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1.
Scand J Urol ; 52(5-6): 349-357, 2018.
Article in English | MEDLINE | ID: mdl-30624128

ABSTRACT

BACKGROUND: Gonadotropin releasing hormone (GnRH) antagonists suppress follicle-stimulating hormone (FSH) to lower levels than GnRH agonists. This may partially explain the differences between these agents on prostate cancer outcomes. In this post-hoc analysis, FSH and prostate specific antigen (PSA) responses and the impact of cross-over from leuprolide to degarelix were evaluated from a 1-year comparative study (CS21) and its extension study (CS21A). MATERIALS AND METHODS: Overall, 610 patients were enrolled in CS21, wherein PSA and FSH levels were evaluated monthly. CS21A evaluated 386 patients, including those previously treated with degarelix (n = 251) who continued to receive degarelix, and those previously treated with leuprolide (n = 135) who crossed-over to receive degarelix. PSA and FSH levels were evaluated in CS21A for 3 months after cross-over. The associations between measurements were assessed using Spearman's correlation coefficient. The impact of class variables on FSH suppression were evaluated using Analysis of Variance. RESULTS: Rapid PSA and FSH suppression was observed and maintained in the degarelix arm (CS21 and CS21A), while patients on leuprolide experienced rising PSA during CS21. Patients crossed-over from leuprolide to degarelix achieved a suppression of FSH and a significant PSA decrease. PSA and FSH levels were significantly (p < .05) correlated at months 1, 3, 6, 12 and 13 in the degarelix arm. CONCLUSIONS: Significant FSH suppression with GnRH antagonists may explain its advantage over GnRH agonists in terms of better prostate cancer control. The effect of profound FSH suppression is analogous to the need for profound testosterone suppression for tumor control.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Follicle Stimulating Hormone/metabolism , Gonadotropin-Releasing Hormone/agonists , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Leuprolide/therapeutic use , Oligopeptides/therapeutic use , Prostatic Neoplasms/drug therapy , Aged , Drug Substitution , Humans , Kallikreins/metabolism , Male , Middle Aged , Prostate-Specific Antigen/metabolism , Prostatic Neoplasms/metabolism
2.
Prostate Cancer Prostatic Dis ; 20(3): 323-327, 2017 09.
Article in English | MEDLINE | ID: mdl-28440322

ABSTRACT

BACKGROUND: Active surveillance (AS) has excellent short to medium term outcomes in well-selected prostate cancer patients. Traditional biopsy-based selection criteria have been criticized for inaccurate determination of cancer grade and extent. We evaluated the incremental benefit of multiparametric magnetic resonance imaging (mpMRI) in patient selection using various AS criteria. METHODS: We retrospectively evaluated men who received mpMRI before radical prostatectomy between 2011 and 2014. Patients were classified as suitable for AS using four criteria: (1) Epstein, (2) National Comprehensive Cancer Network (NCCN) low-risk or (3) extended criteria (Gleason ⩽3+4, PSA ⩽15 ng/ml, clinical stage ⩽T2b) using clinical parameters. The incremental value of mpMRI was evaluated against the referent standard of surgical pathology in determining suitability for AS using sensitivity, specificity, likelihood ratios (LRs) and area under receiver operating curves (AUCs). RESULTS: We evaluated 208 men. Only one man fulfilled Epstein criteria (1) at pathology, who was neither identified using clinical criteria nor mpMRI. Using (2), clinical criteria had a sensitivity of 80%, specificity 75%, LR+ 3.3, LR- 0.3, AUC 0.78, while combined clinical-mpMRI criteria achieved a sensitivity of 80%, specificity 99.5% (P<0.01), LR+ 162, LR- 0.2 and AUC 0.90 (P<0.01 compared to clinical). Using (3), clinical criteria had a sensitivity of 74%, specificity 47%, LR+ 1.4, LR- 0.6, AUC 0.60, while combined clinical-mpMRI criteria achieved a sensitivity of 26% (P<0.01), specificity 97% (P<0.01), LR+ 8.3, LR- 0.8 and AUC 0.62 (P=0.85). CONCLUSIONS: Addition of mpMRI significantly improved selection of men for AS using NCCN low-risk criteria. For selecting men with limited prognostic grade group 2, mpMRI significantly improved specificity at the expense of sensitivity.


Subject(s)
Prostatic Neoplasms/diagnostic imaging , Aftercare , Aged , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Grading , Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Quality Improvement , Treatment Outcome
3.
Prostate Cancer Prostatic Dis ; 19(1): 100-6, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26754260

ABSTRACT

BACKGROUND: In men with high Gleason PC and rapid PSA progression after surgery, failure rates remain unacceptably high despite salvage radiation. We explored a novel multimodality approach of docetaxel with anti-angiogenic therapy before salvage radiotherapy (RT). METHODS: This was a phase 2 single-arm prospective open-label trial with historic controls. Eligible men had a rising PSA of 0.1-3.0 ng ml(-1) within 4 years of radical prostatectomy, no metastases except resected nodal disease, no prior androgen-deprivation therapy (ADT) and Gleason 7-10. Men received four cycles of docetaxel 70 mg m(-2) every 3 weeks with low dose prednisone and sunitinib 37.5 mg daily for 14/21 days each cycle, with no ADT. Salvage prostate bed RT (66 Gy) started at day 100. The primary end point was progression-free survival (PFS) rate at 24 months. Safety data, quality of life (QOL) and dose-limiting toxicities (DLTs) were measured over time. RESULTS: Thirty-four men accrued in this multi-institutional clinical trial: 24% of men were node positive, 47% were Gleason 8-10, median PSA at entry was 0.54. The trial was terminated prematurely owing to excess DLTs (nine) including grade 3 hand-foot syndrome (n=4), neutropenic fever (n=2), AST increase (n=1), fatigue (n=1) and vomiting with diarrhea (n=1). PFS rate at 24 months was 51% (95% CI: 33, 67%) with a median PFS of 26.2 months (95% CI: 12.5, -). Six men (17.6%) had an undetectable PSA at 2 years. CONCLUSIONS: Sunitinib and docetaxel/prednisone followed by salvage RT resulted in excess pre-specified DLTs. Although nearly half of the men experienced durable disease control, efficacy was not greater than expected with radiation alone. The use of the intermediate end point of PFS in this salvage setting permitted an early decision on further development of this combination.


Subject(s)
Indoles/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Prednisone/administration & dosage , Prostatic Neoplasms/drug therapy , Pyrroles/administration & dosage , Taxoids/administration & dosage , Adult , Aged , Disease-Free Survival , Docetaxel , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/radiotherapy , Prostate-Specific Antigen/metabolism , Prostatectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Quality of Life , Salvage Therapy , Sunitinib
4.
Biotech Histochem ; 90(3): 184-9, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25434394

ABSTRACT

In vitro bioassay has been used extensively to test the effects of culturing cancer cells in sera from humans participating in dietary interventions, i.e, studies of modified intake of nutrients for the purpose of reducing cancer risk or progression. It has been hypothesized that cell proliferation rates determined by the in vitro bioassay indicate whether modification of dietary intake could decrease cancer cell growth in vivo. It has been suggested, however, that the in vitro bioassay may not correlate with tumor cell proliferation rates in prostate cancer. We investigated the concordance of cell proliferation rates from surgically excised prostate tumor tissue with the in vitro bioassay using sera from matched patients. We used samples from an earlier randomized clinical trial that showed that supplementation with flaxseed significantly inhibited prostate cancer cell proliferation rates in vivo as indicated by Ki67 staining in tumor specimens. Proliferation rates of LNCaP, DU145 and PC3 cell lines cultured in 10% human sera from participants in the flaxseed trial were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Spearman's Rho correlation coefficients (ρ) indicated no association between Ki67 staining in prostate tumors and the in vitro bioassay for the three cell lines. These disparate findings suggest that the in vitro bioassay may not provide an accurate assessment of the environment in vivo.


Subject(s)
Biological Assay/methods , Cell Proliferation/drug effects , Prostatic Neoplasms/diet therapy , Prostatic Neoplasms/pathology , Aged , Cell Line, Tumor , Diet, Fat-Restricted , Dietary Supplements , Flax/chemistry , Humans , Ki-67 Antigen/metabolism , Male , Middle Aged , Prostatectomy , Seeds
5.
Prostate Cancer Prostatic Dis ; 17(3): 280-5, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25027863

ABSTRACT

BACKGROUND: Selecting appropriate candidates for postprostatectomy radiotherapy is challenging, because adverse pathological features cannot accurately predict clinical recurrence. Biomarkers that identify residual disease activity may assist clinicians when counseling patients on the risks, benefits and costs of secondary treatment. NADiA ProsVue PSA slope results ≤2.0 pg ml(-1) month(-1) are predictive of a reduced risk of clinical recurrence; however, its clinical utility has not yet been studied. METHODS: We prospectively enrolled men treated by radical prostatectomy in a multicenter, institutional review board-approved clinical trial. At postsurgical follow-up, investigators (N=17) stratified men into low-, intermediate- or high-risk groups for prostate cancer recurrence based on clinicopathological findings and other factors. Investigators documented their initial treatment plan for each subject and serially collected three serum samples for ProsVue testing. After the ProsVue result was reported, investigators recorded whether or not the initial treatment plan was changed. The proportion of cases referred for secondary treatment before and after ProsVue was reported, and the significance of the difference determined. RESULTS: Complete assessments were reported for 225 men, 128 (56.9%) of whom were stratified into intermediate- and high-risk groups. Investigators reported that they would have referred 41/128 (32.0%) at-risk men for secondary treatment. However, after results were known, they referred only 15/128 (11.7%) men. The difference in proportions (-20.3%, 95% confidence interval (CI) -29.9 to -10.3%) is significant (P<0.0001). Odds of a referral was significantly reduced after results were reported (odds ratio 0.28, 95% CI 0.15-0.54, P<0.0001). CONCLUSIONS: Knowledge of a ProsVue result had significant impact on the final treatment plan. A ProsVue result ⩽2.0 pg ml(-1) month(-1) significantly reduced the proportion of men at risk of recurrence who otherwise would have been referred for secondary treatment.


Subject(s)
Prostate-Specific Antigen/blood , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Aged , Biomarkers, Tumor/blood , Decision Making , Disease Management , Humans , Immunoassay/methods , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prostatectomy , Prostatic Neoplasms/surgery , Retreatment
6.
Andrology ; 1(2): 256-61, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23413138

ABSTRACT

Changes in sexual bother (SB) following radical prostatectomy (RP) negatively affect health-related quality of life (HRQoL) of prostate cancer survivors. However, post-operative SB tends to be neglected whereas sexual function (SF) is thoroughly assessed in clinical practice and few studies have focused on and evaluated patients' SB. We retrospectively reviewed 2 345 consecutive patients who underwent RP between 2001 and 2009 at a single institution. SF and SB were assessed using Expanded Prostate Cancer Index Composite (EPIC) questionnaires. We stratified our cohort by SB recovery and post-operative SF status, including a subset of men who recovered SB despite persistent post-RP sexual dysfunction. Multivariable logistic regression analyses were conducted to identify factors for men who have SB recovery. Of 319 eligible patients, 133 (41.7%) recovered their SB at a mean of 20 months after RP. Among the 133 men who demonstrated SB recovery, 109 had post-operative sexual dysfunction. Patients with SB recovery despite post-RP sexual dysfunction were more likely to be old (p = 0.004), to have higher clinical T stage (p < 0.001), to have more non-nerve-sparing RP (p < 0.001), to have lower pre-operative EPIC-SF/SB scores (p < 0.001), to have more extracapsular extension (p = 0.031) and to be PDE5i non-users after surgery (p < 0.001). In multivariable analysis, predictors for this subset were lower comorbidity (OR 0.62, p = 0.043), higher clinical cancer stage (OR 2.35, p = 0.026), worse pre-operative SF (OR 0.98, p = 0.010), SB (OR 0.98, p < 0.010) and no PDE5i use (OR 0.37, p = 0.002); age was not related (OR 0.99, p = 0.555). As SB can influence patients' overall HRQoL, expectations of SB recovery should be provided to patients in the same way that SF recovery is presented. This study may help clinicians to discuss SB with patients and assess their potential for SB recovery following RP.


Subject(s)
Postoperative Complications , Prostatectomy/adverse effects , Prostatic Neoplasms/surgery , Sexual Dysfunction, Physiological , Sexual Dysfunctions, Psychological , Adult , Aged , Humans , Male , Middle Aged , Multivariate Analysis , Penile Erection , Postoperative Period , Quality of Life , Retrospective Studies , Sexual Behavior , Surveys and Questionnaires
7.
Prostate Cancer Prostatic Dis ; 16(2): 187-92, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23381694

ABSTRACT

BACKGROUND: Standard treatment options are limited for the management of non-metastatic castration-resistant prostate cancer (CRPC). This study, part of the ENTHUSE (EndoTHelin A USE) phase III programme, evaluated the efficacy and safety of the oral specific endothelin (ET)A receptor antagonist zibotentan vs placebo in patients with non-metastatic CRPC (non-mCRPC). METHODS: This was a multicentre, randomized, double-blind, phase III study. Patients (n=1421) with non-mCRPC and biochemical progression (determined by rising serum PSA levels) were randomized to receive zibotentan 10 mg or placebo once daily. Based on the lack of efficacy signal in another ENTHUSE phase III study, an interim analysis was performed to determine whether the study was likely to achieve the co-primary objectives of improved overall survival (OS) and progression-free survival (PFS). RESULTS: Criteria for continuation of this study were not met. A total of 79 deaths and 293 progression events were recorded at final data cutoff. Zibotentan-treated patients did not significantly differ from placebo-treated patients for OS (hazard ratio (HR): 1.13; 95% confidence interval (CI): 0.73-1.76, P=0.589) or PFS (HR: 0.89; 95% CI: 0.71-1.12, P=0.330). The most commonly reported adverse events in zibotentan-treated patients were peripheral oedema (37.7%), headache (26.2%) and nasal congestion (24.9%); each occurred with >15% higher incidence than in the placebo group. CONCLUSIONS: This trial was terminated early because of failure at interim analysis of the efficacy data to meet the defined criteria for continuation. Owing to the absence of demonstrable survival benefits in the ENTHUSE clinical studies, zibotentan is no longer under investigation as a potential treatment for prostate cancer.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents/administration & dosage , Prostatic Neoplasms, Castration-Resistant/drug therapy , Pyrrolidines/administration & dosage , Adenocarcinoma/mortality , Administration, Oral , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Double-Blind Method , Drug Administration Schedule , Edema/chemically induced , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Prostatic Neoplasms, Castration-Resistant/mortality , Pyrrolidines/adverse effects , Treatment Outcome
8.
Prostate Cancer Prostatic Dis ; 16(1): 85-90, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23069729

ABSTRACT

BACKGROUND: Active surveillance (AS) is increasingly utilized in low-risk prostate cancer (PC) patients. Although black race has traditionally been associated with adverse PC characteristics, its prognostic value for patients managed with AS is unclear. METHODS: A retrospective review identified 145 patients managed with AS at the Duke Prostate Center from January 2005 to September 2011. Race was patient-reported and categorized as black, white or other. Inclusion criteria included PSA <10 ng ml(-1), Gleason sum ≤ 6, and ≤ 33% of cores with cancer on diagnostic biopsy. The primary outcome was discontinuation of AS for treatment due to PC progression. In men who proceeded to treatment after AS, the trigger for treatment, follow-up PSA and biopsy characteristics were analyzed. Time to treatment was analyzed with univariable and multivariable Cox proportional hazards models and also stratified by race. RESULTS: In our AS cohort, 105 (72%) were white, 32 (22%) black and 8 (6%) another race. Median follow-up was 23.0 months, during which 23% percent of men proceeded to treatment. The demographic, clinical and follow-up characteristics did not differ by race. There was a trend toward more uninsured black men (15.6% black, 3.8% white, 0% other, P = 0.06). Black race was associated with treatment (hazard ratio (HR) 2.93, P = 0.01) as compared with white. When the analysis was adjusted for socioeconomic and clinical parameters at the time of PC diagnosis, black race remained the sole predictor of treatment (HR 3.08, P = 0.01). Among men undergoing treatment, the trigger was less often patient driven in black men (8 black, 33 white, 67% other, P = 0.05). CONCLUSIONS: Black race was associated with discontinuation of AS for treatment. This relationship persisted when adjusted for socioeconomic and clinical parameters.


Subject(s)
Prostatic Neoplasms/ethnology , Watchful Waiting , Aged , Black People , Disease Progression , Humans , Male , Middle Aged , Prostatic Neoplasms/therapy , Retrospective Studies , White People
9.
Prostate Cancer Prostatic Dis ; 16(1): 91-4, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23032361

ABSTRACT

BACKGROUND: To investigate racial differences in tumor burden (cancer volume, cancer percentage and cancer to PSA ratios) in a large cohort of men undergoing radical prostatectomy (RP). METHODS: Demographic, clinical and pathological data of patients undergoing RP between 1993-2010 were reviewed and compared between African-American (AA) and non African-American (nAA) men. Further assessments of pathological tumor burden (estimated tumor volume, percent of cancer involvement, and estimated tumor volume/PSA ratios) were performed across Gleason score categories. RESULTS: Of 4157 patients in the analysis, 604 (14.5%) were AA. Overall, AA patients were younger, had higher Gleason scores, PSA levels and incidence of palpable disease (all P < 0.001). Despite comparable prostate weights (39.4 vs. 39.6 g), AA men had higher percent cancer involvement and estimated tumor volume (all P < 0.001) but similar estimated tumor volume/PSA ratios ( P> 0.05). When stratified by Gleason scores, prostate weights were comparable; however, estimated tumor volume, percent cancer involvement and estimated tumor volume/PSA ratios were higher in AA men with low grade (≤ 6) prostate cancer (PCa), similar in intermediate grade (7-8) and lower in high grade (9-10) PCa compared to nAA men. CONCLUSIONS: In this large series, AA patients had higher disease burden (estimated tumor volume, percent cancer involvement, estimated tumor volume/PSA ratios) compared to nAA but this association was especially pronounced in low grade (Gleason ≤ 6) cancers. These data depict a complex picture of relations between race and tumor burden across the spectrum of PCa aggressiveness. Further investigation is warranted to understand the mechanisms of racial disparities in PCa.


Subject(s)
Prostatic Neoplasms/ethnology , Prostatic Neoplasms/pathology , Tumor Burden , Black or African American , Aged , Humans , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , White People
10.
Prostate Cancer Prostatic Dis ; 15(4): 380-5, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22777393

ABSTRACT

BACKGROUND: Incremental cost-effectiveness ratios (ICERs) of finasteride for prostate cancer prevention are consistent with estimates beyond $100 000 per quality-adjusted life-year (QALY). The majority of these analyses are based on chemoprevention starting in men aged 50-55 years. We sought to evaluate the impact of varying both age at commencement of therapy and length of therapy on the cost-effectiveness of finasteride. METHODS: A probabilistic Markov model was designed to estimate lifetime prostate health-related costs and quality-adjusted survival for men receiving or not receiving chemoprevention with finasteride. ICERs across scenarios varying age at start of therapy and duration of chemoprevention were compared. RESULTS: The ICER for men starting chemoprevention at age 50 and continuing to age 75 was $88 800 per QALY when assuming finasteride causes a constant risk reduction across all tumor grades (base case 1) and $142 300 per QALY when assuming a differential treatment effect according to Gleason score (base case 2). When starting age is increased, the ICERs trend downward and nadir at 65 years to $64 700 per QALY (base case 1) and $118 600 per QALY (base case 2). Altering duration of therapy had minimal impact. Patient-level experiences with finasteride and BPH significantly influenced the cost-effectiveness of chemoprevention. CONCLUSIONS: Initiating chemoprevention at ages when prostate cancer incidence is higher improves its cost-effectiveness profile. Only when assuming a constant risk reduction for all tumor grades, did finasteride fall below $100 000 per QALY, but this finding was not upheld when accounting for side effects associated with the drug.


Subject(s)
Age Factors , Cost-Benefit Analysis/economics , Markov Chains , Prostatic Neoplasms/economics , Aged , Chemoprevention/economics , Finasteride/economics , Finasteride/therapeutic use , Health Care Costs , Humans , Male , Middle Aged , Prostatic Neoplasms/drug therapy , Quality-Adjusted Life Years
11.
Prostate Cancer Prostatic Dis ; 14(4): 346-53, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21727906

ABSTRACT

The American Cancer Society's updated screening guidelines for prostate cancer (CaP) render digital rectal examination (DRE) optional. We investigated the impact of DRE on CaP detection among obese men. Data from 2794 men undergoing initial prostate biopsy at three centers were analyzed to assess CaP risk attributed to abnormal DRE across body mass index (BMI) categories. Predictive accuracies of a combination of PSA, age, race, center and biopsy year including or excluding DRE findings were compared by areas under the receiver-operating characteristics curves. In all cohorts, obese men were less likely to have abnormal DREs diagnosed than non-obese men. As BMI category increased, abnormal DREs became stronger predictors for overall CaP in individual (P-trends ≤ 0.05) and combined (P-trend<0.001) cohorts, and for high-grade CaP in the Italian (P-trend=0.03) and combined (P-trend=0.03) cohorts. DRE inclusion improved the predictive accuracy for overall and high-grade CaP detection among all obese men (P ≤ 0.032) but not normal-weight men (P ≥ 0.198). DRE inclusion also near-significantly improved overall CaP detection in obese men with PSA<4 ng ml(-1) (P=0.081). In conclusion, the predictive value of DRE is dependent on obesity and is significantly higher among obese men than normal-weight men.


Subject(s)
Digital Rectal Examination , Early Detection of Cancer , Obesity/complications , Prostatic Neoplasms/diagnosis , Aged , Body Mass Index , Cohort Studies , Humans , Italy/epidemiology , Male , Middle Aged , Predictive Value of Tests , Prostatic Neoplasms/complications , Prostatic Neoplasms/epidemiology , Risk , United States/epidemiology
12.
Prostate Cancer Prostatic Dis ; 13(3): 248-51, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20514082

ABSTRACT

The objective of this study was to preoperatively predict non-organ-confined disease in patients considering radical prostatectomy. To account for the stage migration seen in prostate cancer, we included only those patients who underwent prostatectomy after the year 2000. Information on a cohort of 1895 patients who underwent radical prostatectomy from 2000 to 2008 was retrieved from the Duke Prostate Center database. Race (African American, non-African American), body mass index, age at surgery, PSA, biopsy Gleason sum (<7, 7 and >7) and clinical tumor stage (cT1, cT2/3) were analyzed by univariate analysis followed by logistic regression analysis. The Duke Interactive Clinical Equation for staging (DICE-S score) was calculated from the logistic regression model. The model was then internally validated using a bootstrapping technique. Biopsy Gleason sums 7 and >7 were more likely to have non-organ-confined disease compared with <7 (OR=2.97, Gleason sum=7; OR=3.25, Gleason sum>7). Clinical tumor stage, cT2/3, predicted non-organ-confined disease (OR=1.58). Older age was associated with non-organ-confined disease (OR=1.02), as was greater PSA (OR=1.12). DICE-S equation x=ln (p/1-p)=-3.627+0.019 (age)+0.109 (PSA)+1.087 (bGleason=7)+1.180 (bGleason >7)+0.459 (clinical T stage >T1), where p=(e(x))/(1+e(x)). A concordance index (prediction accuracy) of 0.73 was reached on internal validation. Using the DICE-S score, age, PSA, biopsy Gleason sum and clinical tumor stage, we can predict non-organ-confined disease in radical prostatectomy at an acceptable accuracy. Preoperative information on disease stage may aid in treatment decisions and surgical approach.


Subject(s)
Prostatectomy , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/surgery , Aged , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Prostate-Specific Antigen/blood , Survival Rate
14.
Prostate Cancer Prostatic Dis ; 13(1): 87-93, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19918263

ABSTRACT

To evaluate whether race modifies the accuracy of nomograms to predict biochemical recurrence (BCR) after radical prostatectomy among subjects from the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Center (DPC) databases. Retrospective analysis of 1721 and 4511 subjects from the SEARCH and DPC cohorts, respectively. The discrimination accuracy for BCR of seven previously published predictive models was assessed using concordance index and compared between African-American men (AAM) and Caucasian men (CM). AAM represented 44% of SEARCH and 14% of DPC. In both cohorts, AAM were more likely to experience BCR than CM (P<0.01). In SEARCH, the mean concordance index across all seven models was lower in AAM (0.678) than CM (0.715), though the mean difference between CM and AAM was modest (0.037; range 0.015-0.062). In DPC the overall mean concordance index for BCR across all seven nomograms was 0.686. In contrast to SEARCH, the mean concordance index in DPC was higher in AAM (0.717) than CM (0.681), though the mean differences between CM and AAM was modest (-0.036; range -0.078 to -0.004). Across all seven models for predicting BCR, the discriminatory accuracy was better among CM in SEARCH and better among AAM in DPC. The mean difference in discriminatory accuracy of all seven nomograms between AAM and CM was approximately 3-4%. This indicates that currently used predictive models have similar performances among CM and AAM. Therefore, nomograms represent a valid and accurate method to predict BCR regardless of race.


Subject(s)
Disease-Free Survival , Prostatectomy , Prostatic Neoplasms/ethnology , Black or African American , Databases, Factual , History, 17th Century , History, 18th Century , Humans , Male , Neoplasm Recurrence, Local/surgery , Nomograms , Prostate/pathology , Prostate/surgery , Prostate-Specific Antigen/analysis , Prostatectomy/methods , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Recurrence , White People
15.
Prostate Cancer Prostatic Dis ; 12(3): 209-10, 2009.
Article in English | MEDLINE | ID: mdl-19721468
16.
Prostate Cancer Prostatic Dis ; 12(3): 259-63, 2009.
Article in English | MEDLINE | ID: mdl-19581922

ABSTRACT

Obesity is associated with increased risk of positive surgical margins and prostate specific antigen (PSA) recurrence among men undergoing radical prostatectomy. To what degree positive margins contribute to poorer outcome is unclear. Thus, we sought to examine the association between body mass index (BMI) and more objective measures of tumor aggressiveness, tumor grade and size. We carried out a retrospective analysis of 2302 patients treated with radical prostatectomy at the Duke Prostate Center from 1988-2007. Tumor volume was calculated by multiplying prostate weight by percent of specimen involved with cancer. Associations between BMI and tumor volume and high-grade disease (Gleason >or=4+3) independent of pre-operative clinical characteristics of age, race, PSA, clinical stage, biopsy Gleason sum, and year of surgery were assessed using linear and logistic regression, respectively. Mean and median BMI among all subjects was 28.1 and 27.6 kg m(-2), respectively. Increased BMI was significantly associated with younger age (P<0.001), black race (P<0.001), more recent year of surgery (P<0.001), and positive surgical margins (P<0.001). After adjusting for multiple clinical pre-operative characteristics, higher BMI was associated with a greater percent of the prostate involved with cancer (P=0.003), increased tumor volume (P<0.001), and high-grade disease (P=0.007). Men with a BMI >or=35 kg m(2) had nearly 40% larger mean tumor volumes than normal weight men (5.1 versus 3.7 cc), after adjustment for multiple clinical characteristics. In this study, obese men undergoing radical prostatectomy had higher-grade and larger tumors, providing further evidence that obese men undergoing radical prostatectomy have more aggressive prostate cancers.


Subject(s)
Obesity/pathology , Prostatic Neoplasms/pathology , Body Mass Index , Databases, Factual , Humans , Male , Prostatectomy , Prostatic Neoplasms/surgery , Retrospective Studies
17.
19.
Prostate Cancer Prostatic Dis ; 11(4): 371-6, 2008.
Article in English | MEDLINE | ID: mdl-18427570

ABSTRACT

We hypothesized that factors beyond pathological stage, grade, PSA and margin status would be important predictors of biochemical recurrence (BCR) after radical prostatectomy (RP). A cohort of 3194 patients who underwent RP between 1988 and 2007 and who had neither neoadjuvant therapy nor postoperative adjuvant hormonal therapy was retrieved from the Duke Prostate Center database. Age, prostate-specific antigen (PSA), pathological Gleason score (pG), lymph node status, seminal vesicle invasion (SVI), extracapsular extension (ECE), positive surgical margin (PSM) status, year of surgery, race, adjuvant radiation therapy (XRT), percent tumor involvement in the RP specimen and prostate weight were evaluated as possible predictors of BCR in multivariate Cox regression analysis. BCR was defined as a PSA of 0.2 ng ml(-1) or higher at least 30 days after surgery. A nomogram was developed from the Cox model. Predictive accuracy was obtained by calculating bias-corrected Harrell's c and by bootstrap calibration. In multivariate analysis, PSA (hazard ratio 1.39 (95% confidence interval 1.29-1.51)), ECE (1.22 (1.04-1.44)), pG score (1.38 (1.14-1.68), 2.23 (1.76-2.84), 2.69 (2.12-3.40) for pG 3+4, 4+3, >7, respectively), SVI (1.72 (1.40-2.12)), PSM (2.05 (1.73-2.42)), year of surgery (0.65 (0.54-0.77)), African-American race (1.37 (1.13-1.66)), adjuvant XRT (0.19 (0.11-0.34)) and prostate weight (0.83 (0.76-0.92)) were identified as independent predictors of BCR (P< or =0.018 for all factors). Predictive accuracy of the nomogram was 0.75. Race and prostate weight were independent predictors for BCR after RP. By incorporating these variables, we developed a nomogram, which provides a highly accurate means for estimating risk of BCR after RP.


Subject(s)
Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/pathology , Prostate-Specific Antigen/blood , Prostatectomy , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Aged , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/surgery , Organ Size , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/surgery , Survival Rate , Time Factors
20.
Article in English | MEDLINE | ID: mdl-18268507
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