy in 9/20 tumors (45%) with heterogeneous ploidy status. Underestimation mainly occurred when one or two cores were analyzed. Conclusions. Preoperative prediction of the ploidy status of prostate cancer is hampered by tumor heterogeneity. Analysis of multiple biopsies is important for correct preoperative ploidy estimation.

Multiple transrectal ultrasound-guided biopsies for the detection of prostate cancer and determination of tumor volume, grade, and seminal vesicle invasion.

A total of 251 men with suspected prostate cancer were examined by transrectal ultrasound (TRUS) in order to evaluate the usefulness of TRUS and core biopsies for the detection of prostate cancer and determination of tumor volume, grade, and seminal vesicle invasion (SVI). Biopsies targeting hypoechoic lesions were taken in combination with systematic biopsies obtained from six standardized locations. Bilateral seminal vesicle biopsies were obtained from 168 of the men. A total of 26 patients underwent surgery and a comparison between the results of the histopathological evaluation of core biopsies and the prostatectomy specimen was performed. A total of 137 cancers were detected. In 34 patients (25%) the tumors were diagnosed by systematic biopsies alone. Tumor volume as estimated by TRUS underestimated the volume when compared to a planimetric technique. Correlation between the two methods was not found by regression analysis. Systematic biopsies did not improve grading compared to the grading of prostatectomy specimens. A total of 24 SVIs were detected. Valuable information was obtained for the diagnosis of prostate cancer by taking systematic biopsies.