bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of sexual orientation on contemporary rates of prostate cancer screening.
Authors: Pucheril Daniel , Ingham Matthew D. , Zlatev Dimitar V. , Berg Sebastian , Mossanen Matthew , Chang Steven Lee , Kibel Adam S. , Trinh Quoc-Dien 
Published: February 2018

122 Background: Despite increasing societal acceptance of non-heterosexual persons, sexual minorities continue to face discrimination. The effect of non-heterosexual orientation on adoption of cancer preventive services, particularly prostate cancer screening (PSAS), is not clearly known. We hypothesize that male sexual minorities are less likely to receive PSAS compared to heterosexual (HTS) males. Methods: The 2014-16 Behavioral Risk Factor Surveillance System was queried for males 40-69, without a history of prostate cancer, and having answered all sexual orientation (SO) questions. PSAS occurred if a respondent had a PSA test within the last two years for reasons other than “a prostate problem” or “for prostate cancer”. Descriptive statistics were generated for demographic covariates stratified by year and SO [HTS, homosexual (HMS), bisexual (BIS), transgender (TGR), other, and refused]. The Chi-Square test was used to compare the distribution of covariate proportions amongst SO categories within each year. Multivariable regression was used to determine the independent effect of SO and other covariates on receipt of PSAS in this cohort. Results: A weighted 49.2 million individuals (n = 86,893) met inclusion criteria. In 2014 and 2016, 94% and 93% of the cohort identified as HTS. In both years, a higher proportion of HMS (2014: 40.5%, 2016: 47.4) and BIS (2014: 30.3%, 2016: 31.0%) respondents were college graduates compared to HTS males (2014: 28.8%, 2016: 28.9%). In 2014, rates of PSAS were higher amongst HMS (34.9%), BIS (37.1%) and TGR (37.5%) individuals compared to HTS individuals (34.5%). In 2016, rates of PSAS were clinically similar among HTS (30.4%), HMS (30.2%), BIS (30.1%), and TGR (27.8%) individuals. In the multivariable analysis, increasing age (65-69 OR 8.93, 95%CI 7.80-10.22) and education level (College Graduate OR 2.21, 95%CI 1.93-2.54) along with insurance coverage (OR 2.15, 95%CI 1.85-2.51) and a personal physician (OR 2.88, 95%CI 2.59-3.20) were associated with higher odds of PSAS. Aside from HMS orientation (OR 1.30, 95%CI 1.04-1.62), SO was not an independent predictor of PSAS. Conclusions: Based on this nationally representative sample, disparities in regards to PSAS are not apparent for non-HTS males.
Is BMI a risk factor for active surveillance progression in patients with prostate cancer diagnosed by MRI-Trus fusion biopsy?
Authors: Rayn Kareem , Gold Samuel , Hale Graham R. , Baiocco Joey , Bloom Jonathan , Valera Vladimir , Wood Brad J. , Turkbey Baris , Pinto Peter A. 
Published: February 2018

124 Background: MRI−TRUS fusion biopsy (FBx) use in the diagnosis of prostate cancer (PCa) results in a more accurate assessment of disease burden and has increasingly been incorporated into urologic practice. In addition, with more men choosing active surveillance (AS) and the reports of increased PCa aggressiveness with obesity, we wanted to study the impact of obesity on the risk of PCa progression in men on AS diagnosed and followed by MRI and MRI−TRUS FBx. Methods: A retrospective review was performed on a prospectively maintained database of all men who underwent MRI−TRUS FBx at our institution from January 2007 to May 2015. Patient demographics, clinical data, imaging, pathology, treatment and outcomes were recorded. Patients who enrolled on AS were stratified by BMI into normal weight (BMI 18.5−24.9), overweight (BMI 25.0−29.9), and obese (BMI ≥ 30.0). Statistical analysis was performed using SPSS software. Results: 204 men were enrolled in AS. Within the AS cohort, 51 (25%) had a normal weight, 101 (49.5%) were overweight, and 52 (25.5%) were obese. Age, BMI, PSA and mean estimated progression free survival time are described for each of these groups in Table 1. The overall rate of progression was 32.8%. Of the patients who progressed, 18 (26.9%) were normal weight, 32 (15.7%) were overweight and 17 (25.4%) were obese. On multivariate analysis, BMI was not a risk factor for AS progression, HR = 1.00 (p = 0.99, 95% CI = 0.95−1.06). Conclusions: There is evidence of increased risk of aggressive PCa specific death in obese patients. However, we demonstrate that in patients diagnosed by FBx, obesity does not confer an additional risk of progression on AS. This may be due to the improved characterization of cancer volume and grade by MRI−TRUS fusion biopsy. Further study is required to determine risk factors for AS progression in patients undergoing FBx. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH, Medical Research Scholars Program.
Validation of a genomic risk classifier to predict metastasis and prostate cancer-specific mortality in men with positive lymph nodes.
Authors: Trock Bruce J. , Karnes R. Jeffrey , Claessens Frank , Davis John W. , Haddad Zaid , Yousefi Kasra , Davicioni Elai , Ross Ashley 
Published: February 2018

125 Background: Men with lymph node involvement (LNI) at prostatectomy (RP) are at high risk of dying from prostate cancer. However, survival following RP is highly variable, with some men apparently cured. Nomograms developed for men with LNI have been based on series where all or the vast majority of men received adjuvant treatment. Because administration of adjuvant treatment is not universal, even for LNI, we evaluated whether the Decipher genomic classifier (GC) can improve upon clinical models to predict metastasis within 5 years (MET5) and prostate cancer specific mortality within 10 years (PCSM10) in a cohort of LNI patients, the majority of whom did not receive adjuvant treatment. Methods: 141 patients from 4 institutions (Johns Hopkins, Mayo Clinic, Leuven, MD Anderson) had LNI at RP, had adequate tissue and clinical data for analysis of MET5, and 86 were analyzed for PCSM10. 43% of men received adjuvant therapy. RP tumor tissue was analyzed by Affymetrix Human Exon 1.0 ST GeneChip; the GC was calculated based on 22 genes in the previously trained and validated algorithm. Logistic regression evaluated whether the GC, dichotomized as high risk (GC score > 0.6) vs low-intermediate risk (≤0.6), improved prediction of MET5 and PCSM10 beyond that achieved with established clinical prognostic factors. Results: 62 men (43%) developed MET5, and 35 (41%) developed PCSM10. For both MET5 and PCSM10 CAPRA-S, number of positive lymph nodes, and age were significant; adjuvant therapy was not significant. GC was a significant independent strong prognostic factor when added to the clinical model for prediction of MET5, odds ratio = 4.04 (95% CI: 1.48, 11.02), p = 0.006, and prediction of PCSM10, odds ratio = 6.71 (95% CI: 2.01, 22.38), p = 0.002. Addition of GC to the clinical model improved the AUC from 0.77 to 0.79 for MET5, and from 0.65 to 0.74 for PCSM10. Conclusions: The Decipher GC significantly improves upon clinical variables to predict metastasis and prostate cancer specific mortality in men at high risk due to LNI. This is the first study to show a genomic classifier predicts outcomes in men with LNI; validation is needed to determine if Decipher can improve treatment decisions in men with LNI.
Why are low-risk prostate cancers (PCa) treated aggressively? A population-based cohort analysis.
Authors: Basak Ramsankar , Usinger Deborah S , Godley Paul Alphonso , Chen Ronald C. 
Published: February 2018

127 Background: Per AUA guidelines, active surveillance (AS) is the best option for very low-risk PCa and preferred for all low-risk patients. However, AS continues to be underused. This study examines decision-making factors in low risk patients. Methods: Using Rapid Case Ascertainment of the North Carolina (NC) Cancer Registry, 1,456 patients were enrolled from 2011-13 across NC soon after diagnosis. NCCN risk group and treatments received (or AS) were determined using medical records and registry data. Phone survey asked patients about their perceived cancer aggressiveness, most important decision-making factor (i.e., cure, quality of life, family burden, cost, daily activity), and desire to be involved in the decision process. Results: Of 585 low-risk patients, 38% pursued AS. Multivariable analysis showed that patient desire to pursue aggressive treatment and perceived cancer aggressiveness were significantly associated with aggressive treatment instead of AS (Table). Further, patients indicating primary decision was self (instead of physician) were more likely to receive aggressive treatment (Odds ratio [OR] 1.76). In the subgroup of 346 very low-risk patients, 48% received AS; patient desire for aggressive treatment and perceived aggressiveness remained significant factors. Conclusions: Patient desire for aggressive treatment and (mis)perception of cancer aggressiveness were dominant factors for low-risk patients receiving aggressive treatment instead of AS. Ascertaining patient goals for treatment and more accurate information about low-risk PCa may improve physician counseling and reduce underutilization of AS. [Table: see text]
Single-dose radiotherapy (SDRT) in the management of intermediate risk prostate cancer: Early results from a phase II randomized trial.
Authors: Greco Carlo , Pimentel Nuno , Pares Oriol , Louro Vasco , Fuks Zvi Y. 
Published: February 2018

128 Background: To report initial response, acute treatment-related toxicity and patient-reported quality of life (QoL) after 24Gy SDRT derived from a randomized Phase II study of patients with intermediate-risk adenocarcinoma of the prostate (NCCN definition). Methods: Between November 2015 and December 2016, 30 hormone-naïve patients were enrolled in an IRB-approved prospectively randomized phase II study to receive either 45Gy in 5 consecutive daily fractions (Hypo-SBRT) or 24Gy SDRT. Treatment was based on VMAT-IGRT with urethral sparing via a dose-painting technique and real-time motion management with beacon transponders. The PTV included the MR-delineated prostate gland and seminal vesicles with 2 mm margin. Precise PTV targeting and anatomical reproducibility was achieved via placement of an endorectal air-filled balloon (150 cc) and a Foley catheter. This setup also conferred organ motion mitigation, and online tracking ensured treatment delivery within the 2 mm PTV margin.. Genito-urinary (GU) and gastro-intestinal (GI) toxicity were graded according to the NCI CTCAE v.4, and QoL was assessed by EPIC and IPSS questionnaires. Tumor response was assessed biochemically (PSA) and by follow-up MRI at 3 months after treatment and at 6 months intervals thereafter. Results: With a median follow-up of 16 months (range, 11-24), no grade ≥2 acute GI or GU toxicities were observed in either group. There were no significant differences in mean EPIC scores in all domains. An initial 6% and 8% drop in the EPIC urinary domain score occurred in the hypo and SDRT arm respectively, returning to baselines by 3 months. . PSA reduction kinetics were similar between the two regimens, reaching ≤1 ng/mL by 18 months. Of note, all cases, regardless of treatment regimen, converted to non-detectable disease on MRI at 6 months. Patients in this trial will receive a planned 24 months post-treatment biopsy to validate treatment outcome. Conclusions: These early trial outcomes indicate that 24Gy SDRT can be consistently and safely delivered, yielding the same low acute toxicity as demonstrated with the hypo 5x9Gy schedule, and is associated with excellent QoL measures. Clinical trial information: NCT02570919.
Which patients with localized prostate cancer account for the greatest proportion of prostate cancer deaths?
Authors: Nezolosky Michelle , Nguyen Paul L. , Yang David Dewei 
Published: February 2018

130 Background: We sought to determine which groups of patients, stratified by risk group and age, account for the greatest absolute number of deaths due to prostate cancer. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 437,150 men diagnosed with prostate cancer from 2004 to 2014. Men were excluded if they had N1 or M1 disease, risk group could not be determined, or if prostate cancer was not their first malignancy. Men were categorized as having low (Gleason ≤6, prostate-specific antigen [PSA] < 10 ng/mL, and cT1-T2a), intermediate (Gleason 7, PSA 10-20 ng/mL, or cT2b-T2c), or high risk disease (Gleason 8-10, PSA > 20 ng/mL, or cT3-T4). We calculated the cumulative incidence of prostate cancer-specific mortality (PCSM). Results: Median follow-up was 4.8 years. The overall incidences of diagnosis of low, intermediate, and high risk disease were 29.7% (n = 129,925), 48.0% (n = 209,643), and 22.3% (n = 97,582), respectively. 5-year PCSM for men with low, intermediate, and high risk disease was 0.5%, 1.4%, and 9.4%, respectively, and the 10-year PCSM was 1.6%, 4.0%, and 16.8%. Within 10 years of diagnosis, 6.5% (n = 905) of patients who died of prostate cancer were low risk, 27.4% (n = 3,834) were intermediate risk, and 66.2% (n = 9,278) were high risk. In particular, patients age 70 or older accounted for 49.9% of all high risk prostate cancer diagnoses, but 65.3% of deaths due to high risk prostate cancer. Conclusions: While high risk disease accounted for only 22.3% of the diagnoses, it accounted for 66.2% of the prostate cancer deaths within 10 years of diagnosis. Therefore, high risk patients account for the vast majority of prostate cancer deaths and should remain the focus of the majority of our research efforts. In addition, older patients with high risk disease die of prostate cancer at a disproportionately high rate, which runs counter to the notion that the disease is less of a threat to survival in older men.
Role of core location in targeted MRI-ultrasound fusion biopsy of prostate lesions.
Authors: Lu Amanda , Ghabili Kamyar , Nguyen Kevin , Sprenkle Preston 
Published: February 2018

136 Background: Targeted mpMRI fusion biopsy has gained adoption with superior clinically significant cancer detection rates and accuracy over template biopsy. We sought to establish the role of biopsy location within a prostate lesion to detect clinically significant prostate cancer. Methods: From Nov 2016-Aug 2017, 110 patients with positive multiparametric-MRI (mpMRI) underwent targeted and systematic MRI-US fusion biopsy at our institution for clinical suspicion or known history of prostate cancer. Lesions were scored by Prostate imaging reporting and data system (PI-RADS) classification schema by experienced genitourinary radiologists. Biopsy was performed by an oncology-trained urologist (PS) performing a high volume of fusion biopsies. 5 cores were taken from each lesion, each corresponding to a predetermined location (central, medial, lateral, apex, and base of the lesion). Cancer detection rates (CDR) were calculated on a per lesion basis from biopsy histology. Results: 154 prostate lesions were identified and biopsied with an average volume of 1.31 mL. Detection of clinically significant cancer (G>3+4) did not differ significantly among the 5 locations (Table 1). The central core detected slightly more G≥3+4 cancers than the apex core. No concordance of pathology grade was found between the central core and location of the peripheral core (medial, lateral, apex, or base). In 32% (50/154) of lesions, the peripheral cores had a higher Gleason score than the central core. Biopsy of only the central core missed 40% (21/52) of G≥3+4 cancers and 17% (4/24) of G>3+4 cancers. Lesions with higher PIRADs score were more likely to detect cancer in both the central and peripheral cores, but lesion volume was not a significant predictor. Conclusions: Location of biopsy cores within mpMRI-identified prostate lesions has little correlation with detection of clinically significant cancer. However, targeted biopsy of only the center of a lesion can miss 17% of Gleason >3+4 cancers. [Table: see text]
Regulation of the tumor suppressor PLZF and prostate cancer prognosis.
Authors: Stopsack Konrad Hermann , Gerke Travis A. , Tyekucheva Svitlana , Mucci Lorelei A. , Kantoff Philip W. 
Published: February 2018

137 Background: PLZF ( ZBTB16) is an androgen-regulated tumor suppressor gene. Homozygous PLZF deletions are seen in a proportion of localized as well as castration-resistant prostate cancers (PC). Since PTEN has been shown to regulate PLZF expression in vitro, we hypothesized that PTEN status impacts PLZF expression in men with PC. We further hypothesized that low PLZF is associated with a poorer PC prognosis. Methods: We studied patients diagnosed with PC during prospective follow-up of the Health Professionals Follow-up Study (HPFS; n = 254) and the Physicians’ Health Study (PHS; n = 150). We performed whole transcriptome profiling of tumor specimens from cancer diagnosis and, in a subset of patients ( n = 253), a genomically-validated immunohistochemistry for PTEN. Patients were followed for metastases and PC-specific mortality (lethal cancer) after primary treatment for a median of 14 years. Univariable linear and multivariable logistic regression models for cancer outcomes, adjusted for age and calendar year, were used. For validation, the association of PTEN copy number variations and PLZF mRNA expression was assessed in The Cancer Genome Atlas (TCGA) primary PC cohort (n = 333). Results: Loss of PTEN protein expression was associated with lower PLZF expression (–0.72 standard deviations [SD]; 95% CI, –0.38 to –1.06; p < 0.001; HPFS and PHS cohorts), as were copy number variations in PTEN (TCGA cohort; –0.46 SD for deep deletions vs. diploid status; 95% CI, –0.13 to –0.79; p = 0.006) . PLZF expression did not differ significantly by Gleason grade in any cohort (all p > 0.09). In both the HPFS and PHS cohorts, the 25% of patients with the lowest PLZF expression were significantly more likely than those with higher expression to have progression to lethal cancer. This association was independent from Gleason grade, PTEN loss, and a signature of androgen receptor signaling (adjusted odds ratio for lethal cancer, 2.69; 95% CI, 1.18 to 6.14; p = 0.019). Conclusions: Loss of PTEN expression is associated with lower expression of PLZF amongst primary PC not exposed to ADT. In line with its action as a tumor suppressor, low PLZF expression is associated with lethal PC. Whether further suppression of PLZF with ADT worsens outcomes in advanced PC needs further study.
Effect of pectasol-c modified citrus pectin (P-MCP) treatment (tx) on PSA dynamics in non-metastatic biochemically relapsed prostate cancer (BRPC) patients (pts): Results of a prospective phase II study.
Authors: Keizman Daniel , Frenkel Moshe A. , Peer Avivit , Rosenbaum Eli , Margel David , Sarid David Leonid , Neiman Victoria , Gottfried Maya , Maimon Natalie , Leibovitch Ilan , Dresler Hadas , Eliaz Isaac 
Published: February 2018

14 Background: 30% of pts with localized PC will have a biochemical relapse post local tx. The optimal tx of these pts remains elusive. While androgen deprivation therapy is effective in reducing PSA level, its long-term benefit on survival remain undefined, and it is associated with significant cumulative toxicities.Thus, evaluation of new non-toxic compounds in this pt population is warranted. P-MCP is a competitive inhibitor of galectin-3, a carbohydrate-binding protein, which is known to be involved in cancer pathogenesis. Pre-clinical and clinical data suggest that P-MCP is active in PC. We aimed to evaluate the safety and PSA dynamics of tx with P-MCP in pts with BRPC. Methods: Pts with non-castrate non-metastatic BRPC were enrolled in a prospective phase 2 study of tx with oral P-MCP, at 4.8 grams X 3/day for 6 months (mos). Pts that did not progress clinically, biochemically (PSA), and radiologically, at 6 mos, were treated for subsequent 12 mos. Sample size provided 85% power to assess a decrease in PSA progression rate from 80% (natural history) to 40% (P-MCP tx) at 6 mos. Results: The study was initiated in June 2013. 35 pts were enrolled. Median age was 74 years. Treatment of the primary tumor consisted of surgery in 11% (n = 4), radiation in 69% (n = 24), and both in 20% (n = 7). No pt had tx related grade 3/4 toxicity. One patient withdrew his consent after 1 mos. Of the 34 pts analyzed, 18% (n = 6) had grade 1 toxicity. 62% (n = 21) had a stabilization/decrease of PSA, and negative scans, at 6 mos, and entered the second 12 mos tx phase. A stabilization or improvement (increase) of PSA doubling time was noted in 79% (n = 27) of pts. Disease progression at 6 mos was noted in 38% (n = 13: PSA only 29%, n = 10; PSA and scans 9%, n = 3). Conclusions: The present study suggests a potential benefit of P-MCP tx on progression of BRPC. P-MCP tx is safe. Clinical trial information: NCT01681823.
When can active surveillance be less active? Prediction of long-term nonreclassification for men with low-risk prostate cancer.
Authors: Cooperberg Matthew R. , Faino Anna V , Newcomb Lisa F , Carroll Peter , Kearns James T , Brooks James D. , Fabrizio Michael , Gleave Martin , Morgan Todd Matthew , Dash Atreya , Nelson Peter , Thompson Ian Murchie , Wagner Andrew , Lin Daniel W. , Zheng Yingye 
Published: February 2018

140 Background: Active surveillance is endorsed as the preferred management strategy for most men with low-risk prostate cancer. However, nearly all active surveillance protocols entail prostate specific antigen (PSA) testing every 3-6 months, and prostate biopsies every 1-2 years. For many men with indolent tumors, this regimen is overly intense, and exposes men to the discomfort, risks, and costs of repeated biopsies. We aimed to determine if some men can be safely selected for a less intense surveillance regimen by predicting the probability of non-reclassification over the next 4 years of surveillance. Methods: Data were collected from men in the multicenter Canary Prostate Active Surveillance Study (PASS), in which PSAs are collected q3 months and biopsies performed 12 months of diagnosis and then every 2 years. For inclusion in this study, men had to have undergone ≤ 1 follow up biopsy, and have Gleason grade group 1 at diagnosis. Reclassification was defined as increase in Gleason grade group on subsequent biopsy; those without reclassification were censored at last study contact, treatment or 2 years after last biopsy. A dynamic risk prediction model based on a Cox regression with robust variance estimates was used to construct and test a model predicting non-reclassification. Results: Of 1082 men included, 362 (33%) reclassified and the remaining were censored. The final regression model included percent of biopsy cores involved, prior biopsy history, time since diagnosis, BMI, prostate size, diagnostic PSA, and PSAk (a measure of PSA kinetics). This dynamic risk prediction model was assessed at a measurement time of 1 year after diagnosis, predicting risk of reclassification at 4 years. Men at lowest and highest deciles of this model-based risk faced 6% (95%CI 0-12%) and 73% (55-84%) risks of reclassification within 5 years. For at least 10% of the men in the cohort, the negative predictive value (NPV) for reclassification was 95% or higher. Conclusions: A substantial proportion of men with low-risk prostate cancer can safely be followed with a de-intensified active surveillance protocol, which would improve both the tolerability and cost-effectiveness of this management strategy.