Race/Ethnic Disparities in Treatment Patterns among Newly Diagnosed Primary Prostate Cancer Patients in Florida

Study Purpose: The purpose of this study was to examine whether there were differences in patterns of care between African American (AA) and Non-Hispanic White (NHW) men newly diagnosed with prostate cancer in Florida, and how the treatment patterns compare with the National Comprehensive Cancer Network (NCCN) initial treatment recommendations. Materials and Methods: This retrospective cohort study utilized data from the Florida Cancer Data System (FCDS), to identify incident cases of prostate cancer diagnosed between 1982 and 2012. The variables of interest included: race/ethnicity, marital status, age at diagnosis, stage at diagnosis, tumor grade, year of diagnosis, and treatment modality (singular or multimodality). Adjusted odds ratios (AORs) and 95% confidence intervals were calculated to determine disparities in the receipt of treatment by age at diagnosis, stage at diagnosis and tumor grade between AA and NHW men. Results: A total of 244,449 AA (30,556 cases or 12.5%) and NHW (213,893 cases or 87.5%) men met the study inclusion/exclusion criteria. AA men were significantly less likely to receive surgery only or surgery in combination with other treatment modalities compared to NHW men, localized disease (AOR=0.66, 95% CI (0.63-0.68), regional disease (AOR=0.63, 95% CI (0.57- 0.71), distant disease (AOR=0.50, 95% CI (0.34-0.75). Comparisons of adherence to the NCCN initial treatment recommendations indicate that AA men with(5% versus 13%). Moreover, AA men in the very high risk group had a higher NCCN initial treatment adherence percentage compared to NHW men (76% versus 70%). Conclusion: After adjusting for potential demographic and clinical confounders, significant differences exist in the receipt of first course of treatment where AA men were more likely to receive radiation and/or hormone therapy and less likely to receive surgery compared to NHW men. Further research is needed to address this disparity

Optimizing Time-to-Treatment to achieve durable biochemical disease control after surgery in prostate cancer - A multi-institutional cohort study

BackgroundThe impact of treatment delays on prostate cancer-specific outcomes remains ill-defined. This study investigates the effect of time to treatment on biochemical disease control after prostatectomy.MethodsThis retrospective study includes 1,807 patients who received a prostatectomy as a primary treatment at two large tertiary referral centers from 1987 to 2015. Multivariate cox model with restricted cubic spline was used to identify optimal time to receive treatment and estimate the risk of biochemical recurrence.ResultsMedian follow-up time of the study was 46 (interquartile range, 18-86) months. Time to treatment was subcategorized based on multivariate cubic spline cox model. In multivariate spline model, adjusted for all the pertinent pretreatment variables, inflection point in the risk of biochemical recurrence was observed around 3 months, which further increased after 6 months. Based on spline model, time to treatment was then divided into 0 to 3 months (61.5%), >3 to 6 months (31.1%), and 6 months (7.4%). In the adjusted cox model, initial delays up to 6 months did not adversely affect the outcome; however, time to treatment >6 months had significantly higher risk of biochemical recurrence (HR, 1.84; 95% confidence interval, 1.30-2.60; P < 0.01).ConclusionsThe initial delays up to 6 months in prostate cancer primary treatment may be sustainable without adversely affecting the outcome. However, significant delays beyond 6 months can unfavorably affect biochemical disease control.ImpactTime to treatment can aid clinicians in the decision-making of prostate cancer treatment recommendation and educate patients against unintentional treatment delays

Substantial Gleason reclassification in Black men with national comprehensive cancer network low-risk prostate cancer - A propensity score analysis

Background Emerging evidence suggests that a subset of Black men with National Comprehensive Cancer Network (NCCN) low-risk prostate cancer (PCa) may harbor high volume and genomically aggressive disease. However, limited, and ambiguous research exist to evaluate the risk of extreme Gleason reclassification in Black men with low-risk PCa. Methods This retrospective cohort study included 45,674 low-risk PCa patients who underwent prostatectomy and were not on active surveillance, from National Cancer Database (NCDB). A propensity score matched-pair design was employed, and the final cohort was limited to 1:1 matched 12,340 patients. Gleason score reclassification was used as primary endpoint. As such, any migration to pathologic Gleason score >= 7(3 + 4) was identified as overall, whereas migration to >= 7(4 + 3) was defined as extreme reclassification. A conditional Poisson regression model was used to estimate the risk of reclassification. Whereas spline model was used to estimate the impact of increasing time to treatment as a non-linear function on Gleason reclassification between race group. Results Upon matching there were no differences in the baseline characteristics between race groups. In a matched cohort, higher proportion of low-risk Black men (6.6%) reported extreme reclassification to pathologic Gleason score than White men (5.0%), p < 0.001. In a conditional Poisson regression model adjusted for time to treatment, the risk of overall (RR = 1.09, 95% CI, 1.05-1.13, p < 0.001) and extreme (RR = 1.30, 95% CI, 1.12-1.50, p = 0.004) reclassification was significantly higher in Black men as compared to their White counterpart. In spline model, the probability of Gleason reclassification in Black men was elevated with increasing time to treatment, especially after 180 days (53% vs. 43% between Black and White men). Conclusion Risk of Gleason score reclassification is disparately elevated in Black men with low-risk PCa. Furthermore, time to treatment can non-linearly impact Gleason reclassification in Black men

A Genome-Wide Investigation of MicroRNA Expression Identifies Biologically-Meaningful MicroRNAs That Distinguish between High-Risk and Low-Risk Intraductal Papillary Mucinous Neoplasms of the Pancreas

<div><p>Background</p><p>Intraductal papillary mucinous neoplasms (IPMNs) are pancreatic ductal adenocarcinoma (PDAC) precursors. Differentiating between high-risk IPMNs that warrant surgical resection and low-risk IPMNs that can be monitored is a significant clinical problem, and we sought to discover a panel of mi(cro)RNAs that accurately classify IPMN risk status.</p><p>Methodology/Principal Findings</p><p>In a discovery phase, genome-wide miRNA expression profiling was performed on 28 surgically-resected, pathologically-confirmed IPMNs (19 high-risk, 9 low-risk) using Taqman MicroRNA Arrays. A validation phase was performed in 21 independent IPMNs (13 high-risk, 8 low-risk). We also explored associations between miRNA expression level and various clinical and pathological factors and examined genes and pathways regulated by the identified miRNAs by integrating data from bioinformatic analyses and microarray analysis of miRNA gene targets. Six miRNAs (miR-100, miR-99b, miR-99a, miR-342-3p, miR-126, miR-130a) were down-regulated in high-risk versus low-risk IPMNs and distinguished between groups (<i>P</i><10⁻³, area underneath the curve (AUC) = 87%). The same trend was observed in the validation phase (AUC = 74%). Low miR-99b expression was associated with main pancreatic duct involvement (<i>P</i> = 0.021), and serum albumin levels were positively correlated with miR-99a (r = 0.52, <i>P</i> = 0.004) and miR-100 expression (r = 0.49, <i>P</i> = 0.008). Literature, validated miRNA:target gene interactions, and pathway enrichment analysis supported the candidate miRNAs as tumor suppressors and regulators of PDAC development. Microarray analysis revealed that oncogenic targets of miR-130a (<i>ATG2B, MEOX2</i>), miR-342-3p (<i>DNMT1</i>), and miR-126 (<i>IRS-1</i>) were up-regulated in high- versus low-risk IPMNs (<i>P</i><0.10).</p><p>Conclusions</p><p>This pilot study highlights miRNAs that may aid in preoperative risk stratification of IPMNs and provides novel insights into miRNA-mediated progression to pancreatic malignancy. The miRNAs identified here and in other recent investigations warrant evaluation in biofluids in a well-powered prospective cohort of individuals newly-diagnosed with IPMNs and other pancreatic cysts and those at increased genetic risk for these lesions.</p></div

Heatmap and unsupervised hierarchical clustering of low-risk (adenoma) and high-risk (carcinoma-in-situ) IPMN samples according to the expression of the most differentially expressed miRNAs.

<p>A) The heatmap is supervised, and is ordered by the type of IPMN, and shows the expression for the 25 most deregulated miRNAs. B) Unsupervised hierarchical clustering for the 6 most differentially expressed miRNAs. Expression values for the miRNAs are represented in a matrix format, with columns representing samples and rows representing miRNAs. Low expression values are colored green, and high expression values are colored red. Colored bars indicate the range of normalized log2-based signals. </p

Gene ontology categories of biological pathways overrepresented by miRNA-mediated changes in target gene expression that may differentiate between high- and low-risk IPMNs.

<p>Gene ontology categories of biological pathways overrepresented by miRNA-mediated changes in target gene expression that may differentiate between high- and low-risk IPMNs.</p

Laser capture microdissection (LCM) of epithelium from A) low- grade and B) high-grade IPMN tissue.

<p>Left Panel: Hematoxylin (H&E) stained slide (× 4). Middle Panel: H&E stained slide before LCM (× 4), with the red area representing cells of interest marked for capture. Right Panel: Cap showing adherent cells.</p