Percent free prostate specific antigen is not an independent predictor of organ confinement or prostate specific antigen recurrence in unscreened patients with localized prostate cancer treated with radical prostatectomy

PURPOSE: We studied the controversial relationship of percent free prostate specific antigen (PSA) with organ confined prostate cancer and PSA failure after radical prostatectomy. MATERIALS AND METHODS: We tested the characteristics of the percent free PSA monoclonal Immulite DPC Immunoassay (Diagnostic Products Corp., Los Angeles, California) for predicting organ confinement in 698 consecutive unscreened men treated only with radical prostatectomy between 1995 and 2000. In addition, we assessed the ability of percent free PSA to predict post-radical prostatectomy PSA failure, defined as PSA 0.1 ng./ml. or greater, in a subset of 581 men in whom followup was available. All statistical analyses were repeated for stage T1c cancer with PSA between 2 and 10 ng./ml. RESULTS: On univariate analyses percent free PSA achieved significance for predicting organ confined disease at all clinical stages (p <0.001) and for stage T1c cancer with PSA between 2 and 10 ng./ml. (p = 0.012). However, significance dissipated after controlling for total PSA, biopsy Gleason sum and clinical stage (p = 0.135 and 0.851, respectively). In univariate Cox models percent free PSA failed to predict PSA failure across stages (p = 0.341), as well as in stage T1c cancer (p = 0.93). In multivariate analyses controlling for traditional PSA biopsy grade and clinical stage (p <0.001), percent free PSA failed to contribute to predicting PSA failure (p = 0.342). In the stage T1c subset biopsy Gleason sum (p <0.001) and PSA (p = 0.018) remained significant, in contrast to percent free PSA (p = 0.237). CONCLUSIONS: Percent free PSA has no independent, statistically significant association with organ confined status or posttreatment PSA outcome in unscreened patients who undergo radical prostatectomy for localized prostate cancer.     

Prospective detection of clinically relevant prostate cancer in the prostate specific antigen range 1 to 3 ng./ml. combined with free-to-total ratio 20% or less: the Aarau experience

PURPOSE: Little is known about the incidence rate and clinical relevance of prostate cancer in a low prostate specific antigen (PSA) level. In a prospective PSA based screening study we investigated the incidence and clinicopathological features of prostate cancer that occurred within PSA range 1 to 3 ng./ml. when the free-to-total ratio was 0.20 or less. MATERIALS AND METHODS: Men participating in the Aarau, Switzerland, section of the European Randomized Study of Screening for Prostate Cancer between October 1998 and July 2000 were included in the study. As a side study, all men with PSA between 1 and 3 ng./ml. and free-to-total ratio 0.20 or less were invited to undergo further evaluation with ultrasound guided sextant prostate biopsy. RESULTS: Overall, 168 (7.8%) participants fulfilled inclusion criteria. A total of 158 (94%) patients underwent prostate biopsy, and prostate cancer was detected in 17 (10.8%). There were no statistically significant differences between prostate cancer and benign prostatic hyperplasia in regard to patient age (60.7 versus 59.8 years), prostate volume (23.9 versus 23.0 cc), PSA (1.98 versus 1.86 ng./ml.), free-to-total ratio (0.161 versus 0.160), PSA density (0.089 versus 0.076 ng./ml.) or PSA transition zone density (0.33 versus 0.24 ng./ml., respectively). Median Gleason score was 5 on prostate biopsy versus 6 on retropubic prostatectomy specimen. Of the 14 patients who underwent surgery there were positive lymph nodes in 1, stage pT3b Gleason 7 disease in 1, and pathologically organ confined Gleason 5 in 2, Gleason 6 in 5 and Gleason 7 in 5. Mean tumor volume was 1.01 cc (range 0.02 to 5.17). There were 2 (14.3%) insignificant (less than 0.2 cc, Gleason grade 3 or less), 1 (7.1%) minimal (less than 0.5cc, Gleason grade 3 or less) and 11 (78.6%) clinically relevant and potentially harmful cancers. CONCLUSIONS: There is a significant number of prostate cancer cases diagnosed at PSA as low as 1 to 3 ng./ml. A majority of these tumors are clinically significant. This free-to-total ratio range may be helpful for identifying prostate cancer. The "window of opportunity" for detection of curable cancer may change in populations with higher life expectancy towards lower PSA. Lack of specificity and characterization of tumor aggressiveness remains an unsolved issue for PSA.     

Predicting pathological stage of localized prostate cancer using volume weighted mean nuclear volume

PURPOSE: With the use of prostate specific antigen (PSA) and transrectal ultrasound guided biopsy of the prostate, increasing numbers of clinically localized prostate cancers have recently been detected. Presently, approximately 60% of men newly diagnosed with prostate cancer are believed to have organ confined disease but at the time of surgery less than 50% are ultimately found to have organ confined disease on final pathological analysis. Prediction of pathological stage before surgery using various prognostic factors is needed to determine whether radical prostatectomy is indicated. We have reported that estimates of volume weighted mean nuclear volume can accurately predict the prognosis of clinically localized prostate cancer treated with androgen ablation. In this study we examine whether estimates of mean nuclear volume can predict the pathological stage of cases treated with radical prostatectomy. MATERIALS AND METHODS: A retrospective, prognostic study of 52 patients with clinically localized prostate cancer (21 cases T1c, 27 T2, 4 T3) diagnosed at Kobe City General Hospital between January 1996 and December 1999 and treated with radical prostatectomy was performed. Unbiased estimates of mean nuclear volume measured from transrectal biopsy specimens were compared with PSA at diagnosis, clinical stage, estimated tumor volume and Gleason score with regard to prediction of pathological stage. RESULTS: Univariate analysis revealed that estimates of mean nuclear volume (p <0.0001), PSA at diagnosis (p = 0.0148) and estimated tumor volume (p = 0.0005) significantly correlated with pathological stage but Gleason score did not (p = 0.2011). In addition, multivariate logistic regression analysis demonstrated that estimates of mean nuclear volume (p = 0. 0073), PSA at diagnosis (p = 0.0277) and estimated tumor volume (p = 0.0197) were significantly independent predictors of pathological stage. CONCLUSIONS: The results of our study suggest that combining PSA and estimated tumor volume with estimates of mean nuclear volume can significantly contribute to the prediction of pathological stage of prostate cancer. We recommend use of these 3 factors to predict pathological stage of prostate cancer before surgery.     

A validated strategy for side specific prediction of organ confined prostate cancer: a tool to select for nerve sparing radical prostatectomy

PURPOSE: Nerve sparing radical prostatectomy for prostate cancer should be restricted to patients who harbor tumors without capsular penetration. To our knowledge the selection criteria for nerve sparing radical prostatectomy are not clearly defined. We investigated a panel of preoperative tumor characteristics with respect to their ability to predict organ confined tumor growth for each lobe of the prostate to indicate unilateral or bilateral nerve sparing radical prostatectomy. MATERIALS AND METHODS: Nine preoperative tumor characteristics in 278 patients with clinically localized prostate cancer were included in retrospective univariate and multivariate tree structured regression analysis. The association of clinical stage, serum prostate specific antigen (PSA), PSA density, and results of transrectal ultrasound and systematic sextant biopsy, including a quantitative assessment of cancer in the biopsies with organ confined tumor growth, was statistically evaluated. Except for serum PSA and PSA density preoperative characteristics were considered separately for each prostate lobe. Multivariate analysis results were validated prospectively in 353 patients. RESULTS: On univariate analysis the number of positive biopsies was the most useful single parameter with a positive predictive value of 83% in 274 lobes and a negative predictive value of 55%, followed by mm. of tumor in the biopsy. Of all characteristics included in multivariate analysis only the number of biopsies with high grade cancer, the number of positive biopsies and serum PSA were independent for predicting organ confined cancer. When PSA was less than 10 ng./ml. and not more than 1 biopsy with high grade cancer was identified in a lobe, organ confined tumor growth was present in 86.1% of cases. On prospective validation the same criteria led to an 88.5% incidence of organ confined prostate cancer. Pooling the 2 most favorable groups led to 391 prostate lobes (70.8% of those investigated) with a positive predictive value of 82.1% (95% confidence interval 77.9% to 85.8%). Using the multivariate approach more prostate lobes were assigned to a favorable risk group than on univariate analysis. Clinical stage and simple Gleason grade did not contribute independent information for predicting organ confined disease. CONCLUSIONS: Quantifying cancer and high grade cancer by systematic biopsy and serum PSA concentration are useful preoperative characteristics for predicting organ confined prostate cancer. Side specific analysis of these parameters is a flexible and reliable tool for selecting patients for nerve sparing radical prostatectomy.     

Validation of Partin tables for predicting pathological stage of clinically localized prostate cancer

PURPOSE: The accurate prediction of pathological stage of prostate cancer using preoperative factors is a critical aspect of treatment. In 1997 Partin et al published tables predicting pathological stage using clinical stage, Gleason score and prostate specific antigen (PSA). We tested the validity of the Partin tables. MATERIALS AND METHODS: From 1990 to 1996 inclusively 5,780 patients underwent bilateral pelvic lymphadenectomy and radical prostatectomy for prostate cancer at the Mayo Clinic. However, only 2,475 of these patients met all inclusion criteria of no preoperative treatment, known biopsy Gleason score, available preoperative PSA done either before biopsy or more than 28 days after biopsy and clinical stage T1, T2 or T3a. Among the 2,475 patients 15 had positive lymph nodes and planned prostatectomy was abandoned. The receiver operating characteristics (ROC) curve area, observed and predicted Partin rates of each pathological stage, and positive and negative predictive values were used to compare the Mayo study to the Partin tables. RESULTS: The distribution of pathological stage was organ confined in 67% of Mayo cases versus 48% in the Partin study, extracapsular without seminal vesicle or node involvement in 18% versus 40%, seminal vesicle involvement without nodes in 9% versus 7% and were positive nodes in 6% versus 5%. Using the predicted probabilities of Partin et al the ROC curve area for predicted node positive disease was 0.84 for Mayo cases compared to an estimated 0. 82 in the Partin series. The ROC curve area for predicting organ confined cancer was 0.76 for the Mayo Clinic compared to an estimated 0.73 for the Partin series. The observed rates of node positive disease were similar to those predicted (Partin) based on clinical stage, PSA and Gleason score. For organ confined disease Mayo rates were consistently higher than those predicted from the Partin series using a cut point of 0.50 or greater. Positive and negative predictive values were 0.83 and 0.49 versus 0.63 and 0.70 for the Mayo Clinic and Partin series. CONCLUSIONS: Our study provides strong evidence that sensitivity and specificity of the Partin tables for external clinical sites are similar to what was reported.     

An artificial neural network for prostate cancer staging when serum prostate specific antigen is 10 ng./ml. or less

PURPOSE: An artificial neural network was developed to improve the prediction of pathological stage before radical prostatectomy based on variables available at biopsy and clinical parameters. MATERIALS AND METHODS: We used the prospectively accrued European prostate cancer detection data base to train an artificial neural network to predict pathological stage in 200 men with serum prostate specific antigen (PSA) 10 ng./ml. or less who underwent radical prostatectomy. Variables included in the artificial neural network were patient age, serum PSA, free-to-total PSA ratio, PSA velocity, transrectal ultrasound calculated total and transition zone volumes with their associated PSA parameters (transition zone PSA density and PSA density), digital rectal examination and Gleason score on biopsy. Two multilayer perceptron neural networks were trained on the remaining variables. Data on the 200 patients were divided randomly into a training set, a test set and a validation or prospective set. RESULTS: Overall classification accuracy of the artificial neural network was 92.7% and 84.2% for organ confined and advanced prostate cancer staging, respectively. For preoperatively predicting local versus advanced stage the area under the ROC curve for the artificial neural network was significantly larger (0.91) compared with logistic regression analysis (0.83), Gleason score (0.69), PSA density (0.68), prostate transition zone volume (0.63) and serum PSA (0.62) (all p <0.01). CONCLUSIONS: The artificial neural network outperformed logistic regression analysis and correctly predicted pathological stage in more than 90% of the validation patients with serum PSA 10 ng./ml. or less based on clinical, biochemical and biopsy data. In the future artificial neural networks may represent a significant step for improved staging of prostate cancer when counseling patients referred for radical prostatectomy or other curative treatments.     

Prediction of extraprostatic extension by prostate specific antigen velocity, endorectal MRI, and biopsy Gleason score in clinically localized prostate cancer

Objectives:   To investigate the clinical value of prostate specific antigen velocity (PSAV) in predicting the extraprostatic extension of clinically localized prostate cancer.
Methods:   One hundred and three patients who underwent radical prostatectomy for clinically localized prostate cancer were included in the analysis. The correlation between preoperative parameters, including PSA-based parameters, clinical stage, and histological biopsy findings, and the pathological findings were analyzed. Logistic regression analysis was performed to identify a significant set of independent predictors for the local extent of the disease.
Results:   Sixty-four (60.2%) patients had organ confined prostate cancer and 39 (39.8%) patients had extraprostatic cancer. The biopsy Gleason score, PSA, PSA density, PSA density of the transition zone, and PSAV were significantly higher in the patients with extraprostatic cancer than in those with organ confined cancer. Multivariate logistic regression analysis indicated that the biopsy Gleason score, endorectal magnetic resonance imaging findings, and PSAV were significant predictors of extraprostatic cancer ( P  < 0.01). Probability curves for extraprostatic cancer were generated using these three preoperative parameters.
Conclusions:   The combination of PSAV, endorectal magnetic resonance imaging findings, and biopsy Gleason score can provide additional information for selecting appropriate candidates for radical prostatectomy.     

Expectant management of nonpalpable prostate cancer with curative intent: preliminary results

PURPOSE: We evaluate a strategy of expectant management for men with stage T1c prostate cancer. MATERIALS AND METHODS: A total of 81 men (median age 65 years, range 52 to 72) with stage T1c prostate cancer who were thought to have small volume prostate cancer based on needle biopsy findings and prostate specific antigen (PSA) density were followed for more than 1 year with semiannual PSA and digital rectal examination, and annual prostate biopsies (median followup 23 months, range 12 to 58). A recommendation for treatment was made if disease progression was indicated by unfavorable followup needle biopsy findings (Gleason pattern 4 or 5, greater than 2 biopsy cores with cancer, greater than 50% involvement of any core with cancer). Curable disease was defined on pathological examination of radical prostatectomy specimens as 1) organ confined cancer of Gleason score 7 or less, 2) cancer with extraprostatic extension of Gleason score 7 (3+4) or less with negative margins, seminal vesicles and lymph nodes, or 3) cancer of Gleason score 6 or less regardless of margin status or extraprostatic extension if negative seminal vesicles and lymph nodes. RESULTS: Of the 81 men 25 (31%) had progression of disease at followup. PSA density was statistically significantly higher (p = 0.01) and the percentage of free PSA was statistically significantly lower (p = 0.04) in men with compared to those without disease progression. Disease progression occurred in 22 of 39 men (56%) with every followup biopsy showing cancer compared to 3 of 42 (2%) men with 1 or more negative followup biopsies (p <0.001). Of the 25 men with progression 13 underwent radical prostatectomy and 12 of 13 (92%) had curable cancers. CONCLUSIONS: Expectant management with curative intent may be a reasonable alternative for carefully selected older men who are thought to have small volume cancers.     

血清tPSA、PSAD及Gleason评分在前列腺癌分期中的应用价值

目的:探讨血清前列腺特异性抗原(PSA)系列及穿刺组织活检Gleason评分在前列腺癌病理分期的预测价值。方法:回顾性分析我院1999～2008年病理证实为前列腺腺癌的124例患者资料,将该124例患者根据术后病理、骨扫描和CT或MRI结果分为A、B两组。骨扫描、CT、MRI或术后证实为有周围浸润或远处转移者归为A组;无周围浸润且无远处转移者归为B组。比较两组之间以上各指标的差异。通过多因素回归分析筛选前列腺癌病理分期的影响因子。运用工作特征曲线(ROC曲线)比较各指标的预测价值。结果:tPSA、穿刺活检Gleason评分值A组明显高于B组(P<0.05);多元Logistic回归分析中,仅tPSA进入模型,被认为是最主要的预测因子。ROC曲线对前列腺病理分期预测效力比较:联合分析tPSA与穿刺活检Gleason评分预测效果明显高于其他指标,工作特征曲线下面积(AUC)从大到小依次为Gleason评分+tPSA>tPSA>PSAD+tPSA+Gleason评分。结论:tPSA依然是临床上对前列腺癌病理分期较好的预测因素;联合穿刺组织活检Gleason评分,可以提高预测准确度,对指导临床治疗和预后有重要意义。     

THE VALUE OF THE RATIO OF FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN FOR STAGING PURPOSES IN PREVIOUSLY UNTREATED PROSTATE CANCER

Purpose

We analyzed the use of the ratio of free-to-total prostate specific antigen (PSA), also termed percentage of the free PSA, for predicting tumor stage, volume and grade in patients with clinically localized prostate cancer.

Materials and Methods

A total of 515 consecutive patients underwent further prostate evaluation due to elevated PSA (greater than 4.0 ng./ml.) or abnormal digital rectal examination. Prostate cancer was diagnosed in 307 patients (59.6%), including 170 (55.4%) who underwent radical retropubic prostatectomy. Data on pathological stage, Gleason grade, and total and Gleason grade 4 cancer volume were available in all patients. In the remaining 208 men (40.4%) benign prostate hyperplasia was diagnosed. Total and free PSA was measured in preoperative serum.

Results

Total PSA was significantly higher (p <0.0001) in the 71 men with stage pT3 tumors than in the 91 with pT2 disease. Eight patients had stage pT4 tumors. Cancer volume correlated well with advancing pathological stage (p <0.0001) and total PSA (p <0.0001). The free-to-total PSA ratio was not significantly different (p = 0.93) in stages pT2 and pT3 tumors, and it did not correlate with total (p = 0.71) or pure Gleason grade 4 (p = 0.94) cancer volume. However, the ratio of free-to-total PSA tended to decrease (p = 0.07) in tumors of increasing Gleason grade.

Conclusions

The ratio of free-to-total PSA does not help in the preoperative prediction of final tumor stage and volume. However, disease grading may alter the free-to-total PSA ratio.     

PREDICTORS OF PATHOLOGICAL STAGE BEFORE NEOADJUVANT ANDROGEN WITHDRAWAL THERAPY AND RADICAL PROSTATECTOMY

Purpose

This prospective randomized trial was used to compare predictive factors for organ confined margin negative status after radical prostatectomy with and without a 3-month course of neoadjuvant androgen withdrawal therapy.

Materials and Methods

A total of 213 patients with localized adenocarcinoma of the prostate were randomized to radical prostatectomy with or without a 3-month course of 300 mg. neoadjuvant cyproterone acetate daily. Multivariate logistic regression analysis was used to determine significant predictors of organ confined margin negative status after radical prostatectomy in both groups. Parameters evaluated included baseline prostate specific antigen (PSA 4 or less, 4.1 to 10, greater than 10 ng./ml.), clinical stage (T2c versus T2b or less), biopsy Gleason score and percentage of surface area of biopsies involved with cancer. The multivariate analysis was repeated with PSA density and the natural logarithm of PSA to optimize the model.

Results

In the radical prostatectomy alone arm a model incorporating only PSA density was the best predictor of organ confined margin negative status. In the neoadjuvant androgen withdrawal therapy arm a model incorporating biopsy Gleason score, PSA density and clinical stage was the best predictor.

Conclusions

The conventional predictors of pathology at radical prostatectomy, biopsy Gleason score, PSA density and clinical stage retain significance as predictors in patients treated with a 3-month course of neoadjuvant androgen withdrawal therapy before radical prostatectomy.     

The percent of cores positive for cancer in prostate needle biopsy specimens is strongly predictive of tumor stage and volume at radical prostatectomy

PURPOSE: Pretreatment clinical staging of prostatic adenocarcinoma is important due to the increasing use of nonsurgical treatment options. Using multivariate analysis we assessed the predictive value of biopsy cores positive for cancer as a percent of all cores obtained as well as the percent surface area of needle cores involved with tumor for determining tumor volume and pathological stage at radical prostatectomy. Candidate variables for the multivariate model included patient age, clinical disease stage, serum prostate specific antigen (PSA) and Gleason score of cancer in the needle biopsy. MATERIALS AND METHODS: We reviewed prostate needle biopsy findings in 207 consecutive patients who subsequently underwent radical retropubic prostatectomy. Each biopsy specimen was assessed for tumor involvement by calculating the percent of cores positive for cancer, percent surface area involved in all cores and Gleason score. Initial serum PSA and preoperative clinical disease stage were incorporated with biopsy results into a multivariate model to determine the parameters most predictive of pathological stage and tumor volume at radical retropubic prostatectomy. RESULTS: Of the 207 patients 152 (73.4%) had organ confined cancer and 55 (26.6%) had extraprostatic extension (pathological stages T2 and T3 or greater, respectively). Preoperative clinical staging information was available in 195 cases, in which disease was clinically confined and not confined in 184 (94.4%) and 11 (5.6%), respectively. Needle biopsy revealed a surface area of cancer ranging from less than 5% in 69 patients (33.3%) to 90% (mean 16, median 10). Univariate analysis demonstrated that the risk of extraprostatic extension was predicted by preoperative serum PSA (p = 0.027), the percent of cores and percent of surface area positive for cancer (p <0.0001), and Gleason score (p = 0.0009). Clinical stage approached significance (p = 0.071). Multivariate analysis showed that the percent of positive cores (p = 0.0003), initial serum PSA (p = 0.005) and Gleason score of cancer in the needle biopsy (p = 0.03) were the only parameters that jointly predicted pathological stage (T2 versus T3). Percent of tumor surface area involvement in the needle biopsies did not add any more information after the percent of positive cores was known. Univariate analysis revealed that the percent of cores positive for cancer (Spearman r = 0.52, p <0.0001), Gleason score (Spearman r = 0.34, p <0.0001) and initial serum PSA (Spearman r = 0.24, p = 0.003) were predictive of log tumor volume at radical prostatectomy, while clinical stage was not (rank sum test p = 0.14). On multivariate analysis the percent of positive cores (p <0.0001), Gleason score (p <0.0001) and initial serum PSA (0.0033) were the only variables that jointly were predictive of tumor volume. CONCLUSIONS: The percent of needle biopsy cores and surface area positive for cancer are the strongest predictors of pathological stage and tumor volume on multivariate analysis incorporating preoperative serum PSA and Gleason score.     

Under staging and under grading in a contemporary series of patients undergoing radical prostatectomy: results from the Cancer of the Prostate Strategic Urologic Research Endeavor database

PURPOSE: We determined the prevalence of under staging and under grading in contemporary patients undergoing radical prostatectomy in academic and community based urology practices, and defined important predictors of under staging in this population. MATERIALS AND METHODS: We compared clinical T stage and biopsy Gleason score with pathological T stage and prostatectomy Gleason score in 1,313 patients enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor database, a longitudinal registry of patients with prostate cancer, who underwent radical prostatectomy, including 53% since 1995. Under grading was determined for the primary and secondary Gleason patterns and defined as a biopsy Gleason pattern of 1 to 3 that became pathological Gleason pattern 4 or 5. Under staging was defined as a clinically organ confined tumor that was extraprostatic stages pT3 to 4 or N+ at radical prostatectomy. Univariate and multivariate analysis was performed to determine important risk factors for under staging and significant risk factors were used to identify the likelihood of under staging in clinically relevant patient subgroups. The importance of the percent of positive biopsies in regard to the likelihood of under staging was determined by assigning patients to previously described risk groups based on serum prostate specific antigen (PSA) at diagnosis and biopsy Gleason score. RESULTS: Under grading of primary and secondary Gleason patterns occurred in 13% and 29% of patients, respectively, while under staging occurred in 24%. Univariate and multivariate analysis revealed that PSA at diagnosis, biopsy Gleason score and the percent of positive biopsies were significant predictors of under staging. The percent of positive biopsies appeared to be most important for predicting the likelihood of extraprostatic disease extension in intermediate or high risk disease based on serum PSA at diagnosis and biopsy Gleason grade. CONCLUSIONS: The prevalence of under grading and under staging in contemporary patients undergoing radical prostatectomy may be lower than previously reported. PSA at diagnosis, biopsy Gleason score and the percent of positive biopsies are important predictors of under staging. The percent of positive biopsies should be incorporated into risk assessment models of newly diagnosed prostate cancer.     

Predictors of first repeat biopsy cancer detection with suspected local stage prostate cancer

PURPOSE: We determine demographic and tumor related predictors of repeat biopsy cancer detection in men with suspected stage T1c-2 prostate cancer. MATERIALS AND METHODS: The study population included 298 consecutive men with suspected stage T1c-2 prostate cancer who had a benign prostate biopsy at 1 institution between January 1, 1992 and April 1, 1999 and underwent 1 repeat biopsy. Mean age plus or minus standard deviation was 66.8+/-6.7 years for 133 black (55%) and 165 white (45%) patients. Clinical measures included determination of high grade prostatic intraepithelial neoplasia in benign biopsy specimens, Gleason score of malignant biopsy specimens, prostate specific antigen (PSA), PSA density, annualized interbiopsy PSA change, percent free PSA (201 cases) and PSA velocity (171). RESULTS: Cancer was detected on repeat biopsy in 80 cases (27%). Significant differences between patients with benign and malignant repeat biopsies included age (p = 0.001), PSA density (p = 0.0001), percent free PSA (p = 0.0001) and PSA velocity (p = 0.009). High grade prostatic intraepithelial neoplasia in an initial benign biopsy was not predictive of cancer in repeat biopsy (p = 0.12). Multiple logistic regression analysis of all cases showed that age (p = 0.002) and PSA density (p = 0.0002) were independent predictors of cancer. Subset multiple logistic regression analysis modeled with age, PSA density and percent free PSA demonstrated that age (p = 0.002) and percent free PSA (p = 0.0001) were significant independent predictors of malignancy. Subset multiple logistic regression analysis modeled with age, PSA density, percent free PSA and PSA velocity revealed that age (p = 0.02) and percent free PSA (p = 0.0003) were significant independent predictors of cancer. There were no significant differences between the Gleason scores of cancers detected on repeat biopsy compared to 587 stage T1c-2 cancers detected on initial biopsy during the study period (p = 0.09). PSA, PSA density, percent free PSA and PSA velocity were not significantly different among men without a cancer diagnosis who had high grade neoplasia in 1 or 2 benign biopsies. CONCLUSIONS: Greater than 25% of this population of select patients with suspected stage T1c-2 prostate cancer had malignancy detected on repeat biopsy. Percent free PSA was the most powerful predictor of cancer. High grade prostatic intraepithelial neoplasia was not a predictor of repeat biopsy cancer detection and PSA functions were similar among men without cancer who did and did not have high grade neoplasia in 1 or more benign biopsies. This finding suggests that high grade prostatic intraepithelial neoplasia may not be a reliable indicator of clinically significant existing prostate cancer.     

The use of neural networks and logistic regression analysis for predicting pathological stage in men undergoing radical prostatectomy: a population based study

PURPOSE: Clinical under staging occurs in 40% to 60% of patients who undergo radical prostatectomy for prostate cancer. To decrease under staging several methods of predicting pathological stage preoperatively have been developed based on statistical logistic regression analysis and neural networks. To our knowledge none has been validated in our homogeneous regional patient population to date. We created logistic regression and neural network models, and implemented and adapted them into our practice. We also compared the 2 methods to determine their value and practicality in daily clinical practice. We present the results of our novel approach for predicting pathological staging of prostate adenocarcinoma. MATERIALS AND METHODS: Between 1986 and 1999, 600 white men from the Aragon region of Spain underwent surgery for prostate cancer; of whom 468 were selected for study. Predictive study variables included patient age, clinical stage, biopsy Gleason score and preoperative prostate specific antigen (PSA). The predicted result included in analysis was organ confined or nonorgan confined disease. Data were analyzed by multivariate logistic regression and a supervised neural network (multilayer perceptron and radial basis function). Results were compared by comparing the areas under the receiver operating characteristics curves. RESULTS: We generated 5 logistic regression models. The model created with clinical staging, Gleason biopsy score and PSA distributed in 5 categories (p <0.001) with an area under the receiver operating characteristics curve of 0.840 proved to be most predictive of pathological stage. Similarly of the 6 neural network models evaluated the radial basis function model, which included age, clinical stage, Gleason biopsy score and preoperative PSA distributed in 5 categories with an area under the curve of 0.882, proved the most predictive but not superior to the logistic regression model. The difference in the area under the curves in the 2 chosen models was 0.042 (p = 0.1). CONCLUSIONS: It is possible to generate useful predictive models of organ confined disease using logistic regression or neural networks with high indexes of clinical and statistical validity. However, using these variables neural networks did not prove to be better than logistic regression analysis. Therefore, better predictive variables must be identified, preferably nonlinear characteristics with respect to the probability of organ confined tumor, to generate better predictive models using neural networks.     

An Algorithm for Predicting Nonorgan Confined Prostate Cancer Using the Results Obtained from Sextant Core Biopsies with Prostate Specific Antigen Level

Purpose

We determined the enhanced ability to predict nonorgan confined prostate cancer using several histopathological and quantitative nuclear imaging parameters combined with serum prostate specific antigen (PSA).

Materials and Methods

Several independent pathological and quantitative image analysis variables obtained from sextant biopsy specimens, as well as preoperative PSA were used. The study population included 210 patients with pathologically staged disease (192 with PSA). All variables were examined by univariate and multivariate logistic regression analyses to assess ability to predict disease organ confinement status.

Results

Univariate logistic regression analysis demonstrated that, in decreasing order, quantitative nuclear grade, preoperative PSA, total percent tumor involvement, number of positive sextant cores, preoperative Gleason score and involvement of more than 5 percent of a base and/or apex biopsy were significant (p less than or equal 0.006) for prediction of disease organ confinement status. Backward stepwise logistic regression was applied to these univariately significant variables, including deoxyribonucleic acid ploidy, to calculate a multivariate model for prediction of disease organ confinement status. This algorithm had a sensitivity of 85.7 percent, specificity 71.3 percent, positive predictive value 72.9 percent, negative predictive value 84.7 percent and area under the receiver operating characteristic curve 85.9 percent.

Conclusions

Information from pathological study of sextant prostate biopsies, preoperative PSA blood test and a new image analysis variable termed quantitative nuclear grade can be combined to create a multivariate algorithm that can predict more accurately nonorgan confined prostate cancer compared to previously reported methods.     

Gleason score 7 prostate cancer on needle biopsy: is the prognostic difference in Gleason scores 4 + 3 and 3 + 4 independent of the number of involved cores?

PURPOSE: We addressed whether Gleason score 3 + 4 = 7 and 4 + 3 = 7 cancers on needle biopsy behave differently and whether this behavior is independent of the number of cores involved by cancer. If it is not an independent predictor of prognosis, one may report Gleason score 7 cancer with the number of positive cores without regard to whether the primary pattern was 3 or 4. This practice would remove a source of poor interobserver reproducibility when grading prostate cancer on needle biopsy. MATERIALS AND METHODS: We identified 537 patients with Gleason score 7 tumors on biopsy. The results of patient preoperative digital rectal examination, serum prostate specific antigen (PSA) measurement and age were used to predict 4 outcomes based on assessment of the corresponding radical prostatectomy specimens, including 1) pathological stage (organ confined, focal extraprostatic extension, nonfocal extraprostatic extension or seminal vesicle-lymph node involvement), 2) organ confinement (yes/no), 3) Gleason score and 4) surgical margin status (positive/negative) RESULTS: Multivariate regression of postoperative Gleason score groups against all 5 input variables (3 + 4 versus 4 + 3, number of positive cores, PSA, age and digital rectal examination) yielded a statistically significant positive correlation with preoperative PSA (p <0.001) and preoperative Gleason scores of 4 + 3 versus 3 + 4 on biopsy (p <0.001). Pathological stage correlated with preoperative PSA (p <0.001), Gleason score 4 + 3 disease (p = 0.016), positive digital rectal examination (p <0.001) and 3 or more positive cores (p = 0.016). Positive surgical margins were predicted only by preoperative PSA (p = 0.001). CONCLUSIONS: Because the biological behavior of biopsy Gleason score 3 + 4 or 4 + 3 of Gleason score 7 cancer differs regardless of the number of cores involved, future nomograms predicting pathological stage would benefit from examining 3 + 4 and 4 + 3 disease separately.     

Free-to-Total Prostate Specific Antigen Ratio as a Single Test for Detection of Significant Stage T1c Prostate Cancer

Purpose

We investigated whether impalpable, invisible (stage T1c) but significant prostate cancer can be detected better by determining the free-to-total prostate specific antigen (PSA) ratio of equivocal PSA serum levels.

Materials and Methods

The specificity of free-to-total PSA ratio using research monoclonal enzyme immunoassays was compared to that of PSA greater than 4.0 ng./ml. in 117 consecutive patients with PSA 3 to 15 ng./ml. (Hybritech Tandem-R assay) due to untreated benign prostatic hypertrophy or prostate cancer. Of the patients 77 percent underwent adenectomy or radical prostatectomy with thorough pathological evaluation of surgical specimens.

Results

Benign prostatic hypertrophy had a greater median free-to-total PSA ratio than stages T1c and T2 or greater prostate cancer (0.16 versus 0.09 and 0.11 ng./ml., p = 0.0001 and p = 0.0268, respectively). In stage T1c prostate cancer, areas under receiver operating characteristic curves were 0.58 and 0.84 for PSA and free-to-total PSA ratio, and free-to-total PSA ratio correlated with prostate volume (r = 0.49, p = 0.005) and Gleason score (r = -0.37, p = 0.036). Pathologically, 84 percent of stage T1c cancers were significant and comparable to stage T2 or greater cancers.

Conclusions

Free-to-total PSA ratio enhances the efficacy of PSA measurement by improving specificity for detecting impalpable, invisible but significant stage T1c prostate cancer.     

前列腺癌血清PSA、f/tPSA与Gleason评分、临床分期的相关性研究

目的 探讨前列腺癌病人血清PSA、f/tPSA（血清游离PSA与总PSA的比值）与前列腺癌Gleason评分、临床分期的相关性.方法 查阅我院1998年1月～2005年6月归档的前列腺癌病历资料,建立临床资料数据库,对归档病理切片进行Gleason评分.采用Spearman等级相关分析,分析血清PSA、f/tPSA与前列腺癌Gleason评分、临床分期的关系.结果 269例前列腺癌中,前列腺癌PSA值与Gleason评分呈正相关（r=0.361,P＜0.01）,与前列腺癌临床分期呈正相关（r=0.586,P＜0.01）;f/tPSA与Gleason评分有弱负相关（r=-0.128,P=0.035）,与前列腺癌临床分期呈负相关（r=-0.226,P＜0.01）.结论 血清PSA、f/tPSA与前列腺癌预后密切相关的指标临床分期和Gleason评分有关.     

Preoperative parameters, including percent of positive biopsy cores, in predicting pathological findings after radical prostatectomy

OBJECTIVES: We investigated whether preoperative parameters predict pathological stage at radical prostatectomy for patients with clinically localized prostatic cancer. MATERIALS AND METHODS: We studied a total of 160 men with clinically localized prostatic cancer (less than or equal to clinical T2) who underwent radical rertropubic prostatectomy at Wakayama Medical University. Clinical Ts patients are not included in this study. Preoperative parameters include patient age, Body Mass Index, preoperative serum PSA value, biopsy Gleason score, clinical stage, the percent of positive biopsy cores (%PosBx) and the percent of positive biopsy cores on the dominant side (%DomPosBx). Univariate and multivariate analysis were performed to examine the prognostic significance of these preoperative parameters. Significant independent factors were combined to create a table to predict pathologically organ confined disease. RESULTS: Univariate analysis showed preoperative serum PSA value (p< 0.001), biopsy Gleason score (p =0.001), clinical stage (p = 0.026), %PosBx (p= 0.002) and %DomPosBx (p=0.003) were significantly related to the pathological stage. On multivariate analysis, serum PSA value (p< 0.01), biopsy Gleason score (p<0.05) and %DomPosBx (p<0.05) were significant independent predictors of pathological stage. CONCLUSION: We provide two model combinations using preoperative clinical factors, one is a combination of serum PSA and biopsy Gleason score and the other is a combination of serum PSA and %DomPosBx, which define a new preoperative model for predicting pathological organ confined prostatic cancer. These combinations are useful and provide important information for urologists to determine the appropriate treatment strategy for clinically localized prostatic cancer.