bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical implications of bone scan underuse for patients with high-risk prostate cancer (CaP).
Authors: Falchook Aaron David , Hendrix Laura H. , Chen Ronald C. 
Published: February 2017

124 Background: National practice guidelines recommend bone scans during workup of high-risk CaP patients. Omission of bone scans may lead to aggressive and futile treatments in patients with undiagnosed metastatic disease. We hypothesized that patients who did not vs. did have a bone scan have inferior survival after treatment. Methods: Patients in the Surveillance Epidemiology and End Results (SEER)-Medicare database diagnosed from 2004-07 were included. Prevalence of bone scan use in patients with apparent high-risk CaP (N=19,885) was calculated, without consideration of M-stage which is a downstream result of the scan. Then, we excluded patients with M1 disease and compared prostate cancer specific mortality (PCSM) among 17,450 patients with apparent M0 cancer who received vs. did not receive a staging bone scan. Kaplan-Meier estimates and Cox multivariate models were used. Results: Only 60% of high-risk patients received a bone scan. In patients with apparent M0 disease, 58% of those who did not receive a bone scan received curative-intent treatment – either surgery or radiation (Table). With median follow-up of 3.3 years, PCSM was higher in patients who did not receive a bone scan (4-year 22% vs. 18%, p<.001). When stratified by treatment, a significant PCSM difference was seen among radiation patients (4-year PCSM 19% no bone scan vs. 14% bone scan, p=.006), but not in surgical or no treatment/hormone only patients. On multivariate analysis controlling for age, race, marital status, comorbidity, diagnosis year, regional socioeconomic status, geographic region, and population density, PCSM difference in radiation patients remained significant (hazard ratio 1.36 for no bone scan, p=.04). Conclusions: 40% of high risk CaP patients did not receive recommended bone scan during workup. Patients with apparent non-metastatic CaP but did not receive a staging bone scan often received curative-intent treatments. A worse survival among patients without bone scan suggests a potential overtreatment in patients with undiagnosed metastatic disease. [Table: see text]
Predicting radical prostatectomy outcome: Cell cycle progression (CCP) score compared with primary Gleason grade among men with clinical Gleason less than 7 who are upgraded to Gleason 7.
Authors: Cooperberg Matthew R. , Freedland Stephen J. , Schlomm Thorsten , Reid Julia E. , Stone Steven , Brawer Michael K. 
Published: February 2017

13 Background: Improved prognostic markers for prostate cancer are an important part of addressing the issue of over- and under-treatment in prostate cancer. Gleason score (GS), prostate-specific antigen and clinical stage work well for population risk assessment but lack precision for individual patients. Concern over undergrading on biopsy is felt to be a major barrier to increasing use of active surveillance. Molecular analysis can further refine risk assessment as demonstrated by the cell cycle progression (CCP) score (Prolaris) which has been shown to predict prostate cancer aggressiveness in eight separate cohorts. In these studies, CCP scores typically ranged from −2 to +3 with each one−unit increase in CCP score corresponding to approximately a doubling of the risk of the studied event (recurrence or death from prostate cancer). In the present investigation, we sought to assess how upgrading compared with CCP in predicting failure after radical prostatectomy (RP). Methods: In this study, we examined men from three cohorts (UCSF, Martini Clinic, and Durham VAMC) with clinical GS (cGS) less than 7 who had pathologic GS (pGS) 3+4 or 4+3. The CCP assay was performed using RP specimen from UCSF and biopsy material from the other cohorts. We compared the rates of biochemical recurrence (BCR) as predicted by pGS, CAPRA, or CCP score alone versus CAPRA combined with CCP score using a Cox proportional hazards model stratified by cohort. Results: Among the 230 men with cGS less than 7 and pGS equal to 7 included in this analysis, 207 had pGS 3+4 and 57 had BCR; 23 had pGS 4+3; and eight had BCR. There was no difference in BCR based on GS (p=0.8) or CAPRA (p=0.4). In contrast, CCP score alone and a pre-defined score combining the CCP score and CAPRA were prognostic of BCR (HR=1.82 [95 % CI 1.32-2.52; p<0.001]; HR=1.84 [95 % CI 1.10-3.05; p=0.021] respectively). Conclusions: These data indicate that the risk of BCR is indistinguishable in men with cGS less than 7 who have pGS 3+4 or 4+3. However, the CCP assay does provide stratification of this risk. Tests that can predict BCR on biopsy will aid in initial therapeutic decision making.
The impact of pelvic magnetic resonance imaging on risk stratification in patients with localized prostate cancer.
Authors: Marcus David Mitchell , Rossi Peter John , Nour Sherif , Jani Ashesh B. 
Published: February 2017

130 Background: We aimed to determine the impact of multiparametric magnetic resonance imaging (MRI) of the prostate on established risk stratification criteria in patients with clinically localized adenocarcinoma of the prostate (ACP). Methods: We included patients who had undergone multiparametric prostate MRI at our institution as part of their initial workup for ACP. Traditional risk stratification criteria (prostate specific antigen, clinical T stage, biopsy Gleason score) were recorded, and the initial National Comprehensive Cancer Network (NCCN) risk group was calculated. The NCCN risk group was then recalculated incorporating MRI findings. The impact of MRI findings on changes in risk group classification was evaluated using the Stuart-Maxwell test for marginal homogeneity. Results: Of 71 patients analyzed, 11 (15.5%), 39 (54.9%), and 21 (29.6%) had low, intermediate, and high risk disease, respectively. MRI findings led to risk group upstaging in 12 cases (16.9%). The highest yield was demonstrated in patients with intermediate-risk disease, in whom MRI led to upstaging in 25.6% of patients. The Stuart-Maxwell test demonstrated a significant difference between pre-MRI and post-MRI risk group classifications (p <0.01) for the entire cohort. Pre-MRI and post-MRI risk groups for all patients are shown in the table, with off-diagonal elements representing risk group changes. MRI findings resulted in clearly documented changes in the treatment strategy for 5 patients (7.0%), including addition of androgen deprivation therapy in 2 patients, elimination of definitive therapy in 2 patients determined to have metastatic disease, and elimination of a brachytherapy boost in one patient. Conclusions: In our cohort of patients with clinically localized ACP, MRI findings often led to significant changes in risk stratification and treatment. Our findings support the routine use of MRI in the workup of patients with clinically localized ACP, particularly those with intermediate risk disease . [Table: see text]
Preliminary results of a telomerase-based circulating tumor cell assay in prostate cancer patients undergoing definitive radiotherapy.
Authors: MacArthur Kelly M. , Kao Gary D. , Hahn Stephen M. , Christodouleas John Paul , Bekelman Justin E. , Dorsey Jay Fitzgerald 
Published: February 2017

139 Background: Circulating tumor cell (CTC) analysis provides a minimally invasive tool to serially assess a primary tumor and its response to treatment, which may assist management. We conducted a pilot study among patients with localized prostate cancer to examine the potential effectiveness of a novel telomerase-based CTC assay for tracking the response to definitive radiotherapy (RT). Methods: The assay relies on processing and exposure of peripheral blood samples to an adenoviral vector, utilizing the human telomerase promoter to drive the expression of a fluorescent reporter. Such a system results in high specificity and sensitivity for prostate cancer cell detection since telomerase is elevated in almost all malignancies, but not in normal cells. Peripheral blood samples from patients with localized prostate cancer were obtained up to one month prior to initiating RT (pre-RT), one-half to two-thirds through completion of the RT course (mid-RT), and after completion of RT (post-RT, 3 to 6 months following completion of treatment). Fifty seven subjects were enrolled on this study, with a mean age of 67 (SD 6.7 years). Fifteen had low-risk, 25 had intermediate risk, and 17 had high risk disease at the time of diagnosis. Twenty subjects received androgen suppression. Results: We successfully detected CTCs in the majority of patients undergoing definitive radiotherapy for localized prostate cancer of varying Gleason scores (GS), risk status, and disease stages. The mean CTC counts per ml of blood were: Pre-RT 20.2 (standard error (SE) 8.5), mid-RT 11.0 (SE 2.5), and post-RT 1.0 (SE 0.4). The difference in CTC counts from pre-RT to post-RT was statistically significant (p<0.03). Conclusions: We have successfully detected CTCs in patients undergoing definitive RT for localized prostate cancer with a novel CTC assay. CTC counts appear to decline after definitive radiotherapy. While these promising results may further aid research of CTCs in prostate cancer, the ultimate implications for subsequent patient decisions and management remain to be studied.
The role of IL-23 in regulating metastatic prostate cancer through STAT-3/ROR-gamma signaling.
Authors: Yousif Nasser Ghaly , Alhasani Salam , Slimani H , Doug Jim , Mohammad Bassim I , Machil Suzan , Deb Abdallah Ali , Romalid Niky 
Published: February 2017

142 Background: Interleukin-23 (IL-23) plays an important role in expanding the Th17 cell population and induce signal transducer and activator of transcription 3 (STAT-3) to up-regulates the expression of Retinoic Acid Receptor-Related Orphan Receptor Gamma-T (ROR-gamma). STAT-3 regulates the expression of a variety of genes in response to cellular stimuli, and thus plays a key role in cell growth and apoptosis. Furthermore, recent studies identified a critical role for ROR-gamma in lineage specification of uncommitted CD4+ T helper cells into Th17 cells. The goal of this study is to evaluate prospectively the prognostic importance of circulating IL-23 in patients with metastatic prostate cancer through downstream signaling. Methods: The study involved 140 men diagnosed with stages I to IV prostate cancer and 120 healthy controls. IL-23 serum concentration measure by a quantitative enzyme immunoassay technique associated with clinical-pathological variables. Blocking IL-23 with anti-p19 Ab in mice inoculation with two types of metastatic prostate cancer cell lines (LNCaP and DU-145) to study the pathway of IL-23 in vivo by using western blot and real-time RT-PCR. Results: We found a statistically significant higher systemic IL-23 level in the metastatic group in comparison with non-metastatic group (19.32±5.35 pg/ml vs. 7.25±3.42 pg/ml, p<0.05). Patients with shorter overall survival presented higher IL-23 levels, suggesting a negative prognostic correlation. Furthermore, systemic delivery of blocking Abs directed against IL-23 completely inhibited STAT3/ROR-gamma levels in mice. Conclusions: These results demonstrate that STAT3/ROR-gamma, is a downstream mediator for IL-23–induced prostate metastasis in murine mice. IL-23 may represent an attractive therapeutic target or a biomarker in metastatic prostate cancer by blocking downstream effects. However, further studies are needed in larger samples to better investigate the implications of IL-23 in prostate cancer.
Prevalence of fractures among men with stage IV prostate cancer (S4PC).
Authors: Abdulhalim Abdulla M. , Onukwugha Ebere , Woods Corinne , Qian Yi , Arellano Jorge , Balakumaran Arun , Mullins C. Daniel , Hussain Arif 
Published: February 2017

143 Background: Fractures (fx) are common in men with stage 4 prostate cancer (S4PC), resulting in significant clinical consequences, such as increased pain and decreased quality of life. The aim of this study was to estimate the prevalence of fx among men diagnosed with non-metastatic (M0) or metastatic (M1) S4PC and evaluate risk factors associated with fx. Methods: We estimated the prevalence of fx among men age 66 or older diagnosed with M0 or M1 S4PC using data from the U.S. SEER-Medicare datasets between 2000 to 2007. Men were followed through December 2009 or until they were lost to follow up. Codes indicating “pathologic fracture” or “fracture,” excluding codes suggesting accidents/falls in the 14 days prior to the fx, were used to identify fx. Results: Among 9,826 men with S4PC (M1 = 7301; M0 = 2525), 12.9% experienced a post-diagnosis fx based on the codes used. The prevalence of fx was nearly twice as high in men with M1 versus M0 S4PC (M1 = 14.7%; M0 = 7.5%). The median time from diagnosis of S4PC to first fx was five months for men with M1 S4PC versus 34 months for men with M0 S4PC. Compared to men with no fx, men who experienced fx were more likely to be older (20.3% vs. 17.8%), of white/non-Hispanic race (81.1% vs. 75.3%), have well (cancer grade 1) or moderately (cancer grade 2) differentiated tumors (48.7% vs. 41.7%), have a claim of osteoporosis (2.4% vs. 0.6%) or osteoarthritis (9.3% vs. 6.5%) in the year prior to S4PC diagnosis, and to have taken a bone mineral density (BMD) test (13.5% vs. 8.1%). All differences were significant at p<0.05 level. Overall, 92% of men did not receive BMD testing at any time post diagnosis despite the fact that 67% of the men received ADT. Conclusions: In men with M1 S4PC at diagnosis, the prevalence of fx is higher and the time to fx is substantially shorter than in men with M0 S4PC at diagnosis. Furthermore, most men with S4PC do not receive BMD testing. A significant need remains to monitor bone health and treat fx, particularly among M1 S4PC patients.
Optimal testosterone suppression on medical ADT should strive to suppress free testosterone levels to levels similar to orchiectomy: What is that value?
Authors: Yu Evan Y. , Getzenberg Robert H. , Smith Jordan , Hancock Michael L. , Smith Matthew Raymond , Malkowicz S. Bruce , Sieber Paul , Dalton James T. , Steiner Mitchell S. 
Published: February 2017

144 Background: The goal of medical androgen deprivation therapy (ADT) for advanced prostate cancer is to provide an equivalency to orchiectomy based upon older assays for serum testosterone (T). Literature shows that based on more modern assays, medical ADT does not always provide optimal total T suppression equivalent to orchiectomy. With the understanding that free, or unbound, T is the biologically and clinically relevant component, the therapeutic goal of ADT should be to decrease free T to levels similar to orchiectomy. Free T has not been well studied in a substantial number of orchiectomized men. The purpose of this study was to examine a subpopulation of orchiectomized men in a clinical trial to determine the level of serum-free T in advanced prostate cancer. Methods: Baseline data was utilized from a double blind, randomized, placebo controlled trial (G300203) to determine the capacity of toremifene 80 mg to prevent bone fractures in men on ADT. This study included 1,389 men from 150 sites in the U.S. and Mexico. Baseline characteristics, including whether men were on medical ADT or status post orchiectomy, were available. Free T levels were assayed at baseline by radioimmunoassay (RIA) (Diagnostic Products Corporation) and are reported for men who underwent orchiectomy. Results: A subpopulation of 114 men underwent orchiectomy. Median age was 76 (range 51 to 90). Median serum free T level was 0.92 pg/ml (min. 0.35 pg/ml and max. 33.95 pg/ml) with a mean level of 1.71 pg/ml ± 2.77. Conclusions: This study is believed to be the largest cohort in which free T levels have been reported in men who underwent orchiectomy. In this cohort, median serum free T is approximately 0.9 pg/ml. This value could be considered to be the optimal testosterone suppression of free T with orchiectomy and represents the goal of medical ADT. At the time this study was performed, RIA was considered to be the standard but has since been shown to underestimate free T levels by 20 to 60%. Currently, equilibrium dialysis coupled with LC-MS/MS is the gold standard, but the results from this analysis provide us with increased understanding of the optimal level of free T in treating advanced prostate cancer. Clinical trial information: NCT00129142.
The effects of anticoagulant use in high-risk prostate cancer treated with radiotherapy on overall survival and biochemical control.
Authors: Chun Stephen G. , Jacobs Corbin D , Yan Jingsheng , Xie Xian-Jin , Choe Kevin S , Hannan Raquibul , Pistenmaa David A. , Lotan Yair , Roehrborn Claus G , Kim Dong W. 
Published: February 2017

146 Background: High-risk localized prostate cancer (PC) has suboptimal treatment outcomes due to therapeutic resistance to radiation and hormone therapy. Previous studies suggest that anticoagulant (AC) use may improve treatment outcomes in high-risk PC. We hypothesized that AC therapy confers a freedom from biochemical failure (FFBF) and overall survival (OS) benefit in patients treated with concurrent radiotherapy in patients with high-risk prostate cancer defined as Gleason Score (GS) 8 or higher, Stage T3a or higher, or prostate-specific antigen (PSA) of 20 or more. Methods: Analysis was performed of 74 patients identified who were treated with definitive external beam radiotherapy with National Comprehensive Cancer Network defined high-risk PC from 2005 to 2008 at The University of Texas Southwestern Medical Center. Of these patients, 43 took concurrent AC including aspirin (95.6%), clopidogrel (17.8%), warfarin (20%), and multiple ACs (31.1%). Associations between AC use and FFBF, OS, distant metastasis, and toxicity were explored. A minimum of 5 years of follow-up were available for all patients. Results: For patients taking any AC compared to no AC, there was improved FFBF compared to of 84.4% versus 62.1% (P = 0.0003), and for aspirin the FFBF was 83.7% versus 64% (P = 0.0008). Aspirin was also associated with reduced rates of distant metastasis of 12.2% versus 26.7% in patients who did not take aspirin (P = 0.039). On multivariate analysis, patients taking aspirin with PSA of 20 or more had 5 year OS 95.8% versus 70% (P = 0.031), and GS 9-10 had 5 year OS 88.2% versus 37.5% (P = 0.013). Conclusions: AC use was associated with a FFBF benefit in high-risk PC which translated into an OS benefit in the highest risk PC patients with PSA of 20 or more or GS 9 to 10 who are most likely to experience prostate cancer specific mortality. This hypothesis generating data suggests AC use may represent an opportunity to improve patient outcomes by overcoming therapeutic resistance.
Increasing use of radical prostatectomy for lower-risk prostate cancer in Denmark.
Authors: Roeder M. Andreas , Brasso Klaus , Christensen Ib Jarle , Johansen Jorgen , Langkilde Niels Christian , Hvarness Helle , Jakobsen Henrik , Carlsson Steen , Borre Michael , Iversen Peter 
Published: February 2017

149 Background: Denmark introduced radical prostatectomy (RP) as the last Nordic country in 1995. Since then, a rapid increment in the Danish incidence of prostate cancer (PCa) is indicative of increasing opportunistic prostate-specific antigen (PSA) testing. We hypothesized that an increasing proportion of men undergo RP for lower-risk PCa. Methods: All patients undergoing RP in Denmark between 1995 and 2011 were included. Changes over time in age at surgery, preoperative PSA, clinical T-category, biopsy Gleason score (GS) are described. Tests for statistically significant changes in trends were performed using linear regression and Cochran-Armitage trend test. Results: Median age at surgery increased from 61.4 to 64.8 (p<0.0001) during the 16 year period. Median preoperative PSA declined from 11.5 to 7.9 ng/ml (p<0.0001). Distribution of biopsy GS changed significantly, especially after 2005. Biopsy GS=7 was found in 20.2% of the patients in 2005 compared to 57.1% in 2011. The proportion of T1 disease increased from 32% to 56%. The proportion of patients above age 65 increased from 26.8% to 48.3% in the 16 year period studied. To adjust for grade, PSA, and age migration, we analyzed changes in the proportion of men age over age 65, with PSA less than or equal to 10 ng/ml, biopsy GS≤3+4, and clinical T1 disease over time. In the 16 year period, this proportion increased from 2% to 16% (p<0-001) of the cohort undergoing RP in Denmark. Conclusions: Significant preoperative age, stage, and Gleason grade migration was found in this complete Danish nation-wide cohort of patients undergoing RP during the past 16 years. This has occurred in the absence of any major changes to the national Danish guidelines for diagnosis and treatment of localized PCa. This effect is likely attributed to an increasing use of PSA although national guidelines recommend against PSA screening. Further, new guidelines from the International Society of Urological Pathology have had a major impact on risk classification. According to recently published randomized trials, the risk of overtreatment of localized PCa with RP is an increasing problem in Denmark.
Long-term oncologic outcomes of neoadjuvant chemohormonal therapy followed by radical prostatectomy for patients with clinically localized, high-risk prostate cancer.
Authors: Silberstein Jonathan L , Poon Stephen A , Sjoberg Daniel , Vickers Andrew J. , Bernie Aaron , Konety Badrinath R. , Kelly William Kevin , Eastham James Andrew 
Published: February 2017

153 Background: To determine long-term oncologic outcomes of radical prostatectomy (RP) after neoadjuvant chemo-hormonal therapy for clinically localized, high-risk prostate cancer. Methods: In this phase II multicenter trial of patients with high-risk prostate cancer (prostate-specific antigen greater than 20ng/ml, Gleason greater than or equal to 8, or clinical stage greater than or equal to T3), androgen deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered prior to RP. We report the long-term oncologic outcomes of these patients and compared them to a contemporary cohort who met oncologic inclusion criteria but received RP only. Results: Thirty four patients were enrolled in this study and followed for a median of 13.1 years. Within 10 years most patients experienced biochemical recurrence (BCR-free probability= 22%; 95% CI 10%, 37%). However the probability of disease-specific survival at 10 years was 84% (95% CI 66%, 93%) and overall survival was 78% (95% CI 60%, 89%). The chemohormonal therapy group had higher-risk features than the comparison group (N=123 patients) with an almost doubled risk of calculated preoperative 5-year BCR (69% vs 36%, p<0.0001). After adjusting for these imbalances the CHT group had trends toward improvement in BCR (0.76, 95% CI 0.43, 1.34; p=0.3) and metastasis free survival (0.55, 95% CI 0.24, 1.29; p=.2) although these were not significant. Conclusions: Neoadjuvant chemohormonal therapy followed by RP was associated with lower observed rates of BCR and metastasis compared to a prostatectomy only group; however these results were not significant. Because this treatment strategy has known harms and unproven benefit, this strategy should only be instituted in the setting of a clinical trial.