Adding a Coefficient for Race to the 4Kscore Improves Calibration for Black Men.

PURPOSE: Black men face a higher incidence of high-risk prostate cancer (PCa) compared with non-Black men. While the 4Kscore is a widely utilized commercial test for PCa risk assessment, it does not currently account for racial differences. The aim of this study is to describe and validate a prespecified race coefficient for the 4Kscore with the goal of improving the accuracy of this test for Black men. MATERIALS AND METHODS: Using data from 85 Black men from the initial US prospective validation study, a race coefficient of 0.6 on the log-odds scale was prespecified. We calculated discrimination, calibration, and clinical utility of the 4Kscore with and without this coefficient for Black race in our primary analysis cohort of 205 Black men undergoing biopsy for PCa in a Veterans Affairs (VA) institution. We performed a sensitivity analysis using a combined cohort from the US prospective validation and the VA studies. RESULTS: The mean probability of high-grade PCa from the 4Kscore in the primary cohort increased from 25% to 37% with race coefficient addition. Incorporating the race coefficient improved 4Kscore's calibration in Black men, with consequent improvements in clinical utility based on decision curve analysis. Model discrimination was maintained (AUC 0.825 vs 0.828, P = .14) in the combined cohort of Black and non-Black men from the US prospective and VA studies and the calibration remained largely unchanged. CONCLUSIONS: Incorporating a prespecified coefficient for Black race improved calibration and clinical utility of the 4Kscore among Black men and should be added to the 4Kscore.

Genomic Characterization of Aggressive Breast Cancer in Younger Women.

PURPOSE: Although breast cancer (BC) risk increases with age, BC in younger women is more aggressive with higher mortality compared with older women. We characterize the genomic landscape of BCs in younger women. METHODS: Clinicopathologic, molecular, and genomic differences across age groups (< 40 years, 40-60 years, > 60 years) in female BC patients were investigated in two large cohorts [AACR-GENIE8.1 (n = 11,594) and METABRIC (n = 2509)]. Cox-proportional regression analyzed the prognostic impact of age groups for disease-specific survival (DSS) and recurrence-free survival (RFS) in METABRIC and progression-free survival (PFS) in GENIE cohorts. Chi-squared test was used to assess statistical associations between genomic alterations and age groups. RESULTS: Survival analysis showed that women < 40 years had shorter DSS [hazard ratio (HR): 1.52, p = 0.005], RFS (HR: 1.4, p = 0.006), and PFS (HR: 1.82, p = 0.0003) compared with women 40-60 years, and shorter RFS (HR: 1.5, p = 0.001) and PFS (HR: 2.95, p < 0.0001) compared with women > 60 years. Molecular subtypes in the METABRIC cohort showed women < 40 years were enriched with basal, and HER2+ subtypes, and less enriched with luminal A and B subtype (p < 0.0001). Characterization of genomic alterations in both cohorts demonstrated that BCs in women < 40 years were more enriched with TP53 mutations (FDR < 0.0001), BRCA1 mutations (FDR = 0.01), ERBB2 amplifications (FDR < 0.001), CDK12 amplifications (FDR < 0.001), and PPM1D amplifications (FDR < 0.001). In contrast, BCs in older women (> 60 years) were more enriched with PIK3CA, KMT2C, and CDH1 mutations (FDR < 0.0001). CONCLUSIONS: BCs in young women are associated with shorter survival and more aggressive genomic features, including mutations in TP53 and BRCA1, and amplifications in ERBB2 and CDK12. These findings have the potential to impact clinical trial design and treatment.

Colon Cancer Disparities in Stage at Presentation and Time to Surgery for Asian Americans, Native Hawaiians, and Pacific Islanders: A Study with Disaggregated Ethnic Groups.

BACKGROUND: Vast differences in barriers to care exist among Asian American, Native Hawaiian, and Pacific Islander (AANHPI) groups and may manifest as disparities in stage at presentation and access to treatment. Thus, we characterized AANHPI patients with stage 0-IV colon cancer and examined differences in (1) stage at presentation and (2) time to surgery relative to white patients. PATIENTS AND METHODS: We assessed all patients in the National Cancer Database (NCDB) with stage 0-IV colon cancer from 2004 to 2016 who identified as white, Chinese, Japanese, Filipino, Native Hawaiian, Korean, Vietnamese, Laotian, Hmong, Kampuchean, Thai, Asian Indian or Pakistani, and Pacific Islander. Multivariable ordinal logistic regression defined adjusted odds ratios (AORs), with 95% confidence intervals (CI), of (1) patients presenting with advanced stage colon cancer and (2) patients with stage 0-III colon cancer receiving surgery at ≥ 60 days versus 30-59 days versus < 30 days postdiagnosis, adjusting for sociodemographic/clinical factors. RESULTS: Among 694,876 patients, Japanese [AOR 1.08 (95% CI 1.01-1.15), p < 0.05], Filipino [AOR 1.17 (95% CI 1.09-1.25), p < 0.001], Korean [AOR 1.09 (95% CI 1.01-1.18), p < 0.05], Laotian [AOR 1.51 (95% CI 1.17-1.95), p < 0.01], Kampuchean [AOR 1.33 (95% CI 1.04-1.70), p < 0.01], Thai [AOR 1.60 (95% CI 1.22-2.10), p = 0.001], and Pacific Islander [AOR 1.41 (95% CI 1.20-1.67), p < 0.001] patients were more likely to present with more advanced colon cancer compared with white patients. Chinese [AOR 1.27 (95% CI 1.17-1.38), p < 0.001], Japanese [AOR 1.23 (95% CI 1.10-1.37], p < 0.001], Filipino [AOR 1.36 (95% CI 1.22-1.52), p < 0.001], Korean [AOR 1.16 (95% CI 1.02-1.32), p < 0.05], and Vietnamese [AOR 1.55 (95% CI 1.36-1.77), p < 0.001] patients were more likely to experience greater time to surgery than white patients. Disparities persisted when comparing among AANHPI subgroups. CONCLUSIONS: Our findings reveal key disparities in stage at presentation and time to surgery by race/ethnicity among AANHPI subgroups. Heterogeneity upon disaggregation underscores the importance of examining and addressing access barriers and clinical disparities.

Racial disparities in Black men with prostate cancer: A literature review.

Black men are disproportionately affected by prostate cancer (PCa), with earlier presentation, more aggressive disease, and higher mortality rates versus White men. Furthermore, Black men have less access to PCa treatment and experience longer delays between diagnosis and treatment. In this review, the authors discuss the factors contributing to racial disparities and present solutions to improve access to care and increase clinical trial participation among Black men with PCa. Racial disparities observed among Black men with PCa are multifaceted, evolving from institutional racism. Cultural factors include generalized mistrust of the health care system, poor physician-patient communication, lack of information on PCa and treatment options, fear of PCa diagnosis, and perceived societal stigma of the disease. In the United States, geographic trends in racial disparities have been observed. Economic factors, e.g., cost of care, recovery time, and cancer debt, play an important role in racial disparities observed in PCa treatment and outcomes. Racial diversity is often lacking in genomic and precision medicine studies. Black men are largely underrepresented in key phase 3 PCa trials and may be less willing to enroll in clinical trials due to lack of awareness, lack of diversity in clinical trial research teams, and bias of health care providers to recommend clinical research. The authors propose solutions to address these factors that include educating clinicians and institutions on the barriers Black men experience, increasing the diversity of health care providers and clinical research teams, and empowering Black men to be involved in their treatment, which are keys to creating equity for Black men with PCa. LAY SUMMARY: Prostate cancer negatively affects Black men more than men of other races. The history of segregation and mistreatment in the health care system may contribute to mistrust among Black men. Outcomes are worse for Black men because they are less likely to be screened or to receive treatment for prostate cancer. Black men also are unlikely to participate in clinical research, making it difficult for investigators to understand how Black men are affected by prostate cancer. Suggestions for addressing these differences include teaching physicians and nurses about the issues Black men experience getting treatment and improving how Black men get information on prostate cancer.

Disparities in Primary Breast Cancer Stage at Presentation Among Hispanic Subgroups.

BACKGROUND: Although the United States (US) Hispanic population consists of diverse communities, prior breast cancer studies often analyze this group in aggregate. Our aim was to identify differences in breast cancer stage at presentation in the US population, with a particular focus on Hispanic subgroups. METHODS: Data from the National Cancer Database (NCDB) from 2004 to 2017 were used to select women with primary breast cancer; individuals were disaggregated by racial and ethnic subgroup and Hispanic country of origin. Ordinal logistic regression was used to create adjusted odds ratios (aORs) with 95% confidence intervals (CIs), with higher odds representing presentation at later-stage breast cancer. Subgroup analysis was conducted based on tumor receptor status. RESULTS: Overall, among 2,282,691 women (5.2% Hispanic), Hispanic women were more likely to live in low-income and low-educational attainment neighborhoods, and were also more likely to be uninsured. Hispanic women were also more likely to present at later-stage primary breast cancer when compared with non-Hispanic White women (aOR 1.19, 95% CI 1.18-1.21; p < 0.01). Stage disparities were demonstrated when populations were disaggregated by country of origin, particularly for Mexican women (aOR 1.55, 95% CI 1.51-1.60; p < 0.01). Disparities worsened among both racial and country of origin subgroups in women with triple-negative disease. CONCLUSION: Later breast cancer stage at presentation was observed among Hispanic populations when disaggregated by racial subgroup and country of origin. Socioeconomic disparities, as well as uncaptured disparities in access and/or differential care, may drive these observed differences. Future studies with disaggregated data are needed to characterize outcomes in Hispanic communities and develop targeted interventions.

Shared burden: the association between cancer diagnosis, financial toxicity, and healthcare cost-related coping mechanisms by family members of non-elderly patients in the USA.

PURPOSE: There has been little research on the healthcare cost-related coping mechanisms of families of patients with cancer. Therefore, we assessed the association between a cancer diagnosis and the healthcare cost-related coping mechanisms of participant family members through their decision to forego or delay seeking medical care, one of the manifestations of financial toxicity. METHODS: Using data from the National Health Interview Survey (NHIS) between 2000 and 2018, sample weight-adjusted prevalence was calculated and multivariable logistic regressions defined adjusted odds ratios (aORs) for participant family members who needed but did not get medical care or who delayed seeking medical care due to cost in the past 12 months, adjusting for relevant sociodemographic covariates, including participant history of cancer (yes vs. no) and participant age (18-45 vs. 46-64 years old). The analysis of family members foregoing or delaying medical care was repeated using a cancer diagnosis * age interaction term. RESULTS: Participants with cancer were more likely than those without a history of cancer to report family members delaying (19.63% vs. 16.31%, P < 0.001) or foregoing (14.53% vs. 12.35%, P = 0.001) medical care. Participants with cancer in the 18 to 45 years old age range were more likely to report family members delaying (pinteraction = 0.028) or foregoing (pinteraction < 0.001) medical care. Other factors associated with cost-related coping mechanisms undertaken by the participants' family members included female sex, non-married status, poorer health status, lack of health insurance coverage, and lower household income. CONCLUSION: A cancer diagnosis may be associated with familial healthcare cost-related coping mechanisms, one of the manifestations of financial toxicity. This is seen through delayed/omitted medical care of family members of people with a history of cancer, an association that may be stronger among young adult cancer survivors. These findings underscore the need to further explore how financial toxicity associated with a cancer diagnosis can affect patients' family members and to design interventions to mitigate healthcare cost-related coping mechanisms.

Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis.

BACKGROUND: The international Intermediate Clinical Endpoints in Cancer of the Prostate working group has established metastasis-free survival as a surrogate for overall survival in localised prostate cancer based on the findings of 19 predominantly radiotherapy-based trials. We sought to comprehensively assess aggregate trial-level performance of commonly reported intermediate clinical endpoints across all randomised trials in localised prostate cancer. METHODS: For this meta-analysis, we searched PubMed for all trials in localised or biochemically recurrent prostate cancer published between Jan 1, 1970, and Jan 15, 2020. Eligible trials had to be randomised, therapeutic, reporting overall survival and at least one intermediate clinical endpoint, and with a sample size of at least 70 participants. Trials of metastatic disease were excluded. Intermediate clinical endpoints included biochemical failure, local failure, distant metastases, biochemical failure-free survival, progression-free survival, and metastasis-free survival. Candidacy for surrogacy was assessed using the second condition of the meta-analytical approach (ie, correlation of the treatment effect of the intermediate clinical endpoint and overall survival), using R2 weighted by the inverse variance of the log intermediate clinical endpoint hazard ratio. The intermediate clinical endpoint was deemed to be a surrogate for overall survival if R2 was 0·7 or greater. FINDINGS: 75 trials (53 631 patients) were included in our analysis. Median follow-up was 9·1 years (IQR 5·7-10·6). Biochemical failure (R2 0·38 [95% CI 0·11-0·64]), biochemical failure-free survival (R2 0·12 [0·0030-0·33]), biochemical failure and clinical failure (R2 0·28 [0·0045-0·65]), and local failure (R2 0·085 [0·00-0·37]) correlated poorly with overall survival. Progression-free survival (R2 0·46 [95% CI 0·22-0·67]) showed moderate correlation with overall survival, and metastasis-free survival (R2 0·78 [0·59-0·89]) correlated strongly. INTERPRETATION: Intermediate clinical endpoints based on biochemical and local failure did not meet the second condition of the meta-analytical approach and are not surrogate endpoints for overall survival in localised prostate cancer. Our findings validate metastasis-free survival as the only identified surrogate endpoint for overall survival to date. FUNDING: Prostate Cancer Foundation and National Institutes of Health.

Prostate tumors of native men from West Africa show biologically distinct pathways-A comparative genomic study.

BACKGROUND: Native African men (NAM) experience a disproportionate burden of prostate cancer (PCa) and have higher mortality rates compared to European American men (EAM). While socioeconomic status has been implicated as a driver of this disparity, little is known about the genomic mechanisms and distinct biological pathways that are associated with PCa of native men of African origin. METHODS: To understand biological factors that contribute to this disparity we utilized a total of 406 multi-institutional localized PCa samples, collected by Men of African Descent and Carcinoma of the Prostate biospecimen network and Moffitt Cancer Center/University of Pennsylvania Health science system. We performed comparative genomics and immunohistochemistry to identify the biomarkers that are highly enriched in NAM from west Africa and compared them with African American Men (AAM) and EAM. Quantified messenger RNA expression and Median H scores based on immune reactivity of staining cells, were compared using Mann Whitney test. For gene expression analysis, p values were further adjusted for multiple comparisons using false discovery rates. RESULTS: Immunohistochemical analysis on selected biomarkers showed a consistent association between ETS related gene (ERG) status and race with 83% of NAM exhibiting tumors that lacked TMPRSS2-ERG translocation (ERGnegative ) as compared to AAM (71%) and EAM (52%). A higher proportion of NAM (29%) were also found to be double negative (ERGnegative and PTENLoss ) as compared to AAM (6%) and EAM (7%). NAM tumors had significantly higher immunoreactivity (H-score) for PSMA, and EZH2, whereas they have lower H-score for PTEN, MYC, AR, RB and Racemase, (all p < .05). Comparative genomics revealed that NAM had significant transcriptomic variability in AR-activity score. In pathways enrichment analysis NAM tumors exhibited the enrichment of proinflammatory pathways including cytokine, interleukins, inflammatory response, and nuclear factor kappa B signaling. CONCLUSIONS: Prostate tumors in NAM are genomically distinct and are characterized by the dysregulation of several biomarkers. Furthermore, these tumors are also highly enriched for the major proinflammatory pathways. These distinct biological features may have implications for diagnosis and response to targeted therapy among Black men, globally.

Impact of health literacy on shared decision making for prostate-specific antigen screening in the United States.

BACKGROUND: Current guidelines endorse shared decision making (SDM) for prostate-specific antigen (PSA) screening. The relationship between a patient's health literacy (HL) and SDM remains unclear. In the current study, the authors sought to identify the impact of HL on the rates of PSA screening and on the relationship between HL and SDM following the 2012 US Preventive Services Task Force recommendations against PSA screening. METHODS: Using data from the 2016 Behavioral Risk Factor Surveillance System, the authors examined PSA screening in the 13 states that administered the optional "Health Literacy" module. Men aged ≥50 years were examined. Complex samples multivariable logistic regression models were computed to assess the odds of undergoing PSA screening. The interactions between HL and SDM were also examined. RESULTS: A weighted sample of 12.249 million men with a rate of PSA screening of 33.4% were identified. Approximately one-third self-identified as having optimal HL. Rates of PSA screening were found to be highest amongst the highest HL group (42.2%). Being in this group was a significant predictor of undergoing PSA screening (odds ratio, 1.214; 95% confidence interval, 1.051-1.403). There was a significant interaction observed between HL and SDM (P for interaction, <.001) such that higher HL was associated with a lower likelihood of undergoing PSA screening when SDM was present. CONCLUSIONS: In the uncertain environment of multiple contradictory screening guidelines, men who reported higher levels of HL were found to have higher levels of screening. The authors demonstrated that increased HL may reduce the screening-promoting effect of SDM. These findings highlight the dynamic interplay between HL and SDM that should inform the creation and promulgation of SDM guidelines, specifically when considering patients with low HL.

Risk of cardiovascular mortality with androgen deprivation therapy in prostate cancer: A secondary analysis of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Randomized Controlled Trial.

BACKGROUND: For men with radiation-managed prostate cancer, there is conflicting evidence regarding the association between androgen deprivation therapy (ADT) and cardiovascular mortality (CVM), particularly among those who have with preexisting comorbidities. The objective of this study was to analyze the association between ADT and CVM across patient comorbidity status using prospectively collected data from a large clinical trial. METHODS: In total, 1463 men were identified who were diagnosed with clinically localized, intermediate-risk/high-risk prostate cancer (T2b-T4, Gleason 7-10, or prostate-specific antigen >10 ng/mL) from 1993 to 2001 and managed with either radiation therapy (RT) alone or RT plus ADT during the randomized Prostate, Lung, Colon, and Ovarian (PLCO) Cancer Screening Trial. Adjusted hazard ratios (aHRs) for cause-specific mortality (prostate cancer-specific mortality vs other-cause mortality-including the primary end point of CVM [death from ischemic heart disease, cerebrovascular accident, or other circulatory disease]) were determined using Fine and Gray competing-risk regression analysis and stratified by comorbidity history. RESULTS: There was no difference in the risk of 5-year CVM between ADT plus RT and RT alone (2.3% vs 3.3%, respectively; aHR, 0.69; 95% CI, 0.38-1.24; P = .21) overall or on subgroup analysis among men with a history of ≥1 preexisting comorbidities (3.2% vs 5.3%, respectively; aHR, 0.83; 95% CI, 0.43-1.60; P = .58), ≥2 preexisting comorbidities (6.9% vs 8.3%, respectively; aHR, 0.95; 95% CI, 0.40-2.25; P = .90), or cardiovascular disease/risk factors (3.6% vs 4.3%, respectively; aHR, 0.85; 95% CI, 0.44-1.65; P = .63). These results were all similar when each component of CVM was analyzed separately-either cardiac, stroke, or other vascular mortality (P > .05). CONCLUSIONS: This study provides prospectively collected evidence that the use of ADT plus RT, compared with RT alone, is not associated with an increased risk of CVM, even among subgroups of men who have preexisting comorbidities and cardiovascular disease.

Racial differences in the treatment and outcomes for prostate cancer in Massachusetts.

BACKGROUND: Massachusetts is a northeastern state with universally mandated health insurance since 2006. Although Black men have generally worse prostate cancer outcomes, emerging data suggest that they may experience equivalent outcomes within a fully insured system. In this setting, the authors analyzed treatments and outcomes of non-Hispanic White and Black men in Massachusetts. METHODS: White and Black men who were 20 years old or older and had been diagnosed with localized intermediate- or high-risk nonmetastatic prostate cancer in 2004-2015 were identified in the Massachusetts Cancer Registry. Adjusted logistic regression models were used to assess predictors of definitive therapy. Adjusted and unadjusted survival models compared cancer-specific mortality. Interaction terms were then used to assess whether the effect of race varied between counties. RESULTS: A total of 20,856 men were identified. Of these, 19,287 (92.5%) were White. There were significant county-level differences in the odds of receiving definitive therapy and survival. Survival was worse for those with high-risk cancer (adjusted hazard ratio [HR], 1.50; 95% CI, 1.4-1.60) and those with public insurance (adjusted HR for Medicaid, 1.69; 95% CI, 1.38-2.07; adjusted HR for Medicare, 1.2; 95% CI, 1.14-1.35). Black men were less likely to receive definitive therapy (adjusted odds ratio, 0.78; 95% CI, 0.74-0.83) but had a 17% lower cancer-specific mortality (adjusted HR, 0.83; 95% CI, 0.7-0.99). CONCLUSIONS: Despite lower odds of definitive treatment, Black men experience decreased cancer-specific mortality in comparison with White men in Massachusetts. These data support the growing body of research showing that Black men may achieve outcomes equivalent to or even better than those of White men within the context of a well-insured population. LAY SUMMARY: There is a growing body of evidence showing that the excess risk of death among Black men with prostate cancer may be caused by disparities in access to care, with few or no disparities seen in universally insured health systems such as the Veterans Affairs and US Military Health System. Therefore, the authors sought to assess racial disparities in prostate cancer in Massachusetts, which was the earliest US state to mandate universal insurance coverage (in 2006). Despite lower odds of definitive treatment, Black men with prostate cancer experience reduced cancer-specific mortality in comparison with White men in Massachusetts. These data support the growing body of research showing that Black men may achieve outcomes equivalent to or even better than those of White men within the context of a well-insured population.

Financial worry and psychological distress among cancer survivors in the United States, 2013-2018.

BACKGROUND: A growing proportion of cancer survivors experience financial toxicity. However, the psychological burden of cancer costs and associated mental health outcomes require further investigation. We assessed prevalence and predictors of self-reported financial worry and mental health outcomes among cancer survivors. PATIENTS AND METHODS: Data from the 2013-2018 National Health Interview Survey (NHIS) for adults reporting a cancer diagnosis were used. Multivariable ordinal logistic regressions defined adjusted odds ratios (AORs) of reporting financial worry by relevant sociodemographic variables, and sample weight-adjusted prevalence of financial worry was estimated. The association between financial worry and psychological distress, as defined by the six-item Kessler Psychological Distress Scale was also assessed. RESULTS: Among 13,361 survey participants (median age 67; 60.0% female), 9567 (71.6%) self-reported financial worry, including worries regarding costs of paying for children's college education (62.7%), maintaining one's standard of living (59.7%), and medical costs due to illness or accident (58.3%). Female sex, younger age, and Asian American race were associated with increased odds of financial worry (P < 0.05 for all). Of 13,218 participants with complete responses to K6 questions, 701 (5.3%) met the threshold for severe psychological distress. Participants endorsing financial worry were more likely to have psychological distress (6.6 vs. 1.2%, AOR 2.89, 95% CI 2.03-4.13, P< 0.001) with each additional worry conferring 23.9% increased likelihood of psychological distress. CONCLUSIONS: A majority of cancer survivors reported financial worry, which was associated with greater odds of reporting psychological distress. Policies and guidelines are needed to identify and mitigate financial worries and psychologic distress among patients with cancer, with the goal of improving psychological well-being and overall cancer survivorship care.

Prostate cancer-specific mortality burden by risk group among men with localized disease: Implications for research and clinical trial priorities.

OBJECTIVE: To estimate contemporary population-based patterns of the relative burden of prostate cancer-specific mortality (PCSM) attributable to each N0M0 prostate cancer risk-group, that may guide prioritization in research, trial design, and clinical practice. METHODS: We categorized 2004-2015 Surveillance, Epidemiology, and End Results database patients by risk group (low, favorable intermediate, unfavorable intermediate, high, and very highrisk). Using the Fine-Gray method, we calculated the relative burden of 10-year PCSM attributable to each risk group. RESULTS: Among N = 337 162 men (6.8-year median follow-up; median age 65 years), the relative proportion of low-, favorable intermediate-, unfavorable intermediate-, high-, and very high-risk diagnoses were 29.9% (N = 100 969), 31.1% (N = 104 696), 17.9% (N = 60 360), 18.1% (N = 61 023), and 3.0% (N = 10 114). Within 10 years of diagnosis, among patients who died of prostate cancer (N = 15 064), 5.0% (N = 746) had low-risk, 13.7% (N = 2060) had favorable intermediate-risk, 16.1% (N = 2429) had unfavorable intermediate-risk, 47.8% (N = 7196) had high-risk, and 17.5% (N = 2633) had very high-risk disease at diagnosis. Patients aged 65 and older accounted for 51.9% of all diagnoses and 72.3% of 10-year PCSM. Although black patients accounted for 15.0% of low-risk diagnoses, they accounted for 20.6% of 10-year PCSM. White patients accounted for 80.3% of low-risk diagnoses and 75.7% of 10-year PCSM. CONCLUSION: Although high-risk and very high-risk disease account for one-fifth of diagnoses, they account for two-thirds of 10-year PCSM. Older patients and black patients with low-risk disease accounted for a disproportionately large proportion of deaths. These findings support targeting research toward high-risk disease and ensuring adequate representation of older and black men in clinical trials.

Short-term mortality risks among patients with oropharynx cancer by human papillomavirus status.

BACKGROUND: There is substantial variation in head and neck cancer (HNC) mortality and competing mortality among patients with HNC. In this study, the authors characterize the causes and risks of short-term mortality among patients with oropharynx cancer (OPC) and how these risks differ by human papillomavirus (HPV) status. METHODS: A custom Surveillance, Epidemiology, and End Results (SEER) data set with HPV status was used to identify 4930 patients with OPC who were diagnosed with nonmetastatic (M0) disease from 2013 to 2014, including 3560 (72.2%) HPV-positive patients and 1370 HPV-negative patients. Causes of death and cumulative incidence estimates for HNC-specific mortality, competing mortality, second-cancer mortality, and noncancer mortality were analyzed by HPV status. Risk factors for mortality events were determined using multivariable competing risk regression models. RESULTS: Compared with HPV-negative patients, HPV-positive patients had a lower risk of 2-year cumulative incidence of all-cause mortality (10.4% vs 33.3%; P < .0001) and a lower risk of both HNC-specific mortality (4.8% vs 16.2%; P < .0001) and competing-cause mortality (5.6% vs 16.8%; P < .0001). Second-cancer mortality was the most common cause of non-HNC mortality among HPV-negative patients. Both second-cancer mortality and noncancer mortality were significantly higher among patients who had HPV-negative OPC (10.8% and 6.1%, respectively) compared with those who had HPV-positive OPC (2.4% and 3.2%, respectively; both P < .0001). The median follow-up was 11 months (range 1-23 months) in this cohort with known HPV-status. CONCLUSIONS: Patients with HPV-positive and HPV-negative OPC have significantly different rates of both HNC mortality and competing mortality. HPV-negative patients are at substantial risk of competing mortality, even within 2 years of cancer diagnosis. These differences can inform power calculations for clinical trials and patient management in the acute and survivorship settings.

Validation of a subclassification for high-risk prostate cancer in a prospective cohort.

BACKGROUND: A subgroup of men with favorable high-risk prostate cancer (T1c with either a Gleason score of 4 + 4 = 8 and a prostate-specific antigen [PSA] level <10 ng/mL or a Gleason score of 6 and a PSA level >20 ng/mL) has been associated with improved outcomes in comparison with other standard high-risk patients. This study was designed to validate the prognostic utility of a subclassification for high-risk disease with a prospectively collected data set. METHODS: This study identified 3033 men from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had been diagnosed from 1993 to 2001 with clinically localized prostate cancer-either intermediate-risk disease (clinical stage T2b-c, a Gleason score of 7, or a PSA level of 10 to 20 ng/mL) or high-risk disease (clinical stage T3-T4, a Gleason score of 8-10, or a PSA level >20 ng/mL)-that was managed with radical prostatectomy or radiation therapy. Multivariable logistic regression was used to calculate adjusted odds ratios (aORs) for pathological T3 to T4 or N1 (pT3-T4/pN1) disease. Fine and Gray competing risks regression was used to determine adjusted hazard ratios (aHRs) of prostate cancer-specific mortality (PCSM). RESULTS: The median follow-up was 5.7 years. Patients with favorable high-risk disease had lower 8-year PCSM in comparison with patients with standard high-risk disease (2.2% vs 10.8%; aHR, 0.26; 95% confidence interval [CI], 0.09-0.73; P = .01) but similar PCSM in comparison with patients with intermediate-risk disease (2.2% vs 2.2%; aHR, 0.90; 95% CI, 0.32-2.54; P = .84). Among those who underwent surgery, those with favorable high-risk disease had lower odds of pT3-T4/pN1 disease than those with standard high-risk disease (46.2% vs 63.3%; aOR, 0.50; 95% CI, 0.27-0.94; P = .03). CONCLUSIONS: This study validates the prognostic utility of a subclassification for high-risk disease in a prospectively collected patient cohort. Patients with favorable high-risk disease have PCSM similar to that of patients with intermediate-risk disease and significantly better than that of patients with standard high-risk disease. Future trials are needed to assess possible de-intensification of therapy for favorable high-risk disease.

Genomic and clinical characterization of stromal infiltration markers in prostate cancer.

BACKGROUND: The progression of prostate cancer is a complex, multistep process that involves molecular alterations in cells of the tumor and the microenvironment, with associated interactions between the stroma and epithelium. Genomic expression analyses of stromal infiltration markers were performed to determine the significance thereof in prostate cancer. METHODS: Genome-wide expression profiles of formalin-fixed, paraffin-embedded radical prostatectomy samples were evaluated from a prospective registry cohort (n = 5239) and 3 retrospective institutional cohorts (n = 1135). Two independent stromal gene expression signatures implied stromal infiltration. Cox proportional hazards regression defined the association between stromal infiltration expression and metastasis-free survival (MFS). RESULTS: Stromal expression scores were correlated with stromal signature genes and with other key stromal markers (CAV1, VIM, and TAGLN), basal activity, and CD3 and CD4 immune biomarkers (r > 0.5 for all). The top decile of stromal expression was associated with high genomic risk scores (Decipher ≥ 0.6) , high Cancer of the Prostate Risk Assessment-Postsurgical scores, Gleason 9 to 10 disease, and a higher risk for metastasis (hazard ratio, 2.35; 95% CI, 1.37-4.02; P = .001). A higher stromal infiltration score was also associated with decreased expression of DNA repair genes and higher radiation sensitivity genomic scores. Postoperative radiation therapy (RT) was associated with an MFS benefit for patients with high stromal scores, but not for patients with low stromal scores (Pinteraction  = .02). CONCLUSIONS: Expression of stromal infiltration markers is correlated with prostate cancer aggressiveness/progression and may be predictive of a response to RT. Stromal infiltration markers should be studied and considered for incorporation into clinical prognostication and decision making.

Prostate cancer incidence across stage, NCCN risk groups, and age before and after USPSTF Grade D recommendations against prostate-specific antigen screening in 2012.

BACKGROUND: We sought to determine the extent to which US Preventive Services Task Force (USPSTF) 2012 Grade D recommendations against prostate-specific antigen screening may have impacted recent prostate cancer disease incidence patterns in the United States across stage, National Comprehensive Cancer Network (NCCN) risk groups, and age groups. METHODS: SEER*Stat version 8.3.4 was used to calculate annual prostate cancer incidence rates from 2010 to 2015 for men aged ≥50 years according to American Joint Committee on Cancer stage at diagnosis (localized vs metastatic), NCCN risk group (low vs unfavorable [intermediate or high-risk]), and age group (50-74 years vs ≥75 years). Age-adjusted incidences per 100,000 persons with corresponding year-by-year incidence ratios (IRs) were calculated using the 2000 US Census population. RESULTS: From 2010 to 2015, the incidence (per 100,000 persons) of localized prostate cancer decreased from 195.4 to 131.9 (Ptrend  < .001) and from 189.0 to 123.4 (Ptrend  < .001) among men aged 50-74 and ≥75 years, respectively. The largest relative year-by-year decline occurred between 2011 and 2012 in NCCN low-risk disease (IR, 0.77 [0.75-0.79, P < .0001] and IR 0.68 [0.62-0.74, P < .0001] for men aged 50-74 and ≥75 years, respectively). From 2010-2015, the incidence of metastatic disease increased from 6.2 to 7.1 (Ptrend  < .001) and from 16.8 to 22.6 (Ptrend  < .001) among men aged 50-74 and ≥75 years, respectively. CONCLUSIONS: This report illustrates recent prostate cancer "reverse migration" away from indolent disease and toward more aggressive disease beginning in 2012. The incidence of localized disease declined across age groups from 2012 to 2015, with the greatest relative declines occurring in low-risk disease. Additionally, the incidence of distant metastatic disease increased gradually throughout the study period.

General and Health-Related Internet Use Among Cancer Survivors in the United States: A 2013-2018 Cross-Sectional Analysis.

BACKGROUND: A significant proportion of cancer survivors endorse ongoing health information needs and may use the internet to access information. We assessed patterns and predictors of general and health-specific internet use among cancer survivors. METHODS: Using data from the National Health Interview Survey (NHIS), which was administered in 2013 through 2018, for adults reporting a cancer diagnosis, sample weight-adjusted estimates defined prevalence and multivariable logistic regressions defined adjusted odds ratios (aORs) of general and health-specific internet use, adjusting for relevant sociodemographic covariates, including healthcare satisfaction as the primary independent variable. The analysis for health-specific internet use was also repeated including a sex (female vs male)*healthcare satisfaction (very satisfied/somewhat satisfied vs somewhat dissatisfied/very dissatisfied) interaction term. RESULTS: Among 12,970 survivors of cancer, general and health-specific internet use increased from 2013 to 2018 (from 63.2% to 70.8% and from 46.8% to 52.2%, respectively; P<.05 for both). Survivors who were very dissatisfied with healthcare were more likely to use the internet for health information compared with those who were very satisfied (59.5% vs 48.0%; aOR, 1.78; 95% CI, 1.20-2.64; P=.004). Younger age, female sex, higher educational attainment, and higher socioeconomic status were all associated with increased reported use of the internet for both general and health-specific purposes (P<.001 for all). There was a significant sex*healthcare satisfaction interaction (P=.009) such that for female survivors, healthcare dissatisfaction was associated with higher odds of health-specific internet use (61.4% vs 52.5%; P<.001; men, P=.97). No association was found between healthcare satisfaction and general internet use (P=.42). CONCLUSIONS: The increasing proportion of survivors of cancer using the internet for health-specific information may be associated with self-reported dissatisfaction with healthcare. Efforts are needed to improve both access to the internet and the quality of cancer-relevant online health information, and to enhance patients' online health literacy.

Outcomes of HPV-Associated Squamous Cell Carcinoma of the Head and Neck: Impact of Race and Socioeconomic Status.

BACKGROUND: Socioeconomic factors affecting outcomes of HPV-associated squamous cell carcinoma of the head and neck (SCCHN) are poorly characterized. METHODS: A custom SEER database identified adult patients with primary nonmetastatic SCCHN and known HPV status diagnosed in 2013 through 2014. Multivariable logistic regression defined associations between patient characteristics and HPV status, with adjusted odds ratios (aORs) and 95% confidence intervals reported. Fine-Gray competing risks regression estimated adjusted hazard ratios (aHRs) and 95% confidence intervals for cancer-specific mortality (CSM), including a disease subsite * HPV status * race interaction term. RESULTS: A total of 4,735 patients with nonmetastatic SCCHN and known HPV status were identified. HPV-associated SCCHN was positively associated with an oropharyngeal primary, male sex, and higher education, and negatively associated with uninsured status, single marital status, and nonwhite race (P≤.01 for all). For HPV-positive oropharyngeal SCCHN, white race was associated with lower CSM (aHR, 0.55; 95% CI, 0.34-0.88; P=.01) and uninsured status was associated with higher CSM (aHR, 3.12; 95% CI, 1.19-8.13; P=.02). These associations were not observed in HPV-negative or nonoropharynx SCCHN. Accordingly, there was a statistically significant disease subsite * HPV status * race interaction (Pinteraction<.001). CONCLUSIONS: Nonwhite race and uninsured status were associated with worse CSM in HPV-positive oropharyngeal SCCHN, whereas no such associations were observed in HPV-negative or nonoropharyngeal SCCHN. These results suggest that despite having clinically favorable disease, nonwhite patients with HPV-positive oropharyngeal SCCHN have worse outcomes than their white peers. Further work is needed to understand and reduce socioeconomic disparities in SCCHN.