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PURPOSE: Compared with conventional external-beam radiation therapy (cEBRT) for patients with breast cancer (BC) and prostate cancer (PC), shorter radiation regimens may be associated with lower treatment noncompletion rates. We assess disparities in receipt of shorter radiation regimens and treatment noncompletion for BC and PC. PATIENTS AND METHODS: The 2004-2017 National Cancer Database was queried for adjuvant cEBRT or hypofractionated EBRT (hEBRT) for nonmetastatic BC; and definitive cEBRT, moderate hypofractionation (mEBRT), or stereotactic body radiotherapy (SBRT) for localized PC. Multivariable logistic regression identified factors associated with treatment noncompletion and receipt of shorter regimens. FINDINGS: We identified 170,386 men with PC (median age [interquartile range], 70 [64-75] years; Black, 17.5%; White, 82.5%) and 306,846 women with BC (61 [52-69] years; Black, 12.3%; White, 87.7%). Among patients who received cEBRT for PC, Black men had higher treatment noncompletion rates compared with White (14.1% v 13.0%; odds ratio [95% CI] 1.07 [1.03 to 1.12]; P < .001). In contrast, treatment noncompletion was not disparate with SBRT (Black 1.6% v White 1.3%; 1.20 [0.72 to 2.00], P = .49) or mEBRT (Black 9.0% v White 7.1%; 1.05 [0.72 to 1.54], P = .79). From 2004 to 2017, SBRT (0.07% to 11.8%; 1.32 [1.31 to 1.33]) and mEBRT (0.35% to 9.1%; 1.27 [1.25 to 1.28]) increased (both P < .001); however, Black men were consistently less likely to receive SBRT (7.4% v White, 8.3%; 0.84 [0.79 to 0.89], P < .001). Among women with BC, there were no racial differences in treatment noncompletion; however, hEBRT was associated with lower treatment noncompletion rates (1.0% v cEBRT 2.3%; 0.39 [0.35 to 0.44], P < .001). Although hEBRT for BC increased (0.8% to 35.6%) between 2004 and 2017, Black women were less likely to receive hEBRT (10.4% v 15.3%; 0.78 [0.75 to 0.81], P < .001). INTERPRETATION: Black patients were consistently less likely to receive hypofractionated radiation for PC or BC, despite evidence suggesting that shorter regimens may lower rates of treatment noncompletion with similar oncologic outcomes.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is an emerging imaging modality with greater sensitivity and specificity over conventional imaging for prostate cancer (PCa) staging. Using data from two prospective trials (NCT03368547 and NCT04050215), we explored predictors of overall upstaging (nodal and metastatic) by PSMA PET/CT among patients with cN0M0 National Comprehensive Cancer Network high-risk PCa on conventional imaging (n = 213). Overall, 21.1%, 8.9%, and 23.9% of patients experienced nodal, metastatic, and overall upstaging, respectively, without histologic confirmation. On multivariable analysis, Gleason grade group (GG) and percent positive core (PPC) on systematic biopsy significantly predict overall upstaging (odds ratio [OR] 2.15, 95% confidence interval [CI] 1.33-3.45; p = 0.002; and OR 1.03, 95% CI 1.01-1.04; p

PURPOSE: We identified (1) differences in localized prostate cancer (PCa) risk group at presentation and (2) disparities in access to initial treatment for Asian American, Native Hawaiian, and Pacific Islander (AANHPI) men with PCa after controlling for sociodemographic factors. METHODS: We assessed all patients in the National Cancer Database with localized PCa with low-, intermediate-, and high-risk disease who identified as Thai, White, Asian Indian, Chinese, Vietnamese, Korean, Japanese, Filipino, Hawaiian, Pacific Islander, Laotian, Pakistani, Kampuchean, and Hmong. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% CI of (1) presenting at progressively higher risk group and (2) receiving treatment or active surveillance with intermediate- or high-risk disease, adjusting for sociodemographic and clinical factors. RESULTS: Among 980,889 men (median age 66 years), all AANHPI subgroups with the exception of Thai (AOR = 0.84 [95% CI, 0.58 to 1.21], P > .05), Asian Indian (AOR = 1.12 [95% CI, 1.00 to 1.25], P > .05), and Pakistani (AOR = 1.34 [95% CI, 0.98 to 1.83], P > .05) men had greater odds of presenting at a progressively higher PCa risk group compared with White patients (Chinese AOR = 1.18 [95% CI, 1.11 to 1.25], P < .001; Japanese AOR = 1.36 [95% CI, 1.26 to 1.47], P < .001; Filipino AOR = 1.37 [95% CI, 1.29 to 1.46], P < .001; Korean AOR = 1.32 [95% CI, 1.18 to 1.48], P < .001; Vietnamese AOR = 1.20 [95% CI, 1.07 to 1.35], P = .002; Laotian AOR = 1.60 [95% CI, 1.08 to 2.36], P = .018; Hmong AOR = 4.07 [95% CI, 1.54 to 10.81], P = .005; Kampuchean AOR = 1.55 [95% CI, 1.03 to 2.34], P = .036; Asian Indian or Pakistani AOR = 1.15 [95% CI, 1.07 to 1.24], P < .001; Native Hawaiians AOR = 1.58 [95% CI, 1.38 to 1.80], P < .001; and Pacific Islanders AOR = 1.58 [95% CI, 1.37 to 1.82], P < .001). Additionally, Japanese Americans (AOR = 1.46 [95% CI, 1.09 to 1.97], P = .013) were more likely to receive treatment compared with White patients. CONCLUSION: Our findings suggest that there are differences in PCa risk group at presentation by race or ethnicity among Asian American, Native Hawaiian, and Pacific Islander subgroups and that there exist disparities in treatment patterns. Although AANHPI are often studied as a homogenous group, heterogeneity upon subgroup disaggregation underscores the importance of further study to assess and address barriers to PCa care.

PURPOSE: We assessed sociodemographic factors associated with and survival implications of refusal of potentially survival-prolonging locoregional treatment (LT, including radiotherapy and surgery) despite provider recommendation among men with localized prostate adenocarcinoma. METHODS: The National Cancer Database (2004-2015) identified men with TxN0M0 prostate cancer who either received or refused LT despite provider recommendation. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% CI of refusing LT, with sociodemographic and clinical covariates. Models were stratified by low-risk and intermediate- or high-risk (IR or HR) disease, with a separate interaction analysis between race and risk group. Multivariable Cox proportional hazard ratios compared overall survival (OS) among men who received versus refused LT. RESULTS: Of 887,839 men (median age 64 years, median follow-up 6.14 years), 2,487 (0.28%) refused LT. Among men with IR or HR disease (n = 651,345), Black and Asian patients were more likely to refuse LT than White patients (0.35% v 0.29% v 0.17%; Black v White AOR, 1.75; 95% CI, 1.52 to 2.01; P < .001; Asian v White AOR, 1.47; 95% CI, 1.05 to 2.06; P = .027, race * risk group interaction P < .001). Later year of diagnosis, community facility type, noninsurance or Medicaid, and older age were also associated with increased odds of LT refusal, overall and when stratifying by risk group. For men with IR or HR disease, LT refusal was associated with worse OS (5-year OS 80.1% v 91.5%, HR, 1.65, P < .001). CONCLUSION: LT refusal has increased over time; racial disparities were greater in higher-risk disease. Refusal despite provider recommendation highlights populations that may benefit from efforts to assess and reduce barriers to care.

Background Prostate radiotherapy has been associated with an increased risk of developing a second malignancy (SM). However, relative SM probabilities following treatment with contemporary radiation techniques such as stereotactic body radiotherapy (SBRT) or moderately hypofractionated intensity modulated radiotherapy (HF-IMRT) remain unknown. Methods A cohort analysis was performed of men from a nationally representative database with localized prostate cancer with at least 60 months of follow-up comparing SM probability amongst men receiving either radical prostatectomy (RP), conventionally fractionated intensity-modulated radiotherapy (CF-IMRT), HF-IMRT, brachytherapy (BT), or SBRT, using multivariable logistic models, which were used to generate predicted probabilities. Additionally, propensity score-adjusted pairwise assessments of modalities were performed. Results For 303,432 patients included in the study, median follow-up was 9.08 years (IQR 7.01–11.21). Predicted rates of SM by treatment modality and adjusted odds ratios (AOR) for development of SM (referent: RP) were: 6.0% for RP (AOR n/a), 7.1% for CF-IMRT (AOR 1.20, 95%CI 1.14–1.25, P Conclusions Conventionally fractionated intensity-modulated radiotherapy, moderately hypofractionated intensity-modulated radiotherapy, and brachytherapy but not stereotactic body radiotherapy were associated with increased probability of a second malignancy compared to radical prostatectomy. Patients treated with SBRT may be at lower risk of second malignancy due to improved conformality, radiobiological differences or patient selection. The possibility that SBRT in select patients may minimize the probability of SM underscores the need for assessment of second malignancy risk in prospective studies of SBRT.

Background Much of the Affordable Care Act (ACA) and subsequent US health care policies were designed to address deficiencies in health care access and enhance primary care services. How residency positions and physician incomes have changed in the post-ACA era is not well characterized. Objective We evaluated the growth of US trainee positions and physician income, in the pre- vs post-ACA environment by specialty and among primary care vs specialty care. Methods Total resident complement by specialty and year was extracted from the National Graduate Medical Education (GME) Census and stratified into primary care vs specialty care. Median incomes were extracted from Medical Group Management Association surveys. Piecewise linear regression with interaction terms (pre-ACA, 2001–2010, vs post-ACA, 2011–2019) assessed growth rate by specialty and growth rate differences between primary care and specialty care. Sensitivity analyses were performed by focusing on family medicine and excluding additional GME positions contributed by the introduction of the 2015 single GME accreditation system. Results Resident complements increased for primary care (+0.16%/year pre-ACA to +2.06%/year post-ACA, P < .001) and specialty care (+1.49%/year to +2.07%/year, P = .005). Specialty care growth outpaced primary care pre-ACA (P < .001) but not post-ACA (P = .10). Family medicine had the largest increase in the pre- vs post-ACA era (-0.77%/year vs +2.09%/year, P < .001). Excluding positions contributed by the single GME accreditation system transition did not result in any statistically significant changes to the findings. Income growth increased for primary care (+0.84%/year to +1.37%/year, P = .044), but decreased for specialty care (+1.44%/year to +0.49%/year, P = .011). Specialty care income growth outpaced primary care pre-ACA (P < .001), but not post-ACA (P = .22). Conclusions We found significant growth differences in resident complement and income among primary care versus specialty care in the pre-/post-ACA eras.

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.

To inform treatment decisions for patients with high-risk prostate cancer (PCa), we determined rates of adverse pathologic factors and overall survival (OS) among subgroups of high-risk men.Using the National Cancer Database, 89,450 patients with clinical N0M0 unfavorable intermediate-risk, favorable high-risk (cT1c, Gleason 6, prostate-specific antigen [PSA]20 ng/mL or cT1c, biopsy Gleason 8, PSA10 ng/mL), standard high-risk (all other cT3a, biopsy Gleason ≥ 8, or PSA20 ng/mL), or very high-risk (cT3b-T4 or biopsy primary Gleason pattern 5) PCa treated with radical prostatectomy were identified. Rates of adverse pathologic factors (positive surgical margins, T4 disease, or pathologic lymph node involvement) were compared across subgroups.Patients with unfavorable intermediate-risk (n = 31,381) and favorable high-risk (n = 10,296) disease had similar rates of adverse features (7.6% vs 8.2%, adjusted odds ratio 1.00, 95% confidence interval 0.92-1.08, P= .974). Patients with standard high-risk (n = 30,260) or very high-risk (n = 7513) disease were significantly more likely to have adverse pathologic factors (15.9% and 26.5%, P.001 for both). Patients with unfavorable intermediate-risk and favorable high-risk disease had similar 5-year OS (95.7% vs 95.1%, adjusted hazard ratio 1.06, 95% confidence interval 0.92-1.21, P = .411) but better OS compared to standard and very high-risk patients (93.4% and 88.1%, respectively; P.001).Unfavorable intermediate-risk or favorable high-risk PCa patients had low rates of adverse pathologic factors and similar OS. In contrast, standard and very high-risk PCa patients had significantly higher rates of adverse pathologic factors and worse OS. This 3-tiered subclassification of high-risk disease may allow for improved treatment selection among patients considering surgery.

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.

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 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.

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.

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.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.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 (pA 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.

INTRODUCTION AND OBJECTIVE:Radiation associated muscle-invasive bladder cancer (RA-MIBC) is a potentially lethal late toxicity following definitive radiation for prostate cancer. RA-MIBC can be dif...

Young men (≤55 years) with prostate cancer (PC) may experience treatment delays despite clinical consequences of delays beyond six months. Using the United States National Cancer Database (2004-2017), we employed multivariable logistic regression analysis to retrospectively examine racial disparities in localized PC treatment delays6 months since diagnosis. Of the 89,196 men ≤55 years included, young Black men experienced treatment delays beyond six months more frequently than young White men (7.39% vs. 3.96%; AOR 1.95, 95% CI 1.81-2.09, p 0.001), a disparity that was greater than that among men ages 56-64 (p

Recent data and National Comprehensive Cancer Network (NCCN) guidelines suggest that high-risk prostate cancer (cT3-4, Gleason score ≥8, or prostate-specific antigen [PSA]20 ng/mL) is a heterogenous group in terms of long-term patient outcomes. We sought to determine whether subclassification of high-risk prostate cancer based on clinical factors correlates with genomic markers of risk.We identified 3220 patients with NCCN unfavorable intermediate-risk (n = 2000) or high-risk (n = 1220) prostate cancer from a prospective multi-institutional registry cohort. We defined the following subclassification of high-risk prostate cancer based on previously published data: favorable high risk (cT1c, Gleason 6, and PSA20 ng/mL or cT1c, Gleason 4 + 4 = 8, PSA10 ng/mL); very high risk (cT3b-T4 or primary Gleason pattern 5); and standard high risk (all others with cT3a, Gleason score ≥8, or PSA20 ng/mL). We used a set of 33 previously developed genomic classifiers, including Decipher, to determine whether high-risk genomic features correlate with clinical subclasses of high-risk prostate cancer.Among those with favorable high-risk, standard high-risk, and very high-risk prostate cancer, 50.4%, 64.2%, and 81.6% had a high-risk Decipher score, respectively (P.001). Among 32 other genomic signatures, 29 had a similar trend of increasing risk scores across the 3 subclasses of high-risk disease (P.05 after correction for multiple hypothesis testing). Patients in the 3 subclasses of high-risk disease had a median of 4, 6, and 13 high-risk signatures, respectively. In comparison, among those with unfavorable intermediate-risk prostate cancer, 38.2% had a high-risk Decipher score, and the median number of high-risk signatures was 3.Although NCCN guidelines currently use a 2-tiered system for high-risk prostate cancer, genomic markers of risk correlate with the clinically validated subclassification of high-risk prostate cancer into favorable high-risk, standard high-risk, and very high-risk disease, further confirming the prognostic utility of this 3-tiered stratification.

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

Background While the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) is known to improve overall survival (OS) in Gleason 8–10 (Grade Group 4–5) prostate cancer (PCa), it has been hypothesized that Gleason 9–10 disease, which is less differentiated than Gleason 8 disease, may be less sensitive to ADT. Objective To examine the association between ADT and OS for Gleason 8 versus Gleason 9–10 PCa. Design, setting, and participants A retrospective cohort study of 20 139 men from the National Cancer Database with localized or locally advanced, Gleason 8–10 PCa who received EBRT. Data were collected from 2004 to 2012. Intervention ADT. Outcome measurements and statistical analysis Cox proportional hazards regression was used to examine the association between ADT and OS. Results and limitations Overall, 9509 (78%) of the 12 160 men with Gleason 8 disease and 6908 (87%) of the 7979 men with Gleason 9–10 disease received ADT. On multivariable analysis, ADT was associated with a significant improvement in OS for Gleason 8 patients (adjusted hazard ratio 0.78, 95% confidence interval 0.70–0.87, p Conclusions In contrast to the significant survival advantage of ADT for Gleason 8 disease, our results suggest that Gleason 9–10 disease derives less survival benefit from ADT and that a higher Gleason score predicts lesser benefit. Consideration should be given to treatment intensification for Gleason 9–10 patients through enrollment in clinical trials or potentially adding novel antiandrogens or docetaxel, which have shown efficacy in both castration-resistant and castration-sensitive settings. Patient summary In this study, we examined the effect of androgen deprivation therapy (ADT) for Gleason 8 (Grade Group 4) versus Gleason 9–10 (Grade Group 5) prostate cancer. We found that Gleason 9–10 disease may derive a smaller survival benefit from ADT than Gleason 8 disease.

Purpose: Many improvements in head and neck cancer (HNC) outcomes are related to optimization of radiation therapy (RT) dose, fractionation, normal-tissue sparing, and technology. However, prior work has shown that the literature of randomized controlled trials is dominated by industry-sponsored trials that have lower rates of incorporating RT. We characterized HNC clinical trials, hypothesizing that RT-specific research questions may be relatively underrepresented among HNC randomized controlled trials. Methods and Materials: A web query of all open interventional trials on www.ClinicalTrials.gov was performed using search terms “head and neck cancer” and specific HNC subsites. Trial details were captured including the modality used, principal investigator (PI) specialty, funding, and whether the study tested a RT-modality specific hypothesis. Chi-square testing and logistic regression were used to compare groups. Results: There were 841 open HNC trials, including definitive (47.6%) and recurrent/metastatic (41.9%) populations. Most trials (71.7%) were phase I or nonrandomized phase II studies, rather than phase III or randomized phase II (28.3%). Among single-arm studies, most (79.6%) incorporated systemic therapy (ST), and fewer (25.2%) incorporated RT. Even fewer phase III and randomized phase II trials tested an RT-specific hypothesis (11.1%), compared with ST-related hypotheses (77.1%; P < .001); trials were more likely to test an RT-hypothesis if the study PI was a radiation oncologist (20.9% vs 6.0%; P < .001). Among RT trials, most early-phase studies tested novel modalities (eg, stereotactic body radiation therapy, proton therapy), whereas most later-phase studies tested dose and fractionation. RT-focused trials had low rates of federal (10.4%) or industry (2.6%) funding. Conclusions: RT-specific research hypotheses are a minority of phase II-III HNC trials, which mostly focus on incorporating ST in the definitive or recurrent/metastatic setting and have higher rates of industry funding. Radiation oncologist PI leadership and increased nonindustry funding access may ensure that RT-specific hypotheses are incorporated into trial design.

PURPOSE/OBJECTIVE(S) Radiation associated muscle-invasive bladder cancer (RA-MIBC) is a rare but potentially lethal late toxicity following definitive radiation therapy for prostate cancer. RA-MIBC is associated with worse prognosis compared to primary MIBC, but it remains unknown whether worse outcomes are driven primarily by difficulty with delivering definitive treatment in a previously irradiated pelvis or whether RA-MIBCs harbor specific aggressive biological features. We sought to characterize the genomic features of RA-MIBC to assess whether the underlying genetic alterations differ from primary (non-radiation associated) MIBC. MATERIALS/METHODS We performed whole-exome sequencing of 27 bladder tumors in patients previously treated with definitive radiation therapy for prostate cancer, and we correlated genomic with clinical data. We compared the mutation profile of RA-MIBC with primary MIBC from The Cancer Genome Atlas (TCGA). We used the Kaplan-Meier method to estimate progression-free survival (PFS) and overall survival (OS). RESULTS The median age of included patients was 79.2 years, and the median time from prostate radiation to MIBC diagnosis was 11.5 years. Median PFS was 12.4 months and median OS was 20.2 months. Among RA-MIBCs, we found mutation signatures characteristic of BRCA1/2 mutations, impaired DNA mismatch repair, and microsatellite instability. When compared to de novo MIBC from TCGA, RA-MIBCs also had significantly higher mutation rates of DNA repair genes, such as FANCA (38.1% vs 5.1%, P < 0.001), CHEK2 (26.1% vs 2.5%, P < 0.001) and MSH6 (26.1% vs 2.5%, P < 0.001). The most commonly mutated genes were TP53 (50%) and KDM6A (36%), which harbored mutations at similar rates as de novo MIBC samples from TCGA. CONCLUSION In this study, we characterize the mutational profiles and clinical outcomes of radiation-associated bladder cancer. These patients exhibited significantly worse PFS and OS compared to prior series of de novo MIBC. Genomically, these tumors exhibited higher rates of mutation signatures characteristic of impaired DNA damage repair compared to previously unirradiated tumors. These genomic differences suggest that some RA-MIBCs may represent a biologically distinct entity compared to de novo MIBC and may indicate an opportunity for the use and development of novel therapeutic strategies.

PURPOSE/OBJECTIVE(S) Prostate radiotherapy has been associated with an increased risk of developing a second malignancy (SM). Relative SM probabilities following stereotactic body radiotherapy (SBRT) or moderately hypofractionated radiation (HF-IMRT) remain unknown. We hypothesized that the probability of SM following SBRT or HF-IMRT would differ compared with conventionally fractionated intensity modulated radiotherapy (CF-IMRT). MATERIALS/METHODS Cohort analysis of men from a nationally representative database with localized prostate cancer with at least 60 months of follow-up compared SM probability amongst men receiving either radical prostatectomy (RP), CF-IMRT, HF-IMRT, brachytherapy (BT), or SBRT, using multivariable logistic models. Sensitivity analyses were conducted to evaluate differences in SM stratified by year of treatment and follow up length. Propensity score-adjusted pairwise assessments of modalities were also performed. RESULTS For 303,432 patients, median follow-up was 9.08 years (IQR 7.01 - 11.21), and median age was 64 years (IQR 58-69). Crude rates of SM by treatment modality were: 5.2% for RP, 8.9% for CF-IMRT, 7.7% for HF-IMRT, 7.9% for BT, and 5.3% for SBRT. Adjusted odds ratios (AOR) for development of SM (referent: RP) were: CF-IMRT vs. RP 1.20 (95% CI 1.14-1.25, P < 0.001), HF-IMRT vs. RP 1.25 (95% CI 1.01-1.55, P = 0.045), BT vs. RP 1.11 (95% CI 1.07-1.16, P < 0.001), and SBRT vs. RP 0.95 (95% CI 0.81-1.12, P = 0.567). Sensitivity analyses confirmed higher probability of SM comparing CF-IMRT to RP (P < 0.01 for all) and no statistically significant difference comparing SBRT to RP at all year and follow-up length groupings (P = NS for all). On propensity score-adjusted analysis, SBRT was associated with lower probability of SM compared to CF-IMRT (AOR 0.78, 95% CI 0.66-0.93, P = 0.005); no significant difference was found when SBRT was compared to RP (AOR 0.86, 95% CI 0.73-1.03, P = 0.102). CONCLUSION Conventionally fractionated intensity-modulated radiotherapy, moderately hypofractionated intensity-modulated radiotherapy, and brachytherapy, but not stereotactic body radiotherapy, were associated with increased probability of a second malignancy compared to radical prostatectomy. Our findings underscore the need for assessment of second malignancy risk in prospective studies of SBRT.

PURPOSE/OBJECTIVE(S) Although racial and sociodemographic disparities exist in the rates of treatment noncompletion for patients receiving breast and prostate radiotherapy, shorter regimens may be associated with lower rates of treatment noncompletion. We assessed predictors of treatment noncompletion and racial disparities in access to shorter regimens for patients with prostate cancer (PCa) and breast cancer (BCa). MATERIALS/METHODS Using the 2004-2017 National Cancer Database, men with localized PCa were defined as receiving conventional fractionation if they received 180cGY/fraction (noncompletion: < 41 fractions) or 200cGY/fraction (noncompletion: < 37 fractions). Stereotactic body radiotherapy (SBRT) was defined as five to eight fractions of 600-800cGY/fraction (non-completion: < 5 fractions). Women with non-metastatic BCa who received surgery with radiotherapy were included. Patients receiving 180cGY or 200cGY/fraction were defined as receiving conventional fractionation (noncompletion: < 25 fractions); patients receiving 266cGY, 267cGY, or 270cGY per fraction (noncompletion: < 15 fractions) were defined as receiving hypofractionated regimens. Multivariable logistic regressions assessed predictors of treatment noncompletion and racial disparities in access to shorter regimens. RESULTS 166,436 men with complete data met inclusion criteria (median age 70 years [IQR 64-75]; 19.6% low-risk, 47.3% intermediate-risk; 33.1% high-risk; 17.5% Black; 82.5% white). Black men had higher rates of treatment noncompletion compared with white men (13.5% vs. 12.3%, OR 1.07, 95% CI 1.03-1.12, P < 0.001). SBRT was associated with lower odds of treatment non-completion compared with conventional EBRT (SBRT 1.3% vs. EBRT 13.2%; OR 0.08, 95% CI 0.07-0.1, P < 0.001). Although use of SBRT increased from 0.07% in 2004 to 13.03% in 2017, Black patients were less likely to receive SBRT (5.3% vs. 6.1%, OR 0.77, 95% CI 0.71-0.83, P < 0.001). 306,846 women met inclusion criteria (median age 61 years [IQR 52-69]; 17.4% in situ; 43.0% stage 1; 26.5% stage 2; 13.2% stage 3; 12.3% were Black and 87.7% were white). Treatment noncompletion did not differ significantly for Black (2.8%) vs. White (2.0%) women. Women who received hypofractionated EBRT had lower rates of treatment noncompletion compared to women who received conventional regimens (1.0% vs. 2.3%; OR 0.39, 95% CI 0.35-0.44, P < 0.001). Although rates of hypofractionated EBRT for breast cancer significantly increased from 0.8% in 2004 to 35.6% in 2017, Black patients were significantly less likely to receive hypofractionated EBRT (10.4% vs. 15.3%, OR 0.78, 95% CI 0.75-0.81, P < 0.001). CONCLUSION Although shorter treatment regimens of radiation therapy were associated with lower rates of treatment noncompletion, disparities persisted in receipt of shorter regimens. Our findings underscore the need to identify barriers to treatment completion and racial bias and inequities in access to treatment regimens that are more likely to be completed.

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. 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. 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. 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.

To characterize the presentation, patterns of care, and outcomes of radiation-associated muscle-invasive bladder cancer (RA-MIBC) compared to primary (non-radiation associated) MIBC. RA-MIBC has been suggested to represent a more aggressive disease variant and be more difficult to treat compared to primary (non-radiation associated) MIBC.We identified 60,090 patients diagnosed with MIBC between 1988-2015 using the Surveillance, Epidemiology, and End Results database and stratified patients based on whether radiation had been administered to a prior pelvic primary cancer. We used Fine-Gray competing risks regression to compare adjusted bladder cancer-specific mortality (BCSM) for RA-MIBC compared to primary MIBC.There were 1,093 patients with RA-MIBC and 58,997 patients with primary MIBC. RA-MIBCs were more likely to be T4 at diagnosis (21.0% vs 17.3%, P.001), and less likely to be node-positive (10.3% vs 17.1%, P.001). The rate of 5-year BCSM was significantly higher for patients with RA-MIBC vs primary MIBC (56.1% vs 35.3%, AHR 1.24, P.001), even after stratification by other tumor, treatment and patient-specific factors.RA-MIBCs tended to present with higher grade and T stage disease and were less likely to receive curative treatment. Even when accounting for stage, grade, and receipt of treatment, patients with RA-MIBC had worse survival compared to those with primary MIBC. These findings suggest that RA-MIBC present unique clinical challenges and may also represent a biologically more aggressive disease compared to primary MIBC. Future research is needed to better understand the biology of RA-MIBC and develop improved treatment approaches.

High tumor mutation burden (TMB) and total mutation count (TMC) can be predictive of better response to immune checkpoint blockade (ICB). Nevertheless, TMB and TMC are limited by variation across cancers and inconsistent definitions due to different profiling methods (targeted vs whole genome sequencing). Our objective was to identify genomic alterations (GAs) associated with ICB response and builds a novel genomic signature predictive of ICB response, independent of TMB/TMC.This was a pan-cancer next generation sequencing (NGS)-association study using January 2014-May 2016 data from AACR Project Genomics Evidence Neo-plasia Information Exchange (GENIE). Participants included 6619 patients with metastatic or un-resectable cancer across 9 cancer types (including 1572 ICB-treated patients). GA data was collected using next-generation sequencing (NGS) assays and downloaded from cbioportal.org. Predictive analyses for ICB response were performed to develop the signature (ImmGA).GAs in 16 genes were associated with improved OS in ICB-treated patients (p 0.005). 13 GAs were associated with an OS benefit in ICB-treated patients (PA novel signature predictive of ICB response (ImmGA) was developed from 13 GAs. Further investigation of the utility of ImmGA for treatment and trial selection is warranted.

Treatment noncompletion may occur with radiation therapy (RT), especially with protracted treatment courses such as RT for prostate cancer, and may affect the efficacy of RT. For men with localized prostate cancer managed with primary RT, we evaluated associations between rates of treatment noncompletion and RT fractionation schedules.The National Cancer Database identified men diagnosed from 2004 to 2014 treated with primary RT. Patients receiving 180 cGy/fraction or 200 cGy/fraction were defined as having completed radiation therapy if they received ≥41 fractions of 180 cGy/fraction or ≥37 fractions of 200 cGy/fraction. Stereotactic body radiation therapy (SBRT) was defined as 5 to 8 fractions of 600 to 800 cGy/fraction. Odds ratios compared rates of treatment noncompletion, adjusting for sociodemographic covariates. A propensity-adjusted multivariable Cox regression assessed the association between treatment completion and overall survival.Of 157,657 patients, 95.7% (n = 150,847) received conventional fractionation and 4.3% (n = 6810) received SBRT. Rates of noncompletion were 12.5% (n = 18,803) among patients who received conventional fractionation and 1.9% (n = 131) among patients who received SBRT (odds ratio [OR] versus conventional, 0.21; 95% confidence interval [CI], 0.18-0.26; P.001). The rate of noncompletion among 25,727 African American patients was 12.8%, compared with 11.8% among 126,199 white patients (OR, 1.14; 95% CI, 1.09-1.19; P.001). In a subgroup analysis, the disparity in noncompletion persisted for conventional fractionation (13.2% vs 12.3%, respectively; OR, 1.09; 95% CI, 1.05-1.13; P.001), but not for SBRT (2.2% vs 1.8%, respectively; OR, 1.26; 95% CI, 0.79-2.00; P = .34). Noncompletion was associated with worse survival in a propensity-adjusted multivariable analysis (hazard ratio, 1.25; 95% CI, 1.22-1.29; P.001).SBRT was associated with lower rates of RT noncompletion among men with localized prostate cancer. African American race was associated with greater rates of treatment noncompletion, although the disparity may be decreased among men receiving SBRT.

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 ( 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.

OBJECTIVE Race predicts overall mortality (OM) of laryngeal squamous cell carcinoma (LSCC) in the United States (US). We assessed whether racial disparities affect cancer-specific mortality (CSM) using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS Adults with LSCC from 2004 to 2015 were selected. Univariable and multivariable Cox proportional hazards and Fine-Gray competing-risks regression analysis adjusted for clinicodemographic factors defined hazard ratios (aHR). RESULTS We identified 14,506 patients. The median age was 63 years. Most were male (11,725, 80.8%) and white (11,653, 80.3%), followed by Black (2294, 15.8%). Most had early-stage disease (7544, 52.0%) and received radiotherapy only (4107, 28.3%), followed by chemoradiation (3748, 25.8%). With median follow-up of 60 months, overall 3- and 5-year OM were 34.0% and 43.2%; CSM were 16.0% and 18.9%, respectively. Black patients had higher OM than white patients on univariable (HR 1.35, 95% CI, 1.26-1.44, P

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.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.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 (P0.05 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, P0.001) with each additional worry conferring 23.9% increased likelihood of psychological distress.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.

Purpose The role of multimodality therapy (MMT) in the treatment of Gleason 8–10 prostate cancer remains controversial. We sought to evaluate factors associated with MMT utilization for primary radical prostatectomy (RP) and primary radiation therapy (RT). Methods and Materials From the National Cancer Database, we conducted a retrospective review of 81,528 men with National Cancer Center Network Gleason 8–10 prostate cancer diagnosed between 2004 and 2015, who underwent (1) primary RP with or without early postoperative external beam RT (EBRT) or (2) primary RT (androgen deprivation therapy + EBRT) with or without brachytherapy (BT) boost. Using multivariable logistic regression models, we evaluated factors associated with the utilization of MMT, defined as early postoperative EBRT for primary RP or BT boost for primary RT. Results For primary RP, the percentages of men who underwent MMT for Gleason 8 and 9–10 disease were 12.2% and 24.1%, respectively. On multivariable logistic regression, men with Gleason 9–10 were more likely to undergo MMT (odds ratio 1.03 [1.02, 1.04]), although adverse pathologic features such as T3b-4 (1.24 [1.23, 1.25]) disease demonstrated the strongest associations. For primary RT, the percentages of men who underwent BT boost for Gleason 8 and 9–10 disease were 11.8% and 9.8%, respectively. On multivariable logistic regression, men with Gleason 9–10 disease were less likely to receive BT boost (0.99 [0.98, 0.99]). Conclusions Men with more aggressive Gleason 9 disease were more likely to undergo MMT if they underwent primary RP but not primary RT. Further blood-based or imaging biomarkers may aid in identifying optimal candidates for MMT, especially for primary RT.

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.

INTRODUCTION AND OBJECTIVE:For men with Gleason score 9-10 prostate cancer, studies have demonstrated conflicting results on the outcomes from combination radiation therapy (ComboRT) with external ...

159 Background: Androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer, but treatment tolerance is variable. Prior work has demonstrated the correlation between body composition (BC) and clinical outcomes in prostate cancer. Specifically, high visceral fat density has been associated with fat depletion phenomenon and poor prognosis in prostate cancer. However, the interaction of long-term ADT tolerance and body fat composition is less studied. We investigated if BC could predict for outcomes and treatment tolerance in patients with high-risk prostate cancer with planned ADT. Methods: An IRB-approved retrospective review was conducted at a tertiary care center of patients with high-risk (T3a or prostate-specific antigen [PSA] > 20 ng/mL or Gleason score 8-10 or N/M+) prostate cancer who received definitive external beam radiation therapy (RT) from 2006 to 2013. A previously validated, fully automated deep learning BC analysis pipeline was performed on RT simulation scans to compute BC at the top of L3 slice, including total skeletal muscle (SM), subcutaneous fat (SF), and visceral fat (VF) surface area (cm2) and average CT density (Hounsfield Units (HU)); results were manually validated by experts. BC was stratified by median value. Adult Comorbidity Evaluation-27 (ACE) was used to measure co-morbidity. Long-term ADT was defined as > 2 years, tolerance was defined as unplanned discontinuation > 3-month difference in intended/actual duration of ADT. The association between BC markers, oncologic outcomes, and treatment tolerance was analyzed using univariable Cox regression and chi-square test. Results: A total of 207 men were analyzed with a median follow up time of 10.8 years (range 0.7-17.3y). Median age was 65 (range 42-83), with 61 (29.4%) patients classified as high-risk, 134 (64.7%) very-high-risk, and 12 (5.8%) N+/M+ at diagnosis. High VF density was associated with worse overall survival (OS) (HR 1.71, 95%CI 1.09-2.68, p = 0.0204) but not cancer-specific survival (CSS) (p = 0.08) or biochemical-relapse free survival (bRFS) (p = 0.97). SM and SF density, as well as area of SM, VF, SF, and total fat were not associated with outcomes. N/M stage was associated with bRFS (p = 0.0139), and N/M stage (p = 0.0101) and higher ACE score (p = 0.0218) were associated with OS. Among 88 (42.5%) patients planned for long-term ADT use, 24 (27%) patients discontinued ADT prior to duration, of which 15 (17%) patients discontinued due to toxicity. BC markers did not correlate with tolerance to long-term ADT (p = 0.17). Tolerance to long-term ADT was not associated with bRFS or OS. Conclusions: High VF density is associated with worse OS but not bRFS or CSS in high-risk prostate cancer patients, and not associated with adipose area or ADT tolerance. VF density may be a biomarker of underlying metabolic health in prostate cancer patients independent of disease, and a potential area of intervention.

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).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.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).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.

Background Prior studies have only considered the association between static marital status and cancer-specific outcomes. We aim to measure the effect of recent divorce on cancer-specific outcomes. Methods There were 83,804 patients with 2 malignancies, diagnosed 12 to 60 months apart, from 1973-2006 from the Surveillance, Epidemiology, and End Results database. Patients were identified as newly divorced if married at their first diagnosis and single/divorced at their second. Multivariable logistic regression and competing-risks regression were used to analyze the association of becoming newly divorced or newly married with cancer-specific outcomes from the second malignancy, including advanced diagnosis (T4 or N1 or M1), receipt of treatment, and cancer-specific survival. Results Four percent became newly divorced and 3.4% became newly married. Compared with long-term married, newly divorced patients were most likely to be diagnosed with advanced disease (adjusted odds ratio [AOR] 1.31; 95% confidence interval [CI], 1.19-1.43), followed by long-term divorced (AOR 1.18; 95% CI, 1.11-1.25), and were least likely to receive curative treatment (AOR 0.74; 95% CI, 0.67-0.81). Newly divorced patients had the worst cancer-specific survival (adjusted hazard ratio [AHR] 1.17; 95% CI, 1.05-1.30, P = .005), followed by long-term divorced (AHR 1.08; 95% CI, 1.01-1.16, P = .032), while newly married patients had similar cancer-specific survival to long-term married (AHR 0.96; 95% CI, 0.85-1.08, P = .46). Conclusion Recent divorce, which represents an acute disruption of a patient's social support network, was associated with the worst cancer outcomes, followed by long-term divorce. Clinicians should consider recent divorce as a risk factor for worse cancer outcomes, and encourage appropriate screening, treatment, and access to social and financial supports for recently divorced patients.

Purpose Although level 1 evidence has demonstrated a survival benefit from the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) for patients with high-risk prostate cancer, the benefits of ADT with combined EBRT and brachytherapy for high-risk patients are unclear. We examined the association between ADT and overall survival in a national cohort of high-risk patients treated with EBRT with or without brachytherapy. Methods and Materials We identified 46,325 men in the National Cancer Database with a diagnosis of high-risk prostate cancer (Gleason score 8-10, clinical stage T3-T4, or prostate-specific antigen >20 ng/mL) who were treated with EBRT with or without brachytherapy and ADT from 2004 through 2011. Multivariable Cox regression analysis adjusting for sociodemographic and clinicopathologic factors was used to identify the association between ADT and overall survival. Results The median follow-up period was 48.6 and 59.2 months for patients treated with EBRT only and combined modality RT, respectively. ADT was associated with an improvement in overall survival for the 85.0% (39,361) of the study cohort who underwent EBRT alone (adjusted hazard ratio 0.91, P =.001) but not for patients treated with combined modality RT (adjusted hazard ratio 1.05, P =.496), with a significant interaction ( P interaction =.036). Conclusions In contrast to the known survival benefit when ADT is given with EBRT, our results suggest that ADT might not improve survival for high-risk patients who undergo combined EBRT and brachytherapy. Given the significant adverse effects of ADT, in particular, with long-term therapy, a randomized controlled trial of combined EBRT and brachytherapy with or without ADT for select high-risk patients using a noninferiority design should be undertaken.

Active Surveillance among Blacks with Low-Risk Prostate Cancer Between 2010 and 2015, use of active surveillance or watchful waiting as a management strategy for low-risk prostate cancer increased ...

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 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

Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease.Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3 + 3 = 6, prostate-specific antigen level10 ng/mL, and cT1-T2a) diagnosed from 2004 to 2012 with complete demographic and treatment information. We used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality.Overall ADT use decreased from 17.6% in 2004 to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; P.001; incidence, 14.0% vs 6.0% in 2012); treatment in the South (AOR, 1.51), Midwest (AOR, 1.81), or Northeast (AOR, 1.90) versus West (P.001); and brachytherapy use versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; P.001). Among 25,196 patients who did not receive local therapy, predictors of primary ADT use included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; P.001); and treatment in the South (AOR, 1.26), Midwest (AOR, 1.52), or Northeast (AOR, 1.28) versus West (P≤.008). Primary ADT use was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; P.001) after adjustment for age and comorbidity.ADT use in low-risk prostate cancer has declined nationally but may remain an issue of concern in certain populations and regions.

In 2012, the United States Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA) screening, despite evidence that Black men are at a higher risk of prostate cancer-specific mortality (PCSM). We evaluated whether Black men of potentially screening-eligible age (55-69 years) are at a disproportionally high risk of poor outcomes.The SEER database was used to study 390 259 men diagnosed with prostate cancer in the United States between 2004 and 2011. Multivariable logistic regression modeled the association between Black race and stage of presentation, while Fine-Gray competing risks regression modeled the association between Black race and PCSM, both as a function of screening eligibility (age 55-69 years versus not).Black men were more likely to present with metastatic disease (adjusted odds ratio [AOR] 1.65; 1.58-1.72; P 0.001) and were at a higher risk of PCSM (adjusted hazard ratio [AHR] 1.36; 1.27-1.46; P 0.001) compared to non-Black men. There were significant interactions between race and PSA-screening eligibility such that Black patients experienced more disproportionate rates of metastatic disease (AOR 1.76; 1.65-1.87 versus 1.55; 1.47-1.65; Pinteraction 0.001) and PCSM (AHR 1.53; 1.37-1.70 versus 1.25; 1.14-1.37; Pinteraction = 0.01) in the potentially PSA-screening eligible group than in the group not eligible for screening.Racial disparities in prostate cancer outcome among Black men are significantly worse in PSA-screening eligible populations. These results raise the possibility that Black men could be disproportionately impacted by recommendations to end PSA screening in the United States and suggest that Black race should be included in the updated USPSTF PSA screening guidelines.