bluuebunny/crossref_metadata_2025_split huggingface dataset:
Androgen deprivation therapy (ADT) use in Medicare beneficiaries with nonmetastatic (M0) prostate cancer (PC) in the United States.
Authors: Arneson Thomas J. , Cetin Karynsa , Stryker Scott , Liede Alexander , Murray Tom , Li Shuling , Blaes Anne Hudson 
Published: March 2020

e15169 Background: ADT is well-established for metastatic PC but is also used in men with less advanced PC. Patterns of ADT use in the M0 PC setting have not been well-described. Methods: Medicare claims in 2005 for men aged ≥66 years (yrs) were assessed for use of gonadotropin-releasing hormone agonists or bilateral orchiectomy. The cohort was limited to men who, during the 15 months (mos) prior to their first 2005 ADT claim, had continuous Parts A + B coverage, a diagnosis code for PC, no claims for metastases (except lymph nodes), and no claims for ADT. Follow-up (f/u) was from ADT initiation to 3 yrs, death, or change in Medicare coverage. Regimen duration was defined by combining claim service count and dosage with FDA label dosing. Because ADT has biologic activity beyond the recommended regimen duration, active dose time was calculated by adding 3 and 6 mos to claims for regimens <6 mos and ≥6 mos, respectively. Interruption was defined as ≥180 days from end of active dose time to next ADT claim. Results: We identified 3246 M0 PC patients aged ≥66 yrs who initiated ADT in 2005 but describe results in the 2161 who had 3 full yrs of f/u (data for the entire cohort were similar). Nearly 70% received only 1 type of ADT agent during f/u (25% had 2 types, 5% had 3 or 4 types), and 73% started on a 3-or 4-month regimen. The distribution of patients by first ADT type (and by type received at any point) was: leuprolide injection: 54% (67%); goserelin implant: 36% (43%); triptorelin injection: 6% (19%); leuprolide implant: 2% (4%); orchiectomy: <1% (1%); and histrelin implant: 0% (3%). Use of >1 type of ADT agent was more common in men who began with goserelin (45%) or triptorelin (53%) versus leuprolide (≤24%). At three years after ADT initiation, 36% received ADT for the entire 36-month period, 15% for 24-35 mos, 17% for 12-23 mos, and 32% for <12 mos. Interruption in active therapy occurred in only 13%. Conclusions: Most elderly men with M0 PC initiating ADT in 2005 started on a 3- or 4-month leuprolide or goserelin regimen. Though these agents remained the most commonly used throughout f/u, switching was common (30% used >1 type during f/u). ADT was continued for at least 2 yrs in nearly half and extended to 3 yrs in over one-third of the cohort.
Lifetime cost-effectiveness of denosumab versus zoledronic for prevention of skeletal-related events (SREs) in patients (pts) with castrate-resistant prostate cancer (CRPC) and bone metastases (BM): United States managed care perspective.
Authors: Rader Michael E. , Danese Mark , Cong Ze , Halperin Marc , Qian Yi , Goessl Carsten Dietrich , Chung Karen 
Published: March 2020

e15172 Background: Denosumab (Dmab) is superior to zoledronic acid (ZA) for prevention of SREs in pts with CRPC and BM. As Dmab is not cleared renally, it can be used in pts regardless of renal status or concomitant use of nephrotoxic drugs. Previous economic analyses were limited as the analyses were based on short duration-trial based perspectives and/or did not account for disutility associated with IV vs SC administration of ZA and Dmab, respectively. These analyses assess the lifetime cost-effectiveness of Dmab vs ZA in pts with CRPC and BM from a US managed care perspective, with extensive scenario and sensitivity analyses. Methods: A lifetime Markov model was developed, with efficacy of Dmab vs ZA in SRE prevention from a head-to-head phase 3 trial; clinical practice SRE rate in ZA pts from a large commercial claims database analysis; SRE and mode of administration (IV vs SC) quality adjusted life-year (QALY) decrements estimated using the time trade-off method; and SRE costs estimated from a nationally representative commercial claims database. Drug, drug administration, and renal monitoring costs were also included. Costs and QALYs were discounted at 3% per year. Scenario analyses (including adverse events, drug discontinuation, etc), one-way and multivariate probabilistic sensitivity analyses were conducted. Results: Dmab reduced the number of SREs and increased pts’ QALY vs ZA. In the base case and the scenario analyses, cost per QALY gained was below $50,000, which is commonly considered good value. Cost per SRE avoided was below $9,000. In one-way sensitivity analyses, drug costs and SRE rate were the most influential variables. Probabilistic sensitivity analyses showed the probabilities of Dmab being cost-effective vs ZA were 0.83, 0.94, and 0.98 with willingness-to-pay of $100,000, $150,000 and $200,000 per QALY gained, respectively. Conclusions: Dmab is a cost-effective treatment option in preventing SREs in pts with CRPC and BM compared with ZA from a US managed care perspective. The overall value of Denosumab is based on superior efficacy and more efficient administration.
3T MRI of the prostate correlation to 3D reconstruction of transperineal mapping biopsies.
Authors: Rove Kyle O. , Pshak Thomas J. , Patel Nayana , O'Donnell Colin , Crawford E. David 
Published: March 2020

e15176 Background: MRI is new tool in the diagnosis and surveillance of localized prostate cancer. Studies have examined the sensitivity and specificity of MRI for detecting and localizing prostate cancer as compared to radical prostatectomy specimens. We have previously demonstrated excellent correlation between 3-dimensional transperineal mapping biopsies (3DMB) to radical prostatectomy specimens. We hypothesize that MRI does not perform as well detecting smaller lesions of the prostate as larger ones. In this study, we retrospectively compare the correlation of 3DMB to 3T MRI-positive lesions. Methods: Between 2010 and 2011, 34 men with histologically-proven prostate cancer underwent 3T endorectal coil MRI and subsequent template-guided (5-mm grid) 3DMB. Three-dimensional computer models of the mapping biopsies were created using Proview software to identify clusters of positive biopsies likely belonging to a single lesion. MRIs were read by two trained radiologists blinded to 3DMB results. Disagreement between radiologists was settled by consensus. MRI and 3DMB were then compared in a retrospective fashion. Results: Median age and PSA were 65 years (49-76) and 4.3 ng/mL (0.7-15.0). Median prostate volume was 40 cm3 (21-105 cm3). Median total biopsy cores on 3DMB was 60 (26-151), and mean positive cores was 3 (0-13). 3D reconstruction of patient biopsy sets resulted in 58 distinct foci of cancer. MRI identified 64 individual lesions suspicious for cancer. Of these, 66% (n=42) could be correlated to a positive area on 3DMB consisting of one or more positive biopsies, and 34% (n=22) corresponded to negative regions on 3DMB. When two or more biopsies represented a positive lesion on 3DMB, the positive-predictive value of MRI was 100% (n=24). Conversely, only 72% (n=42) of positive 3DMB areas could be correlated to a lesion on MRI, and 28% (n=16) were not seen on MRI.. Conclusions: MRI has vast potential as a less-invasive method in the detection and surveillance of prostate cancer. While MRI does appear to have excellent positive predictive value, the number of false negatives and relevance to clinically-significant lesions require further illumination.
Independent confirmation of the strong early predictive value of modeled PSA clearance in prostate cancer patients treated by radical prostatectomy: Results of the prospective PSAMODEL study.
Authors: Maillet Denis , Ruffion Alain , Perrin Paul , Wilbaux Melanie , Henin Emilie , Freyer Gilles , Tod Michel , You Benoit 
Published: March 2020

e15182 Background: Early predictors of relapse after radical prostatectomy are needed. We previously showed that mathematical modeling of PSA kinetics provides a parameter, apparent PSA clearance (CLPSA), which may be a significant early predictor of biochemical relapse [1] (You et al; Prostate 2009;69:1325). Validation of these outcomes in an independent prospective study was warranted. Methods: As required by the initial study, four PSA values were prospectively measured during the first 50 days following radical prostatectomy in 119 patients with localized prostate cancer at our center. PSA values were centrally measured. The bi-compartment model previously reported in 2009 [1] was used to calculate patient CLPSA with NONMEM program. The predicted risk of biochemical relapse based on CLPSA cut-off previously defined (threshold at 0.048 [1]) was assessed using survival univariate and multivariate analyses. The primary endpoint was 3-year biochemical relapse free survival (3 y-bRFS). Results: The data from 119 patients treated with radical prostatectomy were analyzed. Among them 13 experienced a relapse after median 6.5 months. Despite large inter-individual variability, individual PSA decline profiles of patients were well fitted by the model. CLPSA categorized by the same cut-off previously described [1] was a significant predictor of 3 y-bRFS using log-rank test (97% vs 66%, p=0.009). Moreover it had independent significant predictive value when adjusted on other prognostic factors (D’Amico score) using multivariate Cox model (p<0.05). Conclusions: This prospective PSAMODEL studyconfirms modeled CLPSA calculated during the first 50 days after radical prostactectomy is a strong independent reproducible early predictor of biochemical relapse. It may easily be calculated using 4 PSA values after surgery. The potential role of this factor in adjuvant treatment adjustment may be studied. [1] You et al; Prostate 2009;69:1325
Cost-utility of proton therapy in the treatment of localized prostate cancer.
Authors: Goyal Ravi K. , Meyer Anne-Marie , Sheets Nathan Christopher , Federspiel Jerome J , Carpenter William Ruffin , Chen Ronald C. , Biddle Andrea K 
Published: March 2020

e15184 Background: Proton therapy (PT) has received much public attention due to its higher costs and lack of evidence of clinical benefit compared to intensity modulated radiation therapy (IMRT) for prostate cancer treatment. In this economic study, we performed a threshold analysis to assess the reduction in toxicity that PT would need to achieve compared with IMRT to be considered cost-effective for the treatment of localized prostate cancer. Methods: SEER-Medicare data was used to identify a cohort, aged 66 years or older, receiving IMRT as definitive radiation therapy (n=4,540). We assumed equal disease control efficacy between IMRT and PT and simulated toxicity outcomes and costs using an incidence-based Markov model. The relative risk of composite toxicity, comparing PT to IMRT, was the efficacy parameter studied. Rates of therapy-induced toxicity associated with IMRT were obtained from SEER-Medicare data. Utility values to calculate quality-adjusted life-years (QALY) and costs (in 2011 US dollars) were obtained from the literature and claims data, respectively. Deterministic threshold analysis using a payer perspective and analytic horizon of 4 years post radiation was performed to determine the relative risk thresholds that would result in incremental cost-effectiveness ratios (ICER) of $50,000 and $100,000/QALY for PT versus IMRT. One-way sensitivity analyses were performed with the lowest and highest treatment costs of PT and IMRT. Results: ComparingPT against IMRT, the threshold values for the relative risk of composite toxicity were 0.318 and 0.588 at cost-effectiveness levels of $50,000/QALY and $100,000/QALY, respectively. Sensitivity analyses showed that the relative risk needed to achieve an ICER of 100,000/QALY ranged from 0.79 and 0.40 for the low and high cost estimates of PT, and from 0.47 to 0.72, for the low and high cost estimates of IMRT. Conclusions: Assuming equal disease control, PT would need to result in a 41% reduction in composite toxicity to be considered cost-effective in the treatment of Medicare beneficiaries with localized prostate cancer at a cost-effectiveness threshold of $100,000/QALY.
Enhancing decision making for treatment options and active surveillance in prostate cancer.
Authors: Gillespie Theresa Wicklin , Rowell Jessica Lauren , Echt Katharina V , Petros John , Lipscomb Joseph , Britan Laura , Herrel Lindsey Allison , Goodman Michael 
Published: March 2020

e15187 Background: Prostate cancer (PCa), the most common malignancy among U.S. males, ranks second in tumor-specific mortality. African-Americans (AA) experience the highest rates of PCa mortality of any group. Many screen-detected PCa represent low-risk disease, and active surveillance (AS) may be a viable option in those cases; however, few men pursue AS. In December 2011, the NIH convened a State-of-the-Science Conference on the role of AS and issued a Draft Statement, highlighting knowledge gaps in treatment decision-making (DM) about AS. The purpose of this study was to determine strategies to enhance DM by men and their significant others (SO) about AS and other PCa therapies. Methods: This mixed methods design study (N=402, enrolled 2010-2011) investigated DM by men (N=204; 68% AA) with normal screening PSA and their SO (N=181; 65% AA) from 5 sites nationwide-51% from rural areas. Each site hosted 6 male and 6 SO focus groups. Data reported here include participant ranking of preferred source(s) for information about PCa therapies, including AS, and desired amount of treatment DM guidance. Results are from quantitative questionnaires analyzed using Fisher’s exact test, accompanied by two-sided p values, and qualitative data analysis utilizing Nvivo8. Results: A greater proportion of participants who were AA (62% vs 36%, p<0.0001), those with lower health literacy (60% vs 47%, p=0.0144), and those self-identifying as having lower income levels (55% vs 43%, p=0.0372) preferred the primary care physician (PCP) vs. specialists or other health care providers as the main resource for DM related to AS and PCa. Qualitatively, PCPs were compared to “quarterbacks” who can solicit and coordinate information from the “whole team”. Over 90% of respondents overall indicated they would prefer major DM guidance (4/5 on scale of 1 to 5) from providers. Acceptance of AS as a treatment strategy was accompanied by themes of worry, insufficient provider-specific information, uncertainty, and need for care coordination. Conclusions: Men and their SO have important needs and preferences related to PCa DM in general, but AS in particular. Critical to better informed DM is more effective communication with providers, coordinated by an engaged PCP.
Cost-effectiveness of denosumab (D) versus zoledronic acid (Z) for skeletal-related event (SRE) reduction in bone-metastatic prostate cancer (mPC) in the United Kingdom.
Authors: Botteman Marc , Carter John A. , Fishman Peter , Chandiwana David , Bains Manjinder , Snedecor Sonya J. 
Published: March 2020

e15189 Background: D reduced SREs vs Z in a phase III trial, but no significant differences in overall survival, disease progression, or serious adverse events were reported. The cost-effectiveness of D vs Z in mPC was assessed from a UK payer perspective. Methods: A literature-based Markov model estimated quality-adjusted life-years (QALYs), number and costs of SREs, and drug/administration costs for mPC pts receiving D or Z for 27 mo (trial timeframe) and 60 mo (extended lifetime analysis). Current list prices/injection (£309.86 for D; £174.14 for Z) were used in the base case. As the model’s analytical horizon starts June 2012 and extends beyond generic Z availability in May 2013, a generic Z price (53% < list price, per data for other now-generic bisphosphonates) was used beyond May 2013 in scenario analysis. In other analyses, discounted prices (–30%) were used for both D and Z to assess the effect of price reductions on cost/QALY. Clinical inputs were selected to reproduce trial outcomes. QALYs were estimated by assigning utility weights to time spent in health states (no SRE; SRE; post-SRE; death). SRE costs were £250 to ≥ £6,000/event. Results: Although D may result in fewer SREs, higher QALYs, and lower SRE-related costs (Table), higher acquisition cost of D results in substantially higher costs and may be cost-ineffective in every pricing scenario. Similar results were found for the 27-mo analysis. Conclusions: The incremental cost/QALY gained with D vs Z ranged from £50,000 to £215,000 (> traditional £30,000 threshold), thus raising important questions about D’s value in mPC. [Table: see text]
Risk of adverse cardiovascular events (CVE) and incident diabetes mellitus (DM) in patients (pts) with prostate cancer (PC) treated with androgen deprivation therapy (ADT): A meta-analysis of adjusted observational results.
Authors: D'Ambrosio Lorenzo , Brusa Federica , D'Ascenzo Fabrizio , Cavallero Erica , Biondi-Zoccai Giuseppe , Boccone Paola , Bironzo Paolo , Levin Glenn N , Eckel Robert H , Milani Richard V , Sagalowsky Arthur I. , Gasparini Mauro , Grignani Giovanni , Gaita Fiorenzo , Ciuffreda Libero , Aglietta Massimo 
Published: March 2020

e15192 Background: ADT is a mainstay treatment in pts with PC and is supposedly associated to an unfavorable metabolic and cardiovascular profile. Recently, a meta-analysis of randomized controlled trials (RCT) found no association between ADT and increased risk of CVE (JAMA 2011). However, no conclusive data were available about ADT association with metabolic changes and adverse CVE or DM because of pts selection in RCT. Therefore, we performed a meta-analysis of adjusted observational results in order to look for DM and CVE onset in an ADT unselected population. Methods: Medline, Cochrane Library and Biomed Central were searched for articles addressing adverse events related to ADT in patients with PC. Selection criteria were: not RCT, pts assigned to ADT or not, adjusted risk of CVE and DM according to ADT. Exclusion criteria were: duplicate publication, comparison of two different strategies of ADT (different drugs or duration). Cardiovascular death was the primary endpoint; non-fatal myocardial infarction (MI), stroke/transient ischemic attack (TIA) and new DM onset were secondary endpoints. Random effects model with generic inverse variance weighting was used to estimate adjusted risks as odds ratios (OR) with 99% confidence interval (CI). Results: We selected 12/2100 screened studies. We included 208643 pts of which 102177 received ADT. At a follow up of 5 years (4-7.5), ADT did not result as an independent risk factor for cardiovascular death (OR= 1.04; 99% CI= 0.94-1.14). No increased risk of MI (OR= 1.13; CI= 0.86-1.48) or of stroke/TIA (OR= 1.11; CI= 0.78-1.57) were detected. Incident DM was more frequent among ADT pts (OR= 1.32; CI= 1.14-1-53). Even in 7205 pts with previous CVE (2450 received ADT), ADT was not associated with an increased risk of overall death (OR= 1.23; CI= 0.87-1.75). Meta-regression analysis showed no significant interactions between duration of ADT and cardiovascular death or incident DM. Conclusions: In non-selected pts,ADT appears to increase the risk of incident DM, but not of CVE or stroke/TIA. Moreover, overall mortality is not increased in pts with a history of CVE.
Patterns of second-line chemotherapy for metastatic prostate cancer in the United States.
Authors: Wang Hongwei , Liao Laura , Obi-Tabot Eliot , Sands Robert , Rose Mathieu , Zhang Quanwu 
Published: March 2020

e15193 Background: Patients with prostate cancer progressing from first-line (1L) docetaxel have limited approved treatment options available. Study is to evaluate patterns of second-line (2L) chemotherapy in a US managed care between 2004 and 2010. Methods: Patients with metastatic prostate cancer (mPC) and treated with docetaxel as 1L chemotherapy after July 1, 2004 were ascertained from the OptumInsight database. We evaluated type and timing of chemotherapy and relationships between patient characteristics, physician specialty, healthcare costs and geographic region, 6 months prior to 1L docetaxel and choice of 2L chemotherapy. Results: Patients (N=1,173) were on average 71 yrs old at onset of 1L docetaxel. During a mean follow-up period of 18 months, 38% of patients received 2L treatment. Out of the patients received 2L therapy, 32% received mitoxantrone (MITO), 24% with docetaxel rechallenge (RECH), 14% carboplatin (CARB), and 12% paclitaxel (PAC), plus 11% on Combo therapy. Examination of the 2L treatment groups showed that during the 6 months prior to 1L docetaxel, the RECH group (n=101) was older (73yrs), had fewer hospital admissions (12%), lower comorbidity burden [Charlson Comorbidity Index (CCI)=7.4], lower total healthcare costs ($10,083), and 78% seeing an oncologist; relative to MITO group (n=143) with 70 yrs, 16% hospital admissions, CCI of 7.5, total healthcare costs of $12,074, and 80% seeing an oncologist. The combo group (n=52) was 66 years old, with 19% hospital admissions, CCI of 8, total healthcare costs of $20,505, and 92% seeing an oncologist. Median time to MITO from the start of 1L docetaxel was 184 days, 309 days to RECH and 223 days to Combo therapy. Midwest (36%) and West (37%) were more frequently using MITO than Northeast (26%) and South (31%), while RECH was more frequently used in Northeast. Conclusions: Patients with mPC in US were most frequently treated with MITO or RECH as 2L chemotherapy after 1L docetaxel. MITO was also given sooner than RECH, hence a valid comparator for comparative effectiveness evaluation on new 2L therapy. Rechallenge with docetaxel increased with time and was given to patients with lower disease burden and healthcare costs than the MITO or Combo group.
Survey on management of metastatic hormone-refractory prostate cancer upon progression during or following first-line chemotherapy in five European countries.
Authors: Auziere Sebastien , Flinois Alain , Obi-Tabot Eliot , Rose Mathieu , Parnaby Adam 
Published: March 2020

e15198 Background: In Europe, docetaxel is the standard first-line chemotherapy (1L) for patients with metastatic hormone-refractory prostate cancer (mHRPC). Upon progression, either during or after 1L chemotherapy, treatment options are limited. This study evaluated how patients who progressed during or after 1L docetaxel between Oct 2009 and Jun 2010 were managed. Methods: A representative sample of 349 physicians (oncologists, urologists) who managed patients with mHRPC selected from Germany, France, UK, Spain and Italy were surveyed. Information on the treatments used at the time of progression (during or within the first 6 months following 1L treatment with docetaxel was provided. Results: Information on a total of 2,870 mHRPC patients was provided of which 2,670 (94 %) had received docetaxel in 1L. 1,389 (52%) patients progressed during 1L docetaxel or within 6 months following treatment; of these, 615 (44 %) received as 2L chemotherapy (Table). Conclusions: In this study, mitoxantrone was the most commonly used chemotherapy agent for 2L treatment of patients with mHRPC who progressed during treatment or within the first 6 months following the end of 1L. Docetaxel rechallenge was uncommon for patients experiencing progression early, during or after the end of 1L. [Table: see text]