Evaluation of medications used for opioid use disorder in emergency departments: A cross-sectional analysis of the 2020 National Hospital Ambulatory Medical Care Survey.

INTRODUCTION: Opioid use disorder (OUD) is a significant health issue impacting millions in the United States (US). Medications used for OUD (MOUD) (e.g., buprenorphine, methadone, naltrexone) and medications for overdose and symptom management (e.g., naloxone, clonidine) have been shown to be safe and effective tools in clinical management. MOUD therapy in Emergency Departments (EDs) improves patient outcomes and enhances engagement with formal addiction treatment; however, provider factors and institutional barriers have created hurdles to ED-based MOUD treatment and heterogeneity in ED based OUD care. We used a nationally representative dataset, the National Hospital Ambulatory Medical Care Survey (NHAMCS) to characterize MOUD prescribing practices across patient demographics, geographic regions, payers, providers, and comorbidities in EDs. METHODS: NHAMCS is a survey conducted by the US Census Bureau assessing utilization of ambulatory healthcare services nationally. Survey staff compile encounter records from a nationally representative sample of EDs. We conducted a cross-sectional study using this data to assess visits in 2020 among patients aged 18-64 presenting with an opioid overdose or OUD. We estimated the proportion of patients who had any MOUD, clonidine, or naloxone treatment and 95% confidence intervals (CI). We modeled the association between patient demographic, location, comorbidities, and provider characteristics with receipt of MOUD treatment as unadjusted odds ratios (OR) and 95% CI. RESULTS: There was a weighted frequency of 469,434 patients who were discharged from EDs after being seen for OUD or overdose. Naloxone, clonidine, and buprenorphine were the most frequent treatments administered and/or prescribed for OUDs or overdose. Overall, 54,123 (11.5%, 95%CI 0-128,977) patients who were discharged from the ED for OUDs or overdose received at least one type of MOUD. Hispanic race, (OR 17.9, 95%CI 1.33-241.90) and Western region (OR43.77, 95%CI 2.97-645.27) were associated with increased odds of receiving MOUDs, while arrival by ambulance was associated with decreased odds of receiving MOUDs (OR0.01, 95%CI 0.001-0.19). Being seen by an APP or physician assistant was associated with MOUD treatment (OR 16.68, 95%CI: 1.41-152.33; OR: 13.84, 95%CI: 3.58-53.51, respectively). CONCLUSION: Our study findings suggest that MOUD and other medications for opioid overdose are infrequently used in the ED setting. This finding was especially notable in race, geographic region, mode of arrival, and those seen by APP, underscoring the need for further study into the root causes of these disparities. Our study provides a foundational understanding of MOUD patterns, guiding future research as the landscape of OUD treatment continues to shift.

Prostate cancer collaborative stage data items--their definitions, quality, usage, and clinical implications: a review of SEER data for 2004-2010.

BACKGROUND: Version 2 of the Collaborative Stage Data Collection System (CSv2) became effective with cases diagnosed in 2010. This report focuses on the CSv2 components required to derive the American Joint Committee on Cancer (AJCC) stage for prostate cancer and on the site-specific factors for prostate cancer captured in CSv2. The report also highlights differences between the AJCC 6th and 7th editions for classifying prostate cancer stage. METHODS: Data from 18 Surveillance, Epidemiology, and End Results (SEER) Program population-based registries (SEER-18) were analyzed for the years 2004-2010, which included 400,591 prostate cancer cases. RESULTS: CSv2 provides specificity with regard to the Gleason grading system by distinguishing between clinical and pathologic patterns and scores. The AJCC 7th edition incorporates prostate-specific antigen values into staging, subdivides stage II into IIA and IIB, and reclassifies extraprostatic invasion with microscopic bladder neck invasion from T4 in the 6th edition to T3a; this latter change affected the AJCC stage of 283 cases in 2010. Of the 44,578 prostate cancer cases diagnosed in 2010 that would have been classified as stage II in the AJCC 6th edition, 32.7%, 27.5%, and 39.8% are classified as stages I, IIA, and IIB, respectively, in the 7th edition. CONCLUSIONS: CSv2 provides more information than was previously available to researchers using SEER prostate data. The absence of a clearly defined clinical stage for each prostate case is the overriding limitation that researchers face in relying on Collaborative Stage information to analyze prostate cancer data.

Bladder cancer collaborative stage variables and their data quality, usage, and clinical implications: a review of SEER data, 2004-2010.

BACKGROUND: Several changes were made to bladder cancer staging guidelines between the 6th and 7th editions of the American Joint Committee on Cancer (AJCC) Staging Manual. Also, Collaborative Stage (CS) Data Collection System version 2 (CSv2) implemented for 2010 Surveillance, Epidemiology, and End Results (SEER) cases involved collection of 3 new site-specific factors (SSFs): World Health Organization/International Society of Urological pathology grade (SSF1), size of metastasis in regional lymph nodes (SSF2), and extranodal extension (SSF3). Our objective was to evaluate these new SSFs to assist researchers in their use/interpretation and to describe data quality issues to be addressed moving forward. METHODS: Staging trends were assessed for invasive and noninvasive bladder cancer cases from 2004 to 2010. Among 2010 cases, staging was compared using the AJCC 6th and 7th edition guidelines, and evaluation of completeness/quality of the SSFs was performed in relevant subgroups. RESULTS: Age-adjusted incidence rates and proportions of cases by stage remained steady from 2004 to 2010. Changes from the AJCC 6th to 7th editions caused no substantial movement between stages. SSF1 had a known value in 82% of cases, which was higher than the traditional SEER grade/differentiation variable. SSF2 and SSF3 were less complete, with 41% and 37% having known values, respectively, among cases with lymph node involvement (according to CS lymph node variable). CONCLUSIONS: SSF1 was more complete and straightforward to interpret than the traditional grade/differentiation variable. SSF2 and SSF3 were less complete, may be associated with data quality issues, and should only be used among cases with known lymph node involvement.

Exploring the Effect of Anti-immigration Rhetoric on Emergency Department Use by Undocumented Adults.

An unwelcoming policy climate can create barriers to health care access and produce a 'Chilling Effect' among immigrant communities. For undocumented immigrants, barriers may be unique and have a greater impact. We used administrative emergency department (ED) data from 2015 to 2019 for a Midwestern state provided under a data use agreement with the state hospital association. General linear modelling was used to estimate the impact of anti-immigrant rhetoric on ED visit intensity among non-elderly adults who were likely Hispanic/Latino with undocumented status. Compared to 2015, the average ED visit intensity among adults who were likely Hispanic/Latino with undocumented status was significantly higher during 2016-2019 when anti-immigrant rhetoric was heightened. The magnitude of this change increased over time (0.013, 0.014, 0.021, and 0.020, respectively). Additionally, this change over time was not observed in the comparison groups. Our findings suggest that anti-immigrant rhetoric may alter health care utilization for adults who are likely Hispanic/Latino with undocumented status. Limitations to our findings include the use of only those likely to be Hispanic/Latino, data from only one Midwestern state and the loss of data due to non-classification using the NYU ED algorithm. Further research should focus on validating these findings and investigating these identification methods and anti-immigrant rhetoric effects among other undocumented groups including children and adults of different race or ethnicity such as black, both those that identify as Hispanic/Latino and those that do not. Developing strategies to improve health care access for undocumented Hispanic/Latino adults also warrants future research.

Preoperative predictors of pathologic stage T2a in low-risk prostate cancer: implications for focal therapy.

OBJECTIVE: To assess preoperative parameters that may be predictive of pathologic stage T2a disease in low-risk prostate cancer patients. METHODS: Data from a cohort of 1,495 consecutive men with low-risk prostate cancer who underwent a radical prostatectomy between 1993 and 2009 were evaluated. Preoperative parameter assessment focused on age, race, clinical stage, diagnostic PSA level, biopsy tumor laterality and diagnostic Gleason score. Preoperative parameters were analyzed by univariate and multivariate methods. Kaplan-Meier method was used to evaluate the biochemical disease-free survival. RESULTS: Among the 1,495 men, 236 (15.8%) had pT2a disease. In univariate analysis, biopsy tumor unilaterality (p < 0.001), diagnostic PSA ≤ 4 ng/ml (p < 0.001) and non-African-American race (p = 0.009) were significant variables. In multivariate analysis, biopsy tumor laterality (OR 0.377; p < 0.001), diagnostic PSA ≤ 4 ng/ml (OR 0.621; p = 0.002) and race (OR 0.583; p = 0.029) were independent predictors. Low-risk patients with pT2a disease showed a better PSA recurrence-free survival rate, compared with men with >pT2a diseases (p = 0.012). CONCLUSIONS: Biopsy tumor unilaterality, diagnostic PSA ≤ 4 ng/ml and race are independent predictors of pT2a in low-risk prostate cancer. These three preclinical variables may be a useful reference to begin the selection process for focal therapy in men with low-risk prostate cancer.

Prostate-specific antigen velocity based risk-adapted discontinuation of prostate cancer screening in elderly men.

OBJECTIVE: • To evaluate weather prostate-specific antigen (PSA) velocity could be used to stratify patients at risk of death from prostate cancer (PCa) and be useful in aiding decision making regarding PSA screening in elderly men, as previous studies have shown that PSA velocity can predict PCa risk. PATIENTS AND METHODS: • The cohort included 3,525 patients aged ≥ 75 years with two or more PSA tests before a diagnosis of PCa. Cox proportional hazard model was used to evaluate which variables at time of last PSA measurement were associated with death from PCa. • The rates of death from PCa after diagnosis in different PSA velocity groups were calculated. Kaplan-Meier and log rank test were used to assess the significant difference in death from PCa after diagnosis, stratified by PSA velocity cutoff. RESULTS: • On multivariate analysis, men with a PSA velocity of PSA velocity ≥ 0.45 ng/mL/year had a 4.8-fold higher risk of death from PCa as compared to men with a PSA velocity of < 0.45 ng/mL/year (p value = 0.013). After a median 6.5 (up to 16.9) years of follow-up from diagnosis, 1.4% of the men with a PSA velocity < 0.45 ng/mL/year had died of PCa as compared to 8.7% of those with a PSA velocity ≥ 0.45 ng/mL/year. • The cumulative rate of death from PCa after diagnosis, stratified by a PSA velocity of 0.45 ng/mL/year, was statistically different (log rank test, P < 0.001). CONCLUSION: • Men age ≥ 75 years old with a PSA velocity of <0.45 ng/mL/year are unlikely to die of PCa. It may be safe to discontinue PSA screening in these men.

Tumor percent involvement predicts prostate specific antigen recurrence after radical prostatectomy only in men with smaller prostate.

PURPOSE: We determined the predictive power of tumor percent involvement on prostate specific antigen recurrence in patients when stratified by prostate weight. MATERIALS AND METHODS: Data on 3,057 patients who underwent radical prostatectomy between 1988 and 2008 was retrieved from our institutional prostate cancer database. Patients with data on tumor percent involvement, prostate volume and prostate specific antigen recurrence were included in analysis. Patients were divided into 3 groups based on prostate volume less than 35, 35 to 45 and greater than 45 cc. The variables tumor percent involvement, age at surgery, race, prostate specific antigen, pathological Gleason score, positive surgical margins, extraprostatic extension, seminal vesicle invasion and surgery year were analyzed using the chi-square and Mann-Whitney tests to determine individual effects on prostate specific antigen recurrence. Tumor percent involvement and prostate specific antigen were evaluated as continuous variables. Significant variables on univariate analysis were included in multivariate Cox regression analysis to compare their effects on prostate specific antigen recurrence. RESULTS: Tumor percent involvement significantly predicted prostate specific antigen recurrence in men with a small prostate (p = 0.006) but not in those with a prostate of greater than 35 cc. Black race was a marginally significant predictor of prostate specific antigen recurrence in men with a medium prostate (p = 0.055). Age at surgery was a predictor of prostate specific antigen recurrence in men with a larger prostate (p = 0.003). Prostate specific antigen, positive surgical margins, seminal vesicle invasion and pathological Gleason score 7 or greater predicted prostate specific antigen recurrence in men with all prostate sizes. CONCLUSIONS: In men with a prostate of less than 35 cc tumor percent involvement is an important variable when assessing the risk of prostate specific antigen recurrence. Tumor percent involvement and prostate volume should be considered when counseling patients and determining who may benefit from heightened surveillance after radical prostatectomy.

Initial prostate specific antigen 1.5 ng/ml or greater in men 50 years old or younger predicts higher prostate cancer risk.

PURPOSE: Studies show that initial prostate specific antigen higher than the median in young men predicts a subsequent higher risk of prostate cancer. To our knowledge this relationship has not been studied in patients stratified by race. MATERIALS AND METHODS: A cohort of 3,530 black and 6,118 white men 50 years or younger with prostate specific antigen 4 ng/ml or less at the first prostate specific antigen screening was retrieved from the prostate center database at our institution. Patients were divided into groups based on initial prostate specific antigen 0.1 to 0.6, 0.7 to 1.4, 1.5 to 2.4 and 2.5 to 4.0 ng/ml. Univariate and age adjusted multivariate logistic regression was done to estimate the cancer RR in these prostate specific antigen groups. We calculated the prostate cancer rate at subsequent followups. RESULTS: Median prostate specific antigen in black and white men was 0.7 ng/ml at age 50 years or less. The prostate cancer rate was not significantly different in the groups with prostate specific antigen less than 0.6 and 0.7 to 1.4 ng/ml in black or white men. Black and white men with initial prostate specific antigen in the 1.5 to 2.4 ng/ml range had a 9.3 and 6.7-fold increase in the age adjusted prostate cancer RR, respectively. At up to 9 years of followup initial prostate specific antigen 1.5 ng/ml or greater was associated with gradually increased detection at followup in black and white men. CONCLUSIONS: An initial prostate specific antigen cutoff of 1.5 ng/ml may be better than median prostate specific antigen 0.7 ng/ml to determine the risk of prostate cancer in black and white men 50 years old or younger.

Multicenter clinical validation of PITX2 methylation as a prostate specific antigen recurrence predictor in patients with post-radical prostatectomy prostate cancer.

PURPOSE: Radical prostatectomy is potentially curative in patients with clinically localized prostate cancer. However, biochemical recurrence affects 15% to 30% of men who undergo radical prostatectomy. We previously reported the prognostic potential of PITX2 gene promoter methylation using conventional assays. In the current study we validated PITX2 methylation status as a biochemical recurrence predictor after radical prostatectomy using a novel microarray based platform in a multi-institutional setting. MATERIALS AND METHODS: PITX2 methylation status was assessed in formalin fixed, paraffin embedded prostatectomy tumor tissue samples from 476 patients from a total of 4 institutions on customized EpiChip PITX2 microarrays. Associations between PITX2 methylation and biochemical recurrence were assessed using the log rank test and Cox regression controlling for prostate cancer features. RESULTS: On multivariate analysis men with high methylation status were at significantly higher risk for biochemical recurrence than those with low methylation status (HR 3.0, 95% CI 2.0-4.5, p <10(-5)). The biochemical recurrence-free survival rate 5 years after surgery was 85% and 61% in the low and high methylation groups, respectively. In men with pathological Gleason 7 tumors the relative risk of biochemical recurrence was twice as high for high than for low PITX2 methylation (HR 2.0, 95% CI 1.2-3.3, p = 0.005). CONCLUSIONS: PITX2 methylation status assessed by EpiChip PITX2 identifies patients with prostate cancer who are most likely to have biochemical recurrence. This test independently adds to the prognostic information provided by standard clinicopathological analysis, improving prostatectomy case stratification into those at high and low risk for biochemical recurrence. This new clinical tool would be of particular benefit to assess intermediate risk cases (Gleason 7) in which risk stratification remains a challenge.

Predicting unilateral prostate cancer on routine diagnostic biopsy: sextant vs extended.

OBJECTIVE: To compare the diagnostic properties of routine office-based sextant and extended biopsies for unilateral prostate cancer, as validated by final pathology, because focal therapy of prostate cancer is gaining acceptance as a viable treatment option and thus patient selection is of paramount consideration. PATIENTS AND METHODS: We retrospectively analysed records of patients who had a radical prostatectomy (RP) for biopsy confirmed prostate cancer at our institution between 1990 and 2007. Records with incomplete data were excluded. Diagnostic properties for sextant and extended biopsies were calculated and compared for diagnostic accuracy, sensitivity, specificity, positive and negative predictive values (PPV, NPV) and false-positive and -negative rates. RESULTS: We identified 882 records (729 sextant, 153 extended biopsies) matching our criteria. Overall, unilateral prostate cancer was confirmed in 151 (16%) of pathological RP specimens. The sensitivity improved from 84.1% to 88.0% on sextant and extended biopsy, respectively. Similarly, the PPV increased from 21.9% to 27.2%, specificity from 37.1% to 53.9% (P < 0.05), and NPV from 91.8% to 95.8% (P < 0.05). These changes are reflected in the decrease in false-positive rates (from 62.9% to 46.1%) and false-negative rates (from 15.9% to 12.0%). The overall diagnostic accuracy increased from 49% on sextant to 59% on extended biopsy (P < 0.05). CONCLUSIONS: Taking more prostate biopsy cores improves the diagnostic properties for identifying unilateral prostate cancer. However, a 12-core biopsy is not an ideal diagnostic test to select patients for focal therapy, and should be interpreted in conjunction with imaging and clinical variables. Additional research should investigate the diagnostic gain associated with a further increase in the number of biopsy cores.

Obese African-Americans with prostate cancer (T1c and a prostate-specific antigen, PSA, level of <10 ng/mL) have higher-risk pathological features and a greater risk of PSA recurrence than non-African-Americans.

OBJECTIVE: to analyse the relationship between African American (AA) race and obesity in men with prostate cancer. PATIENTS AND METHODS: in all, 4196 patients who underwent radical prostatectomy from 1988 to 2008 were identified in the Duke Prostate Center database. A subset of 389 (AA 20.9% and non-AA 79.1%) patients with a body mass index (BMI) of ≥30 kg/m(2) , T1c disease and a prostate-specific antigen (PSA) level of <10 ng/mL were stratified by race and analysed. Age at surgery, race, surgical margin status, pathological tumour stage (pT2, pT3/4), pathological Gleason sum (<7, 3 + 4, 4 + 3, >7), extracapsular extension (ECE), seminal vesicle invasion and tumour percentage were assessed by univariate analysis followed by Cox regression analysis. RESULTS: in the entire cohort, 143 (38.1%) AA men were obese, compared to 509 (25.0%) of the non-AA men. AA men had a significantly higher tumour percentage (15% vs 10%, P= 0.002), and a greater proportion of pT3/4 disease (45.1% vs 26.2%, P= 0.039), pathological Gleason sum ≥ 7 (70.7% vs 50.5%, P= 0.003), positive ECE (37.8% vs 23.1%, P= 0.007), and positive surgical margin (52.4% vs 36.8%, P= 0.010) than non-AA men. AA men had a greater risk of PSA recurrence on Kaplan Meier (P= 0.004) and Cox regression analysis (P= 0.040, hazard ratio 1.72) CONCLUSION: a greater proportion of AA men was obese in this cohort. Obese AA with impalpable cancer and a PSA level of <10 ng/mL have a higher risk of pathological features than obese non-AA men, as well as a higher risk of PSA recurrence. Obesity might be responsible for the racial disparity seen in prostate cancer.

External validation of the SEARCH model for predicting aggressive recurrence after radical prostatectomy: results from the Duke Prostate Center Database.

OBJECTIVE: To validate a model previously developed using the Shared Equal Access Regional Cancer Hospital (SEARCH) database to predict the risk of aggressive recurrence after surgery, defined as a prostate-specific antigen (PSA) doubling time (DT) of <9 months, incorporating pathological stage, preoperative PSA level and pathological Gleason sum, that had an area under the curve (AUC) of 0.79 using a cohort of men from the Duke Prostate Center (DPC). PATIENTS AND METHODS: Data were included from 1989 men from the DPC database who underwent RP for node-negative prostate cancer between 1987 and 2003. Of these men, 100 had disease recurrence, with a PSADT of <9 months, while 1889 either did not have a recurrence but had > or =36 months of follow-up or had a recurrence with a PSADT of > or =9 months. We examined the ability of the SEARCH model to predict aggressive recurrence within the DPC cohort, and examined the correlation between the predicted risk of aggressive recurrence and the actual outcome within DPC. RESULTS: The SEARCH model predicted aggressive recurrence within DPC with an AUC of 0.82. There was a strong and significant correlation between the predicted risk of aggressive recurrence based on the SEARCH tables and the actual outcomes within DPC (r= 0.68, P < 0.001), although the model predictions tended to be slightly higher than the actual risk. CONCLUSIONS: The SEARCH model to predict aggressive recurrence after RP predicted aggressive recurrence in an external dataset with a high degree of accuracy. These tables, now validated, can be used to help select men for adjuvant therapy and clinical trials.

The Shared Equal Access Regional Cancer Hospital (SEARCH) nomogram for risk stratification in intermediate risk group of men with prostate cancer: validation in the Duke Prostate Center database.

OBJECTIVES: To validate the Shared Equal Access Regional Cancer Hospital (SEARCH) nomogram to better risk stratify men with intermediate-risk pathology after prostatectomy (positive surgical margins, PSM, and/or extracapsular disease, ECE, without seminal vesicle or lymph node involvement) in a tertiary referral centre (the Duke Prostate Center, DPC). PATIENTS AND METHODS: We retrospectively analysed 485 men in the DPC cohort with PSM and/or ECE but without seminal vesicle or lymph node involvement. The predicted risk of biochemical progression-free probability at 1, 3 and 5 years was estimated by the SEARCH and updated Kattan postoperative nomograms. Calibration plots were generated and accuracy assessed with the concordance index. RESULTS: The SEARCH nomogram appeared to be well calibrated, with the highest-risk quartile having a predicted <60% progression-free probability at 5 years, vs >80% for the lowest risk. In comparison, overall external calibration appeared to be similar for the updated Kattan nomogram, although there was less separation between the highest- and lowest-risk quartiles. The SEARCH model had an overall predictive accuracy of 0.65, which compared favourably with the updated Kattan nomogram (0.57). CONCLUSION: In an external dataset, the SEARCH nomogram to predict progression-free probability for men at intermediate risk after prostatectomy was well calibrated and performed better than the updated postoperative Kattan nomogram.

Re-calibration and external validation of an existing nomogram to predict aggressive recurrences after radical prostatectomy.

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 < or =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.

Adjuvant versus salvage radiation therapy for prostate cancer and the risk of death.

OBJECTIVE: To investigate whether salvage radiation therapy (RT) for prostate-specific antigen (PSA) failure can provide the same result as adjuvant RT, which decreases the risk of all-cause mortality (ACM) for men with positive margins (R1), or extra-capsular or seminal vesicle extension (pT3). METHODS: We studied 1638 men at Duke University who underwent radical prostatectomy for unfavourable-risk prostate cancer and whose postoperative PSA was undetectable. Cox regression was used to evaluate whether salvage vs adjuvant RT in men with a rapid (<10 months) or slow (≥10 months) PSA doubling time (DT) was associated with the risk of ACM, adjusting for adverse features (pT3, R1, Gleason score 8-10), age, preoperative PSA level, comorbidity and hormonal therapy use. RESULTS: Despite fewer men with two or more adverse features (61 vs 82%; P=0.016), salvage for a rapid PSA DT vs adjuvant RT increased the risk of ACM [adjusted hazard ratio (AHR)=3.42; 95% confidence interval (CI)=1.27-9.20; P=0.015]. There was no difference (AHR=1.39; 95% CI=0.50-3.90; P=0.53) in the risk of ACM among men who received salvage for a slow PSA DT or adjuvant RT. Nearly all (90%) men with a slow PSA DT had Gleason score ≤7 and the majority (59%) had at most pT3 or R1 disease. CONCLUSION: Radiation therapy after PSA failure as compared with adjuvant RT was not associated with an increased risk of ACM in men with Gleason score ≤7 and pT3R0 or pT2R1 disease.

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.

Men older than 70 years have higher risk prostate cancer and poorer survival in the early and late prostate specific antigen eras.

PURPOSE: We clarified whether men older than 70 years have a higher risk of prostate cancer and poorer survival in the early and late prostate specific antigen eras. MATERIALS AND METHODS: A cohort of 4,561 men who underwent radical prostatectomy were stratified into 3 age groups (younger than 60, 60 to 70 and older than 70 years), and early and late prostate specific antigen eras based on the year of surgery (before 2000 and 2000 or later). Race, body mass index, prostate specific antigen, prostate weight, tumor volume, pathological Gleason sum, pathological tumor stage, extracapsular extension, seminal vesicle invasion and surgical margin status were submitted for univariate and multivariable analyses against the previously mentioned groups. Survivals (prostate specific antigen recurrence, distant metastasis and disease specific death) were compared among the 3 age groups using univariate and multivariable methods. RESULTS: Compared with younger age groups (younger than 60, 60 to 70 years) men older than 70 years had a higher proportion of pathological tumor stage 3/4 (33.0 vs 44.3 vs 52.1%, p <0.001), pathological Gleason sum greater than 7 (9.5% vs 13.4% vs 17.2%, p <0.001) and larger tumor volume (3.7 vs 4.7 vs 5.2 cc, p <0.001). Pathological Gleason sum in men older than 70 years did not differ between the early and late prostate specific antigen eras (p = 0.071). Men older than 70 years had a higher risk of prostate specific antigen recurrence, distant metastasis and disease specific death on univariate (p <0.05) but not multivariable analysis. CONCLUSIONS: Men older than 70 years had higher risk disease and poorer survival in the early and late prostate specific antigen eras. Pathological Gleason sums did not change between the 2 eras. Patient age was an important variable in prostate specific antigen screening, biopsy, treatment and prognosis.

Body mass index and prostate specific antigen as predictors of adverse pathology and biochemical recurrence after prostatectomy.

PURPOSE: Preoperative prostate specific antigen is widely used to predict unfavorable pathological features and biochemical relapse after radical prostatectomy. Recent reports that hemodilution may be responsible for lower prostate specific antigen in obese men led to concerns that prostate specific antigen may be less effective for prognosticating in men with increased body mass index. We determined whether the clinical usefulness of prostate specific antigen is negatively impacted by obesity by examining its operating characteristics and predictive accuracy as a function of body mass index. MATERIALS AND METHODS: We performed a multicenter retrospective analysis of the records of 11,705 men who underwent radical prostatectomy from 1988 to 2007 from Veterans Affairs hospitals of the Shared Equal Access Regional Cancer Hospital Database, the Duke Prostate Center and Johns Hopkins Hospital. ROC curve analysis, the concordance index and the test for interaction were used to compare the ability of prostate specific antigen to predict unfavorable tumor characteristics and biochemical recurrence across body mass index categories. RESULTS: There were no significant differences in the area under ROC curves across increasing body mass index categories for prostate specific antigen to predict pathological Gleason sum (7 or greater, 7 [4 + 3] or greater, or 8 or greater), positive surgical margins, extracapsular extension or seminal vesicle invasion in all 3 cohorts. There was no significant difference in prostate specific antigen accuracy to predict biochemical failure across increasing body mass index categories. CONCLUSIONS: In 3 cohorts of men treated with radical prostatectomy the ability of preoperative prostate specific antigen to predict adverse pathological features and posttreatment biochemical recurrence is not significantly affected by obesity. However, adjusting for obesity related hemodilution may still be required to properly interpret prostate specific antigen results in men with increased body mass index.

Factors predicting prostatic biopsy Gleason sum under grading.

PURPOSE: We determined clinical factors affecting the under grading of biopsy Gleason sum compared with prostatectomy pathology and developed a model predicting the probability of under grading. MATERIALS AND METHODS: We analyzed a cohort of 1,701 patients treated for prostate cancer at our institution between 1988 and 2007 with complete biopsy and pathological data available. Patients with a biopsy Gleason sum of 7 or less were included in our analysis. Cases were categorized as under graded or not under graded by comparing biopsy and radical prostatectomy Gleason sums. Logistic regression was used to determine the predictors of under grading based on clinical variables (race, age at diagnosis, body mass index, prostate weight, diagnostic prostate specific antigen, biopsy positive-to-total core ratio, maximal cancer percent in positive cores and time from diagnosis to surgery). A nomogram was developed to calculate the probability of under grading. Results were validated using bootstrapping. RESULTS: Under grading occurred in 46.6% of our cohort. Significant variables predicting under grading were age at diagnosis, biopsy Gleason sum, diagnostic prostate specific antigen, prostate weight, biopsy positive-to-total core ratio and maximal percent of cancer in cores (p <0.05). Nomogram predictive accuracy was 72.4%. CONCLUSIONS: The risk of Gleason sum under grading can be predicted to a satisfactory level using our nomogram. Predicting under grading would improve patient consulting and identify those who should consider repeat biopsy, ultimately enhancing the accuracy of prostate cancer diagnosis.

Robot-assisted laparoscopic prostatectomy is not associated with early postoperative radiation therapy.

OBJECTIVE: To compare open radical prostatectomy (RP) and robot-assisted laparoscopic prostatectomy (RALP), and to determine whether RALP is associated with a higher risk of features that determine recommendations for postoperative radiation therapy (RT). PATIENTS AND METHODS: Patients undergoing RP from 2003 to 2007 were stratified into two groups: open RP and RALP. Preoperative (PSA level, T stage and Gleason score), pathological factors (T stage, Gleason score, extracapsular extension [ECE] and the status of surgical margins and seminal vesicle invasion [SVI]) and early treatment with RT or referral for RT within 6 months were compared between the groups. Multivariate analysis was used to control for selection bias in the RALP group. RESULTS: In all, 904 patients were identified; 368 underwent RALP and 536 underwent open RP (retropubic or perineal). Patients undergoing open RP had a higher pathological stage with ECE present in 24.8% vs 19.3% in RALP (P = 0.05) and SVI in 10.3% vs 3.8% (P < 0.001). In the RALP vs open RP group, there were positive surgical margins in 31.5% vs 31.9% (P = 0.9) and there were postoperative PSA levels of (3) 0.2 ng/mL in 5.7% vs 6.3% (P = 0.7), respectively. On multivariate analysis to control for selection bias, RALP was not associated with indication for RT (odds ratio (OR) 1.10, P = 0.55), or referral for RT (OR 1.04, P = 0.86). CONCLUSION: RALP was not associated with an increase in either indication or referral for early postoperative RT.