Marital Status, Living Arrangement, and Survival among Individuals with Advanced Prostate Cancer in the International Registry for Men with Advanced Prostate Cancer.

BACKGROUND: Studies have shown improved survival among individuals with cancer with higher levels of social support. Few studies have investigated social support and overall survival (OS) in individuals with advanced prostate cancer in an international cohort. We investigated the associations of marital status and living arrangements with OS among individuals with advanced prostate cancer in the International Registry for Men with Advanced Prostate Cancer (IRONMAN). METHODS: IRONMAN is enrolling participants diagnosed with advanced prostate cancer (metastatic hormone-sensitive prostate cancer, mHSPC; castration-resistant prostate cancer, CRPC) from 16 countries. Participants in this analysis were recruited between July 2017 and January 2023. Adjusting for demographics and tumor characteristics, the associations were estimated using Cox regression and stratified by disease state (mHSPC, CRPC), age (<70, ≥70 years), and continent of enrollment (North America, Europe, Other). RESULTS: We included 2,119 participants with advanced prostate cancer, of whom 427 died during up to 5 years of follow-up (median 6 months). Two-thirds had mHSPC. Most were married/in a civil partnership (79%) and 6% were widowed. Very few married participants were living alone (1%), while most unmarried participants were living alone (70%). Married participants had better OS than unmarried participants [adjusted HR: 1.44; 95% confidence interval (CI): 1.02-2.02]. Widowed participants had the worst survival compared with married individuals (adjusted HR: 1.89; 95% CI: 1.22-2.94). CONCLUSIONS: Among those with advanced prostate cancer, unmarried and widowed participants had worse OS compared with married participants. IMPACT: This research highlighted the importance of social support in OS within this vulnerable population.

Pain and Its Association with Survival for Black and White Individuals with Advanced Prostate Cancer in the United States.

Bone pain is a well-known quality-of-life detriment for individuals with prostate cancer and is associated with survival. This study expands previous work into racial differences in multiple patient-reported dimensions of pain and the association between baseline and longitudinal pain and mortality. This is a prospective cohort study of individuals with newly diagnosed advanced prostate cancer enrolled in the International Registry for Men with Advanced Prostate Cancer (IRONMAN) from 2017 to 2023 at U.S. sites. Differences in four pain scores at study enrollment by race were investigated. Cox proportional hazards models and joint longitudinal survival models were fit for each of the scale scores to estimate HRs and 95% confidence intervals (CI) for the association with all-cause mortality. The cohort included 879 individuals (20% self-identifying as Black) enrolled at 38 U.S. sites. Black participants had worse pain at baseline compared with White participants, most notably a higher average pain rating (mean 3.1 vs. 2.2 on a 10-point scale). For each pain scale, higher pain was associated with higher mortality after adjusting for measures of disease burden, particularly for severe bone pain compared with no pain (HR, 2.47; 95% CI: 1.44-4.22). The association between pain and all-cause mortality was stronger for participants with castration-resistant prostate cancer compared with those with metastatic hormone-sensitive prostate cancer and was similar among Black and White participants. Overall, Black participants reported worse pain than White participants, and more severe pain was associated with higher mortality independent of clinical covariates for all pain scales. SIGNIFICANCE: Black participants with advanced prostate cancer reported worse pain than White participants, and more pain was associated with worse survival. More holistic clinical assessments of pain in this population are needed to determine the factors upon which to intervene to improve quality of life and survivorship, particularly for Black individuals.

Quality of life in the year after new diagnosis with advanced prostate cancer for Black and White individuals living in the US.

PURPOSE: To assess differences in baseline and longitudinal quality of life among Black and White individuals in the US with advanced prostate cancer. METHODS: Secondary analysis of data from the International Registry for Men with Advanced Prostate Cancer (IRONMAN) including US participants newly diagnosed with advanced prostate cancer and identifying their race as Black or White from 2017 to 2023. Participants completed the EORTC QLQ-C30 Quality of Life (QoL) Survey at study enrollment and every 3 months thereafter for up to 1 year of follow-up reporting 15 scale scores ranging from 0 to 100 (higher functioning and lower symptom scores represent better quality of life). Linear mixed effects models with race and month of questionnaire completion were fit for each scale, and model coefficients were used to assess differences in baseline and longitudinal QoL by race. RESULTS: Eight hundred and seventy-nine participants were included (20% identifying as Black) at 38 US sites. Compared to White participants at baseline, Black participants had worse constipation (mean 6.3 percentage points higher; 95% CI 2.9-9.8), financial insecurity (5.7 (1.4-10.0)), and pain (5.1 (0.9-9.3)). QoL decreased over time similarly by race; most notably, role functioning decreased by 0.7 percentage points (95% CI -0.8, -0.5) per month. CONCLUSION: There are notable differences in quality of life at new diagnosis of advanced prostate cancer for Black and White individuals, and quality of life declines similarly in the first year for both groups. Interventions that address specific aspects of quality of life in these patients could meaningfully improve the overall survivorship experience.

Experience with the US health care system for Black and White patients with advanced prostate cancer.

OBJECTIVE: The purpose of this study was to assess differences in reported information about treatment, integration into care, and respect by self-identified Black and White individuals with advanced prostate cancer in the United States. PATIENTS AND METHODS: This is a prospective cohort study of 701 participants (20% identifying as Black) enrolled in the International Registry for Men with Advanced Prostate Cancer at 37 US sites from 2017 to 2022. Participants were asked six questions from the Cancer Australia National Cancer Control Indicators about their experience with care at study enrollment. Prevalence differences by self-reported race were estimated using marginal standardization of logistic-normal mixed effects models (adjusted for age at enrollment and disease state at enrollment), and 95% CIs were estimated using parametric bootstrapping. RESULTS: Most participants reported a high quality of care for each question. Black participants generally reported higher care quality compared with White participants. Black participants reported more frequently that they were offered a written assessment and care plan (71%) compared with White participants (58%; adjusted difference, 13 percentage points; 95% CI, 4-23). Black participants also reported more frequently being given the name of nonphysician personnel who would support them (64%) than White participants (52%; adjusted difference, 10; 95% CI, 1-20). Prevalence differences did not differ by disease state at enrollment. CONCLUSIONS: Black participants generally reported a higher quality of care compared with White participants. This study calls attention to the need to study potential mediating factors and interpersonal aspects of care in this population to improve survivorship.

Racial Disparities in Prostate Cancer: Evaluation of Diet, Lifestyle, Family History, and Screening Patterns.

BACKGROUND: Racial disparities in prostate cancer incidence and mortality rates are considerable. We previously found in the Health Professionals Follow-up Study (HPFS) that African-American men had an 80% higher prostate cancer risk than White men. With 21 additional years of follow-up and four-fold increase in cases, we undertook a contemporary analysis of racial differences in prostate cancer incidence and mortality in HPFS. METHODS: For 47,679 men, we estimated HRs and 95% confidence intervals (CI) for the association between race and risk of prostate cancer through 2016 using Cox proportional hazards regression. Multivariable models (mHR) were adjusted for lifestyle, diet, family history, and PSA screening collected on biennial questionnaires. RESULTS: 6,909 prostate cancer cases were diagnosed in White, 89 in African-American, and 90 in Asian-American men. African-Americans had higher prostate cancer incidence (mHR = 1.31; 95% CI, 1.06-1.62) and mortality (mHR = 1.67; 95% CI, 1.00-2.78), and lower PSA screening prevalence than White men. The excess risk was greater in the pre-PSA screening era (HR = 1.68; 95% CI, 1.14-2.48) than the PSA screening era (HR = 1.20; 95% CI, 0.93-1.56). Asian-Americans had lower prostate cancer risk (mHR = 0.74; 95% CI, 0.60-0.92), but similar risk of fatal disease compared with white men. CONCLUSIONS: Racial differences in prostate cancer incidence and mortality in HPFS are not fully explained by differences in lifestyle, diet, family history, or PSA screening. IMPACT: Additional research is necessary to address the disproportionately higher rates of prostate cancer in African-American men.

5-Alpha Reductase Inhibitors and Prostate Cancer Mortality among Men with Regular Access to Screening and Health Care.

BACKGROUND: How 5-alpha reductase inhibitor (5-ARI) use influences prostate cancer mortality is unclear. The objective of this study was to determine whether men taking 5-ARIs with regular health care access have increased prostate cancer mortality. METHODS: We undertook two analyses in the Health Professionals Follow-up Study examining 5-ARI use, determined by biennial questionnaires, and prostate cancer. A cohort analysis followed 38,037 cancer-free men for prostate cancer incidence from 1996 through January 2017 and mortality through January 2019. A case-only analysis followed 4,383 men with localized/locally advanced prostate cancer for mortality over a similar period. HRs and 95% confidence intervals (CI) were calculated for prostate cancer incidence and mortality. RESULTS: Men using 5-ARIs underwent more PSA testing, prostate exams and biopsies. Over 20 years of follow-up, 509 men developed lethal disease (metastases or prostate cancer death). Among men initially free from prostate cancer, 5-ARI use was not associated with developing lethal disease [HR, 1.02; 95% confidence interval (CI), 0.71-1.46], but was associated with reduced rates of overall and localized disease (HR, 0.71; 0.60-0.83). Among men diagnosed with prostate cancer, there was no association between 5-ARI use and cancer-specific (HR, 0.78; 95% CI, 0.48-1.27) or overall survival (HR, 0.88; 95% CI, 0.72-1.07). CONCLUSIONS: Men using 5-ARIs were less likely to be diagnosed with low-risk prostate cancer, without increasing long-term risk of lethal prostate cancer or cancer-specific death after diagnosis. IMPACT: Our results provide evidence that 5-ARI use is safe with respect to prostate cancer mortality in the context of regular health care access. See related commentary by Hamilton, p. 1259.

Tackling Diversity in Prostate Cancer Clinical Trials: A Report From the Diversity Working Group of the IRONMAN Registry.

Prostate cancer disproportionately affects racial and ethnic minority populations. Reasons for disparate outcomes among minority patients are multifaceted and complex, involving factors at the patient, provider, and system levels. Although advancements in our understanding of disease biology have led to novel therapeutics for men with advanced prostate cancer, including the introduction of biomarker-driven therapeutics, pivotal translational studies and clinical trials are underrepresented by minority populations. Despite attempts to bridge the disparities gap, there remains an unmet need to expand minority engagement and participation in clinical trials to better define the impact of therapy on efficacy outcomes, quality of life, and role of biomarkers in diverse patient populations. The IRONMAN registry (ClinicalTrials.gov identifier: NCT03151629), a global, prospective, population-based study, was borne from this unmet medical need to address persistent gaps in our knowledge of advanced prostate cancer. Through integrated collection of clinical outcomes, patient-reported outcomes, epidemiologic data, and biospecimens, IRONMAN has the goal of expanding our understanding of how and why prostate cancer outcomes differ by race and ethnicity. To this end, the Diversity Working Group of the IRONMAN registry has developed informed strategies for site selection, recruitment, engagement and retention, and trial design and eligibility criteria to ensure broad inclusion and needs awareness of minority participants. In concert with systematic strategies to tackle the complex levels of disparate care, our ultimate goal is to expand minority engagement in clinical research and bridge the disparities gap in prostate cancer care.

Diversity of Enrollment in Prostate Cancer Clinical Trials: Current Status and Future Directions.

BACKGROUND: Although there are considerable racial and ethnic disparities in prostate cancer incidence and mortality in the United States and globally, clinical trials often do not reflect disease incidence across racial and ethnic subgroups. This study aims to comprehensively review the reporting of race and ethnicity data and the representation of race and ethnicity across prostate cancer treatment-, prevention-, and screening-based clinical trials. METHODS: Seventy-two global phase III and IV prevention, screening, and treatment prostate cancer clinical trials with enrollment start dates between 1987 and 2016 were analyzed in this study, representing a total of 893,378 individual trial participants. Availability and representation of race and ethnicity data by trial funding type, temporal changes in the racial/ethnic diversity of participants, and geographic representation of countries were assessed. RESULTS: Of the 72 trials analyzed, 59 (81.9%) had available race data, and 11 (15.3%) of these trials additionally reported ethnicity. Of the trials reporting data, participants were overwhelmingly white men (with the highest proportion in U.S. nonpublicly funded trials), comprising over 96% of the study population. The proportion of white participants in prostate cancer clinical trials has remained at over 80% since 1990. Geographically, Africa and the Caribbean were particularly underrepresented with only 3% of countries included. CONCLUSIONS: Trial participants continue to be majority white despite the known racial disparities in prostate cancer clinical outcomes. IMPACT: Current and future trials must use novel recruitment strategies to ensure enrollment of underrepresented men. Targeting the inclusion of African and Caribbean medical centers is crucial to achieve equity in representation.

A Prospective Study of Intraprostatic Inflammation, Focal Atrophy, and Progression to Lethal Prostate Cancer.

BACKGROUND: Inflammation and focal atrophy are common features adjacent to prostate tumors. Limited evidence exists on whether these features have prognostic significance. METHODS: In the Health Professionals Follow-Up Study and Physicians' Health Study, we studied 1,035 men diagnosed with prostate cancer. A genitourinary pathologist centrally reviewed tumor and normal areas of hematoxylin and eosin slides from prostate cancer specimens for the presence of acute and chronic inflammation, and four subtypes of focal atrophy. Cox proportional hazards models adjusted for potential confounders were used to estimate HRs and 95% confidence intervals (CI) for the association of these features with lethal prostate cancer, defined as development of metastatic disease or death during follow-up. RESULTS: During a median of 12 years of follow-up, 153 men developed lethal prostate cancer. A total of 84% of men had histologic evidence of chronic inflammation and 30% had acute inflammation. Both chronic and acute inflammation were inversely associated with lethal prostate cancer in age- and lifestyle-adjusted models. Chronic inflammation remained inversely associated with lethal prostate cancer after additionally adjusting for prognostic clinical features (HR = 0.45; 95% CI, 0.30-0.69 for mild and HR = 0.51; 95% CI, 0.33-0.80 for moderate to severe). None of the atrophic lesions were associated with lethal prostate cancer. CONCLUSIONS: Our data suggest that the presence of inflammation, particularly chronic inflammation, in prostate cancer tissue is associated with better prognosis among patients with prostate cancer. IMPACT: This is the largest prospective cohort study to examine the association between inflammation, focal atrophy, and lethal prostate cancer.

A comparison of different bioinks for 3D bioprinting of fibrocartilage and hyaline cartilage.

Cartilage is a dense connective tissue with limited self-repair capabilities. Mesenchymal stem cell (MSC) laden hydrogels are commonly used for fibrocartilage and articular cartilage tissue engineering, however they typically lack the mechanical integrity for implantation into high load bearing environments. This has led to increased interested in 3D bioprinting of cell laden hydrogel bioinks reinforced with stiffer polymer fibres. The objective of this study was to compare a range of commonly used hydrogel bioinks (agarose, alginate, GelMA and BioINK™) for their printing properties and capacity to support the development of either hyaline cartilage or fibrocartilage in vitro. Each hydrogel was seeded with MSCs, cultured for 28 days in the presence of TGF-ß3 and then analysed for markers indicative of differentiation towards either a fibrocartilaginous or hyaline cartilage-like phenotype. Alginate and agarose hydrogels best supported the development of hyaline-like cartilage, as evident by the development of a tissue staining predominantly for type II collagen. In contrast, GelMA and BioINK™ (a PEGMA based hydrogel) supported the development of a more fibrocartilage-like tissue, as evident by the development of a tissue containing both type I and type II collagen. GelMA demonstrated superior printability, generating structures with greater fidelity, followed by the alginate and agarose bioinks. High levels of MSC viability were observed in all bioinks post-printing (∼80%). Finally we demonstrate that it is possible to engineer mechanically reinforced hydrogels with high cell viability by co-depositing a hydrogel bioink with polycaprolactone filaments, generating composites with bulk compressive moduli comparable to articular cartilage. This study demonstrates the importance of the choice of bioink when bioprinting different cartilaginous tissues for musculoskeletal applications.