Pierre I. Karakiewicz

Outcome of sextant biopsy according to gland volume

OBJECTIVES To reassess positive rate of sextant biopsy according to gland size. METHODS We evaluated 1974 consecutive men with systematic sextant biopsy, among whom we examined biopsy yield according to gland-volume intervals of 10 cc. RESULTS Decreasing yield of sextant biopsy is strongly associated with increasing gland volume (P < 0.001). Highest biopsy rate (39.6%) was recorded among men with prostates smaller than 20 cc. The lowest biopsy rate (10.1%) was recorded among men with prostates between 80 and 89.9 cc. Among men with biopsy-proven cancer, age, serum prostate-specific antigen, and Gleason grade were comparable (P > 0.05) throughout the range of gland-volume intervals. CONCLUSIONS Our findings suggest that gland size represents an important determinant contributing to the yield of sextant biopsy in men at risk of harboring a nonpalpable, isoechoic cancer. Consequently, an individualized sector biopsy approach, based on prostate volume, may warrant consideration because it may ensure superior detection of clinically significant disease among all men at risk, regardless of prostate size.

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

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 1 to 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 remaining 271 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 rectal examination 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.

Comparative evaluation of total PSA, free/total PSA, and complexed PSA in prostate cancer detection

OBJECTIVES To compare the performance of prostate-specific antigen (PSA), the free/total PSA (F/T PSA) ratio, and complexed PSA (cPSA) in prostate cancer detection. METHODS Five hundred thirty-five patients evaluated at the UROMED prostate cancer detection clinic had total PSA, free PSA, and cPSA measured before undergoing transrectal ultrasonography and sextant prostate biopsies. A direct comparison was performed between the different PSA assays to evaluate their ability to detect prostate cancer. RESULTS Of the 535 patients evaluated, 38.1% had prostate cancer detected. The mean age of the entire population was 63.6 years (range 35 to 86). Abnormal digital rectal examination findings were present in 33.4% of the patients. The mean and median values of PSA and cPSA were significantly higher and the F/T PSA ratio was lower in patients with prostate cancer. The F/T PSA ratio performed better than either cPSA or total PSA. A higher specificity was observed with the F/T PSA ratio than with cPSA using either the entire patient population or subsets of patients with PSA levels between 4.0 and 10 ng/mL or 4.0 to 6.0 ng/mL. CONCLUSIONS The use of the F/T PSA ratio offers improved prostate cancer detection compared with either cPSA or total PSA.

Morphologic changes induced by neoadjuvant androgen ablation may result in underdetection of positive surgical margins and capsular involvement by prostatic adenocarcinoma

OBJECTIVE Neoadjuvant androgen ablation (NAAA) causes significant cytoarchitectural changes in both benign and malignant prostatic epithelial cells that may contribute to underdetection of prostate cancer capsular involvement and positive surgical margins. METHODS The aim of this study is to determine the ability of cytokeratin immunohistochemistry to enhance the determination of pathologic stage of prostate cancer following NAAA. RESULTS Cytokeratin AE1/AE3 immunohistochemistry identified 6 (27.3%), 15 (68.2%), 5 (22.7%), and 5 (22.7%) cases of organ-confined disease, capsule penetration, positive surgical margin, and seminal vesicle involvement, respectively, as compared with 10 (45.5%), 10 (45.5%), 3 (13.6%), and 5 (22.7%) cases by hematoxylin-eosin (H&E) staining, respectively. Two cases without detectable tumor by H&E staining had demonstrable residual tumor by cytokeratin immunohistochemical staining. CONCLUSIONS Cytokeratin immunohistochemistry revealed more extensive intracapsular, capsular, and extracapsular tumor involvement and higher rate of positive surgical margin than did conventional H&E staining. Therefore, the beneficial pathologic effects of NAAA observed may, in part, be attributable to the artifact of observation.

Thirty-day mortality rates and cumulative survival after radical retropubic prostatectomy

OBJECTIVES To assess the 30-day mortality rate and overall survival after radical retropubic prostatectomy (RRP). METHODS Identification of all RRPs performed in the Province of Quebec between January 5, 1988 and January 16, 1996 was accomplished through the Quebec Healthcare Plan Database. RESULTS Four thousand nine hundred ninety-seven RRPs were performed by 104 urologists. Overall, 451 deaths were recorded: 32 occurred during the first 30 days (0.6% 30-day mortality rate). A significant decrease in the 30-day mortality rate, from 2.45% to 0.5%, was recorded during the span of the study. The year of surgery, patient age, and hospital type were statistically significant short-term mortality variables (life table analysis). Patient age and year of surgery determined the cumulative survival probability (univariate and multivariate Cox analysis). Cumulative survival at 31 months of follow-up increased from 88.2% in 1988 to 98.1% in 1995. Men 75 years old and older were at a clear disadvantage with regard to survival probability compared with their younger counterparts. CONCLUSIONS In this population-based analysis of RRP outcomes, we demonstrated a significant improvement in short- and long-term outcomes, as evidenced by a decrease in the 30-day mortality rate and an improved cumulative survival, recorded over the span of the study. The recorded outcome trends may be explained by improved patient selection and optimal management. Although we are unable to determine cancer-specific outcomes, the results of this analysis should prove valuable to urologists and patients until there are results from randomized trials.

Three-dimensional computer-assisted analysis of sector biopsy of the prostate☆

OBJECTIVES To assess the relationship between tumor volume, gland volume, number of sectors submitted to biopsy, and prostatic biopsy detection rate. METHODS Using a three-dimensional mathematical model of the prostate, we assessed detection rates achieved with 4-, 6-, 8-, 10-, and 12-sector biopsies for glands ranging from 20 to 100 cc and peripheral zone tumors ranging from 0.3 to 1.4 cc. RESULTS Quadrant and sextant biopsy approaches only yielded from 6.2% to 13.4% and 8.6% to 18.3%, respectively, of lesions in a 40-cc gland. Conversely, 10- and 12-sector approaches yielded, respectively, from 19.8% to 48.8% and 25.4% to 62% of lesions for the same gland size. When assessed according to the density of sampling, one biopsy core used for every 1 .5 to 3.5 cc of prostatic tissue detected 42.5% of 0.5-cc lesions. For the same lesion size, the density of sampling per biopsy core was then decreased to intervals extending from 3.6 to 7.5 cc, 7.6 to 12.5 cc, and 12.6 to 25 cc. These sampling density intervals yielded, respectively, 25.0%, 15.8%, and 9.8% detection rates. CONCLUSIONS On the basis of our results, a gland volume-based biopsy algorithm is likely to result in improved detection of clinically significant prostate cancer.

Computer-assisted comparative analysis of four-sector and six-sector biopsies of the prostate

OBJECTIVES To assess the potential difference in positive biopsy rates between four-sector and six-sector biopsy methods. METHODS This computer-assisted analysis is based on the records of 156 consecutive patients previously diagnosed with T1c cancer on systematic sextant biopsy of the peripheral zone. For each patient the computer randomly deleted one biopsy result from the left and right prostatic lobes. The deletion process was repeated 1000 times. Based on four randomly chosen biopsy cores, we determined the number of undetected cancers initially diagnosed with sextant biopsy. RESULTS Based on four-sector biopsy cores of the peripheral zone, between 6 and 30 (3.8% to 19.2% of cases) nonpalpable, isoechoic prostate cancers that were detected with sextant biopsy would have remained undiagnosed. CONCLUSIONS Our results suggest that the number of biopsy cores used in the early detection of nonpalpable, isoechoic prostate cancer may substantially affect the rate of positive findings.

Patient attitudes regarding treatment-related erectile dysfunction at time of early detection of prostate cancer

OBJECTIVES To assess potency rate and patient attitudes regarding erectile dysfunction. METHODS A multiple choice, self-administered questionnaire distributed to 750 men undergoing testing for early detection of prostate cancer was used. RESULTS Overall, 33.9% of patients reported either partial or complete lack of erections and 31.1% were not sexually active or active less than once per month. Furthermore, 55.4% would be affected or very affected by lack of erections and 73.6% chose definitive treatment despite a 50% chance of erectile dysfunction. Finally, 47.4% found such treatment-induced erectile dysfunction to be an important or very important problem. When asked to ascribe a quantity of life or period of time that they would be willing to sacrifice to preserve sexual function following treatment, only 15.2% of patients were able to do so, but no consensus could be reached regarding its value. CONCLUSIONS Reported differences in quality-adjusted life expectancy when screening was compared to no screening and definitive therapy was compared to expectant management are marginal. Therefore, close attention to seemingly minor variables such as existing impotence rate, attitude regarding erectile dysfunction, and willingness to undergo therapy despite its inherent morbidity may substantially reduce or even reverse this reported disadvantage.

Reassessment of nonplanimetric transrectal ultrasound prostate volume estimates

OBJECTIVES To assess the accuracy and reproducibility of nonplanimetric transrectal ultrasound (TRUS) volume estimates because inaccurate volume estimates may potentially undermine the value of serum prostate-specific antigen density (PSAD) in early prostate cancer detection. METHODS We prospectively evaluated 535 consecutive male patients with two consecutive volume determinations performed by the same ultrasonographer at the time of the same visit. RESULTS Pearson correlation coefficients between two consecutive gland volume estimates ranged from 0.82 to 0.85 depending on the formula used; however, these correlation coefficients corresponded to an average 25% difference between the first and second gland volume estimates. CONCLUSIONS Although two consecutive nonplanimetric TRUS volume estimates show statistically good correlation, clinically up to a 25% volume difference should be expected between two such volume estimates. In consequence, nonplanimetric TRUS volume estimates should be interpreted with caution, especially when used for PSAD calculation, in the early detection of prostate cancer.

Familial Prostate and Breast Cancer in Men Treated with Prostatectomy for Prostate Cancer: A Population based Case-Control Study

PURPOSE We assessed familial prostate and breast cancer in Quebec. MATERIALS AND METHODS Using a self-administered mail survey we assessed the prevalence of prostate and breast cancer in first degree relatives of 1,633 men treated with prostatectomy for prostate cancer in the province of Quebec and in first degree relatives of 1,386 spouse controls. RESULTS The OR of familial breast cancer was 1.1 (95% CI 0.9 to 1.4). The OR of 3.0 (95% CI 2.5 to 3.6) recorded for prostate cancer was modified by francophone versus anglophone linguistic preference (OR 3.2, 95% CI 2.6, 3.9 versus 1.5, 95% CI 0.8 to 2.7, p = 0.02). Male sibship size was a statistically significant parameter modifying this association (p = 0.02), namely no brothers (OR 1.7, 95% CI 1.0 to 2.8), 1 or 2 (OR 3.1, 95% CI 2.2 to 4.3) and 3 or more (OR 3.9, 95% CI 2.9 to 5.2). Geographic regions of the province including and neighboring greater Montreal showed a lower OR than more peripheral regions (2.5, 95% CI 2.0 to 3.2 versus 4.1, 95% CI 2.9 to 5.7, p = 0.02). CONCLUSIONS Francophone men with large male sibships residing in remote areas may be at higher risk for familial prostate cancer and represent the ideal target for further efforts to determine the genetic component of prostate cancer in Quebec.