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.     

Value of the serum prostate-specific antigen-alpha 1-antichymotrypsin complex and its density as a predictor for the extent of prostate cancer.

OBJECTIVE: To determine whether serum levels of the prostate-specific antigen-alpha1-antichymotrypsin complex (PSA-ACT) and its density (ACTD) in patients scheduled to undergo radical prostatectomy for clinically localized prostate cancer can predict organ-confined vs extraprostatic disease. PATIENTS AND METHODS: Serum samples were obtained from 62 patients with clinically localized prostate cancer before they underwent radical prostatectomy. PSA and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT, respectively. Furthermore, the PSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) were calculated. The relationships of serum PSA, PSA-ACT, PSAD, ACTD and the pathological stage of the prostatectomy specimens were analysed. RESULTS: The disease was organ-confined or extraprostatic in 30 and 32 men, respectively. In men with organ-confined cancer, the mean PSA and PSA-ACT levels were significantly lower than in those with extraprostatic disease. Furthermore, there were significantly higher mean PSAD and ACTD levels in men with extraprostatic than with organ-confined disease. There were also significant differences in PSA, PSA-ACT, PSAD and ACTD levels at each pathological stage, whereas there was no significant association between these variables and the Gleason score. Receiver-operating characteristic curve analysis for detecting organ-confined disease showed that PSA-ACT and ACTD had a larger area under the curve than PSA and PSAD, respectively, but these differences were not significant. Furthermore, PSA-ACT and ACTD provided significantly better sensitivity for detecting organ-confined disease than PSA and PSAD, respectively. CONCLUSIONS: Measuring PSA-ACT and ACTD may improve the preoperative evaluation of patients scheduled to undergo radical prostatectomy, because these factors better differentiate extraprostatic from organ-confined disease than PSA and PSAD.     

Are predictive models for cancer volume clinically useful in localized prostate cancer?

Objectives: To evaluate the correlation between preoperatively predicted and pathologically measured prostate cancer volumes and to investigate the clinical use of preoperatively predicted cancer volume in predicting pathological stage. Methods: Correlations between pathological findings and various preoperative parameters, including the cancer volumes as predicted by using two methods (Vca and estimated PCvol), were analyzed in 196 patients who underwent radical prostatectomy for clinically localized prostate cancer. Results: Pathologically measured prostate cancer volume was significantly correlated with the Vca and estimated PCvol, but the correlation coefficients were respectively only 0.46 and 0.35. Prostate‐specific antigen (PSA), PSA density (PSAD), primary Gleason score, Vca, Vca fraction (Vcafx), and estimated PCvol were significantly higher in 82 patients with extraprostatic cancer than in 114 patients with organ‐confined cancer. Magnetic resonance imaging (MRI) findings were significantly correlated with pathological stage. Multivariate logistic regression analysis indicated that the Vcafx and MRI findings were significant predictors of extraprostatic cancer, but receiver operating characteristic analysis revealed that the combination of Vcafx and MRI findings had no advantage over the combination of Gleason score, PSAD, and MRI findings. Conclusions: Vca and estimated PCvol are significantly correlated with the pathologically measured cancer volume but their ability to accurately predict cancer volume is limited. Vcafx and MRI findings were statistically significant predictors of extraprostatic cancer but their combination was not superior to the combination of Gleason score, PSAD, and MRI findings.     

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.     

Prediction of focal extracapsular extension at radical prostatectomy: Relative merit of transrectal ultrasound, endorectal magnetic resonance imaging, prostate specific antigen, prostate specific antigen density, and systematic biopsy

We conducted a study to compare the relative merits of prostate specific antigen (PSA), PSA density (PSAD), transrectal ultrasound (TRUS), endorectal magnetic resonance imaging (MRI), and systematic biopsy in the prediction of focal extracapsular extension (ECE) at radical prostatectomy. A retrospective review of patients who underwent TRUS, endorectal MRI, and radical prostatectomy at our institution was performed. Patients with a diagnosis of prostate cancer who were thought to be surgical candidates by digital rectal examination and TRUS underwent endorectal MRI prior to radical prostatectomy. Imaging, PSA, PSAD, and systematic biopsy results (tumor grade and fraction of positive systematic biopsies) were correlated with step-sectioned, radical prostatectomy pathologic data. Data was analyzed for the entire prostate and on each individual side. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios were calculated for each modality, and receiver operating characteristic (ROC) curves were generated. Stepwise logistic regression analysis was used to weigh the relative contributions of preoperative parameters in predicting ECE.

Data was collected from 54 patients who had sextant systematic biopsy, imaging, and radical prostatectomy. A total of 24 sides demonstrated ECE (19 patients, 5 with bilateral ECE). When assessed for the dominant prostate side and on a side-for-side basis, MRI had the highest sensitivity and NPV for detecting focal ECE. MRI also had the highest PPV, and TRUS had the highest specificity for side-for-side analysis. For the dominant prostate side, PSA had the highest specificity and PPV for detecting focal ECE. Of note, significant overlap was demonstrated in the 95% confidence intervals of all modalities with each other for all analyses. ROC analyses found MRI and Gleason sum to be superior for the dominant prostate side assessment and MRI and the fraction of positive systematic biopsies to be superior for a side-for-side analysis. Optimal likelihood ratios for positive test results were seen for PSA (dominant prostate side) and MRI (side-for-side), and for negative test results for MRI. Logistic regression demonstrated MRI and Gleason sum to be powerful predictors of ECE. Thus, we would conclude that endorectal MRI and tumor grade provide unique information in the prediction of focal ECE in select patients.     

A study on parameters to predict tumor volume for stage T1c prostate cancers of Gleason score 6 or less

The number of cases of stage T1c prostate cancer has dramatically been increasing since the introduction of PSA as a screening test. The patients with T1c prostate cancer are usually treated by radical prostatectomy. In this group, however, some cancers are of small tumor volume and with a Gleason score of less than 7. These cancers are considered to be good candidates for watchful waiting management. We have investigated 40 patients with T1c prostate cancer treated by radical prostatectomy between 1996 and 1998. All 9 patients harboring tumors of Gleason score 7 or greater had tumors larger than 0.5 cm3. We have investigated PSA-related parameters including total PSA (PSA), PSA density (PSAD), free PSA, and % free PSA in 31 patients with T1c cancers of Gleason score 6 or less in order to clarify good preoperative predictors of tumor volume. We compared the distribution of PSA, PSAD, free PSA, and % PSA between the larger and smaller tumor groups. There was no significant difference in PSA, PSAD, or free PSA value. The small tumor group had a greater mean % free PSA than the larger tumor group (23.27 versus 11.88, p = 0.007). Areas under receiver operating characteristic curves were 0.715, 0.794, 0.636, and 0.842 for PSA, PSAD, free PSA and % free PSA. In stage T1c prostate cancer of Gleason score 6 or less, % free PSA may be the most useful preoperative predictor for tumor volume of 0.5 cm3 or greater.     

Value of power Doppler sonography with 3D reconstruction in preoperative diagnostics of extraprostatic tumor extension in clinically localized prostate cancer

Aim: The aim of the study is to investigate the value of preoperative power Doppler sonography with 3D reconstruction (3D‐PDS) for diagnostics of extraprostatic extension of prostate cancer. Patients and Methods: In the prospective study we examined 146 patients with clinically localized prostate cancer who underwent radical prostatectomy. Prior to surgery, each patient underwent 3D‐PDS, transrectal ultrasound (TRUS), and digital rectal examination (DRE). Furthermore, we determined the prostate volume, prostate specific antigen (PSA) level, PSA density (PSAD), and Gleason score. The risk of locally advanced cancer was assessed using Partin tables. We determined the sensitivity, specificity, and predictive values of these diagnostic procedures. We plotted the receiver operating characteristic (ROC) curves and calculated the areas under the curves (AUC). Multivariate logistic regression was used to identify the significant predictors of extraprostatic tumor extension. Based on this we developed diagnostic nomograms maximizing the probability of accurate diagnosis. Results: The significant differences between patients with organ confined and locally advanced tumor (based on the postoperative assessment) were observed in the PSA levels (P < 0.014), PSAD (P < 0.004), DRE (P < 0.037), TRUS (P < 0.003), and 3D‐PDS (P < 0.000). The highest AUC value of 0.776 (P < 0.000) was found for 3D‐PDS. The observed AUC value for TRUS was 0.670 (P < 0.000) and for PSAD 0.639 (P < 0.004). In multivariate regression analysis, the PSAD, preoperative Gleason score, and 3D‐PDS finding were identified as significant preoperative predictors of extraprostatic tumor extension. Conclusion: Our data suggest that the 3D‐PDS is a valuable preoperative diagnostic examination to identify locally advanced prostate cancer. Therefore, it can be used to maximize the probability of the accurate diagnosis of extraprostatic tumor extension.     

PSAD预测前列腺癌根治术前后G1eason评分变化的临床应用价值

目的：探讨前列腺根治术前血清前列腺特异性抗原密度（PSAD）预测术后Gleason评分变化的应用价值。方法：对133例行前列腺癌根治术的患者资料进行回顾,将前列腺癌根治术前术后Gleason评分变化与患者年龄、术前Gleason评分、前列腺特异性抗原（PSA）、前列腺体积和PSAD的相关性进行分析,并进一步分析术前Gleason评分≤6患者中评分升高和Gleason评分≥7患者中评分下降与上述因素的关系。结果：133例患者中经直肠超声（TRUS）引导下前列腺穿刺活检Gleason评分与前列腺癌根治术后Gleason评分保持一致52例（39．1％）,评分下降13例（9．8％）,评分升高68例（51．1％）。PSAD（P=0．002）与Gleason评分升高明显相关,未发现Gleasbn评分≥7患者中评分下降与前列腺特异性抗原（PSA）、前列腺体积和PSAD有相关性。进一步应用受试者工作特征（receiver operating characteristic,ROC）曲线分析得出：TRUS穿刺活检Gleason评分≤6患者PSAD〉0．2435预示根治术后Gleason评分升高可能性较大。结论：TRUS引导下前列腺穿刺活检Gleason评分较低且PSAD较高的前列腺癌患者提示有可能实际Gleason评分升高,进而影响治疗选择和预后。     

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.     

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。     

Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer

PURPOSE: We retrospectively reviewed the clinical followup for a large series of men with clinically localized prostate cancer who underwent radical retropubic prostatectomy to identify clinical and/or pathological indicators of biochemical (prostate specific antigen [PSA]) recurrence. We then used those indicators to develop multivariate models for determination of recurrence probability following radical retropubic prostatectomy. MATERIALS AND METHODS: From 1982 to 1999, 2,091 consecutive men underwent radical retropubic prostatectomy and pelvic lymphadenectomy for clinically localized adenocarcinoma of the prostate (clinical stage T1c or T2 disease with Gleason score 5 or greater). Actuarial analysis was performed comparing freedom from biochemical recurrence after radical retropubic prostatectomy (PSA 0.2 ng./ml. or greater.) using the Kaplan-Meier method. Event time distributions for the time to recurrence were compared using the log rank statistic or the Cox proportional hazards regression model. The first model was developed using preoperative variables only and the second model using all available variables. Observed and predicted recurrence-free survival curves for different models were compared to select a model for calculation of predicted recurrence-free probabilities and confidence intervals. RESULTS: With a median followup of 5.9 years (range 1 to 17) 360 men (17%) had biochemical recurrence. Overall actuarial 5, 10 and 15-year biochemical recurrence-free survival rates were 84%, 72% and 61%, respectively. The relative risk of biochemical recurrence following surgery decreased with time, even after adjusted for other perioperative parameters. Variables identified for the preoperative model were biopsy Gleason score, clinical TNM stage and PSA. Variables identified for the postoperative model were prostatectomy Gleason score, PSA and pathological organ confinement status. Nomograms were generated and corrected for the decreasing relative risk of biochemical recurrence over time. CONCLUSIONS: Using 3 preoperative or postoperative parameters, these nomograms can easily be used to determine the 3, 5, 7 and 10-year biochemical recurrence-free survival probabilities among men who undergo radical retropubic prostatectomy for clinically localized prostate cancer in the modern era.     

Role of radical prostatectomy in patients with prostate cancer of high Gleason score

BACKGROUND: The routine use of serum prostate-specific antigen (PSA) testing combined with digital rectal examination has lowered tumor volume and clinical-pathological stage of men undergoing radical prostatectomy. Therefore, we may identify more men with poorly differentiated tumors of early clinical stage. In order to identify those who may benefit from radical prostatectomy, we evaluated known prognostic variables in patients with prostate cancer of high Gleason score (8-10). METHODS: Of 652 patients who underwent a radical prostatectomy as monotherapy for clinically localized prostate cancer between March 1991-December 1995, 84 patients with prostatectomy specimen Gleason score 8-10 tumors were identified. Clinical-pathological data were obtained from our prostate cancer database. Gleason score, PSA level, margin status, pathologic stage, and tumor volume were analyzed as general prognostic variables for disease-free survival (DFS). Follow-up ranged from 13-84 months (median, 36.2). Biochemical recurrence was defined as a postoperative PSA elevation greater than 0.4 ng/ml. RESULTS: The DFS for patients with Gleason score 8-10 and pathologically organ-confined disease was 62.5%. DFS was 56.2% for patients with PSA < or =10 ng/ml, compared to 19.2% for patients with serum PSA >10 ng/ml (P = 0.009). Patients with nonspecimen-confined disease (positive margins) had a DFS rate of 26.6% vs. 55% for patients with specimen-confined disease (negative margins) (P = 0.009). On multivariable analysis, only preoperative PSA < or =10 ng/ml (P = 0.02) and surgical margin status (P = 0.04) were significant predictors of DFS. CONCLUSIONS: Surgical margin status and preoperative serum PSA level are independent predictors of DFS for patients with high Gleason score prostate cancer treated by radical prostatectomy as monotherapy. Patients with poorly differentiated prostate cancer treated surgically at an early stage can have a favorable prognosis, especially if negative surgical margins are obtained. A preoperative serum PSA level < or =10 ng/ml carries the greatest likelihood of achieving prolonged DFS in this group of patients.     

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.     

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.     

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.     

Nomograms to predict the pathological stage of clinically localized prostate cancer in Korean men: Comparison with Western predictive tools using decision curve analysis

Objectives: To develop and evaluate nomograms to predict the pathological stage of clinically localized prostate cancer after radical prostatectomy in Korean men. Methods: We reviewed the medical records of 2041 patients who had clinical stages T1c–T3a prostate cancer and were treated solely with radical prostatectomy at two hospitals. Logistic regressions were carried out to predict organ‐confined disease, extraprostatic extension, seminal vesicle invasion, and lymph node metastasis using preoperative variables and resulting nomograms. Internal validations were assessed using the area under the receiver operating characteristic curve and calibration plot, and then external validations were carried out on 129 patients from another hospital. Head‐to‐head comparisons with 2007 Partin tables and Cancer of the Prostate Risk Assessment score were carried out using the area under the curve and decision curve analysis. Results: The significant predictors for organ‐confined disease and extraprostatic extension were clinical stage, prostate‐specific antigen, Gleason score and a percent positive core of biopsy. Significant predictors for seminal vesicle invasion were prostate‐specific antigen, Gleason score and percent positive core, and those for lymph node metastasis were prostate‐specific antigen and percent positive core. The area under the curve of established nomograms for organ‐confined disease, extraprostatic extension, seminal vesicle invasion and lymph node metastasis were 0.809, 0.804, 0.889 and 0.838, respectively. The nomograms were well calibrated and externally validated. These nomograms showed significantly higher accuracies and net benefits than two Western tools in Korean men. Conclusion: This is the first study to have developed and fully validated nomograms to predict the pathological stage of prostate cancer in an Asian population. These nomograms might be more accurate and useful for Korean men than other predictive models developed using Western populations.     

Clinical significance of nonpalpable prostate cancer with favorable biopsy features in Japanese men

OBJECTIVE: To assess the clinical significance of nonpalpable localized prostate cancers with relatively favorable six sextant biopsy features in Japanese men. PATIENTS AND METHODS: 136 nonpalpable prostate cancers of which biopsy features confined to (1) a Gleason score of 6 or less, (2) one or two positive cores per six sextant cores, and (3) 50% or less involvement of any positive core were collected. The Gleason score, tumor extension, and cancer volume were compared with preoperative serum PSA and PSA density for the patients who underwent radical prostatectomy. PSA doubling time was measured for the patients who were treated expectantly. RESULTS: Treatments chosen for 136 patients with favorable biopsy features were radical prostatectomy alone for 48 and with preoperative androgen deprivation for 30, radiation to the prostate for 12, androgen deprivation therapy for 21, and watchful waiting for 25. Of 48 patients who underwent radical prostatectomy without androgen deprivation therapy, 25% had nonorgan-confined cancers. Seven cancers (14.6%) were Gleason score of 7, but no cancers were 8 or greater. Among 42 prostatectomy specimens for which cancer volume was measured, 22 (52.4%) had cancer volume >0.5 cm(3). Pretreatment serum PSA levels were correlated neither with the Gleason score, tumor extension nor cancer volume. There was only one nonorgan-confined cancer in the 23 cancers for which PSA density was <0.2 ng/ml/g. The ability of PSA density to predict cancer volume <0. 5 cm(3) was 0.61 using a cut-off of 0.2 ng/ml/g. Of the 25 patients treated expectantly, the PSA doubling time was less than 2 years for 3 patients, while it was stable or fluctuated for 13. CONCLUSIONS: Tumor extension can be predicted based on PSA density in nonpalpable prostate cancer with favorable biopsy features, but predictability of cancer volume based on PSA or PSA density is not satisfactorily high. New parameters or biomarkers that complement needle biopsy findings are needed to predict clinical significance of T1c prostate cancer with favorable biopsy features.     

Prediction of pathological stages before prostatectomy in prostate cancer patients: Analysis of 12 systematic prostate needle biopsy specimens

OBJECTIVE: To identify the most reliable predictor of the pathological stage among multiple parameters obtained by performing systematic biopsies and to assess the predictive value of any identified parameters in combination with the prostate specific antigen and the Gleason scores. METHODS: We examined 5 biopsy parameters from 12 systematic needle biopsy results in 104 consecutive prostate cancer patients who underwent prostatectomy: the number of cores positive for cancer, percentage of positive biopsy cores, total linear cancer length (absolute sum of tumor length at each core), percentage cancer length (total cancer length divided by total length of cores obtained x100), and maximum cancer core length. The predictive values of these parameters were assessed using multivariate logistic analysis and receiver operating characteristic analysis. We evaluated whether the most reliable biopsy parameter in combination with traditional variables show better predictability of the pathological stage than traditional variables alone by receiver operating characteristic analysis. RESULTS: Of 104 patients, 85 (82.9%) had organ confined cancer and 19 (17.1%) showed extraprostatic extension. Of the five parameters examined, maximum cancer length was found to best predict pathological staging. Although insignificant, adding results of maximum cancer length to prostate specific antigen and Gleason scores improved predictability. Of 41 patients with a maximum cancer length of <0.9 cm, PSA of <16 ng/mL, and Gleason score of <7, none showed extraprostatic extension. CONCLUSIONS: The maximum cancer length was found to be the most reliable predictor of disease staging. The findings of a maximum cancer length of <0.9 cm, PSA of <16 ng/mL, and a Gleason score of <7 can suggest an organ-confined disease.     

Outcome of patients with Gleason score 8 or higher prostate cancer following radical prostatectomy alone

PURPOSE: We determine the effect of clinical and pathological variables on the outcome of patients with prostate cancer of Gleason scores 8 or greater treated with radical prostatectomy alone. MATERIALS AND METHODS: Between April 1987 and October 1998, 1,199 patients underwent radical retropubic prostatectomy. We identified 188 patients assigned a Gleason score of 8 or higher in the prostatectomy specimen who did not receive any neoadjuvant or adjuvant therapy. Median followup was 60 months (range 1 to 129). Disease recurrence was defined as any detectable prostate specific antigen level 0.1 ng./ml. or greater. RESULTS: Of 188 patients 128 (68%) had no evidence of prostate cancer after a median followup of 60 months, while 60 (32%) demonstrated a detectable PSA level. There were 58 (31%) patients with disease confined to the prostate with negative surgical margins while 108 (57%) had prostate cancer confined to the surgical specimen. Positive surgical margin with extraprostatic extension was seen in 16 (9%) patients and seminal vesicle invasion was present in 40 (21%). The 5 and 7-year disease-free survival rates for the entire cohort were 71% and 55%, respectively. Patients with specimen confined disease had a significantly higher 5-year disease-free survival rate than those with nonspecimen confined disease (84% and 50%, p <0.0001). On multivariate analysis pathological status of the surgical specimen was the most significant independent predictor of disease recurrence. Age, ethnicity, clinical stage and preoperative PSA had no independent effect on disease recurrence. CONCLUSIONS: Long-term disease-free survival can be expected in those patients with high grade prostate cancer whose disease is confined to the prostate and/or the surgical specimen.     

Perineural invasion on prostate needle biopsy: an independent predictor of final pathologic stage

Objectives. To examine the significance of perineural invasion (PNI) in predicting pathologic findings in patients treated by radical prostatectomy, because a recent study concluded that PNI on needle biopsy has no independent predictive value.Methods. Between 1993 and 1998, radical prostatectomy was performed in 319 consecutive patients. Prostate needle biopsies were reviewed in all cases. We compared PNI with other preoperative parameters, including digital rectal examination, PSA, and biopsy Gleason score, for the ability to predict tumor stage. Clinical records and pathologic findings were reviewed for all cases. Tumor stage was defined as either pT2 (organ confined) or pT3 (extraprostatic extension and/or seminal vesicle invasion).Results. The median age was 61.4 years (range 40 to 75.6). Seventy-two percent of the 95 men with nonpalpable disease and 67% of the 224 men with palpable disease had organ-confined prostate cancer on final pathologic staging. Of 205 men with a Gleason score on biopsy of 6 or less, 159 (78%) had organ-confined disease compared with 59 (52%) of 114 with a Gleason score of 7 to 9 (P <0.001, chi-square test). PNI was identified in 77 (24%) of 319 patients, with 83% specificity and 40% sensitivity for Stage pT3 disease (odds ratio 3.49). Of men with pT3 disease on final pathologic staging, 18%, 27%, and 56% had preoperative PSA levels of 0 to 4, more than 4 to 10, and greater than 10 ng/mL, respectively (P <0.001, Mantel-Haenszel chi-square test). On multivariate analysis, PNI (P = 0.0031), PSA (P = 0.0004), and Gleason score (P = 0.0003) independently predicted stage (pT3 disease).Conclusions. PNI is an important preoperative predictor of pathologic stage and should be reported when adenocarcinoma is diagnosed on prostate needle biopsies.