Predictor Of Prostate-specific Antigen Recurrence Research Articles

PROSTATE-SPECIFIC ANTIGEN LEVEL AT 6 MONTHS AFTER RADICAL PROSTATECTOMY ENABLES STRATIFICATION OF FOLLOW-UP PERIODS IN THE CANCER REGIONAL ALLIANCES CRITICAL PATH

(Objectives)Factors related to prostate-specific antigen (PSA) recurrence, including PSA at 6 months after radical prostatectomy, were evaluated to determine if the postoperative follow-up period in the cancer regional alliances critical path could be individualized using a coordinated path. (Patients and methods)Among 352 patients who underwent laparoscopic radical prostatectomy at our hospital from May 2009 to June 2015, 331 who did not undergo preoperative hormone therapy were examined retrospectively. Cases with PSA < 0.01 ng/mL at 6 months after surgery (group A, n=209) were compared with those with PSA > 0.01 ng/mL at the same time point (group B, n=122). (Results)PSA recurrence was significantly higher in group B (n=21 (10.0%) vs. n=70 (57.4%), p< 0.001) and the time to recurrence was significantly shorter (44 vs.12.5 months, p< 0.001). In multivariate analysis within group A, the Gleason Grade Group (GGG) and extraprostatic extension in surgical specimens were predictors of PSA recurrence. In group A, all cases (n=30) of GGG1 in surgical specimens had no extraprostatic extension and no PSA recurrence. There were 90 cases of surgical specimens with GGG2 and no extracapsular infiltration, and only 4 of these cases had recurrence (4.4%). (Conclusion)The results of the study indicate that follow-up interval stratification is possible using the PSA level at 6 months after radical prostatectomy, GGG and extraprostatic extension in the surgical specimen.

An Exploratory Study of Endorectal Magnetic Resonance Imaging and Spectroscopy of the Prostate as Preoperative Predictive Biomarkers of Biochemical Relapse After Radical Prostatectomy

Radical prostatectomy has significant side effects. Preoperative information predicting its long-term outcome would be valuable to patients and physicians. We determined whether pretreatment endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging predicts biochemical recurrence after radical prostatectomy. Of 202 patients who underwent endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging from January 2000 to December 2002 before radical prostatectomy 130 satisfied study inclusion criteria and were included in analysis. We compared imaging factors with potential predictive capability to biochemical recurrence data, including magnetic resonance imaging risk score based on local disease extent and magnetic resonance spectroscopic imaging index lesion characteristics, such as the number of voxels and degree of metabolic abnormality (magnetic resonance spectroscopic imaging grade). We evaluated associations of these imaging variables with time to biochemical recurrence by Cox proportional hazards regression adjusted for known predictors of biochemical recurrence, such as stage, grade and prostate specific antigen. At a median 68-month followup there were 26 biochemical failures. Risk score, lesion volume and high grade voxels each correlated with time to biochemical recurrence. In a model combining clinical parameters risk score, lesion volume and at least 1 high grade voxel the magnetic resonance spectroscopic imaging variables remained significant but the magnetic resonance imaging score dropped out. Index lesion volume on magnetic resonance spectroscopic imaging and high grade magnetic resonance spectroscopic imaging voxels correlate with time to biochemical recurrence after radical prostatectomy even when adjusted for clinical data. Results suggest the preoperative predictive usefulness of endorectal magnetic resonance imaging/magnetic resonance spectroscopic imaging in patients considering radical prostatectomy.

Maximum tumor diameter: a simple independent predictor for biochemical recurrence after radical prostatectomy

Previous studies have suggested that maximum tumor diameter (MTD) is a predictor of PSA recurrence or biochemical recurrence (BCR) in prostate cancer after radical prostatectomy (RP). The significance of MTD in BCR prediction was evaluated using RP specimens of 364 patients with a BCR of 18% (n=66) during a mean follow-up of 37.4 months (range: 10-109 months). MTD was defined as the largest diameter of the largest tumor, and its median MTD was 15 mm (range: 0.9-50 mm). MTD was significantly associated with pre-operative PSA levels, pathological T stage, Gleason's score and positive surgical margin. In a univariate analysis, pathological T stage, Gleason's score, positive surgical margin and MTD were associated significantly with the risk of BCR. Patients with >20 mm MTD had a significantly higher risk of BCR than did those with < or =20 mm MTD (P<0.001). Cox multivariate models indicated that pathological stage, Gleason's score, positive surgical margin and MTD were independent prognostic factors for BCR. MTD would be a useful tool for predicting BCR, as calculation of MTD is a simple and reliable measure.

Estimated blood loss as a predictor of PSA recurrence after radical prostatectomy: results from the SEARCH database

Diagnosis (exploratory cohort). 2b. To clarify the relationship between estimated blood loss (EBL) and biochemical recurrence, assessed by prostate-specific antigen (PSA) level, as blood loss is a long-standing concern associated with radical prostatectomy (RP), and no studies to date have examined the association between blood loss and cancer control. In all, 1077 patients were identified in the Shared Equal-Access Regional Cancer Hospital database who underwent retropubic RP (between 1998 and 2008) and had EBL and follow-up data available. We examined the relationship between EBL and recurrence using multivariate Cox regression analyses. Increased EBL was correlated with PSA recurrence in a multivariate-adjusted model (P = 0.01). When analysed by 500-mL EBL categories, those with an EBL of <1500 mL had a similar risk of recurrence. However, the risk of PSA recurrence tended to increase for an EBL of 1500-3499 mL, before decreasing again for patients with an EBL of > or =3500 mL. Men with an EBL of 2500-3499 mL had more than twice the risk of recurrence than men with an EBL of <1500 mL (P = 0.02). EBL was not associated with adverse tumour stage, grade or margin status. There was a significant correlation between EBL at the time of RP and biochemical recurrence. We hypothesized that this association might be due to transfusion-related immunosuppression, excessive blood obscuring the operative field, EBL being a marker of aggressive disease, or EBL being a marker of poor surgical technique. However, our data did not completely fit any one of these hypotheses, and thus the ultimate cause for the increased risk of recurrence remains unclear and requires further study.

Tumor Volume, Tumor Percentage Involvement, or Prostate Volume: Which Is Predictive of Prostate-specific Antigen Recurrence?

To compare the effects of tumor volume (TV), tumor percentage involvement (TPI), and prostate volume (PV) on prostate-specific antigen (PSA) recurrence (PSAR) after radical prostatectomy (RP). A cohort of 3528 patients receiving RP between 1988 and 2008 was retrieved from the Duke Prostate Center. Patients were stratified by TV (< 3, 3-6, > 6 cm(3)), TPI (< 10%, 10%-20%, > 20%), and PV (< 35, 35-45, > 45 cm(3)) and their effects on PSAR evaluated using Kaplan-Meier analysis. Clinicopathologic variables included in univariate analysis were age at surgery, race, year of surgery, PSA, pathologic Gleason score, pathologic tumor stage, margin status, extracapsular extension, and seminal vesicle invasion. The effects of TV, TPI, and PV (as continuous and categorical variables) on PSAR were compared using Cox analysis. TPI, TV, and PV were predictive of PSAR (P <.05) in Kaplan-Meier analysis. In multivariate analysis as continuous variables, TPI and PV were predictive of PSAR (hazard ratio [HR] = 1.16 and HR = 0.65, P <.05). As categorical variables, TPI > 20% and PV 10-35 cm(3) were predictive of PSAR (HR = 1.45 and OR = 1.25, P <.05). TV was not predictive of PSAR in either analysis. Pathologic Gleason score > or = 7, PSA, positive margins, seminal vesicle invasion, and tumor stage T3/T4 were found to be predictors of PSAR (P <.05). TV, TPI, and PV were predictive of PSAR in univariate analysis, but in multivariate analysis, only TPI and PV were predictive of PSAR. TPI and PV should be considered when evaluating, assessing, and counseling patients regarding PSAR risk.

Impact of Socioeconomic Factors on Prostate Cancer Outcomes in Black Patients Treated with Surgery

The role of socioeconomic factors in the worse outcome of black men with prostate cancer remains unclear. To determine whether socioeconomic factors affect prostate cancer outcomes, we studied a cohort of only black patients to minimize known confounding factors. We studied black men treated with radical prostatectomy at New York Veterans Administration Medical Center and Memorial Sloan-Kettering Cancer Center between 1990 and 2005. A centralized pathology review process determined the Gleason score of all cases. Prostate-specific antigen (PSA) recurrence at both sites was defined as PSA of 0.2 or greater with a confirmatory rise. By matching patients' home zip codes to the U.S. Census Bureau database, we obtained corresponding socioeconomic data regarding median household income (income) and percentage of population with a high school (degree). We analyzed income, education, and clinical and pathological parameters for the whole cohort. We studied 430 black patients. They resided in neighborhoods where median household income was $41,498.10 and mean percentage of high school graduates was 73.4%. A total of 88 patients (20.9%) had PSA recurrence. Median follow-up for survivors was 37 months. Neither income nor education evaluated as continuous or categorical variables were predictors of PSA recurrence. When evaluated as composite categorical variable, the combination of greater income and education did not predict disease-free survival. Data suggest that socioeconomic factors have limited impact on PSA recurrence in black men treated with radical prostatectomy. Thus, biologic factors might have a role in the poor outcomes in this population.

Radial Distance of Extraprostatic Extension Measured by an Ocular Micrometer is an Independent Predictor of Prostate-specific Antigen Recurrence: A New Proposal for the Substaging of pT3a Prostate Cancer

Extraprostatic extension is an unfavorable prognostic factor for prostate cancer. Consequently, it has been assigned to pT3a in the current 2002 tumor, lymph node, metastasis staging system. The aim of our study is to analyze the extent of extraprostatic extension by 8 quantitative methods and to determine which is best for substaging of pT3a tumors. We studied 83 patients with extraprostatic extension after radical prostatectomy for clinically localized prostatic adenocarcinoma. The extent of extraprostatic extension was evaluated using 8 quantitative methods. Univariate and multivariate analyses were performed to determine which measurement best predicts prostate-specific antigen (PSA) recurrence. In the univariate analysis, the radial distance of extraprostatic tumor measured by ocular micrometer was associated with PSA recurrence (P = 0.02). No significant association was observed between PSA recurrence and other measurements of extraprostatic extension, including focal versus established extraprostatic extension using Epstein's criterion, focal versus established extraprostatic extension using Wheeler's modified criterion, the number of extraprostatic neoplastic glands, unilateral versus bilateral involvement, circumferential length of extraprostatic tumor, unifocal versus multifocal involvement, and volume of extraprostatic tumor. In the multivariate analysis, radial distance remained an independent predictor of PSA recurrence (hazard ratio, 2.4; 95% confidence interval, 1.12-5.01; P=0.02). The radial distance of the extraprostatic extension measured by ocular micrometer is an independent prognostic factor for pT3 prostate cancer. Two-year and 4-year PSA recurrence-free survival was 62% and 35%, respectively, for those patients with radial distance or =0.75 mm. We recommend reporting this parameter routinely for radical prostatectomy specimens. The strength of its prognostic value for PSA recurrence makes it a potential criterion for incorporation into a future tumor, lymph node, metastasis staging system.

A Comparison of the Incidence and Location of Positive Surgical Margins in Robotic Assisted Laparoscopic Radical Prostatectomy and Open Retropubic Radical Prostatectomy

Surgical technique, patient characteristics and method of pathological review may influence surgical margin status. We evaluated the incidence and location of positive surgical margins in 200 sequential robotic assisted laparoscopic radical prostatectomy and 200 sequential open radical retropubic prostatectomy cases. From July 2002 until December 2006 a total of 1,747 patients underwent radical prostatectomy at our institution (robotic assisted laparoscopic radical prostatectomy in 1,238, radical retropubic prostatectomy in 509). From these we selected the last 200 consecutive radical retropubic prostatectomies and 200 robotic assisted laparoscopic radical prostatectomies performed before August 2006. Preoperative clinical characteristics including age, clinical stage, prostate specific antigen and Gleason score were evaluated. Postoperatively pathological specimens were assessed for specimen weight, Gleason score, tumor volume, pathological stage and margin status. The incidence and location of positive surgical margins were compared between robotic assisted laparoscopic radical prostatectomy and radical retropubic prostatectomy. Patients undergoing robotic assisted laparoscopic radical prostatectomy compared to radical retropubic prostatectomy had more favorable tumor characteristics including lower prostate specific antigen, clinical stage and Gleason score. No statistically significant differences were found between groups for prostate volume or tumor volume. However, tumor volume as a percentage of prostate volume was higher among radical retropubic prostatectomy compared to robotic assisted laparoscopic radical prostatectomy cases (17.7% vs 13%, p = 0.001). The overall incidence of positive surgical margins was significantly lower among the robotic assisted laparoscopic radical prostatectomy compared to radical retropubic prostatectomy cases (15% vs 35%, p <0.001). The incidence of positive surgical margins according to pathological stage for robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy cases was 16 of 171 (9.4%) vs 33 of 137 (24.1%) for pT2 (p <0.001) and 14 of 28 (50%) vs 36 of 60 (60%) for pT3. In both groups the apex was the most common site of positive surgical margins with 52% in the robotic assisted laparoscopic radical prostatectomy group vs 37% in the radical retropubic prostatectomy group (p >0.05). In the hands of surgeons experienced in robotic assisted laparoscopic radical prostatectomy and radical retropubic prostatectomy, there was a statistically significant lower positive margin rate for patients undergoing robotic assisted laparoscopic radical prostatectomy. The most common location of a positive surgical margin in robotic assisted laparoscopic radical prostatectomy and radical retropubic prostatectomy cases was at the apex. Patients treated with radical retropubic prostatectomy had higher risk features which may have independently influenced these results. The method of pathological specimen analysis and reporting may account for the higher positive margin rates in both groups compared to some reports.

Adjuvant Radiotherapy in Prostate Cancer: Predictors of Prostate-Specific Antigen Recurrence from the CaPSURE Database

To analyze an observational database of prostate cancer, assessing for patterns of use and predictors of prostate-specific antigen (PSA) recurrence after adjuvant radiotherapy (RT). From the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), 5336 men underwent prostatectomy from 1989 to 2004. Of these 5336 men, 96 men (1.8%) underwent adjuvant RT. These 96 men were classified as having low (Stage T1c-T2a and PSA level of 10 ng/mL or less and Gleason score of 6 or less), intermediate (Stage T2b or PSA level greater than 10 ng/mL and 20 ng/mL or less or Gleason score 7), or high (Stage T2c or higher or PSA level greater 20 ng/mL or Gleason score of 8 or greater) risk of PSA recurrence. PSA recurrence was defined as two consecutive PSA levels greater than 0.2 ng/mL. Differences between patients who experienced failure were assessed by chi-square tests or analysis of variance. Univariate and multivariate analyses were performed using a Cox proportional hazard regression model. Of the 96 men, 27 (28%) experienced PSA failure and 20 (21%) received additional treatment, with a median of 60 months of follow-up. The clinical risk group (P <0.01), PSA level at diagnosis (P <0.01), Gleason score (P <0.01), and seminal vesicle invasion (P <0.01) all significantly associated with PSA recurrence. The clinical risk group was the sole predictor of PSA recurrence-free survival on multivariate analysis (hazard ratio 2.4, 95% confidence interval 1.7 to 8.3, P = 0.007). Adjuvant RT was not frequently used in men enrolled in CaPSURE. PSA recurrence was observed more frequently in men with high-risk disease, suggesting that adjuvant RT is not adequate therapy and that these men might benefit from the combined use of hormonal therapy and RT.

Positive-block Ratio in Radical Prostatectomy Specimens is an Independent Predictor of Prostate-specific Antigen Recurrence

Tumor volume has been considered an important variable in determining the probability of prostate-specific antigen (PSA) recurrence in prostatic adenocarcinoma. There have been many studies that have tried to determine an appropriate method of calculating tumor volume, but no single methodology has been agreed upon. We tested the hypothesis that the ratio of tumor positive tissue blocks to the total number of blocks submitted (positive-block ratio) can be used as an independent prognostic indicator for PSA recurrence. We analyzed 504 patients who underwent total radical retropubic prostatectomy between 1990 and 1998. None of the patients had preoperative radiation or androgen-deprivation therapy. Clinical records were reviewed. The mean positive-block ratio was 0.44 (median, 0.43; range, 0.05 to 1.0). The positive block-ratio was significantly associated with Gleason score, pathologic stage, surgical margin status, extraprostatic extension, seminal vesical invasion, lymph node metastasis, perineural invasion, and preoperative serum PSA level (all P<0.001). Using a multivariate Cox regression model, controlling for pathologic stage, Gleason score, lymph node metastasis, and surgical margin status, positive-block ratio was an independent predictor of PSA recurrence (hazard ratio, 2.3; 95% confidence interval, 1.06-4.83; P=0.03). Five-year PSA recurrence-free survival was 67% for those patients with positive-block ratio <or=0.43, as compared with 42% those with positive-block ratio >0.43 (P<0.001). Positive-block ratio is an independent predictor of PSA recurrence and this simple method of tumor measurement seems to be promising for quantifying tumor volume if our findings are validated by subsequent reports.

Radial Distance of Extraprostatic Extension Measured by Ocular Micrometer is an Independent Predictor of Prostate-specific Antigen Recurrence

Extraprostatic extension is an unfavorable prognostic factor for prostate cancer. Consequently, it has been assigned to pT3a in the current 2002 tumor, lymph node, metastasis staging system. The aim of our study is to analyze the extent of extraprostatic extension by 8 quantitative methods and to determine which is best for substaging of pT3a tumors. We studied 83 patients with extraprostatic extension after radical prostatectomy for clinically localized prostatic adenocarcinoma. The extent of extraprostatic extension was evaluated using 8 quantitative methods. Univariate and multivariate analyses were performed to determine which measurement best predicts prostate-specific antigen (PSA) recurrence. In the univariate analysis, the radial distance of extraprostatic tumor measured by ocular micrometer was associated with PSA recurrence (P = 0.02). No significant association was observed between PSA recurrence and other measurements of extraprostatic extension, including focal versus established extraprostatic extension using Epstein's criterion, focal versus established extraprostatic extension using Wheeler's modified criterion, the number of extraprostatic neoplastic glands, unilateral versus bilateral involvement, circumferential length of extraprostatic tumor, unifocal versus multifocal involvement, and volume of extraprostatic tumor. In the multivariate analysis, radial distance remained an independent predictor of PSA recurrence (hazard ratio, 2.4; 95% confidence interval, 1.12-5.01; P=0.02). The radial distance of the extraprostatic extension measured by ocular micrometer is an independent prognostic factor for pT3 prostate cancer. Two-year and 4-year PSA recurrence-free survival was 62% and 35%, respectively, for those patients with radial distance <0.75 mm, as compared with 35% and 18%, respectively, for those with radial distance > or =0.75 mm. We recommend reporting this parameter routinely for radical prostatectomy specimens. The strength of its prognostic value for PSA recurrence makes it a potential criterion for incorporation into a future tumor, lymph node, metastasis staging system.

Maximum tumor diameter is an independent predictor of prostate-specific antigen recurrence in prostate cancer

Maximum tumor diameter has been shown to correlate with multiple predictors of clinical outcome in prostate cancer. In the current study, we prospectively analyze whether maximum tumor diameter is a significant predictor of prostate-specific antigen (PSA) recurrence. The study population consisted of 364 patients who underwent radical prostatectomy for prostate cancer. Prostatectomy specimens were evaluated by whole-mount processing of the entire prostate. Maximum tumor diameter was measured from the whole-mount sections of the prostate. Spearman’s coefficient of rank correlation was used to correlate tumor diameter with continuous variables. T-tests or analysis of variance (ANOVA) tests were performed to determine if tumor diameter was significantly associated with other clinical and pathologic variables. The effect of clinical and pathologic variables on time to recurrence was analyzed using Cox regression. The mean tumor diameter for all patients was 1.73 cm (range, 0.02–4.40 cm). Maximum tumor diameter was associated with preoperative PSA (r=0.22, P<0.0001), prostate weight (r=−0.12, P=0.028), tumor volume (r=0.87, P<0.0001), Gleason score (r=0.29, P<0.0001), and pathologic stage (P<0.0001). Cox multiple regression was performed to test the prognostic value of maximum tumor diameter adjusting for pathologic stage, Gleason score, and surgical margin status. Increased maximum tumor diameter was associated with shorter time to PSA recurrence (hazard ratio=1.70, 95% confidence interval 1.13–2.56, P=0.01), controlling for risk factors, Gleason score, and surgical margin status. We conclude that maximum tumor diameter is a significant predictor of biochemical recurrence in patients with prostate cancer.

Is tumor vascularity in prostate core biopsies a predictor of PSA recurrence after radical prostatectomy?

The purposes of this study were to evaluate if tumour vascularity by Chalkley counting (TVC) in prostate core biopsies can be a predictor of PSA recurrence after radical prostatectomy in prostate cancer and to estimate the concordance between the TVC in core biopsies and the subsequently examined prostatectomy specimen. All patients, with Gleason score ≤7 in core biopsy, clinical stage T1 or T2 who had a radical prostatectomy during 1990 – 1997 at Sahlgrenska University Hospital, were selected as a primary group. Patients with neoadjuvant hormonal therapy were excluded. The patients were divided into two groups, one with PSA recurrence and one group without PSA recurrence. 25 patients had PSA recurrence during the follow up period and 25 patients from non-recurrence group were randomly selected. TVC was assessed from the prostate tissue by immunostaining against CD34. TVC was statistically significant predictor of PSA relapse. The PSA-free survival rate was only 17% in patients within the highest TVC quartile compared to 67% in patients within the lowest TVC quartile.

1038: Percent of Prostate Needle Biopsy Cores with Cancer from the Most Involved Side of the Biopsy is a Better Predictor of PSA Recurrence Following Radical Prostatectomy than the Total Percent of Cores with Cancer

1038: Percent of Prostate Needle Biopsy Cores with Cancer from the Most Involved Side of the Biopsy is a Better Predictor of PSA Recurrence Following Radical Prostatectomy than the Total Percent of Cores with Cancer

Intratumoral nuclear morphologic heterogeneity in prostate cancer

Objectives. Tumor heterogeneity can be measured by quantifying variance of nuclear characteristics by image analysis. Heterogeneity of cell nuclear features correlated with increased local progression in prostate cancer. In the present study, the influence of tumor heterogeneity on prostate-specific antigen (PSA) recurrence after radical retropubic prostatectomy was analyzed and tumor heterogeneity was compared in patients with and without neoadjuvant hormonal therapy. Methods. Retrospectively, radical prostatectomy material of 44 patients without and 12 patients with neoadjuvant hormonal treatment with a postoperative follow-up of at least 4 years was studied. Each prostatectomy specimen was systematically embedded in paraffin, and each tumor area within the prostate was marked and analyzed by an image analysis system for 32 nuclear features comprising nuclear shape, size, DNA content, and chromatin pattern. Several clinical features were available: preoperative serum PSA, hemoglobin concentration, Karnofsky score, tumor stage, and Gleason score. Results. Increased tumor heterogeneity, as expressed by differences in karyometric values between tumor areas in nuclear shape and chromatin pattern within the tumor, was significantly correlated with earlier PSA recurrence rate. As compared with nonpretreated patients, hormonally pretreated specimens showed smaller and less heterogeneous tumors. In particular, chromatin pattern heterogeneity was decreased in patients who underwent preoperative hormonal treatment compared with patients who were not pretreated. However, decreased heterogeneity was accompanied by a higher percentage of aneuploid areas per tumor in the pretreated patients. Cox regression analysis showed that karyometric determination of nuclear shape heterogeneity in combination with preoperative PSA level could predict time to PSA recurrence after radical prostatectomy in patients without hormonal pretreatment. Conclusions. Increase in karyometric tumor heterogeneity in nuclear shape and chromatin pattern was correlated with a shorter PSA recurrence-free interval after radical prostatectomy. Preoperative PSA and karyometric tumor heterogeneity were the best predictors of PSA recurrence in a multivariate analysis. Intratumoral heterogeneity was decreased in patients with prostate cancer who underwent neoadjuvant hormonal therapy.