Vivek Bhargava

The optimal systematic prostate biopsy scheme should include 8 rather than 6 biopsies: results of a prospective clinical trial.

PURPOSE We define the optimal systematic biopsy regimen to detect carcinoma of the prostate. MATERIALS AND METHODS A total of 483 consecutive patients referred for an abnormal digital rectal examination and/or prostate specific antigen (PSA) 4.0 ng./ml. or greater underwent transrectal ultrasound and systematic biopsy. Lateral biopsies of the peripheral zone at the base and mid gland were added to the routine sextant biopsy regimen for a total of 10 systematic biopsies of the peripheral zone. Patients with a prostate greater than 50 cc also underwent systematic sextant transition zone biopsy in the mid lobar parasagittal plane. Detection rates of the various regions were assessed. Various biopsy schemes were then created and cancer detection rates were compared using McNemars test. RESULTS Of the patients 42% (202 of 483) had cancer on biopsy. Traditional sextant biopsies missed 20%, while a sextant regimen incorporating lateral peripheral zone biopsies of the mid gland and base along with the apex missed 11% of the cancers. The combination of sextant and lateral peripheral zone biopsies (10-biopsy scheme) detected 194 cancers (96%). The 8 missed cancers were detected by lesion directed (5) or transition zone (3) biopsies. Eliminating the mid lobar base biopsies from the systematic 10-biopsy peripheral zone regimen resulting in an 8-biopsy peripheral zone regimen decreased detection from 96% to 95%. CONCLUSIONS The 6 systematic biopsies of the peripheral zone are inadequate and a minimum of 8, including the apex, mid lobar mid gland, lateral mid gland and lateral base, should routinely be performed.

PROSPECTIVE EVALUATION OF LATERAL BIOPSIES OF THE PERIPHERAL ZONE FOR PROSTATE CANCER DETECTION

PURPOSE We evaluate the usefulness of adding 4 lateral biopsies of the peripheral zone to the routine sextant biopsy regimen for prostate cancer. MATERIALS AND METHODS A total of 273 consecutive patients referred for abnormal digital rectal examination and/or prostate specific antigen 4 ng./ml. or greater underwent transrectal ultrasound and systematic biopsy. Lateral biopsies of the peripheral zone taken just medial to the lateral border of the prostate were added to the routine lesion directed and systematic sextant biopsy regimen. Comparisons between positive and negative biopsy groups as well as among various biopsy schemes were performed. RESULTS Of the patients 44% had cancer on biopsy (121 of 273). While routine sextant biopsies detected 82% of cancers, 77% (17 of 22) of missed cancers were detected on lateral biopsies. Overall, lateral biopsies detected 70% of cancers, and tended to be positive in patients with small prostates and high grade tumors. A significant correlation was found between hypoechoic lesions on transrectal ultrasound and positive lateral biopsies (Fishers exact test p = 0.0005). Cancer was found in 74 of 147 patients with lesions on transrectal ultrasound (50%). Routine sextant biopsies detected 76% of cancers (56 of 74 patients) while lateral biopsies detected 80% (59). Of these patients 15 (20%) had positive lateral and negative sextant biopsies. Routine sextant biopsies detected 91% of cancers in 121 patients without lesions on ultrasound (43 of 47). CONCLUSIONS The addition of lateral peripheral zone biopsies increases the sensitivity for cancer detection while nearly eliminating the need for lesion directed biopsies.

LOCALLY RECURRENT PROSTATE TUMORS FOLLOWING EITHER RADIATION THERAPY OR RADICAL PROSTATECTOMY HAVE CHANGES IN KI-67 LABELING INDEX, P53 AND BCL-2 IMMUNOREACTIVITY

PURPOSE We compare the biological phenotype of recurrent prostatic tumors after definitive local therapy (radiation or radical prostatectomy) with that of the same tumors before treatment. MATERIALS AND METHODS Cellular proliferation (Ki-67 labeling index), p53 nuclear reactivity and bcl-2 immunoreactivity were determined in pretreatment and posttreatment tumor specimens from 13 patients with local tumor recurrence following radiation, and in 18 patients with local tumor recurrence following radical prostatectomy. RESULTS Mean Ki-67 labeling index increased approximately 2-fold in locally recurrent tumors after radiation (10.5 versus 5.6%, p=0.0008) or surgery (6.0 versus 3.2%, p=0.0025) when compared with pretreatment tumors. We noted p53 nuclear reactivity in a significantly higher proportion of recurrences than in pretreatment tumors following radiation (54 versus 8%, p=0.032) and surgery (39 versus 5%, p=0.022). Although bcl-2 immunoreactivity was also seen in a higher proportion of recurrent tumors, this difference did not reach statistical significance for either radiation or surgery. CONCLUSIONS Recurrent tumors following either radiation or surgery differ significantly from the corresponding pretreatment tumors with respect to cellular proliferation and p53 nuclear reactivity.

Positive fraction of systematic biopsies predicts risk of relapse after radical prostatectomy

OBJECTIVES To determine whether the positive fraction of systematic sextant biopsies contributes to the prediction of serologic relapse after radical prostatectomy. METHODS A retrospective review of patients who underwent transrectal ultrasound-guided systematic sextant biopsy and radical prostatectomy was performed. No patients received neoadjuvant or adjuvant therapy. The relationship between the positive fraction of systematic biopsies and risk of prostate-specific antigen recurrence was assessed with Kaplan-Meier and multivariate analyses. RESULTS Patients with three or fewer positive sextant biopsies were at a significantly lower risk of relapse after radical prostatectomy than patients with four or more positive biopsies. Tumor grade and systematic biopsy results were the most powerful predictors of serologic relapse. CONCLUSIONS The positive fraction of systematic biopsies contributes to the prediction of risk of relapse after radical prostatectomy.

Systematic sextant biopsies in the prediction of extracapsular extension at radical prostatectomy

OBJECTIVES To evaluate the clinical utility of transrectal ultrasound-guided systematic sextant needle biopsies in the prediction of extracapsular extension (ECE) at radical prostatectomy. METHODS A retrospective analysis of 104 men who underwent systematic biopsy and radical prostatectomy at our institution was performed. All patients underwent preoperative staging by transrectal ultrasound and transrectal ultrasound-guided systematic sextant biopsy. The presence of pathologic ECE was correlated to the number of positive core biopsies on each side of the prostate by chi-square analysis. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios (LRs) were calculated for both positive (two or three biopsies positive per side) and negative (no or one positive biopsy per side) test results. RESULTS Forty-two (20.2%) of 208 sides demonstrated evidence of ECE at radical prostatectomy. Chi-square analysis demonstrated a significant correlation between the number of positive biopsies and the presence of ECE at radical prostatectomy (P = 0.001). Overall, the finding of multiple positive core biopsies (two or three per side) had predictive value with regard to the presence of ECE (sensitivity 62%, specificity 77%, positive predictive value 40%, negative predictive value 89%). The corresponding LRs were 2.5 for a positive and 0.5 for a negative test result. CONCLUSIONS The probability of ECE at radical prostatectomy can be more accurately assessed preoperatively by the combined use of transrectal ultrasound and systematic sextant needle biopsies.

Prospective Evaluation of Prostate Specific Antigen and Prostate Specific Antigen Density in the Detection of Carcinoma of the Prostate: Ethnic Variations

PURPOSE We evaluated prospectively the ethnic variations in prostate specific antigen (PSA) and prostate specific antigen density in the detection of carcinoma of the prostate. MATERIALS AND METHODS A total of 297 consecutive patients with an elevated serum PSA and/or abnormal digital rectal examination underwent transrectal ultrasound with lesion directed and systematic biopsy (6 if the prostatic volume was 50 cc or less and 12 if it was greater than 50 cc). Receiver operating characteristic curves, predictive values and likelihood ratios were calculated for PSA and PSA density for white and black patients. Ethnic analysis was performed for the entire group, patients with a normal digital rectal examination, and those with a normal digital rectal examination and PSA of 4 to 10 ng./ml. RESULTS Of the 297 patients 131 (44%) had cancer, including 48 of 97 black (50%) and 83 of 200 white (42%) patients. Median PSA, PSA density and prostate size did not differ between the positive or negative biopsy groups, or between the ethnic groups in any of the analyses. If all digital rectal examinations were considered PSA density was superior to PSA by receiver operating characteristic analysis for cancer detection in both ethnic groups when all values or PSA of 4 to 10 ng./ml. were considered. However, the significance was lost if only patients with a normal digital rectal examination were considered. In general, predictive values were greater in black patients. Likelihood ratios for a negative test result in black patients demonstrated significant changes in the post-test probability if a PSA density cutoff of 0.1 was used to determine the need for biopsy. Many unnecessary biopsies could be avoided and few cancers would be missed. CONCLUSIONS A PSA density cutoff of 0.1 may be warranted in determining the need for prostate biopsy in black men with a normal digital rectal examination.

Comparison of systematic sextant and lesion directed biopsies in prostate cancer detection.

This study was designed to determine the value of performing separate lesion directed biopsies in addition to systematic random sextant biopsies for the detection, grading, and assessment of bilaterality of prostate cancer. A prospective study of 82 consecutive patients who had peripheral zone hypoechoic regions visualized on transrectal ultrasound was performed. All patients had either an abnormal prostate-specific antigen or an abnormal digital rectal examination and underwent random systematic and lesion directed biopsies. Cancer detection, laterality, and histologic grade of lesion directed biopsies were compared with those from systematic random biopsies. Prostate cancer was detected in 35 (40%) of 82 patients who had a hypoechoic lesion visualized. Three (9%) cancers would have been missed if only systematic biopsies had been performed, while nine (26%) cancers would have been missed if only lesion directed biopsies had been performed. In all but one patient, the Gleason score of the lesion directed biopsy was equal to or within one grade of the highest Gleason score determined from systematic biopsy. Systematic random biopsies detected cancer on the opposite side of a positive lesion directed biopsy in 48% of patients. In no case did a lesion directed biopsy add to the detection of bilateral disease. In conclusion, lesion directed biopsies increase the detection of prostate cancer when performed in addition to systematic random sextant biopsies. However, lesion directed biopsies alone would result in a substantial miss rate of prostate cancer. They do not add to the determination of bilateral disease, nor do they add to the pathologic grading of the detected cancer.