Disparities in Diagnosis, Treatment Access, and Time to Treatment Among Hispanic Men With Metastatic Prostate Cancer.

PURPOSE: Reporting racial/ethnic disparities in aggregate obscures within-group heterogeneity. We sought to identify disparities in diagnosis and treatment in Hispanic subpopulations with metastatic prostate cancer (mPCa). METHODS: We disaggregated men with prostate adenocarcinoma from the National Cancer Database from 2004 to 2017 by racial subgroup and Hispanic background. We assessed (1) presenting with mPCa, (2) receiving any treatment, and (3) receiving delayed treatment beyond 90 days. Logistic regression and adjusted odds ratios (aOR) were reported. RESULTS: Hispanic men had greater odds of presenting with mPCa (aOR, 1.54; 95% CI, 1.50 to 1.58; P < .001) compared with non-Hispanic White (NHW) men. All Hispanic racial subgroups were more likely to present with mPCa, with the highest risk in Hispanic Black (HB) men (aOR, 1.68; 95% CI, 1.46 to 1.93; P < .01). Men from all Hispanic backgrounds had higher odds of presenting with mPCa, especially Mexican men (aOR, 1.99; 95% CI, 1.86 to 2.12; P < .01). Hispanic men were less likely to receive any treatment (aOR, 0.60; 95% CI, 0.53 to 0.67; P < .001), and this effect was particularly strong for Hispanic White patients (aOR, 0.58; 95% CI, 0.52 to 0.66; P < .001) and Dominican men (aOR, 0.52; 95% CI, 0.28 to 0.98; P = .044). Hispanic men were more likely to experience treatment delays compared with NHW men (aOR, 1.38; 95% CI, 1.26 to 1.52; P < .001) and in particular HB (aOR, 1.83; 95% CI, 1.22 to 2.75; P = .002) and South/Central American men (aOR, 1.48; 95% CI, 1.07 to 2.04; P = .018). CONCLUSION: Differences exist in stage at presentation, treatment receipt, and delays in treatment on disaggregation by racial subgroup and Hispanic heritage. We need to study the potential mechanisms of the observed variations to help develop targeted interventions.

Localized prostate cancer disparities in risk group at presentation and access to treatment for Hispanic men.

BACKGROUND: Despite great heterogeneity amongst Hispanic groups, prostate cancer studies often report Hispanic patients in aggregate. We sought to identify differences in prostate cancer risk group at presentation and treatment status among Hispanic subgroup populations. METHODS: Patients with localized prostate adenocarcinoma diagnosed from 2004-2017 were identified in the National Cancer Database (NCDB) and disaggregated by racial subgroup and Hispanic country of origin. Ordinal logistic regression defined adjusted odds ratios (AORs) with 95% CI of (1) presenting at progressively higher risk group and (2) receiving treatment with intermediate-unfavorable or high-risk disease. RESULTS: In our sample (n = 895,087), Hispanic men had greater odds of presenting with higher-risk localized prostate cancer compared with non-Hispanic White men (AOR = 1.18 95% CI 1.16-1.21, p < 0.001). Additionally, Hispanic Black men were less likely to present with higher-risk disease than non-Hispanic Black men. Disparities also existed when disaggregated by country of origin, particularly for Mexican men. Amongst men with unfavorable-risk disease, Hispanic men were less likely to receive treatment than non-Hispanic White men (95% CI 0.57-0.67, p < 0.001). The odds of Hispanic Black patients receiving treatment was 2.00 times the odds (95% CI 1.17-3.41 p = 0.011) of non-Hispanic Black patients receiving treatment. Upon disaggregation by country of origin, disparities persisted, particularly for Mexican men. CONCLUSION: We found marked heterogeneity when risk group at presentation and treatment for higher-risk disease were disaggregated by racial subgroup and country of origin. Our findings support further collection of disaggregated data in Hispanic communities and study of potential mechanisms underlying the observed differences.

Distinct Profiles of DNA Repair Activity Define Favorable-risk Prostate Cancer Subtypes With Divergent Outcome.

INTRODUCTION: Understanding if divergent molecular profiles of DNA damage and repair (DDR) pathway activity, a biomarker of disease progression, exist in prostate tumors with favorable-risk features is an unmet need, which this study aim to unearth. MATERIALS AND METHODS: This was a multicenter registry genome-wide expression profiling study of prospectively collected radical prostatectomy (RP) tumor samples from 2014 to 2016. DDR activity was calculated from average expression of 372 DDR genes. Consensus hierarchical clustering was used to arrive at a robust clustering solution based on DDR gene expression patterns. Genome-wide differential expression between clusters was performed, and outcomes were evaluated across expression patterns. RESULTS: Of 5239 patients from the prospective registry, 376 had favorable-risk disease (Grade group [GG] 1 to 2, PSA prior to RP <10ng/ml, pT2 or less). DDR activity score was correlated with prognostic genomic signatures that predict for metastatic risk (r = 0.37, P < 2e-16) and high grade groups (P < .001). High DDR activity (top-quartile) was observed in 28% of patients with favorable-risk disease. In favorable-risk disease, 3 distinct clusters with varied DDR activity emerged with consensus clustering. Cluster I (compared with cluster II-III and GG3-GG5 disease) had the highest expression of all DDR sub-pathways, MYC, PAPR1, AR, and AR activity (P < .001 for all). Furthermore, cluster I was associated with poorer metastasis-free survival (MFS) and Overall survival (OS) compared with other clusters (MFS; HR: 2.43, 95%CI, [1.22-4.83], P = .01; OS; HR: 2.77, 95%CI, [1.18-6.5], P = .01). CONCLUSIONS: Cluster I is a novel subgroup of favorable-risk disease with high DDR activity, AR activity, PARP1 and chr8q/MYC expression, and poorer MFS and OS.

Chromosome 8q arm overexpression is associated with worse prostate cancer prognosis.

OBJECTIVE: Chromosome 8q arm (chr8q) is the most amplified chromosomal segment in advanced metastatic castration-resistant prostate cancer after chXq12. These regions harbor important oncogenes driving prostate cancer progression, including MYC that plays a role in various hallmarks of cancer, including cell cycle progression and immune surveillance. Herein we characterize the co-expression patterns of chr8q genes and their clinical utility in more than 7,000 radical prostatectomy samples. MATERIALS AND METHODS: Copy Number alterations of 336 genes on chr8q21 to chr8q24 were extracted from 2 primary prostate cancer cohorts (TCGA, n = 492; MSK-primary, n = 856) and 3 metastatic prostate cancer cohorts (MSK-met, N = 432; MSK-mCSPC, N = 424; SU2CPNAS, n = 444) from cBioPortal. Expression data for the 336 genes was extracted from 6,135 radical prostatectomy samples from Decipher GRID registry. For survival analysis, patients were grouped into top 10% and top 25% by band expression and were compared with the remaining cohort. Hazard ratios were calculated using Cox proportional hazards models. RESULTS: Genes on chr8q were highly co-amplified and co-expressed. Copy number alterations and overexpression of chr8q genes in primary disease were associated with higher Gleason scores, increased risk of metastases, and increased prostate cancer specific mortality. Additionally, our data demonstrated high expression of MYC alone was not associated with differences in metastases free survival while high expression of other chr8q bands was associated with decreased metastases free survival. By combining chr8q data with an established genomic classifier like Decipher, we were able to develop a new model that was better at predicting metastases than Decipher alone. CONCLUSIONS: Our findings highlight the clinical utility of chr8q data, which can be used to improve prognostication and risk prediction in localized prostate cancer.

Genomic alterations predictive of poor clinical outcomes in pan-cancer.

BACKGROUND: Genomic alterations are highly frequent across cancers, but their prognostic impact is not well characterized in pan-cancer cohorts. Here, we use pan-cancer cohorts from TCGA and MSK-IMPACT to evaluate the associations of common genomic alterations with poor clinical outcome. MATERIALS AND METHODS: Genomic alterations in commonly altered genes were extracted from Pan-Cancer TCGA and MSK-IMPACT cohorts. Multivariable Cox regression analyses stratified by cancer type defined adjusted hazard ratios (AHRs) for disease-specific survival (DSS), progression-free survival (PFS) and overall survival (OS). RESULTS: Using TCGA we identified 32 mutated genes, and 15 copy number (CN) genes with frequency >= 4% in 9,104 patients across 28 cancers. On UVA, having a TP53-mutations or any mutation in the 31 genes (mut31) were associated with worse PFS (HR: 1.22, p < 0.0001 and HR: 1.1, p = 0.04, respectively) and DSS (HR: 1.38, p < 0.0001, and HR: 1.16, p = 0.03, respectively). CDKN2A, PTEN deletions, and MYC-amplifications were associated with PFS and DSS (p < 0.05 for all). On MVA, including TP53-mutations, mut31, CDKN2A-deletion, PTEN-deletion, and MYC-amplification, all five alterations were independently prognostic of poor PFS and DSS. Similar results were observed in an independent cohort from MSK-IMPACT (n = 7,051) where TP53 was associated with poor OS independent of mut31 and CN alterations in CDKN2A, PTEN, and MYC in primary tumors (p < 0.0001). CONCLUSIONS: TP53-mutations, CDKN2A-deletion, PTEN-deletion, and MYC-amplification are independent pan-cancer prognostic genomic alterations.

Operative Reports in Orthopaedic Surgery: The Need for Assessment and Education.

BACKGROUND: The ability to complete an operative report is a vital skill for an orthopaedic surgeon. We hypothesized that most programs do not have formal operative report teaching, that resident operative reports at our institution are incomplete, and that a formal teaching program would improve operative reports. METHODS: A survey of residencies in the United States was conducted assessing the state of operative report education. In addition, resident operative reports were collected at our institution both pre and post a formal educational session. Scores were given for each report out of a possible 35 points. RESULTS: Total 54 institutions responded to the survey, of which 83% indicated that they had no formal resident operative report teaching. Within our institution, 100 resident operative dictations were assessed prior to instituting a formal education session, with a mean score of 24.5. The most commonly missed items in the report were preoperative antibiotics, deep venous thrombosis prophylaxis, and tourniquet time. The mean score of 100 resident operative dictations following the educational session improved to 31.8. CONCLUSION: Most residency programs do not conduct formal resident operative report teaching. Formal instruction on how to complete a comprehensive operative report resulted in a significant improvement in their quality.

Adherence to the American Academy of Orthopaedic Surgeons Clinical Practice Guidelines for Nonoperative Management of Knee Osteoarthritis.

BACKGROUND: The American Academy of Orthopaedic Surgeons (AAOS) has published evidence-based Clinical Practice Guidelines (CPGs) for the nonarthroplasty management of knee osteoarthritis (OA). The purpose of this study is to determine how closely our orthopedic providers adhered to the recommendations included in those CPGs. METHODS: We retrospectively reviewed 1096 consecutive ambulatory visits with primary diagnosis of knee OA at a single center. Demographic, radiographic, and treatment information was collected. The primary outcome was the frequency of agreement between our treatment recommendations and the AAOS CPGs. A secondary outcome was the associated costs of care. RESULTS: The total number of interventions generated during the visits was 1955. Adherence to the AAOS guidelines was 65% (362/557), 60% (226/377), and 40% (413/1021) in new/never treated, new/previously treated, and return patients, respectively. Intra-articular injection with either corticosteroids or hyaluronic acid was the most common intervention (32%) followed by physical therapy (29%). As the severity of OA increased, adherence to the AAOS guidelines decreased (61%, 60%, 54%, and 49% for Kellgren-Lawrence grades I through IV, respectively). The estimated annual costs associated with our treatment recommendations were $2,403,543.18, of which $1,206,757.8 (50.2%) was supported by evidence. The most expensive treatment intervention was intra-articular hyaluronic acid injection, which carried a strong evidence against its use. CONCLUSION: Adherence to the recommendations contained within the AAOS CPGs was modest regardless of the Kellgren-Lawrence grade or history of treatment. Given the size of the affected patient population, there is a need for uniformly accepted guidelines to clarify the role and timing of the different treatment interventions. CPGs should be combined with education, patient engagement, and shared decision-making to minimize variation in treatment patterns, improve patient outcomes, and lower overall costs of care.