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Schroeck F.R.,Urologic | Schroeck F.R.,Duke University | Kattan M.W.,Veterans Affairs Medical Center Durham | Moul J.W.,Urologic | And 11 more authors.
BJU International

Study Type - Prognosis (case series) Level of Evidence 4 Objective to re-calibrate the previously published Duke Prostate Center (DPC) nomogram for the prediction of biochemical recurrence (BCR) after radical prostatectomy (RP) to not only predict overall BCR but also the clinically more relevant endpoint of an aggressive recurrence (i.e. a BCR with a postoperative PSA doubling time (PSADT) of <9 months). Patients and Methods Using the established point-scale system based upon the previously published DPC nomogram, we re-calibrated this point system to predict not just BCR, but also aggressive BCR within 2599 men treated with RP from the DPC database. PSADT was computed on all patients meeting the recurrence definition who had a minimum of two PSA values, separated by at least 3 months, and ≤2 years after recurrence. External validation was performed using data from 1695 men treated with RP within the Shared Equal Access Regional Cancer Hospital (SEARCH) database by calculating the concordance index c and by plotting calibration curves. Results The median follow-up for patients with no BCR was 56 and 47 months for DPC and SEARCH, respectively. In the DPC modelling cohort and the SEARCH validation cohort, 645 (25%) and 557 (33%) men had BCR, while 83 (3.2%) and 71 (4.2%) patients had an aggressive recurrence. In external validation, predictive accuracy for an aggressive BCR was high (c = 0.83) and the nomogram showed good calibration. Conclusions We re-calibrated an existing nomogram to not only predict overall BCR after RP but also aggressive recurrence after RP. Our new tool can provide valuable information for patient counselling and patient selection for adjuvant therapy trials. © 2009 BJU INTERNATIONAL. Source

Jayachandran J.,Duke University | Jayachandran J.,Veterans Affairs Medical Center Durham | Aronson W.J.,Urology Section | Aronson W.J.,University of California at Los Angeles | And 7 more authors.
Cancer Epidemiology Biomarkers and Prevention

Background: Diabetes is associated with lower prostate cancer risk. The association of diabetes with prostate cancer outcomes is less clear. We examined the association between diabetes and outcomes after radical prostatectomy and tested whether associations varied by race and/or obesity. Materials and Methods: This study is a retrospective analysis of 1,262 men treated with radical prostatectomy between 1988 and 2008 within the Shared Equal-Access Regional Cancer Hospital database. We examined the multivariate association between diabetes at surgery and adverse pathology, biochemical recurrence (BCR), and prostate-specific antigen doubling time at recurrence using logistic, proportional hazards, and linear regression, respectively. Data were examined as a whole and stratified by race and obesity. Results: Diabetes was more prevalent among black (22% versus 15%, P < 0.001) and more obese men (P < 0.001). Diabetes was associated with higher tumor grade (odds ratio, 1.73; P = 0.002), seminal vesicle invasion (odds ratio, 1.73; P = 0.04), but not BCR (P = 0.67) or PSADT at recurrence (P = 0.12). In the secondary analysis, among white obese men, diabetes was associated with 2.5-fold increased BCR risk (P = 0.002) and a trend toward shorter PSADT, whereas among all other men (nonobese white men and black men), diabetes was associated with 23% lower recurrence risk (P = 0.09) and longer PSADT (P = 0.04). Conclusion: In a radical prostatectomy cohort, diabetes was not associated with BCR. In the secondary analysis, diabetes was associated with more aggressive disease in obese white men and less aggressive disease for all other subsets. If externally validated, these findings suggest that among men with prostate cancer, the association between diabetes and prostate cancer aggressiveness may vary by race and obesity. ©2010 AACR. Source

Moreira D.M.,Mayo Medical School | Howard L.E.,Duke University | Howard L.E.,Veterans Affairs Medical Center Durham | Sourbeer K.N.,Veterans Affairs Medical Center Durham | And 21 more authors.
Prostate Cancer and Prostatic Diseases

Background:To evaluate PSA levels and kinetic cutoffs to predict positive bone scans for men with non-metastatic castration-resistant prostate cancer (CRPC) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.Methods:Retrospective analysis of 531 bone scans of 312 clinically CRPC patients with no known metastases at baseline treated with a variety of primary treatment types in the SEARCH database. The association of patients' demographics, pathological features, PSA levels and kinetics with risk of a positive scan was tested using generalized estimating equations.Results:A total of 149 (28%) scans were positive. Positive scans were associated with younger age (odds ratio (OR)=0.98; P=0.014), higher Gleason scores (relative to Gleason 2-6, Gleason 3+4: OR=2.03, P=0.035; Gleason 4+3 and 8-10: OR=1.76, P=0.059), higher prescan PSA (OR=2.11; P<0.001), shorter prescan PSA doubling time (PSADT; OR=0.53; P<0.001), higher PSA velocity (OR=1.74; P<0.001) and more remote scan year (OR=0.92; P=0.004). Scan positivity was 6, 14, 29 and 57% for men with PSA<5, 5-14.9, 15-49.9 and ≥50 ng ml -1, respectively (P-trend <0.001). Men with PSADT ≥15, 9-14.9, 3-8.9 and <3 months had a scan positivity of 11, 22, 34 and 47%, correspondingly (P-trend <0.001). Tables were constructed using PSA and PSADT to predict the likelihood of a positive bone scan.Conclusions:PSA levels and kinetics were associated with positive bone scans. We developed tables to predict the risk of positive bone scans by PSA and PSADT. Combining PSA levels and kinetics may help select patients with CRPC for bone scans. © 2015 Macmillan Publishers Limited. Source

Moreira D.M.,Duke University | Moreira D.M.,Veterans Affairs Medical Center Durham | Presti J.C.,Stanford University | Presti J.C.,Veterans Affairs Medical Center | And 9 more authors.
Prostate Cancer and Prostatic Diseases

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. © 2010 Nature Publishing Group. All rights reserved. Source

Allott E.H.,Duke University | Allott E.H.,Cancer Prevention Pharmaceuticals | Allott E.H.,Veterans Affairs Medical Center Durham | Howard L.E.,Duke University | And 10 more authors.
Cancer Epidemiology Biomarkers and Prevention

Background: Evidence for an association between total cholesterol, low- and high-density lipoproteins (LDL and HDL, respectively), triglycerides, and prostate cancer is conflicting. Given that prostate cancer and dyslipidemia affect large proportions of Western society, understanding these associations has public health importance. Methods: We conducted a retrospective cohort analysis of 843 radical prostatectomy (RP) patients who never used statins before surgery within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analysis was used to investigate the association between cholesterol, LDL, HDL, and triglycerides and biochemical recurrence risk. In secondary analysis, we explored these associations in patients with dyslipidemia, defined using National Cholesterol Education Program guidelines. Results: Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence [HRper 10 mg/dl, 1.03; 95% confidence interval (CI), 1.01-1.05] but associations between total cholesterol, LDL and HDL, and recurrence risk were null. However, among men with dyslipidemia, each 10 mg/dl increase in cholesterol and HDL was associated with 9% increased recurrence risk (HR, 1.09; 95% CI, 1.01-1.17) and 39% reduced recurrence risk (HR, 0.61; 95% CI, 0.41-0.91), respectively. Conclusions: Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence. Cholesterol, LDL, or HDL were not associated with recurrence risk among all men. However, among men with dyslipidemia, elevated cholesterol and HDL levels were associated with increased and decreased risk of recurrence, respectively. Impact: These findings, coupled with evidence that statin use is associated with reduced recurrence risk, suggest that lipid levels should be explored as a modifiable risk factor for prostate cancer recurrence. ©2014 AACR. Source

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