Death of a Partner and Risks of Ischemic Stroke and Intracerebral Hemorrhage: A Nationwide Danish Matched Cohort Study

Background Stress has been reported to trigger stroke, and the death of a loved one is a potentially extremely stressful experience. Yet, previous studies have yielded conflicting findings of whether bereavement is associated with stroke risk, possibly because of insufficient distinction between ischemic stroke (IS) and intracerebral hemorrhage (ICH). We therefore examined the associations between bereavement and IS and ICH separately in contemporary care settings using nationwide high‐quality register resources. Methods and Results The study cohort included all Danish individuals whose partner died between 2002 and 2016 and a reference group of cohabiting individuals matched 1:2 on sex, age, and calendar time. Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) and corresponding 95% CIs during up to 5 years follow‐up. During the study period, 278 758 individuals experienced partner bereavement, of whom 7684 had an IS within the subsequent 5 years (aHR, 1.11; CI, 1.08–1.14 when compared with nonbereaved referents) and 1139 experienced an ICH (aHR, 1.13; CI, 1.04–1.23). For ICH, the estimated association tended to be stronger within the initial 30 days after partner death (aHR, 1.66; CI, 1.06–2.61), especially in women (aHR, 1.99; CI, 1.06–3.75), but the statistical precision was low. In absolute numbers, the cumulative incidence of IS at 30 days was 0.73 per 1000 in bereaved individuals versus 0.63 in their referents, and the corresponding figures for ICH were 0.13 versus 0.08. Conclusions Statistically significant positive associations with partner bereavement were documented for both IS and ICH risk, for ICH particularly in the short term. However, absolute risk differences were small.

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Abstract 2646: Aortic Arch Plaques and Risk of Vascular Events in Subjects Without Prior Stroke

Circulation ◽

10.1161/circ.118.suppl_18.s_760 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Cesare Russo ◽

Zhezhen Jin ◽

Ralph L Sacco ◽

Shunichi Homma ◽

Tatjana Rundek ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Aortic Arch ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Vascular Events ◽

Increased Risk ◽

Prior Stroke

BACKGROUND: Aortic arch plaques (AAP) are a risk factor for cardiovascular embolic events. However, the risk of vascular events associated with AAP in the general population is unclear. AIM: To assess whether AAP detected by transesophageal echocardiography (TEE) are associated with an increased risk of vascular events in a stroke-free cohort. METHODS: The study cohort consisted of stroke-free subjects over age 50 from the Aortic Plaques and Risk of Ischemic Stroke (APRIS) study. AAP were assessed by multiplane TEE, and considered large if ≥ 4 mm in thickness. Vascular events including myocardial infarction, ischemic stroke and vascular death were recorded during the follow-up. The association between AAP and outcomes was assessed by univariate and multivariate Cox proportional hazards models. RESULTS: A group of 209 subjects was studied (mean age 67±9 years; 45% women; 14% whites, 30% blacks, 56% Hispanics). AAP of any size were present in 130 subjects (62%); large AAP in 50 (24%). Subjects with AAP were older (69±8 vs. 63±7 years), had higher systolic BP (146±21 vs.139±20 mmHg), were more often white (19% vs. 8%), smokers (20% vs. 9%) and more frequently had a history of coronary artery disease (26% vs. 14%) than those without AAP (all p<0.05). Lipid parameters, prevalence of atrial fibrillation and diabetes mellitus were not significantly different between the two groups. During the follow up (94±29 months) 30 events occurred (13 myocardial infarctions, 11 ischemic strokes, 6 vascular deaths). After adjustment for other risk factors, AAP of any size were not associated with an increased risk of combined vascular events (HR 1.07, 95% CI 0.44 to 2.56). The same result was observed for large AAP (HR 0.94, CI 0.34 to 2.64). Age (HR 1.05, CI 1.01 to 1.10), body mass index (HR 1.08, CI 1.01 to 1.15) and atrial fibrillation (HR 3.52, CI 1.07 to 11.61) showed independent association with vascular events. In a sub-analysis with ischemic stroke as outcome, neither AAP of any size nor large AAP were associated with an increased risk. CONCLUSIONS: In this cohort without prior stroke, the incidental detection of AAP was not associated with an increased risk of future vascular events. Associated co-factors may affect the AAP-related risk of vascular events reported in previous studies.

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Abstract WP312: The Association of Chronic Kidney Disease (CKD) With 30-day and 1-year Post Ischemic Stroke Mortality and Rehospitalization: Get With the Guidelines (GWTG) Stroke

Stroke ◽

10.1161/str.47.suppl_1.wp312 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Nada El Husseini ◽

Gregg C Fonarow ◽

Eric E Smith ◽

Christine Ju ◽

Lee H Schwamm ◽

...

Keyword(s):

Ischemic Stroke ◽

Hospital Mortality ◽

Proportional Hazards ◽

Reference Group ◽

Cox Proportional Hazards ◽

Fee For Service ◽

Stroke Mortality ◽

Medicare Beneficiaries ◽

Cox Proportional Hazards Models ◽

Ckd Stage

Background: The extent to which CKD is associated with 30-day and 1-year post ischemic stroke mortality and rehospitalization rates has not been well studied. Methods: Data from 232,236 fee for service Medicare patients admitted with ischemic stroke to 1581 AHA GWTG-Stroke participating hospitals between January 2009 and December 2012 were analyzed. Estimated GFR in mL/min/1.73 m2 was determined based on the MDRD study equation categorized as: no CKD (GFR ≥60); stage 3a CKD (GFR 45-59); stage 3b CKD (GFR 30-44); stage 4 CKD, (GFR 15-29); stage 5 CKD (GFR <15 excluding those on dialysis). Dialysis was identified by ICD-9 codes. Multivariable Cox proportional hazards models adjusted for demographics, medical history, NIHSS, arrival hour, and hospital characteristics were used to determine the independent associations of CKD (reference group those without CKD) with mortality and readmission at 30 days and 1 year. Results: After adjustment, 30-days poststroke mortality was highest among those with CKD stage 5 (HR 1.94, 95%CI 1.72-2.18), even after excluding in-hospital mortality and patients discharged to hospice (HR 2.09, 95%CI 1.66-2.63). Unadjusted 1-year mortality and readmission rates were highest among patients on dialysis (Figure). After adjustment, 1-year post-stroke mortality remained highest among patients on dialysis (HR 2.19, 95%CI 2.08-2.31), even after excluding in-hospital mortality and discharge to hospice (HR 2.65, 95%CI 2.49-2.81). For those discharged alive, 30-day and 1-year rehospitalization rates were also highest among patients on dialysis (HR 2.10, 95%CI 1.95-2.26; HR 2.55, 95%CI 2.44-2.66, respectively) as was the 30-day and 1-year composite of mortality and rehospitalization (HR 2.04, 95%CI 1.90-2.18; HR 2.46, 95% CI 2.36-2.56, respectively). Conclusion: Among Medicare beneficiaries with acute ischemic stroke, poststroke mortality and rehospitalization varied by CKD stage and were highest among those with advanced CKD.

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Plasma C-Reactive Protein, Systolic Hypertension and Risk of Ischemic Stroke and TIA: The Framingham Study

Stroke ◽

10.1161/str.32.suppl_1.330-e ◽

2001 ◽

Vol 32 (suppl_1) ◽

pp. 330-331

Author(s):

Natalia S Rost ◽

Carlos S Kase ◽

Philip A Wolf ◽

Joseph M Massaro ◽

Margaret Kelly-Hayes ◽

...

Keyword(s):

Ischemic Stroke ◽

Risk Ratio ◽

Reference Group ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Framingham Study ◽

C Reactive Protein ◽

Reactive Protein ◽

Increased Risk ◽

Elevated Systolic Blood Pressure

83 Background: The role of plasma C-reactive protein (CRP) as marker of cerebrovascular risk is currently under investigation. We evaluated relative risk of developing first ischemic stroke and TIA among the patients with elevated systolic blood pressure (SBP) and/or elevated plasma CRP levels versus those patients with unelevated SBP and unelevated CRP. Methods: We studied 591 men and 868 women of the original Framingham Study cohort who were free of stroke and TIA at the time of their 1980–1982 clinic exam. Sex-specific Cox proportional hazards regressions were used to quantify the risk of 14-year incidence of ischemic stroke/TIA associated with elevated SBP and CRP. Unadjusted models and models adjusted for age, smoking, total & HDL cholesterol, and diabetes were used. SBP and CRP were included in the Cox models as sex-specific quartiles. Risk ratios of first ischemic stroke/TIA for individuals with elevated (in the upper quartile) SBP (SBP+) and CRP (CRP+) were determined using the SBP-/CRP- individuals as a reference group. Similarly, simultaneous evaluation of the risk of first ischemic stroke/TIA was done for SBP+/CRP- and SBP-/CRP+ using the individuals in SBP-/CRP- as a reference group. Results: Relative to SBP-/CRP- men (incidence of first ischemic stroke/TIA of 36/328, or 11.0%), SBP+/CRP+ men (where incidence was 8/32, or 25.0%) had unadjusted risk ratio of 3.56 (p=0.001). This ratio was nearly twice that for SBP+/CRP- men (incidence=20/115, or 17.4%; RR=1.89, p=0.023). Relative to SBP-/CRP- women (incidence= 45/485, or 9.3%), the unadjusted risk ratio increased from 2.03 in SBP+/CRP- women (incidence=27/166, or 16.3%; p=0.001) to 3.44 in SBP+/CRP+ women (incidence=15/58, or 25.9%; p<0.001). Adjustment for age did not significantly alter this relationship. Following multivariate adjustment, risk of developing first ischemic stroke/TIA remained significantly elevated in SBP+/CRP+ men (RR=2.7; p=0.018) and women (RR=2.06; p=0.027). Conclusion: Having both CRP levels and systolic BP above the 75 th percentile for each of these parameters significantly increased risk of developing first ischemic stroke/TIA in both sexes.

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Abstract 74: Obesity and the Risk of Recurrent Vascular Events in Patients with Ischemic Stroke: Insights from the Insulin Resistance Intervention after Stroke (IRIS) Trial

Stroke ◽

10.1161/str.48.suppl_1.74 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Jennifer L Dearborn ◽

Catherine M Viscoli ◽

Silvio E Inzucchi ◽

Lawrence H Young ◽

Walter N Kernan

Keyword(s):

Ischemic Stroke ◽

Lower Risk ◽

Proportional Hazards ◽

Cox Model ◽

Recurrent Stroke ◽

Absolute Risk ◽

Cox Proportional Hazards ◽

Metabolic Risk ◽

Obese Patients ◽

Vascular Events

Background: In epidemiologic research, patients with obesity have, on average, a lower risk for recurrent cardiovascular events after ischemic stroke compared with non-obese patients. Despite this “obesity paradox,” we hypothesized that clinical features associated with more severe metabolic disease would identify overweight and obese stroke patients at high risk for recurrent vascular events. Methods: The IRIS trial examined the efficacy of pioglitazone compared with placebo, for prevention of stroke/ myocardial infarction (MI) among non-diabetic insulin resistant patients with a recent ischemic stroke or TIA. Patients were followed for a median of 4.8 years. Among 3,707 participants, we first examined risk of recurrent stroke/MI by obesity status at baseline (overweight or obese [BMI ≥25] vs <25) using Cox proportional hazards models with and without adjustment for sociodemographic factors, smoking and vascular disease history. Next, for 3,142 participants with BMI ≥ 25, a Cox model including 7 baseline features (systolic blood pressure, C-reactive protein, HOMA-IR, hemoglobin A1C, waist circumference, triglycerides and high density lipoprotein) was used to stratify patients into tertiles of “metabolic risk”. The hazard of stroke/MI was then calculated across risk tertiles(T). Results: Overweight and obese participants had a lower incidence of stroke or MI compared with non-obese patients (10.1% vs.12.6%; hazard ratio [HR] 0.77, [0.59-0.99]) and the difference was attenuated after adjustment (HR 0.85 [0.66-1.11]). Among overweight and obese patients, a metabolic risk score identified patients at higher risk of stroke or MI (T3 12.2%, T2 9.2%, T1 9.0%; T3 vs. T1 HR 1.40 [1.08, 1.83]). This association remained significant after adjustments (HR 1.33 [1.02, 1.75]). Conclusion: Although overweight and obese patients may on average have lower risk of recurrent stroke or MI after an ischemic stroke or TIA compared with non-obese individuals, those with advanced metabolic impairment also have a high absolute risk of recurrence.

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Adherence to the EAT-Lancet Diet and Risk of Stroke and Stroke Subtypes: A Cohort Study

Stroke ◽

10.1161/strokeaha.121.036738 ◽

2021 ◽

Author(s):

Daniel B. Ibsen ◽

Anne H. Christiansen ◽

Anja Olsen ◽

Anne Tjønneland ◽

Kim Overvad ◽

...

Keyword(s):

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Lower Risk ◽

Proportional Hazards ◽

National Registry ◽

Healthy Eating Index ◽

Cox Proportional Hazards ◽

Stroke Subtypes ◽

Cox Proportional Hazards Models ◽

Hazard Ratios

Background and Purpose: We investigated the association between adherence to the EAT-Lancet diet, a sustainable and mostly plant-based diet, and risk of stroke and subtypes of stroke in a Danish population. For comparison, we also investigated the Alternate Healthy Eating Index-2010 (AHEI). Methods: We used the Danish Diet, Cancer and Health cohort (n=55 016) including adults aged 50 to 64 years at baseline (1993–1997). A food frequency questionnaire was used to assess dietary intake and group participants according to adherence to the diets. Stroke cases were identified using a national registry and subsequently validated by review of medical records (n=2253). Cox proportional hazards models were used to estimate hazard ratios and 95% CIs for associations with the EAT-Lancet diet or the AHEI and risk of stroke and stroke subtypes. Results: Adherence to the EAT-Lancet diet was associated with a lower risk of stroke, although not statistically significant (highest versus lowest adherence: hazard ratio, 0.91 [95% CI, 0.76–1.09]). A lower risk was observed for AHEI (0.75 [95% CI, 0.64–0.87]). For stroke subtypes, we found that adherence to the EAT-Lancet diet was associated with a lower risk of subarachnoid hemorrhage (0.30 [95% CI, 0.12–0.73]), and the AHEI was associated with a lower risk of ischemic stroke (0.76 [95% CI, 0.64–0.90]) and intracerebral hemorrhage (0.58 [95% CI, 0.36–0.93]). Conclusions: Adherence to the EAT-Lancet diet in midlife was associated with a lower risk of subarachnoid stroke, and the AHEI was associated with a lower risk of total stroke, mainly ischemic stroke and intracerebral hemorrhage.

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Outcome disparities in elder patients with colorectal cancer receiving definitive surgery: A nationwide population-based study in Taiwan.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15119 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15119-e15119

Author(s):

Chia-Jen Liu ◽

San-Chi Chen ◽

Chueh-Chuan Yen ◽

Hao Wei Teng ◽

Ming-Huang Chen ◽

...

Keyword(s):

Colorectal Cancer ◽

Elderly Patients ◽

Cancer Treatment ◽

Proportional Hazards ◽

Reference Group ◽

Cox Proportional Hazards ◽

Postoperative Treatment ◽

Study Cohort ◽

Curative Surgery ◽

Definitive Surgery

e15119 Background: There are increasing numbers of elderly patients with colorectal cancer (CRC). With the advance of cancer treatment in recent years, more elderly CRC patients receive curative surgery and multidisciplinary cancer treatment. The purpose of this study is to identify the risk factors of mortality and to improve survival of these patients. Methods: We recruited newly diagnosed CRC patients between 2005 and 2012 from Taiwan's nationwide health insurance database. Patients without definitive surgery for CRC were excluded. CRC patients aged < 65 years (non-elderly) were served as a reference group. The study cohort was followed until the end of 2013. Univariate and multivariate Cox proportional hazards models were applied to find the predictors of death among our study cohort. Results: During the 9-year study period, 10,818 (30.6%) died among 35,298 elderly CRC patients receiving definitive surgery, with a median follow-up period of 3.0 years. The median overall survival (OS) of the elderly patients was improved 1.4% per year (95% confidence interval [CI] 0.5–2.4%). Multivariate analysis showed that adjusted hazard ratios (HRs) for OS were 1.00, 1.23, 1.56, 2.15 in the patients aged 65–70, 70–75, 75–80, and ≥ 80 compared to those aged < 65, respectively. The older patients had a higher probability of having ≥ 2 underlying comorbidities (71.4% vs. 31.4%) and without postoperative treatment (42.1% vs. 28.8%), which might be associated with the increase of mortality risk. Conclusions: This largest cohort study demonstrated an increasing risk of mortality in elderly CRC patients, especially those with ≥ 2 underlying comorbidities and those without postoperative treatment. [Table: see text]

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Maternal diabetes and risk of multiple sclerosis in the offspring: A Danish nationwide register-based cohort study

Multiple Sclerosis Journal ◽

10.1177/1352458520977120 ◽

2020 ◽

pp. 135245852097712

Author(s):

Nete Munk Nielsen ◽

Sanne Gørtz ◽

Henrik Hjalgrim ◽

Klaus Rostgaard ◽

Kassandra L Munger ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cohort Study ◽

Proportional Hazards ◽

Maternal Diabetes ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Quality Register ◽

Increased Risk ◽

National Patient ◽

Diabetic Mothers

Background: Previous studies suggest a 3- to-10-fold increased risk of multiple sclerosis (MS) in offspring of mothers with diabetes mellitus (DM). Objectives: To examine MS risk in offspring of diabetic mothers, overall and according to type of maternal DM, that is, pregestational DM or gestational DM, as well as to examine MS risk among offspring of diabetic fathers. Methods: The study cohort included all 1,633,436 singletons born in Denmark between 1978 and 2008. MS diagnoses were identified in the Danish Multiple Sclerosis Registry, and parental DM diagnoses in the National Patient Register. We used Cox proportional hazards regression analyses to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association of parental DM with MS risk in the offspring. Results: MS risk among individuals whose mothers had pregestational DM was 2.3-fold increased compared with that among individuals with nondiabetic mothers (HR = 2.25; 95% CI: 1.35–3.75, n = 15). MS risk was statistically non-significant among offspring of mothers with gestational DM (HR = 1.03 (95% CI: 0.49–2.16), n = 7) and among offspring of diabetic fathers (HR = 1.40 (95% CI: 0.78–2.54), n = 11). Conclusion: Our nationwide cohort study utilizing high-quality register data in Denmark over several decades corroborates the view that offspring of diabetic mothers may be at an elevated risk of developing MS.

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Adherence to the EAT-Lancet diet and risk of stroke and stroke subtypes: A Danish cohort study

10.1101/2021.04.14.21255371 ◽

2021 ◽

Author(s):

Daniel B Ibsen ◽

Anne H Christiansen ◽

Anja Olsen ◽

Anne Tjoenneland ◽

Kim Overvad ◽

...

Keyword(s):

Ischemic Stroke ◽

Intracerebral Hemorrhage ◽

Lower Risk ◽

Proportional Hazards ◽

National Registry ◽

Healthy Eating Index ◽

Cox Proportional Hazards ◽

Stroke Subtypes ◽

Cox Proportional Hazards Models ◽

Hazard Ratios

Objective To investigate the association between adherence to the EAT-Lancet diet, a sustainable and mostly plant-based diet, and risk of stroke and subtypes of stroke in a Danish population. For comparison, we also investigated the Alternate Healthy Eating Index-2010 (AHEI). Methods We used the Danish Diet, Cancer and Health cohort (n=55,016) including adults aged 50-64 years at baseline (1993-1997). A food frequency questionnaire was used to assess dietary intake and group participants according to adherence to the diets. Stroke cases were identified using a national registry and subsequently validated by review of medical records (n=2253). Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations with the EAT-Lancet diet or the AHEI and risk of stroke and stroke subtypes. Results Adherence to the EAT-Lancet diet was associated with a lower risk of stroke, although not statistically significant (highest vs lowest adherence: HR 0.91; 95% CI 0.76, 1.09). A lower risk was observed for the AHEI (0.75; 0.64, 0.87). For stroke subtypes we found that adherence to the EAT-Lancet diet was associated with a lower risk of subarachnoid hemorrhage (0.30; 0.12, 0.73) and the AHEI was associated with a lower risk of ischemic stroke (0.76; 0.64, 0.90) and intracerebral hemorrhage (0.58; 0.36, 0.93). Conclusions Adherence to the EAT-Lancet diet was associated with a lower risk of subarachnoid stroke and the AHEI was associated with a lower risk of total stroke, mainly ischemic stroke and intracerebral hemorrhage.

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Clinical outcomes of pediatric macular edema associated with non-infectious uveitis

Journal of Ophthalmic Inflammation and Infection ◽

10.1186/s12348-021-00236-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anh Hong Nguyen ◽

Bethlehem Mekonnen ◽

Eric Kim ◽

Nisha R. Acharya

Keyword(s):

Visual Acuity ◽

Macular Edema ◽

San Francisco ◽

Pediatric Patients ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Study Cohort ◽

Common Diagnosis ◽

Corticosteroid Injections

Abstract Background Macular edema (ME) is the most frequent cause of irreversible visual impairment in patients with uveitis. To date, little data exists about the clinical course of ME in pediatric patients. A retrospective, observational study was performed to examine the visual and macular thickness outcomes of ME associated with chronic, noninfectious uveitis in pediatric patients. Methods Pediatric patients with noninfectious uveitis complicated by ME seen in the University of California San Francisco Health System from 2012 to 2018 were identified using ICD-9 and ICD-10 codes. Data were collected from medical records including demographics, diagnoses, ocular history, OCT imaging findings, complications, and treatments at first encounter and at 3, 6, 9, and 12-month follow-up visits. Cox proportional hazards regression was used to investigate the association between different classes of treatment (steroid drops, steroid injections, oral steroids and other immunosuppressive therapies) and resolution of macular edema. Results The cohort comprised of 21 children (26 eyes) with a mean age of 10.5 years (SD 3.3). Undifferentiated uveitis was the most common diagnosis, affecting 19 eyes (73.1%). The majority of observed macular edema was unilateral (16 patients, 76.2%) and 5 patients had bilateral macular edema. The mean duration of follow-up at UCSF was 35.3 months (SD 25.7). By 12 months, 18 eyes (69.2%) had achieved resolution of ME. The median time to resolution was 3 months (IQR 3–6 months). Median best-corrected visual acuity (BCVA) at baseline was 0.54 logMAR (Snellen 20/69, IQR 20/40 to 20/200). Median BCVA at 12 months was 0.1 logMAR (Snellen 20/25, IQR 20/20 to 20/50) Corticosteroid injections were associated with a 4.0-fold higher rate of macular edema resolution (95% CI 1.3–12.2, P = 0.01). Conclusions Although only 15% of the pediatric patients with uveitis in the study cohort had ME, it is clinically important to conduct OCTs to detect ME in this population. Treatment resulted in 69% of eyes achieving resolution of ME by 12 months, accompanied with improvement in visual acuity. Corticosteroid injections were significantly associated with resolution of macular edema.

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Overall survival (OS) and metastasis-free survival (MFS) by depth of prostate-specific antigen (PSA) decline in the phase III PROSPER trial of men with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with enzalutamide (ENZA).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.94 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 94-94

Author(s):

Maha H. A. Hussain ◽

Cora N. Sternberg ◽

Eleni Efstathiou ◽

Karim Fizazi ◽

Qi Shen ◽

...

Keyword(s):

Proportional Hazards ◽

Reference Group ◽

Specific Antigen ◽

Cox Proportional Hazards ◽

Phase Iii ◽

Castration Resistant Prostate Cancer ◽

Analysis Model ◽

Increased Risk ◽

Psa Nadir ◽

Post Hoc

94 Background: The PROSPER trial demonstrated prolonged MFS and OS for men with nmCRPC and rapidly rising PSA treated with ENZA vs placebo, both in combination with androgen deprivation therapy (ADT). The final survival analysis of PROSPER (Sternberg et al. NEJM 2020) recently reported a median OS of 67.0 months (95% CI, 64.0 to not reached) with ENZA and 56.3 months (95% CI, 54.4 to 63.0) with placebo (hazard ratio [HR] for death, 0.73; 95% CI, 0.61 to 0.89; P = .001). Post hoc analyses of PROSPER evaluating PSA dynamics have demonstrated longer MFS with greater PSA decline (Hussain et al. ESMO Sept 19-21, 2020. Poster 685P) and increased risk of metastases in patients with even modest PSA progression vs those without (Saad et al. Eur Urol 2020). Here we further explored the relationship between PSA dynamics and outcomes in PROSPER using uniquely defined PSA subgroups of decline. Methods: Eligible men in PROSPER had nmCRPC, a PSA level ≥ 2 ng/mL at baseline, and a PSA doubling time ≤ 10 months. Men continued ADT, were randomized 2:1 to ENZA 160 mg once daily vs placebo, and had PSA evaluation at week 17 and every 16 weeks thereafter. This post hoc analysis evaluated OS and MFS for 4 mutually exclusive subgroups defined by PSA nadir using men with PSA reduction < 50% as the reference group. The HR is based on an unstratified Cox proportional hazards analysis model. Results: 1401 men were enrolled in PROSPER; 933 were treated with ENZA and PSA data were available for 905. Measured at nadir, 38% of these men achieved PSA reduction ≥ 90% (actual nadir < 0.2 ng/mL), and another 27% achieved PSA reduction ≥ 90% (actual nadir ≥ 0.2 ng/mL). Among men in the placebo arm of PROSPER only 3/457 reported PSA reduction ≥ 90%. Median OS and MFS increased with increasing depth of PSA decline (Table). Conclusions: In men with nmCRPC and rapidly rising PSA treated with ADT plus ENZA, there was a close relationship between the degree of PSA decline and survival outcomes. Defining PSA by both percent decline and actual decline below 0.2 ng/mL revealed a previously under-appreciated relationship between these PSA metrics and highlights the importance of PSA nadir as an intermediate biomarker in nmCRPC. Clinical trial information: NCT02003924. [Table: see text]

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