Search

PurposeCirculating inflammatory markers may predict prostate cancer (PC) outcomes. For example, a recent study showed that higher peripheral blood monocyte counts were associated with aggressive PC in Asian men undergoing radical prostatectomy (RP). Herein, we investigated whether peripheral monocyte count can predict long-term PC outcomes after RP in black and white men.MethodsWe retrospectively reviewed data on 2345 men undergoing RP from 2000 to 2017 at eight Veterans Affairs hospitals. Data on monocyte count within 6 and 12 months prior to surgery were collected. The study outcomes were biochemical recurrence (BCR), castration-resistant PC (CRPC), metastasis, all-cause mortality (ACM), and PC-specific morality (PCSM). Cox-proportional hazard models were used to assess the associations between pre-operative monocyte count and the above-mentioned outcomes accounting for confounders.ResultsOf 2345 RP patients, 972 (41%) were black and 1373 (59%) were white men. In multivariable analyses, we found no associations between monocyte count and BCR among all men (HR: 1.36, 95%CI 0.90-2.07) or when analyses were stratified by race (HR: 1.30, 95%CI 0.69-2.46, in black men; HR:1.33, 95%CI 0.76-02.33, in white men). Likewise, no overall or race-specific associations were found between monocyte count and CRPC, metastases, ACM, and PCSM, all p ≥ 0.15. Results were similar for monocyte count measured at 12 months prior to RP.ConclusionIn black and white PC patients undergoing RP, peripheral monocyte count was not associated with long-term PC outcomes. Contrary to what was found in Asian populations, monocyte count was not associated with PC outcomes in this study.

BackgroundIn this study among men who underwent radical prostatectomy (RP), African American men (AAM) were 28% more likely to develop recurrent disease compared with Caucasian men (CM). However, among those who had nonmetastatic, castration-resistant prostate cancer (CRPC), race did not predict metastases or overall survival. Whether race predicts metastases among men who receive androgen-deprivation therapy (ADT) after a biochemical recurrence (BCR) (ie, before CRPC but after BCR) is untested.MethodsThe authors identified 595 AAM and CM who received ADT for a BCR that developed after RP between 1988 and 2015 in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database. Univariable and multivariable Cox models were used to test the association between race and the time from ADT to metastases. Secondary outcomes included the time to CRPC, all-cause mortality, and prostate cancer-specific mortality.ResultsDuring a median follow-up of 66 months after ADT, 62 of 354 CM (18%) and 38 of 241 AAM (16%) developed metastases. AAM were younger at the time they received ADT (63 vs 67 years; P < .001), had received ADT in a more recent year (2008 vs 2006; P < .001), had higher prostate-specific antigen levels at RP (11.1 vs 9.2 ng/mL; P < .001), lower pathologic Gleason scores (P = .004), and less extracapsular extension (38% vs 48%; P = .022). On multivariable analysis, there was no association between race and metastases (hazard radio, 1.20; P = .45) or any of the other secondary outcomes (all P > .5).ConclusionsAmong veterans who received ADT post-BCR after RP, race was not a predictor of metastases or other adverse outcomes. The current findings suggest that research efforts to understand racial differences in prostate cancer biology should focus on early stages of the disease (ie, closer to the time of diagnosis).

OBJECTIVE:To assess whether obesity is associated with progression to metastasis, prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM), in patients with non-metastatic castration-resistant prostate cancer (non-mCRPC). At the population level, obesity is associated with prostate cancer mortality; however, some studies have found that higher body mass index (BMI) is associated with better long-term prostate cancer outcomes amongst men with mCRPC. PATIENTS AND METHODS:We identified 1 192 patients with non-mCRPC from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BMI was calculated from height and weight abstracted from the medical records at the time closest to but prior to CRPC diagnosis and categorised as underweight (

PurposeSystemic inflammation, as measured by C-reactive protein, has been linked with poor prostate cancer (PC) outcomes, predominantly in white men. Whether other immune measures like white blood cell counts are correlated with PC progression and whether results vary by race is unknown. We examined whether complete blood count (CBC) parameters were associated with PC outcomes and whether these associations varied by race.MethodsAnalyses include 1,826 radical prostatectomy patients from six VA hospitals followed through medical record review for biochemical recurrence (BCR). Secondary outcomes included castration-resistant PC (CRPC), metastasis, all-cause mortality (ACM), and PC-specific mortality (PCSM). Cox-proportional hazards were used to assess the associations between pre-operative neutrophils, lymphocytes, platelets, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) with each outcome. We used a Bonferroni-corrected p-value of 0.05/5 = 0.01 as the threshold for statistical significance.ResultsOf 1,826 men, 794 (43%) were black and 1,032 (57%) white. Neutrophil count (p

An array of phenotypically diverse myeloid cells and macrophages (MC&M) resides in the tumor microenvironment, requiring multiplexed detection systems for visualization. Here we report an automated, multiplexed staining approach, named PLEXODY, that consists of five MC&M-related fluorescently-tagged antibodies (anti - CD68, - CD163, - CD206, - CD11b, and - CD11c), and three chromogenic antibodies, reactive with high- and low-molecular weight cytokeratins and CD3, highlighting tumor regions, benign glands and T cells. The staining prototype and image analysis methods which include a pixel/area-based quantification were developed using tissues from inflamed colon and tonsil and revealed a unique tissue-specific composition of 14 MC&M-associated pixel classes. As a proof-of-principle, PLEXODY was applied to three cases of pancreatic, prostate and renal cancers. Across digital images from these cancer types we observed 10 MC&M-associated pixel classes at frequencies greater than 3%. Cases revealed higher frequencies of single positive compared to multi-color pixels and a high abundance of CD68+/CD163+ and CD68+/CD163+/CD206+ pixels. Significantly more CD68+ and CD163+ vs. CD11b+ and CD11c+ pixels were in direct contact with tumor cells and T cells. While the greatest percentage (~70%) of CD68+ and CD163+ pixels was 0-20 microns away from tumor and T cell borders, CD11b+ and CD11c+ pixels were detected up to 240 microns away from tumor/T cell masks. Together, these data demonstrate significant differences in densities and spatial organization of MC&M-associated pixel classes, but surprising similarities between the three cancer types.

BackgroundUridine 5'-diphosphate-glucuronosyltransferase 2B (UGT2B) genes code for enzymes that catalyze the clearance of testosterone, dihydrotestosterone (DHT), and DHT metabolites in the prostate basal and luminal tissue. The expression of the UGT2B15, UGT2B17, and UGT2B28 enzymes has not been evaluated in prostate tissue samples from hormone therapy-naïve patients.MethodsWe determined the expression of UGT2B15, UGT2B17, and UGT2B28 enzymes in 190 prostate tissue samples from surgical specimens of a multiethnic cohort of patients undergoing radical prostatectomy at the Durham Veterans Affairs Medical Center. The association between each protein's percent positive and H-score, a weighted score of staining intensity, and the risk of biochemical recurrence (BCR) was tested using separate Cox proportional hazards models. In an exploratory analysis, UGT2B17 total positive and H-score were divided at the median and we tested the association between UGT2B17 group and risk of BCR.ResultsThe median follow-up for all patients was 118 months (IQR: 85-144). Of 190, 83 (44%) patients developed BCR. We found no association between UGT2B15 or UGT2B28 and risk of BCR. However, there was a trend for an association between UGT2B17 and BCR (HR = 1.01, 95% CI 1.00-1.02, p = 0.11), though not statistically significant. Upon further investigation, we found that patients with UGT2B17 higher levels of expression had a significant increased risk of BCR on univariable analysis (HR = 1.57, 95% CI 1.02-2.43, p = 0.041), although this association was attenuated in the multivariable model (HR = 1.50, 95% CI 0.94-2.40, p = 0.088).ConclusionsOur findings suggest that UGT2B17 overexpression may be associated with a significant increased risk of BCR. These results are consistent with previous reports which showed UGT2B17 significantly expressed in advanced prostate cancer including prostate tumor metastases.

BackgroundBlack race is associated with prostate cancer (PC) diagnosis and poor outcome. Previously, the authors reported that black men undergoing radical prostatectomy (RP) in equal-access hospitals had an increased risk of biochemical disease recurrence (BCR), but recurrences were equally aggressive as those occurring in white men. The authors examined the association between race and long-term outcomes after RP.MethodsData regarding 1665 black men (37%) and 2791 white men (63%) undergoing RP were analyzed. Using Cox models, the authors tested the association between race and BCR, BCR with a prostate-specific antigen (PSA) doubling time

ObjectiveTo determine whether there are subsets of men with pathological high grade prostate cancer (Gleason score 8-10) with particularly high or low 2-year biochemical recurrence (BCR) risk after radical prostatectomy (RP) when stratified into groups based on combinations of pathological features, such as surgical margin status, extracapsular extension (ECE) and seminal vesicle invasion (SVI).Materials and methodsWe identified 459 men treated with RP with pathological Gleason score 8-10 prostate cancer in the SEARCH database. The men were stratified into five groups based on pathological characteristics: group 1, men with negative surgical margins (NSMs) and no ECE; group 2, men with positive surgical margin (PSMs) and no ECE; group 3, men with NSMs and ECE; group 4, men with PSMs and ECE; and group 5, men with SVI. Cox proportional hazards models and the log-rank test were used to compare BCR among the groups.ResultsAt 2 years after RP, pathological group was significantly correlated with BCR (log-rank, P < 0.001) with patients in group 5 (+SVI) having the highest BCR risk (66%) and those in group 1 (NSMs and no ECE) having the lowest risk (14%). When we compared groups 2, 3, and 4, with each other, there was no significant difference in BCR among the groups (~50% 2-year BCR risk; log-rank P = 0.28). Results were similar when adjusting for prostate-specific antigen, age, pathological Gleason sum and clinical stage, or after excluding men who received adjuvant therapy.ConclusionsIn patients with high grade (Gleason score 8-10) prostate cancer after RP, the presence of either PSMs, ECE or SVI was associated with an increased risk of early BCR, with a 2-year BCR risk of ≥50%. Conversely, men with organ-confined margin-negative disease had a very low risk of early BCR despite Gleason score 8-10 disease.

ObjectivesTo determine if men with adverse pathology but undetectable ultrasensitive (

Abstract: INTRODUCTION: At the population level among otherwise “healthy” men, obesity is associated with prostate cancer mortality. However, few studies analyzed the associations between obesity and long-term progression after surgery, such as castration-resistant prostate cancer (CRPC) and prostate cancer-specific mortality (PCSM). We examined the effect of obesity at the time of radical prostatectomy (RP) on long-term prostate cancer-specific outcomes among men treated at Veterans Affairs Hospitals in the USA. METHODS: We combined data from patients undergoing RP at six Veterans Affairs Medical Centers (West Los Angeles, San Diego, and Palo Alto, CA; Augusta, GA; and Durham and Asheville, NC) into the SEARCH database. Our exposure, body mass index (BMI) was abstracted from the medical records at the time of but prior to RP and categorized as normal weight (