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1.  The Effect of Race and Socioeconomic Status on Surgical Margins and Biochemical Outcomes in an Equal-access Healthcare Setting: Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database 
Cancer  2012;118(20):4999-5007.
Background
The impact of race and socioeconomic status (SES) in prostate cancer (CaP) outcomes has been well-studied, but controversy remains. We explored in an equal-access setting the associations of race/SES with intermediate CaP outcomes including positive surgical margin (PSM) and biochemical recurrence (BCR).
Methods
Data were retrospectively collected from 2502 men in the Shared Equal-Access Regional Cancer Hospitals (SEARCH)database who underwent radical prostatectomy from 1989–2010. SES (income, education, employment, and poverty) was estimated from linkage of home zip-code to census data. Logistic regression with adjustment for pre-and post-operative covariates estimated risk for associations between race/SES and pathologic outcomes. Cox proportional hazards models estimated risk for associations between race/SES and time to BCR.
Results
Black men were more likely to have lower SES than white men (p<0.001). On multivariate analysis, race was not associated with PSM, but higher SES was associated with less PSM and fewer Gleason sum ≥ 7 pathologic tumors when SES was assessed by education, employment, or poverty (p-trend ≤ 0.051) and income, employment, or poverty (p-trend ≤ 0.059), respectively. Crude Cox models showed black men had higher BCR risk (Hazards Ratio [HR] 1.20, 95% Confidence Interval [CI] 1.05–1.38, p=0.009) that persisted after adjustment for covariates including SES (HR ≥ 1.18, p ≤ 0.040). Higher SES measured by income and poverty were associated with less BCR but only for black men (p-trend ≤ 0.048).
Conclusions
Even in an equal-access setting, higher SES predicted lower PSM risk, and race persisted in predicting BCR despite adjustment for SES. Low SES black patients may be at greatest risk for post-prostatectomy BCR.
doi:10.1002/cncr.27456
PMCID: PMC3376692  PMID: 22415377
socioeconomic status; race; positive surgical margin; biochemical recurrence; prostate cancer; equal-access
2.  Combined use of EUS-guided FNA and immunocytochemical stains discloses metastatic and unusual diseases in the evaluation of mediastinal lymphadenopathy of unknown etiology 
Annals of Thoracic Medicine  2012;7(2):84-91.
PURPOSE:
Mediastinal lymphadenopathy (ML) is a cause for concern, especially in patients with previous malignancy. We report our experience with the use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with immunocytochemical stains in patients being evaluated for ML.
METHODS:
Retrospective analysis of patients with ML of unknown origin who underwent EUS-FNA. On-site evaluation was performed by experienced cytologist, and special immunocytochemical stains were requested as indicated.
RESULTS:
A total of 116 patients were included, and a total of 136 mediastinal LN were sampled. Prior malignancy was present in 45%. The most common site of examined lymph node (LN) were subcarinal (76%, 103 LN). The median long and short axis diameters were 28 mm and 13 mm, respectively. FNA was read on-site as malignant, 21 (16%); benign, 100 (76.9%); suspicious, six (4%); atypical, 3 (2%); and inadequate sample, six (4%). Sixty-four LN were deferred for additional studies; 22 for immunocytochemical and 26 for Gimesa (GMS) stain and 21 for flow cytometry. Final FNA read was malignant in 28 (21%), benign in 103 (76%), suspicious in three (2%), and atypical in two (1%). Metastatic malignancies disclosed included Hodgkin's and Non-Hodgkin's lymphoma, melanoma, hepatoma, breast, lung, colon, renal, endometrial, Fallopian tube, and unknown carcinoma. The sensitivity, specificity, and accuracy of the final FNA read to predict malignancy were 100%.
CONCLUSION:
EUS-guided FNA with additional ancillary studies is useful in disclosing metastatic ML from a variety of neoplasms. Due to its safety and accuracy profile, it should be considered the test of choice in evaluating abnormal ML in appropriately selected patients.
doi:10.4103/1817-1737.94527
PMCID: PMC3339209  PMID: 22558013
Endoscopic ultrasound; fine needle aspiration; immunostains; lung cancer; metastatic disease
3.  EVALUATING THE PROSTATE CANCER PREVENTION TRIAL HIGH GRADE PROSTATE CANCER RISK CALCULATOR IN TEN INTERNATIONAL BIOSY COHORTS: RESULTS FROM THE PROSTATE BIOPSY COLLABORATIVE GROUP 
World journal of urology  2012;32(1):185-191.
OBJECTIVES
To assess the applicability of the Prostate Cancer Prevention Trial High Grade (Gleason grade ≥ 7) Risk Calculator (PCPTHG) in ten international cohorts, representing a range of populations.
METHODS
25,512 biopsies from 10 cohorts (6 European, 1 UK, and 3 US) were included; 4 implemented 6-core biopsies and the remaining had 10- or higher schemes; 8 were screening cohorts and 2 were clinical. PCPTHG risks were calculated using prostate-specific antigen (PSA), digital rectal examination, age, African origin and history of prior biopsy and evaluated in terms of calibration plots, areas underneath the receiver operating characteristic curve (AUC), and net benefit curves.
RESULTS
The median AUC of the PCPTHG for high grade disease detection in the 10- and higher-core cohorts was 73.5% (range 63.9% to 76.7%) compared to a median of 78.1 (range = 72.0 to 87.6) among the four 6-core cohorts. Only the 10-core Cleveland Clinic cohort showed clear evidence of under-prediction by the PCPTHG, and this was restricted to risk ranges less than 15%. The PCPTHG demonstrated higher clinical net benefit in higher- compared to six-core biopsy cohorts, and among the former, there were no notable differences observed between clinical and screening cohorts, nor between European and US cohorts.
CONCLUSIONS
The PCPTHG requires minimal patient information and can be applied across a range of populations. PCPTHG risk thresholds ranging from 5 to 20%, depending on patient risk averseness, are recommended for clinical prostate biopsy decision-making.
doi:10.1007/s00345-012-0869-2
PMCID: PMC3702682  PMID: 22527674
Calibration; Discrimination; Net Benefit; High Grade Prostate Cancer; Risk; Prostate Cancer Prevention Trial
4.  Smoking and prostate cancer survival and recurrence 
Asian Journal of Andrology  2011;13(6):787-788.
doi:10.1038/aja.2011.126
PMCID: PMC3739564  PMID: 21927042
5.  Postoperative prostate-specific antigen nadir improves accuracy for predicting biochemical recurrence after radical prostatectomy: Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Center databases 
Objectives
We previously showed that prostate-specific antigen (PSA) nadir after radical prostatectomy (RP) significantly predicts biochemical recurrence (BCR). Herein, we sought to explore the effect of including PSA nadir into commonly used models on their accuracy to predict BCR after RP.
Methods
This was a retrospective analysis of 943 and 1792 subjects from the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Cancer (DPC) databases, respectively. The discrimination accuracy for BCR of seven previously published models was assessed using concordance index and compared with and without adding PSA nadir level in SEARCH. Using data from SEARCH, we developed a new nomogram incorporating PSA nadir to other known predictors (preoperative PSA, pathological Gleason score, PSA nadir level, surgical findings, prostate weight, body mass index and race) of BCR and externally validated it in the DPC.
Results
In SEARCH, the mean concordance index across all seven nomograms was 0.687. After the inclusion of PSA nadir, the concordance index increased by nearly 7% (mean = 0.753). The concordance index of the new nomogram in SEARCH was 0.779 (bias-corrected = 0.767), which was 5% better than the next best model. In DPC, the new nomogram yielded a concordance index of 0.778.
Conclusion
The addition of postoperative PSA nadir to commonly used nomograms increased their accuracies by nearly 7%. Based upon this, we developed and externally validated a new nomogram, which was well calibrated and highly accurate, and is a potentially valuable tool for patients and physicians to predict BCR after RP.
doi:10.1111/j.1442-2042.2010.02631.x
PMCID: PMC3188446  PMID: 20880361
disease-free survival; nomograms; prostate cancer; prostate-specific antigen; prostatectomy; validation studies
6.  Association of Cigarette Smoking With Interval to Biochemical Recurrence After Radical Prostatectomy: Results from the SEARCH Database 
Urology  2010;76(5):1218-1223.
OBJECTIVES
To analyze the association between cigarette smoking and biochemical recurrence (BCR) after radical prostatectomy among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.
METHODS
We performed a retrospective analysis of 1267 subjects from the SEARCH cohort treated from 1998 to 2008 with smoking status available from the preoperative notes. A comparison of the baseline patient and disease characteristics between the current smokers and nonsmokers (past and never smokers combined) was performed using the chi-square and rank sum tests. The univariate and multivariate associations between smoking status and BCR-free survival were analyzed using Kaplan-Meier plots, the log-rank test, and Cox proportional hazard models.
RESULTS
Of the 1267 patients, 408 (32%) were active smokers and 859 (68%) were nonsmokers at surgery. The current smokers were younger (P < .001), more likely to be black (P < .001), and had a lower body mass index (P < .001), a greater percentage of positive biopsy cores (P = .039), a greater preoperative prostate-specific antigen level (P = .003), more extracapsular extension (P = .003) and seminal vesicle invasion (P = .029), and lower prostate volumes (P = .002). On univariate analysis, smokers had a risk of BCR similar to that of nonsmokers (hazard ratio 1.19, P = .129). On multivariate analysis, smoking was associated with an increased risk of BCR when adjusted for body mass index only (hazard ratio 1.37, P = .008). However, after adjustment for multiple preoperative characteristics, the association was attenuated and no longer statistically significant (hazard ratio 1.12, P = .325). After additional adjustment for postoperative features, such as tumor grade and stage, smoking was unrelated to the risk of BCR (hazard ratio 0.91, P = .502).
CONCLUSIONS
Among patients undergoing radical prostatectomy in the SEARCH cohort, cigarette smoking was associated with slightly more advanced disease but a similar risk of BCR.
doi:10.1016/j.urology.2010.01.066
PMCID: PMC3177236  PMID: 20381838
7.  Predictors of malignancy in EUS-guided FNA for mediastinal lymphadenopathy in patients without history of lung cancer 
Annals of Thoracic Medicine  2011;6(3):126-130.
BACKGROUND:
Mediastinal lymphadenopathy (ML) poses a great diagnostic challenge.
OBJECTIVE:
To investigate the predictors of malignancy in endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of ML in patients without known lung cancer.
DESIGN:
Retrospective study.
SETTING:
Tertiary referral center.
METHODS:
One hundred eight patients without known lung cancer who underwent EUS guided-FNA for ML between 2000 and 2007. All subjects underwent EUS-guided FNA. Data was collected on patients′ demographics, and lymph node (LN) characteristics. Diagnosis of LN malignancy was based on FNA findings and clinical follow-up.
RESULTS:
One hundred eight patients were analyzed; 58 (54%) were men and 87 (79%) were Caucasian. Mean age was 55 years. Prior malignancy was present in 48 (43%) patients. A total of 126 FNA samples from 126 distinct LNs were performed. Twenty-five (20%) LNs were positive for malignancy. Mean short and long-axis for LNs were 13 and 29 mms respectively. Round shape and sharp borders were found in 29 (15%) and 25 (22%) LNs, correspondingly. Independent predictors of a malignant FNA were: Prior cancer (OR 13.10; 95% CI 2.7-63.32; P = 0.001), short axis (OR 1.10; 95% CI 1.00-1.22; P = 0.041) and sharp LN borders (OR 5.47; 95% CI 1.01-29.51; P = 0.048). Age, race, gender, long axis, round shape were not associated with cancer in our cohort.
LIMITATIONS:
Retrospective design and lack of surgical gold standard.
CONCLUSIONS:
Increased risk of malignancy was associated with prior history of cancer, larger LN short axis and presence of LN sharp borders. These predictors may help guide endoscopists perform FNA in malignant LNs, increasing the overall efficiency of EUS-FNA for ML.
doi:10.4103/1817-1737.82442
PMCID: PMC3131754  PMID: 21760843
Endoscopic ultrasound; lung cancer; mediastinal lymphadenopathy; staging; fine needle aspiration
8.  A natural history of weight change in men with prostate cancer on androgen-deprivation therapy (ADT): results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database 
BJU international  2010;107(6):924-928.
OBJECTIVE
To better understand the natural history of weight change with androgen-deprivation therapy (ADT), we investigated the effect of ADT on body weight among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.Men undergoing ADT lose lean muscle but gain fat mass, contributing to an overall gain in weight.
PATIENTS AND METHODS
We identified 132 men in SEARCH who received ADT after radical prostatectomy.‘Weight change’ was defined as the difference in weight before starting ADT (6 months before ADT) and the on-ADT weight (between 6 and 18 months after starting ADT).In a subanalysis, baseline characteristics of weight-gainers and -losers were analysed using univariate and multivariate analysis to test association with weight change.
RESULTS
In all, 92 men (70%) gained weight, and 40 (30%) either lost or maintained a stable weight.On average, weight on ADT was 2.2 kg higher than the weight before ADT, with the mean change for weight-gainers and -losers being +4.2 kg and −2.4 kg, respectively.This compared with no significant weight change in the year before starting ADT (paired t-test, change −0.7 kg, P = 0.19) or in the second year on ADT (paired t-test, change −0.5 kg, P = 0.46) for 84 men in whom these additional weight values were recorded.There was no significant association between any of the features examined and weight change on univariate and multivariate analysis.
CONCLUSIONS
In this longitudinal study, ADT was accompanied by significant weight gain (+2.2 kg). This change occurred primarily in the first year of therapy, with men neither losing nor gaining additional weight thereafter.
doi:10.1111/j.1464-410X.2010.09679.x
PMCID: PMC3055926  PMID: 20860651
prostate cancer; androgen deprivation; side-effects; weight
9.  Evaluating The PCPT Risk Calculator in Ten International Biopsy Cohorts: Results from the Prostate Biopsy Collaborative Group 
World journal of urology  2011;30(2):181-187.
Objectives
To evaluate the discrimination, calibration and net benefit performance of the Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) across five European Randomized study of Screening for Prostate Cancer (ERSPC), 1 United Kingdom, 1 Austrian and 3 US biopsy cohorts.
Methods
PCPTRC risks were calculated for 25,733 biopsies using prostate-specific antigen (PSA), digital rectal examination, family history and history of prior biopsy, and single imputation for missing covariates. Predictions were evaluated using the areas underneath the receiver operating characteristic curves (AUC), discrimination slopes, chi-square tests of goodness of fit, and net benefit decision curves.
Results
AUCs of the PCPTRC ranged from a low of 56% in the ERSPC Goeteborg Rounds 2-6 cohort to a high of 72% in the ERSPC Goeteborg Round 1 cohort, and were statistically significantly higher than that of PSA in 6 out of the 10 cohorts. The PCPTRC was well-calibrated in the SABOR, Tyrol and Durham cohorts. There was limited to no net benefit to using the PCPTRC for biopsy referral compared to biopsying all or no men in all five ERSPC cohorts and benefit within a limited range of risk thresholds in all other cohorts.
Conclusions
External validation of the PCPTRC across ten cohorts revealed varying degree of success highly dependent on the cohort, most likely due to different criteria for and work-up before biopsy. Future validation studies of new calculators for prostate cancer should acknowledge the potential impact of the specific cohort studied when reporting successful versus failed validation.
doi:10.1007/s00345-011-0818-5
PMCID: PMC3616370  PMID: 22210512
receiver operating characteristic curve; risk; prostate cancer; calibration; net benefit
10.  Importance of prostate volume in the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators: results from the prostate biopsy collaborative group 
World Journal of Urology  2011;30(2):149-155.
Objectives
To compare the predictive performance and potential clinical usefulness of risk calculators of the European Randomized Study of Screening for Prostate Cancer (ERSPC RC) with and without information on prostate volume.
Methods
We studied 6 cohorts (5 European and 1 US) with a total of 15,300 men, all biopsied and with pre-biopsy TRUS measurements of prostate volume. Volume was categorized into 3 categories (25, 40, and 60 cc), to reflect use of digital rectal examination (DRE) for volume assessment. Risks of prostate cancer were calculated according to a ERSPC DRE-based RC (including PSA, DRE, prior biopsy, and prostate volume) and a PSA + DRE model (including PSA, DRE, and prior biopsy). Missing data on prostate volume were completed by single imputation. Risk predictions were evaluated with respect to calibration (graphically), discrimination (AUC curve), and clinical usefulness (net benefit, graphically assessed in decision curves).
Results
The AUCs of the ERSPC DRE-based RC ranged from 0.61 to 0.77 and were substantially larger than the AUCs of a model based on only PSA + DRE (ranging from 0.56 to 0.72) in each of the 6 cohorts. The ERSPC DRE-based RC provided net benefit over performing a prostate biopsy on the basis of PSA and DRE outcome in five of the six cohorts.
Conclusions
Identifying men at increased risk for having a biopsy detectable prostate cancer should consider multiple factors, including an estimate of prostate volume.
doi:10.1007/s00345-011-0804-y
PMCID: PMC3321270  PMID: 22203238
PSA; Risk; Prostate cancer; Prostate volume; Calibration; Net benefit
11.  The relationship between prostate-specific antigen and prostate cancer risk: the Prostate Biopsy Collaborative Group 
PURPOSE
The relationship between prostate specific antigen (PSA) level and prostate cancer risk remains subject to fundamental disagreements. We hypothesize that the risk of prostate cancer on biopsy for a given PSA level is affected by identifiable characteristics of the cohort under study.
EXPERIMENTAL DESIGN
We used data from 5 European and 3 US cohorts of men undergoing biopsy for prostate cancer; six were population-based studies and two were clinical cohorts. The association between PSA and prostate cancer was calculated separately for each cohort using locally-weighted scatterplot smoothing.
RESULTS
The final data set included 25,772 biopsies and 8,503 cancers. There were gross disparities between cohorts with respect to both the prostate cancer risk at a given PSA level and the shape of the risk curve. These disparities were associated with identifiable differences between cohorts: for a given PSA level, a greater number of biopsy cores increased risk of cancer (odds ratio for >6 vs. 6 core biopsy 1.35; 95% C.I. 1.18, 1.54; p<0.0005); recent screening led to a smaller increase in risk per unit change in PSA (p=0.001 for interaction term) and US cohorts had higher risk than the European cohorts (2.14; 95% C.I. 1.99, 2.30; p<0.0005).
CONCLUSIONS
Our results suggest that the relationship between PSA and risk of a positive prostate biopsy varies, both in terms of the probability of prostate cancer at a given PSA value and the shape of the risk curve. This poses challenges to the use of PSA-driven algorithms to determine whether biopsy is indicated.
doi:10.1158/1078-0432.CCR-10-1328
PMCID: PMC2937360  PMID: 20736330
prostate cancer; PSA; prediction; multicenter studies; screening

Results 1-11 (11)