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.

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.

Availability of TNM Staging Data Elements in the Medical Record and Training Needs Assessment: Results from the 2014 SEER Training Needs Assessment for TNM Study.

BACKGROUND: In 2016, the cancer registry community will directly assign T, N and M components of stage. The Surveillance, Epidemiology, and End Results program implemented a field study to determine how often T, N and M were not available in the medical record, requiring the registrar to directly assign clinical or pathologic TNM stage components. The field study also identified specific training needs. METHODS: T, N and M status were collected from multiple sources within medical records for a total of 280 cases, 56 each from breast, prostate, colon, lung, and ovarian cancer. TNM data elements were also directly assigned by a series of reviewers and by study participants using the medical records with TNM information redacted. Availability of physician-assigned TNM was estimated from the medical record. Also, participant responses were compared to preferred answers. RESULTS: Pathologic T, N and M were available more often in the medical records than were clinical values and varied by site. Pathologic T and N were available for about two-thirds of the cases, but the clinical elements were available for only about 20% of cases. The agreement between participant responses and review panel assignments varied by data element and cancer site. Agreement was modest for most data elements and cancer sites, ranging from 54% for clinical T to 92% for clinical M for all cancer sites combined. CONCLUSIONS: The data elements for TNM staging and stage group were often missing from the medical records, so registrars in the field will need to assign TNM frequently. Furthermore, the results of this study strongly suggest that more training is required, even among those who currently assign TNM.

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.

Preoperative predictors of pathologic stage T2a and pathologic Gleason score ≤ 6 in men with clinical low-risk prostate cancer treated with radical prostatectomy: reference for active surveillance.

To assess preoperative parameters that may be predictive of pathologic stage T2a (pT2a) and pathologic Gleason score (pGS) ≤ 6 disease in low-risk prostate cancer patients considering active surveillance. A cohort of 1,495 men with low-risk prostate cancer between 1993 and 2009 was utilized. Preoperative assessment focused on patient age, race, diagnostic PSA level, clinical stage, diagnostic biopsy Gleason score, and prostate cancer laterality. Kaplan-Meier curves and a Cox regression model were used for analysis of PSA recurrence. Preoperative parameters were analyzed by univariate and multivariate logistic regression methods. Of 1,495 patients, 187 (12.5 %) were identified with pT2a and pGS ≤ 6 disease. Of the 187 men with pT2a and pGS ≤ 6 disease, only 6 (3.2 %) cases had PSA recurrence. Kaplan-Meier PSA recurrence-free survival curves identified a difference between prostate cancers with pT2a and pGS ≤ 6 and prostate cancers with >pT2a or pGS ≥ 7 disease (p = 0.002). Only biopsy tumor unilaterality (OR, 10.452; p ≤ 0.001) and low diagnostic PSA levels (OR, 0.887; p = 0.003) were independent predictors of prostate cancers with pT2a and pGS ≤ 6 disease on univariate and multivariate logistic regression. Biopsy tumor unilaterality and low diagnostic PSA levels are the independent predictors of pT2a and pGS ≤ 6 disease in low-risk prostate cancer patients. Unilateral cancer by prostate biopsy and low diagnostic PSA level may be the reference to improving the selection of appropriate candidates for active surveillance within a low-risk prostate cancer cohort.

Development and clinical validation of a real-time PCR assay for PITX2 DNA methylation to predict prostate-specific antigen recurrence in prostate cancer patients following radical prostatectomy.

Prostate cancer is the most common cancer among men. The prospective discrimination of aggressive and clinically insignificant tumors still poses a significant and, as yet, unsolved problem. PITX2 DNA methylation is a strong prognostic biomarker in prostate cancer. Recently, a diagnostic microarray for prostate cancer prognosis based on PITX2 methylation has been developed and validated. Because this microarray requires nonstandard laboratory equipment, its use in a diagnostic setting is limited. This study aimed to develop and validate an alternative quantitative real-time PCR assay for measuring PITX2 methylation that can easily be established in clinical laboratories, thereby facilitating the implementation of this biomarker in clinical practice. A methylation cut-off for patient stratification was established in a training cohort (n = 157) and validated in an independent test set (n = 523) of men treated with radical prostatectomy. In univariate Cox proportional hazards analysis, PITX2 hypermethylation was a significant predictor for biochemical recurrence (P < 0.001, hazard ratio = 2.614). Moreover, PITX2 hypermethylation added significant prognostic information (P = 0.003, hazard ratio = 1.814) to the Gleason score, pathological T stage, prostate-specific antigen, and surgical margins in a multivariate analysis. The clinical performance was particularly high in patients at intermediate risk (Gleason score of 7) and in samples containing high tumor cell content. This assay might aid in risk stratification and support the decision-making process when determining whether a patient might benefit from adjuvant treatment after radical prostatectomy.

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.

Association between percentage of tumor involvement and Gleason score upgrading in low-risk prostate cancer.

To find the predictors of Gleason score upgrading in a cohort of low-risk prostate cancer patients, data were analyzed comprising 1,632 consecutive men with low-risk prostate cancer who underwent radical prostatectomy between 1993 and 2009. Assessment focused on preoperative parameters including patient age, race, diagnostic prostate-specific antigen (PSA) levels, clinical stage and biopsy Gleason score, along with pathological parameters including percentage of tumor involvement (PTI), tumor laterality, pathological stage, extra-capsular extension, seminal vesicle invasion, and surgical margins. These parameters were analyzed using univariate and multivariate methods. Kaplan-Meier curves compared differences in biochemical disease-free survival in men having cancers with and without Gleason score upgrading. Cases involving pathological Gleason score upgrading were identified in 723 (44.3 %) of 1,632 patients. Kaplan-Meier PSA recurrence-free survival curves showed a difference in outcome between men with and without Gleason score upgrading (p < 0.001). Of Gleason score upgraded patients, 35 (4.8 %) men had PTI of <5 %, 237 (32.8 %) had PTI of 5-9.9 %, 177 (24.5 %) had PTI of 10-14.9 %, and 274 (37.9 %) had PTI ≥ 15 % (p < 0.001). PTI (p < 0.001) along with diagnostic PSA, patient age, diagnostic biopsy Gleason score, pathologic stage, and surgical margin status were independent predictors of pathological Gleason score upgrading on multivariate logistic regression. PTI correlates closely with Gleason score upgrading in a low-risk prostate cancer cohort. Low-risk prostate cancer patients with clinical findings suggestive of high PTI or large volume cancers should not benefit from active surveillance strategies.

Comparison of three different tools for prediction of seminal vesicle invasion at radical prostatectomy.

BACKGROUND: Statistical prediction tools are increasingly common, but there is considerable disagreement about how they should be evaluated. Three tools--Partin tables, the European Society for Urological Oncology (ESUO) criteria, and the Gallina nomogram--have been proposed for the prediction of seminal vesicle invasion (SVI) in patients with clinically localized prostate cancer who are candidates for a radical prostatectomy. OBJECTIVES: Using different statistical methods, we aimed to determine which of these tools should be used to predict SVI. DESIGN, SETTINGS, AND PARTICIPANTS: The independent validation cohort consisted of 2584 patients treated surgically for clinically localized prostate cancer at four North American tertiary care centers between 2002 and 2007. INTERVENTIONS: Robot-assisted laparoscopic radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was the presence of SVI. Traditional (area under the receiver operating characteristic [ROC] curve, calibration plots, the Brier score, sensitivity and specificity, positive and negative predictive value) and novel (decision curve analysis and predictiveness curves) statistical methods quantified the predictive abilities of the three models. RESULTS AND LIMITATIONS: Traditional statistical methods (ie, ROC plots and Brier scores) could not clearly determine which one of the three SVI prediction tools should be preferred. For example, ROC plots and Brier scores seemed biased against the binary decision tool (ESUO criteria) and gave discordant results for the continuous predictions of the Partin tables and the Gallina nomogram. The results of the calibration plots were discordant with those of the ROC plots. Conversely, the decision curve indicated that the Partin tables represent the best strategy for stratifying the risk of SVI, resulting in the highest net benefit within the whole range of threshold probabilities. CONCLUSIONS: When predicting SVI, surgeons should prefer the Partin tables over the ESUO criteria and the Gallina nomogram because this tool provided the highest net benefit. In contrast to traditional statistical methods, decision curve analysis gave an unambiguous result applicable to both continuous and binary models, providing an insight into clinical utility.

Biopsy accuracy in identifying unilateral prostate cancer depends on prostate weight.

OBJECTIVE: To evaluate the association between prostate weight and the diagnostic performance of routine biopsy schemes in detecting unilateral prostate cancer (PCa) that may be amenable to focal therapy. METHODS AND MATERIALS: Retrospective analysis of patients undergoing radical prostatectomy at Duke University Medical Center from 1990 to 2007. The cohort was dichotomized according to prostate weight (≤40 and >40 g) and further divided by biopsy scheme: 6-9 (sextant) and 10-20 cores (extended). Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values were calculated within each prostate weight group and compared between biopsy schemes. RESULTS: A total of 859 patients were included in the study. Patients with prostates >40 g were generally older and had higher PSA levels (P < 0.0001 and P = 0.036, respectively). Unilateral disease was more common in prostates >40 g both on biopsy (69% vs. 60%, P = 0.009) and on final pathology (21% vs. 14%, P = 0.017) despite larger total tumor volume (6.1 vs. 4.8 cc, P < 0.001). Low grade PCa was also more common in larger glands (P = 0.003). Overall, extended biopsy schemes performed better than sextant but the benefit was statistically significant only in prostates >40 g. CONCLUSIONS: Despite having higher tumor volumes, men with prostate weight >40 g were more likely to have unilateral PCa than those with smaller prostates. In prostates >40 g, increasing the number of cores harvested at biopsy increased the diagnostic performance for detecting cancer laterality. Therefore, our results suggest that the benefit of more extensive tissue sampling may be higher in larger prostates compared with smaller ones when selecting candidates for prostate hemiablation.

SEER and NAACCR data completeness methods: how do they impact data quality in Central Cancer Registries?

There are 2 widely accepted methods for calculating data completeness in central cancer registries: The Surveillance, Epidemiology and End Results (SEER) Program's data completeness method and the North American Association of Central Cancer Registries' (NAACCR's) data completeness method. In recent years, the pros and cons of these methods have been discussed and debated by CTRs nationwide. The results from a myriad of studies have shown that each method offers its own set of strengths and unique applications. The aims of this paper are to provide an overview of both the SEER and NAACCR data completeness methods and to discuss the need for an alternative data completeness method.

Impact of primary Gleason grade on risk stratification for Gleason score 7 prostate cancers.

PURPOSE: To evaluate the primary Gleason grade (GG) in Gleason score (GS) 7 prostate cancers for risk of non-organ-confined disease with the goal of optimizing radiotherapy treatment option counseling. METHODS: One thousand three hundred thirty-three patients with pathologic GS7 were identified in the Duke Prostate Center research database. Clinical factors including age, race, clinical stage, prostate-specific antigen at diagnosis, and pathologic stage were obtained. Data were stratified by prostate-specific antigen and clinical stage at diagnosis into adapted D'Amico risk groups. Univariate and multivariate analyses were performed evaluating for association of primary GG with pathologic outcome. RESULTS: Nine hundred seventy-nine patients had primary GG3 and 354 had GG4. On univariate analyses, GG4 was associated with an increased risk of non-organ-confined disease. On multivariate analysis, GG4 was independently associated with seminal vesicle invasion (SVI) but not extracapsular extension. Patients with otherwise low-risk disease and primary GG3 had a very low risk of SVI (4%). CONCLUSIONS: Primary GG4 in GS7 cancers is associated with increased risk of SVI compared with primary GG3. Otherwise low-risk patients with GS 3+4 have a very low risk of SVI and may be candidates for prostate-only radiotherapy modalities.

Contemporary radical prostatectomy.

Purpose. Patients diagnosed with clinically localized prostate cancer have more surgical treatment options than in the past. This paper focuses on the procedures' oncological or functional outcomes and perioperative morbidities of radical retropubic prostatectomy, radical perineal prostatectomy, and robotic-assisted laparoscopic radical prostatectomy. Materials and Methods. A MEDLINE/PubMed search of the literature on radical prostatectomy and other new management options was performed. Results. Compared to the open procedures, robotic-assisted radical prostatectomy has no confirmed significant difference in most literatures besides less blood loss and blood transfusion. Nerve sparing is a safe means of preserving potency on well-selected patients undergoing radical prostatectomy. Positive surgical margin rates of radical prostatectomy affect the recurrence and survival of prostate cancer. The urinary and sexual function outcomes have been vastly improved. Neoadjuvant treatment only affects the rate of positive surgical margin. Adjuvant therapy can delay and reduce the risk of recurrence and improve the survival of the high risk prostate cancer. Conclusions. For the majority of patients with organ-confined prostate cancer, radical prostatectomy remains a most effective approach. Radical perineal prostatectomy remains a viable approach for patients with morbid obesity, prior pelvic surgery, or prior pelvic radiation. Robot-assisted laparoscopic prostatectomy (RALP) has become popular among surgeons but has not yet become the firmly established standard of care. Long-term data have confirmed the efficacy of radical retropubic prostatectomy with disease control rates and cancer-specific survival rates.

Can the conventional sextant prostate biopsy accurately predict unilateral prostate cancer in low-risk, localized, prostate cancer?

We evaluate the reliability of routine sextant prostate biopsy to detect unilateral lesions. A total of 365 men with complete records including all clinical and pathologic variables who underwent a preoperative sextant biopsy and subsequent radical prostatectomy (RP) for clinically localized prostate cancer at our medical center between January 1996 and December 2006 were identified. When the sextant biopsy detects unilateral disease, according to RP results, the NPV is high (91%) with a low false negative rate (9%). However, the sextant biopsy has a PPV of 28% with a high false positive rate (72%). Therefore, a routine sextant prostate biopsy cannot provide reliable, accurate information about the unilaterality of tumor lesion(s).

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.

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.

Baseline PSA as a predictor of prostate cancer-specific mortality over the past 2 decades: Duke University experience.

BACKGROUND: A diagnosis of prostate cancer is not often predictive of death from prostate cancer because of competing causes of mortality. Identification of the risk of death from prostate cancer and death from all causes using information available at the time of baseline prostate-specific antigen (PSA) measurement appears to be particularly pertinent. METHODS: The Duke Prostate Center database was used to identify men who had their PSA level measured over the past 20 years. The Cox proportional hazards model was used to assess whether baseline PSA, race, and age at baseline PSA could predict death from prostate cancer and death from all causes after baseline PSA measurement. The receiver operating characteristic (ROC) curve was performed to analyze the accuracy of baseline PSA as a continuous variable in predicting death from prostate cancer. RESULTS: A total of 4568 men diagnosed with prostate cancer after baseline PSA measurement were included. On multivariate analysis, baseline PSA levels of 4.0 to 9.9 ng/mL and ≥10 ng/mL were associated with significantly higher rates of death from prostate cancer compared with PSA levels <2.5 ng/mL. An advanced age at baseline PSA and African American race were associated with a higher death rate from prostate cancer and death from all causes. The area under the ROC curve for baseline PSA predicting death was 0.839. When a baseline PSA of 10 ng/mL was chosen to predict death from prostate cancer, the corresponding sensitivity and specificity were 77% and of 78%, respectively. CONCLUSIONS: Baseline PSA appears to be a reliable and independent predictor of death from prostate cancer. A baseline PSA of ≥4 ng/mL has been associated with higher risk of death from prostate cancer.

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.

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.