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.

Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation.

Metabolic regulation influences cell proliferation. The influence of pyruvate kinase isoforms on tumor cells has been extensively studied, but whether PKM2 is required for normal cell proliferation is unknown. We examine how PKM2 deletion affects proliferation and metabolism in nontransformed, nonimmortalized PKM2-expressing primary cells. We find that deletion of PKM2 in primary cells results in PKM1 expression and proliferation arrest. PKM1 expression, rather than PKM2 loss, is responsible for this effect, and proliferation arrest cannot be explained by cell differentiation, senescence, death, changes in gene expression, or prevention of cell growth. Instead, PKM1 expression impairs nucleotide production and the ability to synthesize DNA and progress through the cell cycle. Nucleotide biosynthesis is limiting, as proliferation arrest is characterized by severe thymidine depletion, and supplying exogenous thymine rescues both nucleotide levels and cell proliferation. Thus, PKM1 expression promotes a metabolic state that is unable to support DNA synthesis.

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.

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.

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.

Chemoradiation-Related Lymphopenia and Its Association with Survival in Patients with Squamous Cell Carcinoma of the Anal Canal.

BACKGROUND: Although treatment-related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, few data exist for anal cancer. We evaluated TRL and its association with survival in patients with anal cancer treated with chemoradiation (CRT). MATERIALS AND METHODS: A retrospective analysis of 140 patients with nonmetastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by grade (G)4 TRL (<0.2k/µL) 2 months after initiating CRT. Kaplan-Meier and log-rank tests were used to compare OS between patients with versus without G4 TRL. RESULTS: Median time of follow-up was 55 months. Prior to CRT, 95% of patients had a normal TLC (>1k/µL). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7-fold increased risk of death. On log-rank test, the 5-year OS rate was 32% in the cohort with G4 TRL versus 86% in the cohort without G4 TRL. CONCLUSION: TRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS suggests an important role of the host immunity in anal cancer outcomes. IMPLICATIONS FOR PRACTICE: This is the first detailed report demonstrating that standard chemoradiation (CRT) commonly results in treatment-related lymphopenia (TRL), which may be associated with a poorer overall survival (OS) in patients with anal squamous cell carcinoma. The association between TRL and worse OS observed in this study supports the importance of host immunity in survival among patients with anal cancer. These findings encourage larger, prospective studies to further investigate TRL, its predictors, and its relationship with survival outcomes. Furthermore, the results of this study support ongoing efforts of clinical trials to investigate the potential role of immunotherapy in anal cancer.

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.

Local management of preinvasive and clinical T1-3 penile cancer: utilization of diverse treatment modalities.

Aim: To explore management trends in preinvasive and cT1-T3 penile cancer. Materials & methods: The National Cancer Database was queried (2004-2013) for cT1-T3 M0 penile cancer with specified nonpalliative surgical techniques and histologies (n = 5,728). Results: Local excision (39%) and partial penectomy (38%) were most commonly utilized. Patients with cTis/Ta or cT1 disease more often received nonpenectomy approaches (p < 0.05); cT2-T3 cases more likely underwent penectomy (p < 0.001). No survival differences were observed between penectomy (49.3 months) and nonpenectomy approaches (50.3 months) in the overall cohort (p = 0.107) and when stratifying by T-stage (p > 0.20 for all). Conclusion: This study provides contemporary insight into the landscape for management of this rare disease and can serve as a benchmark for future evaluation of treatment trends.

Use and early mortality outcomes of active surveillance in patients with intermediate-risk prostate cancer.

BACKGROUND: Certain patients with intermediate-risk prostate cancer (PCa) may be appropriate candidates for active surveillance (AS). In the current study, the authors sought to characterize AS use and early mortality outcomes for patients with intermediate-risk PCa in the United States. METHODS: The novel Surveillance, Epidemiology, and End Results Active Surveillance/Watchful Waiting database identified 52,940 men diagnosed with National Comprehensive Cancer Network intermediate-risk PCa (cT2b-c, Gleason score of 7, or a prostate-specific antigen level of 10-20 ng/mL) and actively managed (AS, radiotherapy, or radical prostatectomy) from 2010 through 2015. The Cuzick test assessed AS time trends, and logistic multivariable regression characterized features associated with AS. Fine-Gray and Cox modeling determined PCa-specific mortality (PCSM) and overall survival, respectively. RESULTS: The rate of AS increased from 3.7% in 2010 to 7.3% in 2015, and from 7.2% to 11.7% among men aged ≥70 years. Among men with favorable and unfavorable intermediate-risk disease, the use of AS increased from 7.2% to 14.9% and from 2.2% to 3.8%, respectively (all P value for trend, <.001). The mean age of those patients managed with AS decreased from 69.9 years to 67.9 years (P = .0004). Factors found to be associated with AS included favorable risk disease; black race; higher socioeconomic status; older age; and diagnosis in the West, Northwest, or Midwest regions of the United States. The 5-year PCSM rate was comparable to AS versus treatment among patients with low-risk and favorable intermediate-risk disease, but was worse with AS among those with unfavorable intermediate-risk disease (PCSM, 1.3% vs 0.5%; adjusted hazard ratio, 2.48 [95% CI, 1.11-5.50; P = .026]) and intermediate-risk disease overall (PCSM, 1.1% vs 0.4%; adjusted hazard ratio, 2.34 [95% CI, 1.25-4.37; P = .008]). CONCLUSIONS: The use of AS for patients with intermediate-risk PCa is increasing across the United States, particularly for older men and those with favorable intermediate-risk disease. Early estimates of cancer-specific and overall mortality rates are low with AS, although significantly higher compared with treatment.

Conservative management of low-risk prostate cancer among young versus older men in the United States: Trends and outcomes from a novel national database.

BACKGROUND: Management for men aged ≤55 years with low-risk prostate cancer (LRPC) is debated given quality-of-life implications with definitive treatment versus the potential missed opportunity for cure with conservative management. The objective of this study was to define rates of conservative management for LRPC and associated short-term outcomes in young versus older men in the United States. METHODS: The nonpublic Surveillance, Epidemiology, and End Results Prostate with Active Surveillance/Watchful Waiting (AS/WW) Database identified 50,302 men who were diagnosed with LRPC from 2010 through 2015. AS/WW rates in the United States were stratified by age (≤55 vs ≥56 years). Prostate cancer-specific mortality and overall mortality were defined by initial management type (AS/WW vs definitive treatment [referent]) and age. RESULTS: AS/WW utilization increased from 8.61% (2010) to 34.56% (2015) among men aged ≤55 years (P for trend <0.001) and from 15.99% to 43.81% among men aged ≥56 years (P for trend <.001). Among patients who had ≤2 positive biopsy cores, AS/WW rates increased from 12.90% to 48.78% for men aged ≤55 years and from 21.85% to 58.01% for men aged ≥56 years. Among patients who had ≥3 positive biopsy cores, AS/WW rates increased from 3.89% to 22.45% for men aged ≤55 years and from 10.05% to 28.49% for men aged ≥56 years (all P for trend <.001). Five-year prostate cancer-specific mortality rates were <0.30% across age and initial management type subgroups. CONCLUSIONS: AS/WW rates quadrupled for patients aged ≤55 years from 2010 to 2015, with favorable short-term outcomes. These findings demonstrate the short-term safety and increasing acceptance of AS/WW for both younger and older patients. However, there are still higher absolute rates of AS/WW in older patients (P < .001), suggesting some national ambivalence toward AS/WW in younger patients.

Combined External Beam Radiation Therapy and Brachytherapy versus Radical Prostatectomy with Adjuvant Radiation Therapy for Gleason 9-10 Prostate Cancer.

PURPOSE: It remains controversial whether external beam radiation therapy with a brachytherapy boost provides oncologic outcomes equivalent to those of radical prostatectomy with or without adjuvant radiation therapy in men with Gleason 9-10 prostate cancer. We compared external beam radiation therapy plus brachytherapy to radical prostatectomy plus adjuvant radiation therapy for Gleason 9-10 prostate cancer in terms of overall survival and prostate cancer specific mortality in 2 large national databases. MATERIALS AND METHODS: Using the NCDB (National Cancer Database) and the SEER (Surveillance, Epidemiology, and End Results) database, we identified 4,367 and 2,276 patients, respectively, diagnosed with clinical T1-T3N0M0, Gleason 9-10, prostate specific antigen 0 to 40 ng/ml prostate cancer treated with external beam radiation therapy plus brachytherapy or radical prostatectomy plus adjuvant radiation therapy. We compared overall survival and prostate cancer specific mortality using inverse probability of treatment weighted multivariable Cox proportional hazards regression modeling after accounting for clinical and demographic factors. RESULTS: Median followup in the NCDB and SEER cohorts was 6.0 years and 5.8 years, respectively. In the NCDB cohort there was no significant difference in 5-year overall survival between radical prostatectomy plus adjuvant radiation therapy vs external beam radiation therapy plus brachytherapy (86.7% vs 87.0%, AHR 1.10, 95% CI 0.95-1.27, p=0.220). Results were unchanged when including only patients who received androgen deprivation therapy. In the SEER cohort there was no difference in 5-year prostate cancer specific mortality (6.0% vs 5.7%, AHR 1.22, 95% CI 0.0.88-1.71, p=0.234). There was no significant interaction between patient age (65 years or greater vs less than 65) and treatment modality in the NCDB or SEER cohorts. CONCLUSIONS: In men with Gleason 9-10 prostate cancer multimodality surgical therapy is equivalent to external beam radiation therapy plus brachytherapy.

Practice Patterns and Outcomes Among Patients With N0M0 Prostate Cancer and a Very High Prostate-Specific Antigen Level.

BACKGROUND: Management of patients with a very high prostate-specific antigen (PSA) level (≥98.0 ng/mL) but clinically localized (N0M0) prostate cancer is challenging. This study sought to determine practice patterns and outcomes among these patients. PATIENTS AND METHODS: A total of 748,825 patients with prostate cancer from 2004 through 2012 were identified using the National Cancer Database. These patients were subdivided by PSA level (0-9.9, 10.0-19.9, 20.0-39.9, 40.0-59.9, 60.0-79.9, 80.0-97.9, and ≥98.0 ng/mL), nodal status (N0 vs N1), and distant metastases (M0 vs M1). Rates of locoregional treatment and 5-year overall survival (OS) in each group were determined. Survival was compared using Cox regression after adjusting for multiple patient-specific factors. RESULTS: The rate of locoregional treatment for patients with N0M0 disease and PSA level ≥98.0 ng/mL was significantly lower than for those with N1M0 disease (52.6% vs 60.4%; P<.001) or N0M0 disease and PSA level <98.0 ng/mL (52.6% vs 86.6%; P<.001). The 5-year OS rate was similar for patients with N1M0 disease and those with N0M0 disease and a very high PSA level (63.2% vs 59.1%; adjusted hazard ratio [aHR], 0.91; P=.063). The survival benefit associated with locoregional treatment was higher among those with N0M0 disease and a very high PSA level than among those with N1M0 disease (aHR, 0.28 vs 0.44; P<.001). CONCLUSIONS: Patients with clinical N0M0 disease and a very high PSA level (≥98.0 ng/mL) have outcomes similar to those with N1 disease but receive locoregional treatment at a lower rate. Future work is needed to investigate the utility of locoregional treatment in this population.

Travel distance and stereotactic body radiotherapy for localized prostate cancer.

BACKGROUND: Definitive stereotactic body radiotherapy (SBRT) represents an emerging and debated treatment option for patients with prostate cancer, with potential economic savings and reports of short-term efficacy since 2006. The current study sought to define national trends in definitive prostate SBRT use and determine whether patterns vary by travel distance for treatment. METHODS: The National Cancer Data Base identified 181,544 men with localized prostate cancer who were treated with definitive external beam radiotherapy from 2004 through 2012. Joinpoint regression analyzed definitive prostate SBRT trends over time, whereas multivariable logistic regression defined the odds for its receipt by travel distance for treatment. RESULTS: Definitive prostate SBRT use increased from 1.8% in 2004 to 5.9% in 2012 (P for trend <.0001), with a joinpoint for increased use noted in 2006 (P<.0001). Higher SBRT use was found to be associated with longer travel distance for treatment, younger age, white race, more affluent zip code of residence, academic treatment center, favorable disease characteristics, and fewer comorbidities (all P<.0001). Compared with travel distances <25 miles for treatment, travel distances of 25 to 50 miles and >50 miles were associated with increasing adjusted odds of receipt of definitive prostate SBRT (1.63 [95% confidence interval, 1.51-1.76] and 2.35 [95% confidence interval, 2.14-2.57], respectively; both P < .0001). CONCLUSIONS: Definitive prostate SBRT use increased more than 3-fold since 2004, with a significant increase in use coinciding with early reports of short-term efficacy. Long-distance travel for treatment was associated with greater than twice the odds of receipt of definitive prostate SBRT compared with short-distance travel, suggesting that treatment decisions with unknown long-term clinical implications may be strongly driven by sociodemographic factors. Cancer 2018;124:1141-9. © 2017 American Cancer Society.

Association Between Very Small Tumor Size and Decreased Overall Survival in Node-Positive Pancreatic Cancer.

BACKGROUND: In pancreatic adenocarcinoma (PDAC), increasing tumor size usually correlates with a worse prognosis. However, patients with a very small primary tumor who experience lymph node involvement may have a different disease biology. This study sought to determine the interaction between tumor size and lymph node involvement in terms of overall survival (OS). METHODS: The study identified 17,073 patients with a diagnosis of M0 resected PDAC between 1983 and 2013 using the Surveillance, Epidemiology, and End Results database. The patients were stratified by lymph node involvement (N0 vs N+) and T stage (T1a-T1b vs T1c vs T2 vs T3 vs T4). The Kaplan-Meier method was used to estimate OS, and Cox regression analysis was used to compare survival between subgroups after adjustment for patient-specific factors. RESULTS: Lymph node involvement and T stage significantly interacted (p < 0.001). Among the patients with node-negative disease, 5-year OS decreased monotonically with increasing T stage (59.1%, 30.6%, 22.9%, 16.6%, and 8.0%, respectively; p < 0.001). In contrast, among the patients with node-positive disease, those with T1a-T1b tumors (< 10 mm) had worse 5-year OS than those with T1c tumors (7.4% vs 17.6%; adjusted hazard ratio, 0.70; 95% confidence interval, 0.50-0.97; p = 0.034) and similar survival compared with those who had T2, T3, or T4 tumors (9.7%, 8.2%, and 4.8%, respectively; p > 0.2 in all cases). CONCLUSIONS: Among patients with lymph node-positive PDAC, very small primary tumors are associated with decreased OS. This finding raises the possibility that small tumors capable of lymph node metastasis might represent more biologically aggressive cancers.