BACKGROUND:We aim to evaluate whether increased lymph node yield at prostatectomy (RP) is associated with improved outcomes in NRG/RTOG 9601, a randomized clinical trial of men who underwent either radiation (RT) alone or RT + bicalutamide for PSA elevation following RP for pT2/T3 prostate cancer. METHODS:We reviewed available pathology reports for patients in NRG/RTOG 9601 to determine the nodal count at RP. Cox proportional hazards models were used to assess effect of lymph nodes yield, arm (RT alone or RT + bicalutamide), Gleason score, positive margins, and seminal vesicle invasion on the following endpoints: times to local and distant failure and overall and disease-specific survival. RESULTS:Of 760 patients, 552 (73%, 276 in each arm) had complete data available. Median node count in the entire cohort was 6 (range: 0-33, IQR: 3-9). There were no significant differences between arms in terms of patient demographic or clinical characteristics, including total lymph nodes removed in either arm. There was no significant association between total lymph nodes and overall or disease-specific survival with both arms combined and when adjusting for arm. Notably, interaction analysis revealed that in seminal vesicle invasion, there was a significant association between lymph node yield and OS and DSS (HR = 0.91, 95% CI: 0.83-0.99, p = 0.034; HR = 0.87, 95% CI: 0.77-0.99, p = 0.029, respectively). CONCLUSIONS:Although lymph node yield in NRG/RTOG 9601 did not show association with adverse outcomes in the entire cohort or either arm alone, there was significant association between lymph node yield and adverse outcomes when seminal vesicle invasion was present. The therapeutic benefit of extensive lymph node dissection remains uncertain but could be more relevant in higher risk patients.

Purpose NRG/RTOG 1115 was a phase 3 trial evaluating the addition of orteronel, a CYP17A1 inhibitor, to radiation therapy (RT) plus androgen deprivation therapy (ADT) in men with high-risk prostate cancer. Methods and Materials The study was designed to evaluate overall survival for 900 men with high-risk prostate cancer (Gleason 9-10, prostate specific antigen (PSA) > 20, or clinical stage T2 or higher with Gleason ≥ 8). Patients were randomized 1:1 to standard of care (SOC) therapy (RT plus 2 years of ADT) or SOC plus 2 years of orteronel. RT entailed image guided conventionally fractionated dose-escalated external beam RT to the prostate and pelvis to 45 Gy using intensity modulated RT with either intensity modulated RT (to 79.2 Gy) or brachytherapy boost. Health-related quality of life (HRQOL) was measured using the Expanded Prostate cancer Index Composite (EPIC), Patient-Reported Outcome Measurement Information System (PROMIS) fatigue, and EQ-5D. Accrual was halted early because of discontinuation of orteronel development and the trial redesigned to focus on a composite biochemical failure endpoint. Results There were a total of 231 eligible randomized patients. Only 29% in the orteronel arm received ≥80% of the planned dose. With median follow-up of 6.2 years, the cumulative incidence of grade 3+ adverse events was higher on orteronel than on the standard arm (P < .001; hazard ratio [HR], 2.32; 95% CI, 1.52-3.47) with 5-year estimates of 59.0% and 35.1%, respectively. No significant differences in overall survival (P = .28; HR, 0.71; 95% CI, 0.39-1.32) or biochemical failure (P = .56; HR, 0.84; 95% CI, 0.47-1.51) were observed. Use of orteronel had a transient negative impact on all prostate cancer-specific QOL domains of the EPIC, but did not increase the magnitude of decline once RT started and had minimal impact on other HRQOL measures. Conclusions The addition of orteronel to RT and ADT did not result in significant improvement in any efficacy outcomes, although information was limited by poor drug tolerance and early termination of accrual, thus limiting statistical power.

Collaborating with climate justice practitioners, we conducted a nationally representative survey of U.S. adults (n = 1,011) to measure and explore predictors of Americans’ climate justice beliefs and intentions to engage in related behaviors. We find that only about one-third of Americans have heard of climate justice, but about half of Americans support climate justice goals once they are explained. Support for climate justice is predicted by many factors, including views about global warming, perceptions of climate and racial injustice, cultural worldviews, and demographics including racial identity, gender, and political party/ideology. Our study suggests a need to build public awareness of the term “climate justice,” the disproportionate harms of climate change, and how climate justice initiatives will address these harms. Our study also illustrates how researchers might incorporate practitioner perspectives in national and international studies on climate justice.

Climate beliefs shape engagement with climate action, yet research often overlooks their interconnections. This research frames climate beliefs as a belief system and examines two structural features: density (the strength of all connections) and inconsistency (conflicts between beliefs). Using Facebook survey data from 110 geographic areas (n = 99,074), we show that global north presents higher density networks, where climate beliefs are more tightly correlated, while many global south areas have positive but less interconnected beliefs. Inconsistency appears in geographic areas where opposition to reducing fossil fuel use conflicts with support for renewable energy and government prioritization of climate policies, such as in the Middle East. Information exposure is positively correlated with density and negatively with inconsistency. Gross domestic product per capita is positively associated with density and carbon resource dependence positively correlates with inconsistency. These findings offer communication strategies to enhance climate belief endurance while addressing conflicting beliefs that may undermine climate action.

Some climate activists use nonviolent civil disobedience (NVCD) to protest the slow pace of climate policy action. Civil disobedience theorists posit that building a critical mass of support for and participation in NVCD increases the likelihood of policy success. Here we investigate predictors of public support for and personal willingness to engage in NVCD using data from a nationally representative survey of U.S. adults (n = 1303). Linear regression analysis revealed the following significant predictors of public willingness to support and engage in NVCD: collective efficacy; anger; identification with climate activists; descriptive norms and exposure to liberal news media. Similarly, all these variables were significant in the relative weight analysis. These findings provide theoretical and practical insights into the role of NVCD in the climate movement.

Climate change is a pressing issue that requires action across multiple levels, from individual behavior to international cooperation. On the individual level, one of the easiest and most important actions people can take is to talk about climate change. However, relatively few Americans engage in climate change discussions with family and friends, creating what has been referred to as “climate silence”. Here we investigate factors that predict how often people have these discussions. Using data from three recent waves of a nationally representative survey of American adults, we find that worry, perceived risk, perceived social norms (descriptive and injunctive), perceived scientific consensus, and exposure to media coverage of global warming all significantly predict discussion of global warming with family and friends. We conclude with suggestions that can stimulate climate conversations.

PURPOSE:Salvage radiation therapy (RT) is used in men with prostate cancer (PC) recurrence following radical prostatectomy signaled by a persistent or delayed elevation in prostate specific antigen. It was previously reported that the use of antiandrogen therapy (AAT) with RT improved cancer control and overall survival (OS). Long-term follow-up results are presented in this study. METHODS AND MATERIALS:From 1998 to 2003, 760 eligible postradical prostatectomy patients with stage pT3N0 or with pT2N0 and positive margins and prostate specific antigen from 0.2 to 4.0 ng/mL were randomly assigned on a double-blinded, placebo-controlled trial of RT + placebo versus RT + AAT (24 months of bicalutamide, 150 mg daily) during and after RT (64.8 Gy in 36 fractions prostate bed). The primary endpoint was OS estimated using Kaplan-Meier method. Time to PC death and metastatic PC (competing risk of death without an event) was estimated using cumulative incidence. The hazard ratio (HR) was obtained using Cox models (OS) and subdistribution HRs (sHRs) used the Fine-Gray model (time to PC death and metastatic PC). RESULTS:Median follow-up for surviving patients was 18.9 years. OS at 18 years was 53% (95% CI, 47%-58%) for RT + AAT and 43% (95% CI, 38%-49%) for RT + placebo (adjusted HR = 0.82; 95% CI, 0.67-1.00; 1-sided P = .025). The 18-year incidence of centrally reviewed PC deaths was 18% (95% CI, 14%-22%) RT + AAT and 28% (95% CI, 23-33%) RT + placebo (unadjusted sHR = 0.63; 95% CI, 0.46-0.84; 2-sided P = .002). The 18-year incidence of metastatic PC was 22% (95% CI, 18-26%) and 31% (95% CI, 26-36%) for AAT and placebo arms, respectively (unadjusted sHR = 0.62; 95% CI, 0.46-0.83; 2-sided P = .001). CONCLUSIONS:Long-term results of 24-month duration AAT during and after salvage RT are consistent with the primary report with significantly improved long-term OS, reduced incidence of metastatic PC, and PC death for RT + AAT. In comparison with previous reports, the improvement in OS with AAT has risen from 5% at 12 years to 9.8% at 18 years.

Climate change communication campaigns can reach many audiences cost-effectively. However, some climate messages may not work universally as there may be heterogeneity in message effects across audiences. An online experiment (N = 57,968) across 23 countries found that three climate messages had modest positive effects on support for climate action. An "Urgency & Generational" message had the strongest effect overall and had, on average, stronger effects in countries with lower baseline support for climate action (e.g., developed countries, democratic countries). While the size of this message's positive effects varied across countries, effects were positive across all audience subgroups investigated and there was no evidence of backfire effects. For instance, this message had positive effects across the political spectrum and effects were marginally stronger among the political Right. Although the average message effects were small, the results indicate that, when deployed at a large scale, climate change messages have the potential to strengthen public support for climate action.

BACKGROUND AND OBJECTIVE:NRG/RTOG 0521 randomized men with high-risk localized prostate cancer (PC) to androgen suppression (AS) and definitive radiotherapy (RT) ± docetaxel-based chemotherapy (CT). The overall survival (OS) benefit with CT initially reported was lost on longer follow-up. The Decipher genomic classifier (GC) measures multiple transcripts relevant to docetaxel action. Basal/luminal differentiation portends differential response to AS and CT for high-risk localized and metastatic hormone-sensitive PC. We validated the Decipher GC in pretreatment biopsy samples for risk stratification and examined basal-luminal subtyping to predict docetaxel response. METHODS:Decipher GC scores and basal-luminal cellular subtypes were generated for specimens from NRG/RTOG 0521. The primary objective was to validate the independent prognostic ability of GC for metastasis-free survival (MFS). Treatment effects in luminal proliferating (LP) and non-LP cell subtypes were examined in relation to MFS, OS, and distant metastasis (DM). KEY FINDINGS AND LIMITATIONS:Samples were obtained from 283 patients and yielded 183 GC scores. Over median follow-up of 9.9 yr, 67 metastasis events were observed, including 34 DM events. Multivariable analysis revealed that GC was independently associated with DM (subdistribution hazard ratio 1.45) and MFS (hazard ratio 1.20). No biomarker-by-treatment interaction with GC and docetaxel was detected. The 10-yr restricted mean survival time difference in OS with CT was 13.7 mo for LP (p = 0.053) and 2.5 mo for non-LP (p = 0.63) tumors. CONCLUSIONS AND CLINICAL IMPLICATIONS:The Decipher GC score was independently associated with DM and MFS, and LP tumors may benefit from addition of CT. Validation of these findings may allow more effective use of CT in men with localized PC. The original NRG/RTOG 0521 trial is registered on ClinicalTrials.gov as NCT00288080.

BACKGROUND AND OBJECTIVE:Optimal management for high-risk prostate cancer is unclear. Using individual patient data from two contemporaneous North American cooperative group phase 3 randomized controlled trials (RCTs), we compared the outcomes of high-risk prostate cancer patients treated with radiotherapy-based and radical prostatectomy (RP)-based treatment strategies. METHODS:Data were collected from newly diagnosed high-risk prostate cancer patients enrolled in NRG/RTOG 0521 who received radiotherapy-based treatment (2005-2009), and those enrolled in CALGB 90203 who received surgery-based treatment (2006-2015). Patients received radiotherapy plus 24 mo of androgen deprivation therapy (ADT) ± six cycles of adjuvant docetaxel versus RP with personalized postoperative therapy ± neoadjuvant six cycles of docetaxel and 18-24 wk of ADT. The primary objective was to compare the cumulative incidence of distant metastasis considering death as a competing event using the inverse probability of treatment weighting (IPTW). KEY FINDINGS AND LIMITATIONS:Overall, 1290 patients (radiotherapy n = 557, RP n = 733) were included with similar follow-up (median 6.4 [interquartile range {IQR}: 5.6-6.9] yr and 6.4 [IQR: 4.7-8.5] yr, respectively). Patients who received surgery had generally more favorable prognostic features and were younger relative to those who received radiotherapy. After IPTW, the cumulative incidence of distant metastasis was significantly lower in patients who underwent radiotherapy-based compared with RP-based treatment (8-yr distant metastasis: 15% [95% confidence interval {CI} 9.3-21] vs 22% [95% CI 18-26]; adjusted subdistribution hazard ratio [sHR] 0.58 [95% CI 0.42-0.81]; p = 0.001). We did not find any significant difference in the incidence of deaths after distant metastasis (adjusted sHR 0.98 [95% CI 0.61-1.58]) between the two groups. CONCLUSIONS AND CLINICAL IMPLICATIONS:High-risk prostate cancer patients enrolled in RCTs had a significantly lower incidence of distant metastasis with a radiotherapy-based treatment strategy than with an RP-based treatment strategy, while the risk of deaths after distant metastasis was similar in the two groups.

Research shows that opinions rooted in moral justifications may be more stable over time. This suggests that communicators could create more durable persuasion by adding explicit moral claims (i.e., stating that the issue is a matter of right vs. wrong) to persuasive messages. Here, using animated videos about the transition from fossil fuels to renewable energy, we conducted a three-stage longitudinal experiment ( N = 4,488) to test whether messages with explicit moral claims have more durable persuasive effects than similar messages without. We replicated this test across two distinct moral dimensions: harm to innocent people and contamination of nature’s purity. Our findings show that all message versions had strong immediate persuasive effects relative to a control condition, and much of those effects remained after a 3-week period. However, there were no clear advantages—in immediate effects or in durability—from adding explicit moral claims to the messages.

In 2021, the Indian government announced the goal of net-zero carbon emissions in India by 2070. India’s vulnerability to climate impacts and central role in reducing global emissions make it essential to understand the policy features that affect Indians’ support for the 2070 goal. We conducted a conjoint experiment (N = 1,500) to test Indians’ support for the 2070 goal depending on differences among possible policy features including economic programs, allocation of funds collected via coal taxes, policies to mitigate pollution, who participates in the policy-making process, and adaptation policy. We find that Indians express stronger support for the 2070 goal when it includes jobs programs for Indians who lose their job in a coal-fired power plant, policies to mitigate pollution, investment or redistribution of funds collected via coal taxes, and adaptation policies to protect the most vulnerable Indians and critical infrastructure. Support for certain policy features varies depending on income, education, and caste.

309 Background: Standard of care (SOC) treatment options for HR-PCa include RT with long-term androgen deprivation (LT-ADT) or RP with selective use of post-operative RT +/- androgen deprivation therapy (ADT). The optimal treatment approach has been assessed in retrospective population-based and multi-center comparisons, which have yielded mixed results with substantial bias. Therefore, we conducted an emulated randomized comparison of RT vs RP in HR-PCa leveraging patients enrolled in RCTs. Methods: We searched Medline for RCTs in HR-PCa with a SOC arm of an RT- or RP-based regimen. Inclusion required similar experimental treatment and contemporaneous enrollment in the same country to reduce bias. This identified 2 trials, NRG/RTOG 0521 (RT+LT-ADT +/- 6 cycles docetaxel [doce]), and CALGB 90203 (RP +/- neoadjuvant 6 cycles doce and ADT). Due to inherent difference in the biochemical recurrence criteria after RT vs RP, we chose inverse probability of treatment weighted (IPTW) cumulative incidence of distant metastasis (DM) as the primary endpoint, considering deaths as competing events. Death after DM was measured to create a harmonized metric of deaths likely attributed to PCa. To assess potential residual selection bias, death without DM to capture non-cancer associated deaths was analyzed. Results: Overall, 1290 patients (RT n=557, RP n=733) were included, with similar median follow-up of 6.4 years. Prior to IPTW, RP patients were significantly younger with lower baseline PSA compared to RT patients. Adjuvant (18%) and salvage therapy (44%) was used in RP cohort. Cumulative incidence of DM was significantly lower in patients who underwent RT compared to RP (8-year DM: 16% vs 23%; p=0.01; subdistribution hazard ratio [sHR] 0.48 [95%CI 0.34-0.69], p<0.001). 8-year rates of death after DM were 10% vs 8% (p=0.72) in the RP and RT patients, respectively. RT patients had significantly greater risk of death without DM (HR 2.09 [1.01-4.34], p=0.048) with early differences measured. On a cross-arm comparison, 8-year cumulative incidence of DM when comparing SOC RT+LT-ADT group versus the doce+ADT+RP group was 18% vs 21%, respectively (sHR 0.75 [0.45-1.24], p=0.26). Conclusions: HR-PCa patients enrolled on RCTs had significantly lower incidence of DM with an RT-based strategy compared to an RP-based approach. Longer follow-up is needed to assess deaths attributed to PCa. Despite the strengths of the comparison (use of cooperative group RCT data, contemporaneous enrollment in the same country, patients fit enough for chemotherapy, and IPTW adjustments) there appears to be residual unmeasured bias, as expected, based on greater early deaths without DM in the RT arm. Utilization of post-operative radiotherapy and ADT+Doce may mitigate differences between RP and SOC RT+LT-ADT.

Extreme weather, including heat waves, poses a significant threat to ecosystems and human health. As global temperatures continue to rise, the frequency and severity of heat waves will increase. Because of this, communicating heat-related risks to the public is increasingly important. One commonly-used communication tool is the Climate Shift Index (CSI), which establishes how much more likely an extreme weather event, such as a heat wave, has been made by climate change. To test the impact of the CSI on people’s understanding of the links between climate change and extreme weather, we conducted an experiment informing 3,902 American adults that climate change made the July 2023 heat wave in the U.S. at least 5 times more likely. In addition to this standard CSI wording and 2 control messages, we also explored the effectiveness of reframing magnitude as a percentage, and whether mechanistic and attribution explanations of the relationship between climate change and heat waves further increase understanding. All treatments increased the belief that climate change made the July 2023 heat wave more likely and is making heat waves in general more likely as well. Additionally, we found that expressing the magnitude as a percentage was more effective than the standard CSI framing. We also found that just talking about the heatwave, without mentioning climate change, was enough to change beliefs.

Background Intensification of therapy may improve outcomes for patients with high-risk localized prostate cancer. Objective To provide long-term follow-up data from phase III RTOG 0521, which compared a combination of androgen deprivation therapy (ADT) + external beam radiation therapy (EBRT) + docetaxel with ADT + EBRT. Design, setting, and participants High-risk localized prostate cancer patients (>50% of patients had Gleason 9–10 disease) were prospectively randomized to 2 yr of ADT + EBRT or ADT + EBRT + six cycles of docetaxel. A total of 612 patients were accrued, and 563 were eligible and included in the modified intent-to-treat analysis. Outcome measurements and statistical analysis The primary endpoint was overall survival (OS). Analyses with Cox proportional hazards were performed as prespecified in the protocol; however, there was evidence of nonproportional hazards. Thus, a post hoc analysis was performed using the restricted mean survival time (RMST). The secondary endpoints included biochemical failure, distant metastasis (DM) as detected by conventional imaging, and disease-free survival (DFS). Results and limitations After 10.4 yr of median follow-up among survivors, the hazard ratio (HR) for OS was 0.89 (90% confidence interval [CI] 0.70–1.14; one-sided log-rank p = 0.22). Survival at 10 yr was 64% for ADT + EBRT and 69% for ADT + EBRT + docetaxel. The RMST at 12 yr was 0.45 yr and not statistically significant (one-sided p = 0.053). No differences were detected in the incidence of DFS (HR = 0.92, 95% CI 0.73–1.14), DM (HR = 0.84, 95% CI 0.73–1.14), or prostate-specific antigen recurrence risk (HR = 0.97, 95% CI 0.74–1.29). Two patients had grade 5 toxicity in the chemotherapy arm and zero patients in the control arm. Conclusions After a median follow-up of 10.4 yr among surviving patients, no significant differences are observed in clinical outcomes between the experimental and control arms. These data suggest that docetaxel should not be used for high-risk localized prostate cancer. Additional research may be warranted using novel predictive biomarkers. Patient summary No significant differences in survival were noted after long-term follow-up for high-risk localized prostate cancer patients in a large prospective trial where patients were treated with androgen deprivation therapy + radiation to the prostate ± docetaxel.

Social media has become an important medium for climate change communication, where sponsored content can be delivered to specific audiences. However, studying message effects on social media platforms has limitations and therefore scholars often rely on surveys and controlled experiments, which can lack external validity. Here, we use survey methods to predict the real-world performance of advertisements on Facebook. We found that a 10 percentage point increase in self-reported likelihood of sharing a post predicted 55% more actual shares, and a 10 percentage point increase in perceptions that the post would be interesting to others predicted 86% more shares. We also found a U-shaped relationship between people's emotional reactions to the posts and the number of shares, such that emotionally-neutral posts were shared less often than posts that elicited either a strongly positive or negative emotional response. We then discuss the strategic and practical applications of these findings.

BACKGROUND:Androgen deprivation therapy (ADT) has been associated with coronary heart disease and myocardial infarction (MI) in prostate cancer patients, but controversy persists regarding its effects on cardiovascular mortality (CVM). OBJECTIVE:We assessed the long-term relationship between ADT and CVM in a prostate cancer randomized trial (NRG Oncology/Radiation Therapy Oncology Group 9202). DESIGN, SETTING, AND PARTICIPANTS:From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-T4, prostate-specific antigen <150 ng/ml) received radiotherapy with 4 mo (short-term [STADT]) versus 28 mo (longer-term [LTADT]) of ADT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Using the Fine-Gray and Cox regression models, the relationship between ADT and mortality was evaluated. RESULTS AND LIMITATIONS:With a median follow-up of 19.6 yr, LTADT was associated with improved overall survival (OS) versus STADT (adjusted hazard ratio [HR] 0.88; p = 0.03) and prostate cancer survival (subdistribution HR [sHR] 0.70, p = 0.003). Comparing LTADT with STADT, prostate cancer mortality improved by 6.0% (15.6% [95% confidence interval 13.0-18.3%] vs 21.6% [18.6-24.7%]) at 15 yr, while CVM increased by 2.2% (14.9% [12.4-17.6%] vs 12.7% [10.4-15.3%]). In multivariable analyses, LTADT was not associated with increased CVM versus STADT (sHR 1.22 [0.93-1.59]; p = 0.15). An association between LTADT and MI death was detected (sHR 1.58 [1.00-2.50]; p = 0.05), particularly in patients with prevalent cardiovascular disease (CVD; sHR 2.54 [1.16-5.58]; p = 0.02). CONCLUSIONS:With 19.6 yr of follow-up, LTADT was not significantly associated with increased CVM in men with locally advanced prostate cancer. Patients may have increased MI mortality with LTADT, particularly those with baseline CVD. Overall, there remained a prostate cancer mortality benefit and no OS detriment with LTADT. PATIENT SUMMARY:In a long-term analysis of a large randomized prostate cancer trial, radiation with 28 mo of hormone therapy did not increase the risk of cardiovascular death significantly versus 4 mo of hormone therapy. Future studies are needed for patients with pre-existing heart disease, who may have an increased risk of myocardial infarction death with longer hormone use.

The mental health impacts of climate change are increasingly documented; however, less research has investigated the relationship between climate change-related psychological distress and engagement with the issue. The results from two national probability samples of U.S. adults show that 16% report at least one feature of climate change psychological distress and that certain groups have higher levels of distress than others (e.g., Hispanic/Latinos, lower income adults, younger adults). Importantly, people experiencing distress are more likely to engage in collective action on climate change or express a willingness to do so, even when controlling for several correlates of environmental behavior (e.g., political ideology, collective efficacy beliefs). These findings highlight that many Americans are experiencing psychological distress from climate change, and those who do are more involved in collective climate action. People experiencing such distress may benefit from resources to support mental health and engagement with climate change.

Beliefs and attitudes form the core of public opinion about climate change. Network analysis can reveal the structural configuration of these beliefs and attitudes. In this research, we utilize a belief system framework to identify key psychological elements, track change in the density of these belief systems over time and across political groups, and analyze the structural heterogeneity of belief systems within and between political groups in the United States. Drawing on fifteen waves of nationally representative survey data from 2010 to 2021 (N = 16,742), our findings indicate that worry about climate change is the most central psychological element. Interestingly, we find that among politically unaffiliated individuals, the connections between psychological elements have strengthened over time, implying an increase in the consistency of belief systems within this group. Despite the political polarization in beliefs about climate change between Republicans and Democrats, our findings reveal that the ways these two groups organize and structure climate change beliefs systems are not markedly different compared to those of other groups. These findings provide theoretical and practical insights for climate change experts and communicators.