bluuebunny/crossref_metadata_2025_split huggingface dataset:
CaPSURE update: Examining primary treatment and survival among men with prostate cancer and bony metastatic disease.
Authors: Borno Hala , Cowan Janet E. , Zhao Shoujun , Carroll Peter , Ryan Charles J. 
Published: February 2018

275 Background: New data is emerging to guide primary treatment of patients with metastatic (M+) disease. Among the CHAARTED and LATITUDE cohorts, 27.2% and 5% of patients with M+ disease had prior local therapy, respectively. This study utilizes the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry to examine survival among patients with M+ disease. Methods: CaPSURE is a registry of men diagnosed with prostate cancer. We examined sociodemographics, disease biology, primary therapy, and survival among patients who were diagnosed with cM+ disease or developed metastasis. We performed a multivariate Cox model to evaluate the association between timing of metastasis and prostate cancer specific mortality (PCSM), adjusted for age, primary treatment, and follow-up therapy. Results: Of the 14,753 patients diagnosed with prostate cancer from 1990-2016, 717(4.9%) had M+ disease. 328(2.2%) had cM+ disease and 389(2.6%) progressed to bony metastasis. For all patients with M+ disease, 490(68.3%) were > = 65 yo, 627(87.4%) had Medicare, and 239(33.3%) had an annual income < $30,000 (P < 0.01). PSA at diagnosis was > 20 ng/mL for 355(49.5%) and biopsy Gleason was 4+3 or 8 to 10 for 403(56.2%) (P < 0.01). Among patients with cM+ disease, 49(14.9%) received primary local therapy and 279(85.1%) received primary hormonal therapy. Among patients who progressed to M+ disease, 258(66.3%) received primary local therapy and 131(33.7%) received primary hormonal therapy. The risk of PCSM was worse for patients with M+ disease who received hormonal therapy for primary treatment compared to patients who received combined local and hormonal therapy (HR 1.47 (95% CI 1.15 to 1.88), P < .01). Timing of metastatic disease was not associated with PCSM. Primary treatment with hormonal therapy compared to local therapy was associated with higher risk of PCSM (HR 1.40 (95% CI 1.00-1.97), P = 0.05) for patients diagnosed with Gleason > = 4+3 disease. Conclusions: In our analysis, patients with primary local therapy were examined as a subset of all patients with M+ disease. We observed that patients with cM+ disease have a worse prognosis then patients who develop M+ disease with antecedent primary local therapy.
Statin use and outcomes of patients (pts) with metastatic castration resistant prostate cancer (mCRPC) being treated with abiraterone (Abi).
Authors: Gordon Jacob A , Eigl Bernhard J. , Locke Jennifer A. , Pond Gregory Russell , Chehroudi Cyrus , Khalaf Daniel , Chi Kim N. , Cox Michael E. 
Published: February 2018

277 Background: Epidemiologic studies support an association between statin use and improved prostate cancer specific mortality. Several different biologic mechanisms for such an effect have been proposed, including a potential role in reducing androgen precursor bioavailability. It is hypothesized that statins may therefore improve outcomes specifically in patients treated with the CYP17 inhibitor Abi. Di Lorenzo (2017) recently published an analysis of 187 pts showing a relationship between Abi and improved survival (OS). We report the results of a larger confirmatory analysis in a separate cohort. Methods: Disease outcome and statin use were assessed retrospectively in locally advanced or metastatic CRPC patients receiving Abi in British Columbia, Canada. The Kaplan-Meier method was used to estimate survival times, Cox proportional hazards and logistic regression were used to investigate factors potentially prognostic of overall survival and PSA response respectively. A multivariable model was constructed using factors with limited missing data and known biologic rationale. Impact of statins was then assessed adjusting for factors included in the multivariable model. Results: 301 patients receiving Abi were assessed, of whom 84 (28%) were statin users. Median OS of Abi patients was 11.3 months for non-statin users and 16.2 months for statin users (hazard ratio = 0.79, 95% CI = 0.61-1.03, p = 0.079). Effect of statin use remained borderline after adjusting (n = 279, hazard ratio = 0.78, 95% CI = 0.59-1.04, p = 0.087) for age, prior prostatectomy, radiation, Docetaxel, time from diagnosis, neutrophils-lymphocyte ratio and presence of metastases. Forty-eight percent of statin users and 37% of non-statin users had a PSA response (multivariable odds ratio = 1.59, 95% CI = 0.91-2.78, p = 0.11). Conclusions: Although limited by sample size, our data showed a trend that statins may mildly enhance the anti-tumor effects of Abi in CRPC patients. These results support the findings of Di Lorenzo et al. (2017), and suggest that depletion of de novo cholesterol production may further limit androgen synthesis in concert with CYP17A1 inhibition. Further studies are warranted.
Incidences of visceral metastases from prostate cancer increase after progression of castration-resistant status.
Authors: Iwamoto Hiroaki , Izumi Kouji , Kadono Yoshifumi , Mizokami Atsushi 
Published: February 2018

291 Background: Recent advances in castration-resistant prostate cancer (CRPC) therapy are remarkable, but we often experience a case of visceral metastases caused after CRPC progression and few data regarding the onset of visceral metastases after CRPC are available. In the present study, we retrospectively examined visceral metastases of prostate cancer (PCa) at our hospital. Methods: Between 2000 and 2014, 1038 patients with PCa were treated at our hospital. We collected and retroactively analyzed data from medical charts. Variables of interest included the ratio to cause CRPC and visceral metastases, the relationship between the number of therapeutic agents and visceral metastases, overall survival (OS), etc. Results: Patients were diagnosed with T1-2 (72.1%), T3-4 (24.5%), N1 (10.3%), M1 (11.7%), and M1c (1.8 %). There were 144 (19.8 %) patients with CRPC and 43 (33.1%) patients with visceral metastases after CRPC progression. Patients with CRPC showed significantly longer OS than patients without CRPC (p < 0.01). Of those with CRPC, patients with visceral metastases exhibited significantly shorter OS (p < 0.01). Patients with liver/adrenal gland metastases exhibited the shortest OS of all patients with CRPC (p = 0.02). At diagnosis, the sites of visceral metastases included lung (89.5%), liver (5.3%), and adrenal glands (5.3%). After CRPC progression, new visceral metastases were found in the lung (47.3%), liver (43.6%), and adrenal gland (9.1%). Liver and adrenal gland metastases significantly increased after CRPC progression (p < 0.01). Additionally, the rate of new visceral metastases significantly increased as the number of therapeutic agents increased (p < 0.0001). The median number of therapeutic agents being used was determined at the onset of visceral metastases to the lung (1), liver , and adrenal grand (5) (p < 0.001). Conclusions: Our findings confirmed that visceral metastases, especially liver and adrenal gland metastases, confer the worst survival. These metastases significantly increased as patients underwent powerful androgen deprivation therapy . Future prognostic improvements are expected through continued development of therapies for visceral metastases.
NanoVelcro CTC purification systems for expressional analysis of circulating tumor cells from prostate cancer patients.
Authors: Jan Yu Jen , Chen Jie-Fu , You Sungyong , Yao Nu , Cheng Shirley , Freeman Michael , Tseng Hsian-Rong , Posadas Edwin M. 
Published: February 2018

295 Background: Circulating tumor cells (CTCs) are blood borne tumor cells shed from all present disease sites, including primary and metastatic tumors. Researchers have been exploring the use of CTCs to identify important transcriptomic features such as androgen receptor splicing variants in prostate cancer (PCa). Newer transcriptomic profiles such as the prostate cancer classification system (PCS) have been developed that may be useful clinically. Over the past decade, we have been developing the NanoVelcro CTC purification system which includes different stimuli-responsive strategies to capture and release viable CTCs with high efficiency and preserve intact RNA. The purified CTCs can then be subjected to transcriptomic analysis such as qPCR, ddPCR and NanoString’s nCounter system. In this study, we benchmarked the efficiency of these platforms for purification of CTCs from blood specimens and the feasibility for detection of PCa-related RNA signatures from purified CTCs. Methods: NanoVelcro CTC purification system is combined with qPCR and ddPCR platform to detect PCa-specific RNA targets in purified CTCs from patients' blood samples. We also developed a modified PCS panel of 30 genes adapted to the nCounter platform and tested purified CTCs from PCa patient blood samples and performed differential expression analysis for PCa disease profiling. Results: PCa-related RNA signals were detected in 16/17 CTC(+) PCa patients, including 3 of 4 non-metastatic patients. We also tested the gene expressions of the modified PCS panel using 48 patient blood samples. Upon performing clustering of samples based on the RNA signatures, we found the differential expression of CTC-target genes grouped patients in a manner which strongly related to drug response and clinical status. Conclusions: We have shown the capability of purifying CTCs with high efficiency using our system, while retaining cell viability and molecular integrity, allowing for detection of PCa-specific RNA signatures from CTCs. Our non-invasive, blood-based assay will be useful for detecting and continuous monitoring molecular alterations related to disease evolvement, addressing an unmet need for PCa clinical care.
PROSPER: A phase 3, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC).
Authors: Hussain Maha , Fizazi Karim , Saad Fred , Rathenborg Per , Shore Neal D. , Demirhan Eren , Modelska Katharina , Phung De , Krivoshik Andrew , Sternberg Cora N. 
Published: February 2018

3 Background: Men with M0 CRPC and rapidly rising prostate-specific antigen (PSA) are at high risk of developing metastatic (M1) CRPC. ENZA improves overall survival (OS) and radiographic progression-free survival in men with M1 CRPC. We hypothesized that ENZA will improve metastasis-free survival (MFS) in men with M0 CRPC. Methods: Eligible men with M0 CRPC, PSA doubling time ≤ 10 mo and PSA ≥ 2 ng/mL at screening continued androgen deprivation therapy (ADT) and were randomized 2:1 to ENZA 160 mg or PBO. The primary endpoint was MFS. Secondary endpoints included time to PSA progression, time to first use of new antineoplastic therapy, OS and safety. Results: In 1401 men, ENZA significantly prolonged median MFS (36.6 mo vs 14.7 mo [ P < .0001]), time to first use of new antineoplastic therapy (39.6 mo vs 17.7 mo [ P < .0001]) and time to PSA progression (37.2 mo vs 3.9 mo [ P < .0001]) compared to PBO (Table). In the first interim analysis of OS there was a trend in favor of ENZA (hazard ratio [HR] = 0.80; P = .1519). Median duration of treatment was 18.4 mo vs 11.1 mo for ENZA vs PBO. Adverse events (AEs) were higher with ENZA vs PBO (any grade: 87% vs 77%; grade ≥ 3: 31% vs 23%; serious: 24% vs 18%); 10% with ENZA discontinued treatment due to AE vs 8% with PBO. Conclusions: In men with M0 CRPC and rapidly rising PSA, ENZA treatment resulted in a clinically meaningful and statistically significant 71% reduction in the risk of developing M1 CRPC. AEs were consistent with the established safety profile of ENZA. Clinical trial information: NCT02003924. [Table: see text]
Adverse effect of docetaxel versus surveillance after radical prostatectomy for high risk prostate cancer: Post-hoc analysis of the prospective randomized, open-label phase III SPCG 12 trial.
Authors: Ahlgren Goran M. , Borre Michael , Sengelov Lisa , Tammela Teuvo L. J. , Kellokumpu-Lehtinen Pirkko , Sverrisdottir Asgerdur , Iversen Jon Reidar ,   Scandinavian Prostate Cancer GROUP
Published: February 2018

30 Background: Adjuvant chemotherapy is standard treatment for other solid tumours, but so far has not proven effective in prostate cancer. Methods: Open-label, randomised multinational phase III trial. Enrolment 459 patients after prostatectomy. Inclusion criteria high risk (pT2 margin positive or pT3a Gleason score (GS) ≥4+3, pT3b or lymph node positive disease ≥GS 3+4). Patients assigned (1:1) to either six cycles of adjuvant docetaxel 75mg/m2 every three weeks without daily prednisone (ArmA) or surveillance (Arm B) until endpoint was reached. Primary endpoint was PSA progression ≥0.5ng/ml. Results: Median time to progression, death or last follow up was 56.8 months. Primary endpoint was reached in 190/459 patients (41.4%), 103 of 230 (44.8%) patients in Arm A and 87 (38.0%) of 229 in Arm B. In Kaplan-Myer analysis, there was evidence of non-proportional hazards over time. When 76 patients with PSA > 0.2 after surgery were excluded from the analysis, the outcome showed proportional hazards and favoured surveillance in the KM-analysis (p = 0.02). The significant favour of surveillance remained in a Cox multivariate analysis including Gleason score, pT-stage, surgical margins and lymph node status (p = 0.03). Limitations were that not all patients received docetaxel by protocol, some patients received radiation treatment before end-point and lack of stratification for PSA after surgery. Conclusions: Adjuvant docetaxel without hormonal therapy or continuous corticosteroids may have an adverse effect on biochemical progression in patients with low or undetectable levels of PSA after surgery. Clinical trial information: NCT00376792.
Clinical utility of Foundation One tissue molecular profiling in men with metastatic prostate cancer.
Authors: Zhu Jason , Tucker Matthew D , Healy Patrick , Humeniuk Michael Sandon , Jarvis Casey , George Daniel J. , Armstrong Andrew J. 
Published: February 2018

318 Background: In the era of precision medicine, significant effort has been placed on identifying clinically actionable molecular targets to aid in the treatment of metastatic prostate cancer (mPC). Recent data supports homologous repair and mismatch repair deficiencies to guide the use of PARP inhibitors/platinum chemotherapy or pembrolizumab, respectively. We analyzed the clinical utility of Foundation One (FO) somatic genomic profiling in men with mPC. Methods: We performed a retrospective review of men with mPC in the Duke Cancer Center who received FO testing 01/2010 - 04/2017. We asked whether FO testing identified actionable genomic lesions that led to a change in clinical practice, and if men benefited from this novel genomic matched approach to treatment. Results: We identified 77 men with FO tests. Of these, 77% (59/77) had adequate tissue for FO testing. 76% had mCRPC, 42% had > 3 prior systemic therapies (enzalutamide 51%, docetaxel 39%, abiraterone 41%, sip-T 34%, radium-223 22%). The most common FO genomic alterations were: TP53 deletion/mutation (37%), TMPRSS2-ERG fusion (32%), and PTEN loss (31%). FO revealed 207 genomic alterations, classified into actionable (6), potentially actionable (44), non-actionable (126), and non-informative (31). Of the 6 patients with actionable mutations (BRCA2, ATM, PALB mutation/loss), 4 (67%) received matched olaparib therapy and 3 had PSA or prolonged radiographic stabilization, with durations of therapy of 3-19 months. Of 28 men with potentially actionable genomic findings, 3 (11%) received targeted therapies, including olaparib for a CDK12 mutation, and pembrolizumab for a PMS2 mutation and for a PD-L2 genomic gain. No responses to pembro were observed; the man with a CDK12 mutation responded to olaparib for 8 months. Overall, 42% (25/59) of evaluable men did not have a targetable mutation; 4/77 (5%) had clinical benefits from testing. Conclusions: A small but significant minority (~5%) of men with mPC appear to benefit from FO somatic tumor profiling, particularly those with homologous repair deficiencies. Larger prospective studies are needed with clinical outcomes in order to further understand the clinical utility of routine FO testing in this setting.
The role of reference pathology to assess MRI-TRUS fusion prostate biopsies in a tertiary referral center.
Authors: Kohl Tobias , von Brandenstein Melanie , Kuru Timur H. , Hansen Nienke , Persigehl Thorsten , Porres-Knoblauch Daniel , Pfister David , Hartmann Arndt , Heidenreich Axel 
Published: February 2018

32 Background: Risk stratification for patients diagnosed with prostate cancer (PCa) through MR-TRUS fusion biopsy still relies on Gleason (GL) grading of the biopsy specimens. GL grading of the same sample can differ between pathologists. In our tertiary high-volume center GL grading of the biopsy specimens is crucial for further therapy planning. Methods: Reference pathology of 42 patients after transperineal MR-TURS fusion plus saturation biopsy was assessed by one specialized genitourinary pathologist. GL grading of the original pathology and the reference pathology for the saturation and targeted biopsy cores were compared. Risk groups for this study were set as GL 6 for low, GL 7a and GL 7b for intermediate and GL 8, GL 9 and GL 10 for high-risk. Results: In 42 patients 49 lesions were identified by mpMRI (PI-RADS 3-5) in which 150 biopsy cores were taken. In addition, 709 cores were taken as saturation biopsies. The highest GL grading per patient differed in 18 (43 %) of the cases. In 16 cases, there was a difference within the targeted biopsies but only in 8 cases there was a difference in the saturation biopsies. In 6 cases both saturation and fusion biopsies were different. Taking risk stratification into account there was a misclassification with low- and intermediate risk in 9 (21 %) cases, an intermediate- and high risk in 2 cases and a misclassification within the same risk group in 6 (14 %) cases. In 16 of the 18 differences there was an upgrading of the Gleason score by the reference pathologist whereas only in 2 cases there was a downgrading. Conclusions: The data shows that in times of mpMRIs and transperineal MRI-TRUS fusion biopsies it still is the GL score graded by the pathologist who accounts for many potential therapy plan mistakes. In this study 21 % of the patients were misclassified as GL 6 while reference pathology graded for GL 7a or GL 7b. The demonstrated data suggests that there should be a reference pathology at least for every GL 6 cancer and that the quality of GL grading should be monitored. Also this data again addresses the need for a better risk stratification irrespective of the GL score that can be done in a more objective way with less potential for misclassification.
Patterns of prostate cancer management across Canadian prostate cancer treatment specialists.
Authors: Shayegan Bobby , So Alan I. , Malone Shawn , Hotte Sebastien J. , Finelli Antonio , Canil Christina M. , Hew Huong , Park-Wyllie Laura , Chi Kim N. , Saad Fred 
Published: February 2018

321 Background: The Canadian GU Research Consortium (GURC) was recently established to bring comprehensive prostate cancer centres together to collaborate on research, education, and adoption of best practices. As an initial step to inform the work of the GURC, an electronic questionnaire was designed to assess management of advanced prostate cancer care in Canada and better understand patterns of care. Methods: A 59-item online questionnaire was developed by a multidisciplinary scientific committee to measure physician practices, patterns of care, treatment sequencing, and management of mCRPC. After pre-testing, the online questionnaire was sent to 93 urologists, uro-oncologists, medical oncologists, radiation oncologists, and general practitioner oncologists who are actively involved in the treatment of prostate cancer. Results: A total of 49 (53%) respondents completed the questionnaire between April 17, 2017 to May 17, 2017. Although all respondents indicated a role in initiating life-prolonging oral therapy for mCRPC and monitoring treatment and side effects, chemotherapy initiation was mainly a medical oncologist role compared to other specialties (p < 0.05, chi-square). Symptom management such as palliative care and end-of-life care were provided mainly by radiation oncologists (100%) and medical oncologists (81%) compared to urologists (33%) and uro-oncologists (50%), p < 0.05, chi-square). Patient mix varied across the disciplines. Urologist practices were composed primarily of non-metastatic prostate cancer patients (73%), as were radiation oncologist practices (77%), while uro-oncologist practices included both non-metastatic (58%) and metastatic (40%) patients. Medical oncologists practices were mainly (91%) metastatic patients. Referral patterns also varied by discipline. Conclusions: In Canada, prostate cancer treatment involves multiple disciplines providing a range of care at different points across the treatment continuum. We plan to do further research to better understand variation in practice and improve multidisciplinary coordination for patients with advanced prostate cancer.
Impact of new agents (NAs) on survival of metastatic castration-resistant prostate cancer (mCRPC) patients (pts): A single-Institution retrospective analysis.
Authors: Caffo Orazio , Kinspergher Stefania , Maines Francesca , Macrini Sveva , Veccia Antonello 
Published: February 2018

323 Background: Until few years ago, docetaxel (DOC) was the only agent able to significantly prolong overall survival (OS) of mCRPC pts: at the time of disease progression, other drugs without any survival benefit (mitoxantrone, vinorelbine, cyclophosphamide) or DOC re-challenge (DOC-re) in selected cases could be proposed. In the last years several NAs [abiraterone (AA), cabazitaxel (CAB), enzalutamide (ENZ), radium 223(RA223)] have been introduced in the clinical practice since they demonstrated an OS improvement. Moreover, a hypothetical cumulative OS advantage could derive from their sequential use. The present report is aimed to assess the impact on NAs on mCRPC pts’ OS in the daily clinical practice. Methods: We retrospectively evaluated all mCRPC pts treated in our Institution from 02/2002 to 06/2015 and recorded their medical history, anticancer treatments and survival outcomes. For the purpose of the present study, we consider pts who never received at least one NA (group A) and pts who received at least one NA (group B). To avoid selection bias due to a fast performance status worsening preventing further treatments, we consider only pts who received at least one agent after first line progression. For the OS analysis we considered the start of mCRPC first line. Results: We selected a consecutive series of 212 pts: 80 not treated (Group A) and 132 treated (Group B) with NAs. In the Group A 50 pts received first-line DOC followed by DOC-re only, while the remaining 30 pts received also agents different than DOC. In the group B 78, 35, and 19 pts received one, two, and three NAs, respectively. Group A pts were significantly younger and had higher baseline levels of PSA and lactate dehydrogenase (LDH). The OS was significantly longer in Group B than in Group A (36.0 vs 19.6 mos, p < 0.0001). The impact of NAs use on OS was confirmed at the multivariate analysis comprising the other factors which significantly affected OS (hemoglobin, LDH, alkaline phosphatase, pain, performance status, PSA). Conclusions: Although the limitation due to its retrospective nature, our analysis confirms that the introduction of NAs in the daily clinical practice led to an OS improvement.