Life-prolonging Therapies Research Articles

The impact of time-to-castration resistance on survival in patients with metastatic hormone-naïve prostate cancer: A multicenter retrospective study.

213 Background: To evaluate the prognostic impact of time to castration resistance (TCR) in patients with metastatic hormone-naïve prostate cancer (mHNPC). Methods: We retrospectively evaluated 283 mHNPC patients with metastatic castration-resistant prostate cancer (mCRPC) who were initially treated with androgen deprivation therapy as metastatic hormone-naïve prostate cancer in 14 hospitals between September 2008 and October 2018. Overall survival (OS) and OS after castration resistance (OS-CR) were compared between the <12 months (TCR <12M) and ≥12 months (TCR ≥12M). The association between the first-line life-prolonging therapy (docetaxel or new androgen receptor-targeted agents: ART) and TCR on OS-CR was investigated using multivariate Cox regression analysis via inverse probability of treatment weighting (IPTW) model. Results: Median age and time to CRPC were 72 years and 12 months, respectively. The number of patients in the TCR<12M and ≥12M groups were 137 and 146, respectively. Of 283, baseline parameters such as age, extent of disease (EOD), hemoglobin (Hgb), lactate dehydrogenase (LDH), and serum albumin levels were significantly differences in between the groups. We observed significantly poor OS and OS-CR in the TCR <12M group than those in the TCR ≥12M group. First-line docetaxel therapy did not significantly improved OS-CR regardless of TCR. Background (age, ECOG PS, GS, Hgb, tumor volume, serum data, and TCR)-adjusted multivariate Cox regression analyses showed that first-line docetaxel therapy was significantly associated with shorter OS-CR than first-line ART therapy in the TCR <12M group. Conclusions: The prognostic impact of TCR on OS was significant. However, the association between the first-line life-prolonging therapy and TCR on OS need further study.

Treatment Patterns and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer in a Real-world Clinical Practice Setting in the United States.

Clinical trials have demonstrated the efficacy of several life-prolonging therapies for metastatic castration-resistant prostate cancer (mCRPC); however, real-world data on their use, survival effect, and safety are limited. Using electronic health record data from the Flatiron Health database, we studied real-world treatment patterns and health outcomes in patients with mCRPC. We conducted a retrospective, non-interventional cohort analysis of electronic health record data of patients with confirmed mCRPC between January 2013 and September 2017. The primary objective was to describe real-world treatment patterns, including treatment type, duration, and sequencing. Secondary objectives included describing patient characteristics and clinical outcomes. Of 2559 patients with mCRPC, 1980 (77%) received at least 1 line of life-prolonging therapy (abiraterone, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, or radium-223). Of patients receiving first-line therapy, 49% received second-line therapy, and of these, 43% received third-line therapy. Abiraterone/prednisone and enzalutamide accounted for 65% of first-line therapies and 54% of second-line therapies. Docetaxel was the most common third-line therapy (24%). Back-to-back use of abiraterone/prednisone and enzalutamide was common. Radium-223 monotherapy use was 2% in the first-line setting, 3% in the second-line setting, and 8% in the third-line setting. The median overall survival was longer in patients who received life-prolonging therapies (23.7 months; 95% confidence interval: 22.3-25.1 months) than in those who did not (10.1 months; 95% confidence interval: 9.1-11.5 months). These real-world insights on over 2500 patients with mCRPC supplement findings from randomized controlled trials and may help to inform clinical trial design, treatment guidelines, and clinical decision-making.

The Conversation: A Vital Element of Nephrology Care for Older Americans Who are Medically Complex

The U.S. population is aging, supported in part by continued development of life-prolonging medical therapies and technologies. These innovations, including kidney replacement therapies, have been effective in providing additional options to patients facing serious illness, but they have also introduced a new level of complexity in the provider assessment of treatment for these patients. Health care providers are being tasked to decide if medical care is appropriate for an aging and medically complex population, a decision complicated by a variety of factors. Patient-focused conversations surrounding goals of care, prognosis, medical futility, and quality of life need to become part of the routine practice pattern for nephrology care in the United States.

Empowering interpreters to partner in palliative care (PC) conversations: Effect of a dialogue-based curriculum.

21 Background: Effective communication across cultural and linguistic barriers during breaking bad news, DNR, and EOL conversations requires professional medical interpreters skilled in PC communication and clinicians skilled in working with interpreters. But interpreters are rarely included in meetings preceding these conversations, or made aware of the patient’s prognosis or the emotionally-charged subjects likely to arise. They may know the patient and family, cultural norms, and identify the decision makers, but often do not feel empowered to offer this crucial information to clinicians. To be effective cultural brokers, interpreters must be trained in PC terminology and feel empowered to contribute. Methods: A six-session curriculum: Palliative Care Dialogues with Interpreters, facilitated by an experienced PC social worker (SW) and physician, was delivered to medical interpreters from Brigham and Women’s Hospital and Dana-Farber Cancer Institute. The curriculum included links to relevant materials, and structured 1-hour sessions including role-plays on: Initiating and managing a pre-encounter conference; Family meetings; Terms used in PC meetings; Family meetings to discuss code status and end of life-prolonging therapies; Cultural Mediating; Interpreting for SWs and chaplains (with SW and chaplains doing role plays); and Experiencing being a cultural mediator in End of Life Care. 41 participants completed a 23-question pre- and post-course survey on their confidence in interpreting these conversations. Results: There was a highly significant improvement in interpreter post-course confidence ( N = 41. p=1.4080 x 10−11). Facilitated dialogues enabled interpreters to assert concerns, share knowledge, and practice new behaviors in a “safe” space, behaviors they reported they then used in clinical practice. Dialogues provided clinicians an opportunity to learn about the challenging linguistic, cultural and emotional experiences of medical interpreters. Conclusions: Facilitated and well-structured dialogues, including didactics, discussions and roleplaying caused highly significant improvements in interpreter confidence in interpreting PC conversations.

Changes in End-of-Life Practices in European Intensive Care Units From 1999 to 2016

End-of-life decisions occur daily in intensive care units (ICUs) around the world, and these practices could change over time. To determine the changes in end-of-life practices in European ICUs after 16 years. Ethicus-2 was a prospective observational study of 22 European ICUs previously included in the Ethicus-1 study (1999-2000). During a self-selected continuous 6-month period at each ICU, consecutive patients who died or had any limitation of life-sustaining therapy from September 2015 until October 2016 were included. Patients were followed up until death or until 2 months after the first treatment limitation decision. Comparison between the 1999-2000 cohort vs 2015-2016 cohort. End-of-life outcomes were classified into 5 mutually exclusive categories (withholding of life-prolonging therapy, withdrawing of life-prolonging therapy, active shortening of the dying process, failed cardiopulmonary resuscitation [CPR], brain death). The primary outcome was whether patients received any treatment limitations (withholding or withdrawing of life-prolonging therapy or shortening of the dying process). Outcomes were determined by senior intensivists. Of 13 625 patients admitted to participating ICUs during the 2015-2016 study period, 1785 (13.1%) died or had limitations of life-prolonging therapies and were included in the study. Compared with the patients included in the 1999-2000 cohort (n = 2807), the patients in 2015-2016 cohort were significantly older (median age, 70 years [interquartile range {IQR}, 59-79] vs 67 years [IQR, 54-75]; P < .001) and the proportion of female patients was similar (39.6% vs 38.7%; P = .58). Significantly more treatment limitations occurred in the 2015-2016 cohort compared with the 1999-2000 cohort (1601 [89.7%] vs 1918 [68.3%]; difference, 21.4% [95% CI, 19.2% to 23.6%]; P < .001), with more withholding of life-prolonging therapy (892 [50.0%] vs 1143 [40.7%]; difference, 9.3% [95% CI, 6.4% to 12.3%]; P < .001), more withdrawing of life-prolonging therapy (692 [38.8%] vs 695 [24.8%]; difference, 14.0% [95% CI, 11.2% to 16.8%]; P < .001), less failed CPR (110 [6.2%] vs 628 [22.4%]; difference, -16.2% [95% CI, -18.1% to -14.3%]; P < .001), less brain death (74 [4.1%] vs 261 [9.3%]; difference, -5.2% [95% CI, -6.6% to -3.8%]; P < .001) and less active shortening of the dying process (17 [1.0%] vs 80 [2.9%]; difference, -1.9% [95% CI, -2.7% to -1.1%]; P < .001). Among patients who had treatment limitations or died in 22 European ICUs in 2015-2016, compared with data reported from the same ICUs in 1999-2000, limitations in life-prolonging therapies occurred significantly more frequently and death without limitations in life-prolonging therapies occurred significantly less frequently. These findings suggest a shift in end-of-life practices in European ICUs, but the study is limited in that it excluded patients who survived ICU hospitalization without treatment limitations.

Emerging Ethical Challenges in Critical Care for the 21st Century: A Case-Based Discussion.

Ethical challenges for doctors and other health care professionals have existed since the practice of medicine began. Many of the oldest challenges live on to this day, such as who has more authority to make key decisions (autonomy vs. paternalism) and what are the boundaries of life at the beginning and at the end. Two powerful driving forces are new technologies and an ever-changing culture and society. The practice of medicine in intensive care units (ICUs) has been the source of many ethical challenges. Once firmly fixed concepts, such as death or "brain death" are now coming under increasing debate. In other areas, the concept of patient autonomy has been used to request life-prolonging therapies, once thought "futile." New technologies for procreation have necessitated new ethical challenges as well. In this paper, we will use a series of cases, based on experiences from our hospital ethics committee, that occurred over the course of several years and illustrate ethical challenges which are either new to us or not new but growing in frequency due to technological or societal changes. Each one of these topics is complex and worthy of its own large review but for this overview, we will briefly discuss the key points of each dilemma.

843O - Apalutamide (APA) and overall survival (OS) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Updated results from the phase III SPARTAN study

843O - Apalutamide (APA) and overall survival (OS) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Updated results from the phase III SPARTAN study

Metastatic Hormone-Sensitive Prostate Cancer: Clinical Decision Making in a Rapidly Evolving Landscape of Life-Prolonging Therapy.

Metastatic Hormone-Sensitive Prostate Cancer: Clinical Decision Making in a Rapidly Evolving Landscape of Life-Prolonging Therapy.

Periodontal Microbiological Status Influences the Occurrence of Cyclosporine-A and Tacrolimus-Induced Gingival Overgrowth

Immune suppressed renal transplant patients are more prone to developing oral tissue alterations due to medications associated with a pleiotropic set of side effects involving the oral cavity. Drug-induced gingival overgrowth (DIGO) is the most commonly encountered side effect resulting from administration of calcineurin inhibitors such as cyclosporine-A (CsA), the standard first-line treatment for graft rejection prevention in transplant patients. Pathogenesis of gingival overgrowth (GO) is determined by the interrelation between medications and a pre-existing inflammatory periodontal condition, the main modifiable risk factor. Severity of gingival hyperplasia clinical manifestation is also related to calcium channel blocker association, frequently provided in addition to pharmacological therapy of transplant recipients. Specifically, nifedipine-induced enlargements have a higher prevalence rate compared to amlodipine-induced enlargements; 47.8% and 3.3% respectively. Available epidemiological data show a gender difference in prevalence, whereby males are generally more frequently affected than females. The impact of GO on the well-being of an individual is significant, often leading to complications related to masticatory function and phonation, a side effect that may necessitate switching to the tacrolimus drug that, under a similar regimen, is associated with a low incidence of gingival lesion. Early detection and management of GO is imperative to allow patients to continue life-prolonging therapy with minimal morbidity. The purpose of this study was threefold: firstly, to determine the prevalence and incidence of GO under the administration of CsA and Tacrolimus; secondly, to assess the correlation between periodontal status before and after periodontal therapy and medications on progression or recurrence of DIGO; and finally, to analyse the effect of immunosuppressant in association to the channel blocker agents on the onset and progression of gingival enlargement. We compared seventy-two renal transplant patients, including 33 patients who were receiving CsA, of which 25% were also receiving nifedipine and 9.72% also receiving amlodipine, and 39 patients who were receiving tacrolimus, of which 37.5% were also receiving nifedipine and 5.55% also receiving amlodipine, aged between 35 and 60 years. Medical and pharmacological data were recorded for all patients. Clinical periodontal examination, in order to establish the inflammatory status and degree of gingival enlargement, was performed at baseline (T0), 3 months (T1), 6 months (T2), and 9 months (T3). All patients were subjected to periodontal treatment. Statistically significant correlation between the reduction of the mean value of periodontal indices and degree of gingival hyperplasia at the three times was revealed. The prevalence of GO in patients taking cyclosporine was higher (33.3%) in comparison with those taking tacrolimus (14.7%). In accordance with previous studies, this trial highlighted the clinical significance of the pathological substrate on stimulating drug-induced gingival lesion, confirming the key role of periodontal inflammation in pathogenesis of gingival enlargement, but did not confirm the additional effect of calcium-channel blocker drugs in inducing gingival enlargement.

Should providers prescribe sacubitril/valsartan based on trial eligibility, approval indication, or guideline recommendations?

Should providers prescribe sacubitril/valsartan based on trial eligibility, approval indication, or guideline recommendations?

Use of public health service increased risk kidneys in pediatric renal transplant recipients.

With the opioid epidemic and expansion of "IR" classification, 25% of deceased donors are categorized PHS-IR. Studies have assessed utilization of PHS-IR organs among adults, but little is known about pediatric recipients. This retrospective cohort study from 2004-2016 (IR period) aimed to: (a) assess IR kidney utilization patterns between adults and children; (b) identify recipient factors associated with transplant from IR donors among pediatric kidney recipients; and (c) determine geography's role in IR kidney utilization for children. The proportion of pediatric recipients receiving IR kidneys was significantly lower than adults (P<0.001), even when stratified by donor mechanism of death (non-overdose/overdose) and era. In mixed effects models accounting for clustering within centers and regions, older recipient age, later era (post-PHS-IR expansion), and blood type were associated with significantly higher odds of receiving an IR kidney (17years era 5: OR 5.16 [CI 2.05-13.1] P<0.001; 18-21years era 5: OR 2.72 [CI 1.05-7.06] P=0.04; blood type O: OR 1.32 [CI 1.06-1.64] P=0.013). The median odds ratio for center within region was 1.77 indicating that when comparing two patients in a region, the odds of receiving an IR kidney were 77% higher for a patient from a center with higher likelihood of receiving an IR kidney. Utilization of PHS-IR kidneys is significantly lower among pediatric recipients versus adult counterparts. More work is needed to understand the reasons for these differences in children in order to continue their access to this life-prolonging therapy.

Abstract 3747: Radium 223 inhibits prostate cancer in bone via zonal cytotoxicity

Abstract Bone metastases are the initial site of progression and account for many complications experienced by men with metastatic prostate cancer (PCa), with limited therapeutic options. Targeting the bone environment has recently resulted in the approval of Radium-223 (Rad-223), a new life-prolonging therapy for patients with metastatic castrate-resistant prostate cancer. Rad-223 is a rare earth metal radioisotope that displays chemical properties similar to calcium, becomes enriched in bone after in vivo administration and emits alpha particles with locally high energy but limited penetrance in tissues (&amp;lt;100 µm). Confoundingly, the clinical response to Radium-223 is often followed by detrimental relapse and progression, and whether Radium-223 causes tumor-cell directed cytotoxicity in vivo remains unclear. We hypothesized that limited radiation penetrance in situ defines outcome and addressed the principles discriminating Radium-223 efficacy from failure by combining 3D intravital microscopy, in silico modeling and end-point analysis in preclinical PCa models in bone. Radium-223 induced profound but zonally confined cancer cell lethality along the bone interface (200-300 µm), while the more distant tumor core remained unperturbed. As consequence, macro-lesions persisted and grew, whereas micro-tumors in the bone niche showed severe growth delay or eradication. The relative inefficacy in controlling large tumors points to application of Radium-223 in secondary prevention of early bone-metastatic disease and regimens co-targeting the tumor core or broadening the zonal toxicity. Citation Format: Eleonora Dondossola, Stefano Casarin, Claudia Paindelli, Elena De-Juan-Pardo, Dietmar Hutmacher, Christopher Logothetis, Peter Friedl. Radium 223 inhibits prostate cancer in bone via zonal cytotoxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3747.

Overall survival (OS) of African-American (AA) and Caucasian (CAU) men who received sipuleucel-T for metastatic castration-resistant prostate cancer (mCRPC): Final PROCEED analysis.

5035 Background: Prostate cancer risk and mortality are higher in AAs versus CAUs. Post-hoc analyses of pooled Phase 3 data (n = 737) suggested substantial OS benefit for AA men receiving sipuleucel-T (n = 33) vs placebo (n = 10) (McLeod 2012). Compared with pooled placebo patients (n = 249), number needed to treat for OS benefit at 3 years was 3 for AAs and 8 for all sipuleucel-T-treated patients (n = 488) (Moses 2019). Herein we analyzed PROCEED (NCT01306890), a large real-world registry, in which all patients received sipuleucel-T. Methods: In PROCEED, 1902 mCRPC patients received ≥1 sipuleucel-T infusion. OS of all AA (n = 221) and CAU (n = 1649) men were compared. Baseline prostate-specific antigen (PSA), the most important prognostic variable for OS after sipuleucel-T (Schellhammer 2013), substantially differed by race. Thus, OS for a PSA-matched cohort (n = 219 AA; n = 438 CAU) was compared and univariable/multivariable analyses were performed. Post-sipuleucel-T use of OS-prolonging anticancer interventions was also assessed. Results: After a median follow-up of 46.6 mo, median OS was 35.2 (all sipuleucel-T-treated AAs) and 29.9 mo (all sipuleucel-T-treated CAUs): HR 0.81, 95% CI 0.68–0.97; P = 0.03. In the PSA-matched cohort, median OS was 35.3 and 25.8 mo, respectively (HR 0.70, 95% CI 0.57–0.86; P &lt; 0.001). Sipuleucel-T-treated AAs with lower baseline PSA had markedly longer median OS vs sipuleucel-T-treated CAUs. Among those with ≤ median baseline PSA (29.48 ng/ml), median OS was 54.3 mo (AA) vs. 33.4 (CAUs); HR 0.52, 95% CI 0.37–0.72; p &lt; 0.001. Along with other known prognostic factors, AA race was independently associated with prolonged OS on detailed multivariable analyses (HR 0.60, 95% CI 0.48–0.74; p &lt; 0.001) and confirmed on sensitivity analyses. Post-sipuleucel-T life-prolonging anti-cancer therapies were balanced between groups. Conclusions: Sipuleucel-T-treated AAs had significantly improved OS vs sipuleucel-T-treated CAUs. This analysis marks the largest known racial difference in OS in response to any therapy for mCRPC, a finding with implications for both prostate cancer pathophysiology and cancer immunotherapy. Clinical trial information: NCT01306890.

Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS) in Norway: Protocol for validation and a prospective cohort study.

In amyotrophic lateral sclerosis (ALS) cognitive impairment may occur. This could detrimentally influence communication between patient and health-care professionals and make clinical assessment difficult. Given the short life expectancy after diagnosis, it is crucial to accurately identify ALS patients early. Although suitable cognitive screening tools for patients with ALS are available, they have not been evaluated in a Norwegian population. Interpretation of scores for available tests and practical application of scoring is also not well established. The protocol described here involves two related studies that aim to improve the quality of ALS clinical testing instruments used in the Norwegian population. The first is a validation study that evaluates the psychometric properties of the ECAS-Norwegian. The second is a prospective cohort study that evaluates the ECAS-Norwegian as a tool to predict early changes in ability to work, drive a car and the need for advanced therapy. Study 1 is a multicenter study using international quality criteria. Patients with ALS, healthy control subjects, and control subjects with dementia will be included. Primary outcome is ECAS-Norwegian scores. In study 2, patients with ALS will be included. ECAS-Norwegian compared to Clinical Dementia Rating score and Montreal Cognitive Assessment scores will be used as a prognostic tool for working, driving, and initiating advanced life-prolonging therapy. Before clinical implementation, the ECAS-Norwegian needs to be evaluated and validated. Successful validation and implementation of the ECAS-Norwegian may provide early identification of cognitive impairment in ALS, leading to more proactive, individualized treatment.

Carotid Artery Blood Flow and Its Association with Stroke during Left Ventricular Assist Device Support

Purpose Left ventricular assist device (LVAD) surgery is a life-prolonging therapy for advanced heart failure (HF). Despite many improvements over the years, LVADs continue to be associated with a high incidence of stroke and other vascular complications such as gastrointestinal bleeding (GIB). At present, the pathogenesis of these complications during LVAD support remains unclear. Abnormal structure and hemodynamics in large arteries are a potential contributor. We hypothesized that structural abnormalities and flow alterations will be significantly associated with stroke and a composite outcome of stroke, GIB, and death in HF patients before and during LVAD support. Methods We conducted a retrospective analysis of 141 carotid duplex studies in adult patients who received the HeartMate II LVAD. Clinical Doppler exams were evaluated before and after LVAD implantation. Parameters evaluated included peak-systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV), pulsatility index (PI), ICA/CCA PSV ratio, plaque burden, and ICA stenosis. In addition, we noted demographics, outcomes, and LVAD speed parameters. Results Compared with HF patients, LVAD patients had decreased PSV (CCA: 80 vs. 50 cm/s, ICA: 72 vs. 56 cm/s; both P Conclusion We conclude that structural arterial disease in HF patients, namely carotid artery stenosis and plaque as evidenced by Doppler evaluation, was associated with stroke, GIB, and death during LVAD support while arterial flow parameters were not. Flow parameters during LVAD support were likewise unrelated to adverse events. Our findings support routine carotid duplex evaluation for clinical outcome prediction and encourage further study of the unique vascular physiology resulting from LVAD support.

Management of Castration-Resistant Prostate Cancer: First-Line Therapy

The development of castration-resistant prostate cancer (CRPC) heralds significant morbidity and an incurable condition. Since 2004, there are now six proven life-prolonging therapies available, including androgen receptor pathway inhibitor (ARPI) , chemotherapeutic agents, radiopharmaceutical, and immunotherapy for the first-line management of metastatic CRPC. Recent advances have seen enzalutamide and apalutamide approved by US FDA for the treatment of nonmetastatic CRPC, with darolutamide the latest ARPI demonstrating efficacy in nonmetastatic CRPC. ARPI is the treatment of choice in the first-line setting for most CRPC patients, and this approach has been endorsed by clinical guidelines and expert consensus, although treatment must be individualized. Advances in the molecular profiling of CRPC promise to select suitable patients for trials involving targeted therapy and identify biomarkers to guide treatment selection. This review contains 2 figures, 1 table, and 54 references. Keywords: abiraterone acetate, apalutamide, cabazitaxel, castration-resistant prostate cancer, docetaxel, enzalutamide, first-line treatment, radium-223, sipuleucel-T

Treatment patterns and outcomes for metastatic castration-resistant prostate cancer (mCRPC) in a real-world setting: A retrospective study of greater than 2500 patients.

256 Background: In the era of expanding therapeutic options for mCRPC, there is a growing need to develop an optimal treatment sequence. This real-world study evaluated treatment patterns and outcomes in mCRPC patients. Methods: This retrospective cohort study used the Flatiron prostate cancer core registry (Jan 2013 to Sep 2017) to assess real-world treatment patterns (lines of therapy and transitions to subsequent lines) and outcomes (overall survival, OS) in patients with mCRPC. Descriptive analysis was performed for treatment patterns, and the Kaplan–Meier method was used to analyze OS. Results: This study comprised 2559 patients with mCRPC who received up to three lines of therapy. 23% of patients did not receive a life-prolonging therapy after the initial diagnosis of mCRPC. In the first-line (1L) setting, abiraterone (Abi, 37%) was the most-prescribed therapy, followed by enzalutamide (Enza, 28%) and docetaxel (15%). In the second line (2L), combination therapies were frequent (17%), with rates similar to taxane-based chemotherapy (docetaxel or cabazitaxel). Enza was the most-common 2L therapy used after Abi, and vice versa. Radium-223 (Ra-223) was prescribed as 1L therapy in 5% and 2L therapy in 9% of patients, either as monotherapy or part of a combination regimen. When Ra-223 was used in the 1L setting, similar proportions of patients received subsequent therapy with Enza (14%), Abi (13%), or chemotherapy (11%). Ra-223 was commonly used in the third line (14%), but less frequently than chemotherapy (36%). After each line, ~50% of patients did not receive a subsequent life-prolonging agent. Overall, 66% of patients used bone health agents at any time (denosumab, 48%; zoledronic acid, 24%). The median OS from the diagnosis of mCRPC was 21 months. Conclusions: This real-world study shows that not all patients with mCRPC received a life-prolonging therapy. Among patients who received an anti-cancer therapy, approximately half did not receive a subsequent life-prolonging therapy. Abi and Enza were the most-common 1L therapies, and their back-to-back use was common despite reported cross-resistance and limited benefit.

Oligometastatic Prostate Cancer Should Be Studied and Treated Differently to High-volume Disease. Con: The Underlying Biology is the Same, So They Should Not Be Treated Differently

The biology of oligo- and polymetastatic disease is likely to be similar. However, the prognosis is different and this may drive different therapy choices. Men should not be deprived of life-prolonging therapies unless the benefits of these therapies are outweighed by the risks from competing causes of mortality.

Palliative Care Education in U.S. Adult Neuro-Oncology Fellowship Programs (S854)

1.Describe the current need for palliative education in neuro-oncology fellowship programs as identified by program directors.2.List the preferred education methods and tools of neuro-oncology fellowship program directors for teaching palliative care to fellows.3.Know which barriers program directors face when providing palliative care education for neuro-oncology fellows. Palliative care (PC) for patients with neuro-oncological diseases positively impacts morbidity and mortality. No studies have evaluated whether neuro-oncology fellows receive formal PC education during fellowship. The purpose of this study was to describe the PC education and identify education needs of US neuro-oncology fellowship programs. Program directors (PDs) of US neuro-oncology fellowships were surveyed. The electronic survey included qualitative and quantitative questions. Of 26 programs fellows, 17 completed surveys (65% response rate) of which 3 (18%) offered no formal PC education. The methods most utilized were formal didactics (seminars/conferences) and self-directed reading materials. One-third of programs have developed their own teaching materials. Communication was the domain identified as most important, the domain fellows were most well-trained in, and the domain PDs felt most comfortable providing for their own patients. Addressing spiritual distress and initiating life-prolonging therapies were the domains PDs identified as being least important, fellows were least well trained in, and PDs were least comfortable providing for their own patients. Most programs (83%) were satisfied with the PC education available at their program. Time for teaching and faculty availability were the most common barriers. Neuro-oncology PDs recognize the need for PC education, which is currently offered in some form by most programs, but the content and methods of delivery are heterogeneous. Interdisciplinary educational teams and nationally-available PC educational material may improve implementation of PC education in neuro-oncology.

A Life or “Good Death” Situation? A Worldwide Ecological Study of the National Contexts of Countries That Have and Have Not Implemented Palliative Care

ContextPalliative care advocates argue that service implementation is feasible in all settings. Yet, services have developed patchily in low- and middle-income settings. Beyond Human Development Index indicators, there has been limited engagement with the broader development challenges facing nations tasked with implementing palliative care. ObjectiveThe objective of this study was to describe how indicators of national development relate to levels of palliative care services in 207 countries around the world. MethodsWe conducted a ecological study to identify relationships between potential predictor variables and the level of national palliative care development. A total of 28 predictor variables from the following six domains were selected using hypothesized relationships with levels of palliative care development: disease demographics, socioeconomics, health systems, politics, demographics, and economics. The outcome variable was level of national palliative care development on a six-point scale. Spearman's correlation was used to measure the strength of the association. ResultsTwenty-six of 28 variables were statistically significantly associated with levels of palliative care development in 207 countries. Palliative care is more developed in countries with high—percentage of deaths from noncommunicable disease, population proportion aged 65+ years, gross national income, and tourism. Development is lower in countries with high levels of political corruption, infant mortality, deaths by infectious diseases, and weak democracy. Prevalence of undernourishment and levels of private health expenditure were not significantly associated with palliative care development. ConclusionPalliative care development is highly consistent with broader national development indicators. It is less in countries where sudden deaths are more likely and benefits from palliative care provision are likely to be very limited. In such countries, resources may be prioritized toward life-prolonging therapies and key aspects of palliative care need only be implemented before fully integrated palliative services. Findings suggest that there may be a “tipping point” in societies, where the relative need for life-prolonging therapies becomes less than the need for integrated palliative care services.