A randomized patient education trial investigating treatment-related distress and satisfaction with the use of an at-home gynecologic brachytherapy educational video.

BACKGROUND: Physician explanation of gynecologic brachytherapy can be overwhelming or induce patient anxiety, and may be time-constrained given clinical limitations. We report the first randomized trial of an educational video intervention in gynecologic brachytherapy on patient-reported outcomes. METHODS: Between February 2020 and January 2022, 80 gynecologic cancer patients prescribed brachytherapy were randomly assigned to either standard informed consent (Arm A) or a supplemental 16 min brachytherapy educational video (https://vimeo.com/403385455/d0716e3cc8) via the internet (Arm B). Primary outcome was treatment-related distress (National Comprehensive Cancer Network (NCCN) distress scale scored 0 (no distress) to 10 (maximum distress)). Secondary outcome was patient satisfaction (summated Likert-scale scored 11-55). Surveys were administered at baseline, after first treatment, and prior to brachytherapy completion. RESULTS: All patients completed the prescribed brachytherapy. In Arm B, 19/40 (48%) patients and 10/40 (25%) patients' family/friends viewed the video. For patients that completed all surveys (Arm A n=29, Arm B n=28), there was no difference between arms in the sociodemographic, clinical, or treatment variables. Distress scores were low at baseline (Arm A median 4, Arm B median 4, p=0.65) and there was no detectable change in distress between arms on surveys 1 and 2 (ß 0.36, p=0.67) or surveys 1 and 3 (ß -1.02, p=0.29) in multivariable analysis. Satisfaction scores were high at baseline (Arm A median 54, Arm B median 54.5, p=0.64) and there was no detectable change in satisfaction between arms on surveys 1 and 2 (ß 0.22, p=0.93) or surveys 1 and 3 (ß 0.63, p=0.85) in multivariable analysis. CONCLUSIONS: Among patients randomized to an educational video tool for gynecologic brachytherapy, approximately 50% of the cohort and 25% of the cohort's family/friends used the video. Overall, patients had low distress scores and high satisfaction scores with no significant differences between the standard and video intervention arms. Further work is needed to understand factors contributing to gynecologic brachytherapy anxiety. TRIAL REGISTRATION NUMBER: NCT04363957.

Outcomes from a 3-fraction high-dose-rate brachytherapy regimen for patients with cervical cancer.

PURPOSE: To estimate local control, survival, and toxicity associated with a 3-fraction (3F) image-guided brachytherapy (IGBT) regimen compared to longer fraction (LF) for cervical cancer. METHODS: 150 patients treated between 2015-2020 with 3F (24Gy in 3 fractions) or LF (28...30 Gy in 4-5 fractions) were reviewed. The primary outcome was 2-year local failure. We compared overall survival (OS), disease-free survival (DFS), hospitalizations, and toxicity. RESULTS: There were 32 patients in the 3F group and 118 in the LF group, with a median follow up of 22 months. The 3F had worse performance status (p = 0.01) but otherwise similar characteristics. The 2-year local failure rate was 3.6% (95% CI 0%, 10.6%) for 3F, and 7.5% (95% CI 2.4%, 12.6%) for LF. The univariable hazard ratio (HR) for local failure for 3F was 0.43 (0.05, 3.43; p = 0.43). Moreover, 2 of 32 (6.3%) 3F patients experienced Grade ...3 toxicity compared to 7 of 118 (5.9%) LF patients (p = 1.0), with no difference in hospitalization within 2 years (p = 0.66) and no treatment-related deaths. CONCLUSIONS: Local control was excellent, with long term survival and toxicity similar between the groups. These findings support consideration of 3F.

Association Between Primary Care Use Prior to Cancer Diagnosis and Subsequent Cancer Mortality in the Veterans Affairs Health System.

Importance: Primary care physicians (PCPs) are significant contributors of early cancer detection, yet few studies have investigated whether consistent primary care translates to improved downstream outcomes. Objective: To evaluate the association of prediagnostic primary care use with metastatic disease at diagnosis and cancer-specific mortality (CSM). Design, Setting, and Participants: This cohort study used databases with primary care and referral linkage from multiple Veterans' Affairs centers from 2004 to 2017 and had a 68-month median follow-up. Analysis was completed between July 2021 and September 2022. Participants included veterans older than 39 years who had been diagnosed with 1 of 12 cancers. Inclusion criteria included known clinical staging, survival follow-up, cause of death, and receiving care at the Veterans Affairs health system (VA). Exposures: Prediagnostic PCP use, measured in the 5 years prior to diagnosis. PCP visits were binned into none (0 visits), some (1-4 visits), and annual (5 visits). Main Outcomes and Measures: Metastatic disease at diagnosis, cancer-specific mortality (CSM) for entire cohort and stratified by tumor subtype. Results: Among 245 425 patients representing 12 tumor subtypes, mean age was 65.8 (9.3) years, and the cohort skewed male (97.6%), and White (76.1%), with higher levels of comorbidity (58.6% with Charlson Comorbidity Index scores ≥2). Compared with no prior visit, some PCP use was associated with 26% decreased odds of metastatic disease at diagnosis (odds ratio [OR], 0.74; 95% CI, 0.71-0.76; P < .001) and 12% reduced risk of CSM (subdistribution hazard ratio [SHR], 0.88; 95% CI, 0.86-0.89; P < .001). Annual PCP use was associated with 39% decreased odds of metastatic disease (OR, 0.61; 95% CI, 0.59-0.63; P < .001) and 21% reduced risk of CSM (SHR, 0.79; 95% CI, 0.77-0.81; P < .001). Among tumor subtypes, prostate cancer had the largest effect size for prior PCP use on metastatic disease at diagnosis (OR for annual use, 0.32; 95% CI, 0.30-0.35; P < .001) and CSM (SHRfor annual use, 0.51; 95% CI, 0.48-0.55; P < .001). Conclusions and Relevance: In this cohort study, increased primary care use before cancer diagnosis was associated with significant decreases in metastatic disease at diagnosis and cancer-related death, with potentially the greatest difference from annual use. PCPs play a vital role in cancer prevention, and additional resources should be allocated to assist these physicians.

Incomplete cisplatin regimens in chemoradiation and its effect on outcomes for locally advanced cervical cancer.

OBJECTIVE: To identify factors associated with receipt of incomplete cisplatin during chemoradiation for locally advanced cervical cancer and its impact on outcomes. METHODS: Patients with locally advanced cervical cancer treated with chemoradiation at our institution between November 2015 and August 2020 were retrospectively identified. Patients who received ≤4 cycles were identified as the 'incomplete' cohort and those who received 5-6 cycles as the 'complete' cohort. The primary endpoint of incomplete chemotherapy was evaluated with multivariable logistic regression. Secondary endpoints of locoregional failure, overall survival, and distant failure were evaluated in multivariable Cox and Fine-Gray models. RESULTS: Of 140 patients with locally advanced cervical cancer that underwent chemoradiation, 22 (15.7%) received an incomplete cisplatin regimen (8 with 0 cycles, 14 with 1-4 cycles). The most common reasons for receiving incomplete treatment were comorbidities/infections (41%), unmet laboratory parameters (27%), and cisplatin intolerance (14%). In multivariable models, only poor (2-4) Eastern Cooperative Oncology Group performance status was a significant predictor as these patients were 41 times more likely to receive incomplete chemotherapy (odds ratio (OR), 95% confidence interval (CI) 4.57 to 375.15, p<0.001). Median follow-up time was 20 months (range 4-64). In multivariable models, receipt of incomplete cisplatin was significantly associated with higher recurrence (locoregional failure hazard ratio (HR) 3.02, 95% CI 1.08 to 8.45, p=0.03; distant failure HR 2.71, 95% CI 1.13 to 6.47, p=0.02) and worse survival (overall survival HR 4.91, 95% CI 1.27 to 18.98, p=0.02). CONCLUSION: Incomplete cisplatin regimen was associated with worse oncologic outcomes. Poor performance status was the only factor associated with receiving an incomplete regimen. This notable proportion of patients may be a target for better tolerated novel targeted anticancer agents in order to improve outcomes.

Association Between Prostate-Specific Antigen Screening and Prostate Cancer Mortality Among Non-Hispanic Black and Non-Hispanic White US Veterans.

Importance: Black men have higher prostate cancer incidence and mortality than non-Hispanic White men. However, Black men have been underrepresented in clinical trials of prostate-specific antigen (PSA) screening; thus, there is a lack of data to guide screening recommendations for this population. Objective: To assess whether PSA screening is associated with reduced risk of prostate cancer-specific mortality (PCSM) among non-Hispanic Black men. Design, Setting, and Participants: This retrospective cohort study used data from the US Veterans Health Administration Informatics and Computing Infrastructure for men aged 55 to 69 years who self-identified as non-Hispanic Black or non-Hispanic White and were diagnosed with intermediate-, high-, or very high-risk prostate cancer from January 1, 2004, to December 31, 2017. Data were analyzed from August 2021 to March 2022. Exposures: Prostate-specific antigen screening rate, defined as the percentage of years in which PSA screening was conducted during the 5 years before diagnosis of prostate cancer. Main Outcomes and Measures: The primary outcome was risk of PCSM among Black men and White men. The association between PSA screening and risk of PCSM was assessed using Fine-Gray regression analysis. Risk of PCSM was also assessed categorically among patients classified as having no prior PSA screening, some screening (less than annual), or annual screening in the 5 years before diagnosis. Results: The study included 45 834 veterans (mean [SD] age, 62.7 [3.8] years), of whom 14 310 (31%) were non-Hispanic Black men and 31 524 (69%) were non-Hispanic White men. The PSA screening rate was associated with a lower risk of PCSM among Black men (subdistribution hazard ratio [sHR], 0.56; 95% CI, 0.41-0.76; P = .001) and White men (sHR, 0.58; 95% CI, 0.46-0.75; P = .001). On subset analysis, annual screening (vs some screening) was associated with a significant reduction in risk of PCSM among Black men (sHR, 0.65; 95% CI, 0.46-0.92; P = .02) but not among White men (sHR, 0.91; 95% CI, 0.74-1.11; P = .35). Conclusions and Relevance: In this cohort study, PSA screening was associated with reduced risk of PCSM among non-Hispanic Black men and non-Hispanic White men. Annual screening was associated with reduced risk of PCSM among Black men but not among White men, suggesting that annual screening may be particularly important for Black men. Further research is needed to identify appropriate populations and protocols to maximize the benefits of PSA screening.

Evaluating High-Dimensional Machine Learning Models to Predict Hospital Mortality Among Older Patients With Cancer.

PURPOSE: Older hospitalized cancer patients face high risks of hospital mortality. Improved risk stratification could help identify high-risk patients who may benefit from future interventions, although we lack validated tools to predict in-hospital mortality for patients with cancer. We evaluated the ability of a high-dimensional machine learning prediction model to predict inpatient mortality and compared the performance of this model to existing prediction indices. METHODS: We identified patients with cancer older than 75 years from the National Emergency Department Sample between 2016 and 2018. We constructed a high-dimensional predictive model called Cancer Frailty Assessment Tool (cFAST), which used an extreme gradient boosting algorithm to predict in-hospital mortality. cFAST model inputs included patient demographic, hospital variables, and diagnosis codes. Model performance was assessed with an area under the curve (AUC) from receiver operating characteristic curves, with an AUC of 1.0 indicating perfect prediction. We compared model performance to existing indices including the Modified 5-Item Frailty Index, Charlson comorbidity index, and Hospital Frailty Risk Score. RESULTS: We identified 2,723,330 weighted emergency department visits among older patients with cancer, of whom 144,653 (5.3%) died in the hospital. Our cFAST model included 240 features and demonstrated an AUC of 0.92. Comparator models including the Modified 5-Item Frailty Index, Charlson comorbidity index, and Hospital Frailty Risk Score achieved AUCs of 0.58, 0.62, and 0.71, respectively. Predictive features of the cFAST model included acute conditions (respiratory failure and shock), chronic conditions (lipidemia and hypertension), patient demographics (age and sex), and cancer and treatment characteristics (metastasis and palliative care). CONCLUSION: High-dimensional machine learning models enabled accurate prediction of in-hospital mortality among older patients with cancer, outperforming existing prediction indices. These models show promise in identifying patients at risk of severe adverse outcomes, although additional validation and research studying clinical implementation of these tools is needed.

Disparities in time to start of definitive radiation treatment for patients with locally advanced cervical cancer.

BACKGROUND: Chemoradiation or radiation therapy alone are curative standards for patients with locally advanced cervical cancer. OBJECTIVE: To investigate factors that influence time to initiation of chemoradiation or radiation and the subsequent impact of time to treatment on recurrence and survival outcomes. METHODS: Patients with locally advanced cervical cancer treated with definitive chemoradiation or radiation at our institution between November 2015 and August 2020 were retrospectively identified. Time to treatment initiation was defined as the number of days from date of diagnosis (via biopsy) to the start date of radiation. The cohort was stratified by the median time to treatment into early (<75 days) and delayed (≥75 days) cohorts. Multivariable logistic regression was conducted to examine factors associated with delayed time to treatment. RESULTS: We identified 143 patients with locally advanced cervical cancer who underwent definitive chemoradiation or radiation. Median follow-up time was 18 months (range 2-62). A total of 71 (49.7%) patients had time to treatment <75 days and 72 (50.3%) patients had time to treatment ≥75 days. The delayed cohort had a higher proportion of Hispanic patients (51.4% vs 31.0%, p=0.04). In multivariable modeling, Hispanic women were 2.71 times more likely (p=0.04) to undergo delayed time to treatment than non-Hispanic white women. Additionally, patients with stage >IIB disease were less likely to undergo delayed time to treatment (OR 0.26, p=0.02) than patients with stage

Advances in immunotherapy for cervical cancer: recent developments and future directions.

There is an unmet need for novel therapies to improve clinical outcomes for patients with locally advanced, recurrent, or metastatic cervical cancer. Most cases of cervical cancer are driven by infection with human papillomavirus (HPV), which uses multiple mechanisms to avoid immune surveillance. Several classes of agents have been developed that seek to activate the immune system in order to overcome this resistance and improve treatment outcomes. These include immune checkpoint inhibitors, therapeutic vaccines, engineered T cells, and antibody-drug conjugates. Here, we review the immune landscape of cervical cancer and the growing clinical data regarding the use of immunotherapy. Checkpoint inhibitors are the best studied treatments, with encouraging phase II studies available in the definitive setting and recently published phase III data defining a new standard of care for patients with recurrent or metastatic disease. Vaccines and engineered T cells are generally in earlier phases of development but use unique mechanisms of immune activation. It is possible that combination of immunotherapy, with either conventional systemic therapy or multiple immunomodulatory agents, may provide further benefit. We also discuss possible synergies between immunotherapy and radiation therapy, which is frequently used in the management of cervical cancer. Ultimately, immunotherapy represents an emerging treatment option for patients with cervical cancer. It is an appropriate component of first-line treatment in the recurrent or metastatic setting and may soon be incorporated into definitive management of locally advanced disease.

Outcomes by time to definitive chemoradiation treatment for patients with muscle-invasive bladder cancer.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has raised concerns about delaying treatment for localized cancer and its impact on long-term outcomes. OBJECTIVE: We aimed to investigate the impact of time to chemoradiation (CRT) on recurrence and survival outcomes for patients with muscle-invasive bladder cancer (MIBC). METHODS: In the national Veterans Affairs' database, we identified patients with urothelial histology, MIBC (T2-4a/N0-3/M0) diagnosed between 2000 to 2018 and treated with definitive CRT. Time to treatment was defined as the number of days between date of diagnosis and start date of CRT. The cohort was stratified into < 90 (early) or ≥ 90 days (delayed) groups. Endpoints of locoregional failure (LRF), distant failure (DF), overall survival (OS), and bladder cancer-specific survival (BCS) were evaluated in multivariable Cox and Fine-Gray models. RESULTS: 305 patients with MIBC underwent CRT - 190 (62.3%) received early CRT, 115 (37.7%) received delayed CRT. Multivariable analysis (including success of transurethral resection of bladder tumor and type of chemotherapy) revealed no difference in recurrence between groups - LRF HR 1.12 (95%CI 0.76-1.67, P = 0.56) and DF HR 1.03 (95%CI 0.70-1.53, P = 0.88). Similarly, there were no differences in survival outcomes. The lack of association was maintained at both earlier and later time cutoffs (60-120 days). CONCLUSIONS: Our findings suggest that a short-term delay in definitive therapy may not affect long-term outcomes for patients with MIBC undergoing CRT. This study does not endorse delays in therapy, but rather provides information to aid patients and clinicians navigate the unique challenges of MIBC care in both pandemic and non-pandemic times.

Metastasis and Mortality in Men With Low- and Intermediate-Risk Prostate Cancer on Active Surveillance.

BACKGROUND: Active surveillance (AS) is a safe treatment option for men with low-risk, localized prostate cancer. However, the safety of AS for patients with intermediate-risk prostate cancer remains unclear. PATIENTS AND METHODS: We identified men with NCCN-classified low-risk and favorable and unfavorable intermediate-risk prostate cancer diagnosed between 2001 and 2015 and initially managed with AS in the Veterans Health Administration. We analyzed progression to definitive treatment, metastasis, prostate cancer-specific mortality (PCSM), and all-cause mortality using cumulative incidences and multivariable competing-risks regression. RESULTS: The cohort included 9,733 men, of whom 1,007 (10.3%) had intermediate-risk disease (773 [76.8%] favorable, 234 [23.2%] unfavorable), followed for a median of 7.6 years. The 10-year cumulative incidence of metastasis was significantly higher for patients with favorable (9.6%; 95% CI, 7.1%-12.5%; P<.001) and unfavorable intermediate-risk disease (19.2%; 95% CI, 13.4%-25.9%; P<.001) than for those with low-risk disease (1.5%; 95% CI, 1.2%-1.9%). The 10-year cumulative incidence of PCSM was also significantly higher for patients with favorable (3.7%; 95% CI, 2.3%-5.7%; P<.001) and unfavorable intermediate-risk disease (11.8%; 95% CI, 6.8%-18.4%; P<.001) than for those with low-risk disease (1.1%; 95% CI, 0.8%-1.4%). In multivariable competing-risks regression, favorable and unfavorable intermediate-risk patients had significantly increased risks of metastasis and PCSM compared with low-risk patients (all P<.001). CONCLUSIONS: Compared with low-risk patients, those with favorable and unfavorable intermediate-risk prostate cancer managed with AS are at increased risk of metastasis and PCSM. AS may be an appropriate option for carefully selected patients with favorable intermediate-risk prostate cancer, though identification of appropriate candidates and AS protocols should be tested in future prospective studies.

Treatment Discontinuation in Patients With Muscle-Invasive Bladder Cancer Undergoing Chemoradiation.

PURPOSE: Chemoradiation (CRT) is a definitive treatment option for muscle-invasive bladder cancer (MIBC). Despite its effectiveness, CRT is underused, in part owing to concerns of tolerability and the need for integrated multidisciplinary care. We investigated factors associated with and the impact of treatment discontinuation in patients with MIBC treated with CRT. METHODS AND MATERIALS: In the US Veterans Affairs' national database, we identified patients with urothelial histology, MIBC (T2-4a/N0-3/M0) diagnosed between 2000 and 2018 and treated with definitive-intent CRT. The primary endpoint of discontinued radiation was evaluated in a multivariable logistic regression. Secondary endpoints of 30-day and 90-day mortality, overall mortality, and nonbladder cancer mortality were evaluated in multivariable models. RESULTS: Of 369 veterans with MIBC who underwent CRT, 30 patients (8.1%) did not complete radiation. The most common reasons for treatment discontinuation included comorbidities or infections necessitating hospital admission (63.3%) and treatment intolerance or declining performance status (26.7%). In multivariable logistic regression, variables associated with radiation discontinuation were creatinine clearance ≤ 50 (odds ratio [OR], 3.93; 95% CI, 1.63-9.50; P = .002), incomplete transurethral resection of bladder tumor (TURBT) (OR, 3.16; 95% CI, 1.15-8.63; P = .02), and nonpreferred chemotherapy (OR, 3.31; 95% CI, 1.31-8.36; P = .01). In the cohort that discontinued radiation, 30-day mortality was 33.3% and 90-day mortality was 50.0%, with the majority of deaths attributed to nonbladder cancer causes. No patient or tumor variables were associated with either endpoint. In the cohort that completed radiation, 30-day mortality was 2.7% and 90-day mortality was 6.8%. In multivariable analysis, radiation discontinuation was associated with worse overall mortality (hazard ratio [HR], 2.48; 95% CI, 1.36-4.50; P = .003) and worse nonbladder cancer mortality (HR, 2.32; 95% CI, 1.24-4.34; P = .008). CONCLUSIONS: With a low rate of treatment discontinuation, CRT is an effective and feasible treatment option for the typically elderly and comorbid population of patients with MIBC. In addition to identified predictors of treatment discontinuation (poor renal function, incomplete TURBT, etc.), further research is required to develop evidence-based guidelines for optimal patient selection.

Patterns of Failure After Definitive Treatment of T4a Larynx Cancer.

OBJECTIVE: Recurrence is known to predict laryngeal squamous cell cancer (LSCC) survival. Recurrence patterns in T4a LSCC are poorly characterized and represent a possible explanation for observed survival discrepancies by treatment rendered. STUDY DESIGN: Retrospective database review. SETTING: Veterans Affairs national database. METHODS: Patients with T4a LSCC between 2000 and 2017 were identified and stratified by treatment (chemoradiotherapy [CRT] vs total laryngectomy + neck dissection + adjuvant therapy [surgical]). Primary outcomes were locoregional and distant recurrence. Secondary outcomes of overall mortality, larynx cancer mortality, and noncancer mortality were evaluated in Cox and Fine-Gray models. RESULTS: A total of 1043 patients had comparable baseline demographics: 438 in the CRT group and 605 in the surgical group. Patients undergoing CRT had higher proportions of node positivity (64.6% vs 53.1%, P < .001). Locoregional and distant recurrence were less common in the surgical group (23.0% vs 37.2%, P < .001; 6.8% vs 13.3%, P < .001, respectively); however, distant metastatic rates did not differ within the N0 subgroup (P = .722). On multivariable regression, surgery demonstrated favorable locoregional recurrence (hazard ratio [HR], 0.49; 95% CI, 0.39-0.62; P < .001), distant recurrence (HR, 0.47; 95% CI, 0.31-0.71; P < .001), overall mortality (HR, 0.75; 95% CI, 0.64-0.87; P < .001), and larynx cancer mortality (HR, 0.69; 95% CI, 0.56-0.85; P < .001). CONCLUSION: T4a LSCC survival discrepancies between surgical and nonsurgical treatment are influenced by varying recurrence behaviors. Surgery was associated with superior disease control and improved survival. Beyond the known benefit in locoregional control with surgery, there may be a protective effect on distant recurrence that depends on regional disease burden.

Frailty Index as a Predictor of Readmission in Patients With Head and Neck Cancer.

OBJECTIVE: To evaluate the predictive utility of the Hospital Frailty Risk Score (HFRS), a stratification tool based on the ICD-10 (International Classification of Disease, Tenth Revision), and other risk factors for 30-day readmissions and mortality in a nationally representative cohort. STUDY DESIGN: Retrospective database review. SETTING: Nationwide Readmissions Database (2017). METHODS: Patients with head and neck cancer who underwent major surgical procedures were identified from the 2017 Nationwide Readmissions Database, representing 116 medical centers nationwide. Bivariate and multivariable logistic regression methods were used to identify factors associated with unplanned 30-day readmission, 30-day readmission mortality, and increased length of hospital stay. RESULTS: A total of 14,420 patients underwent major head and neck cancer surgery. Unplanned readmission occurred in 11% of patients. The most common reasons for unplanned readmission were procedural complications (26.5%), sepsis (7.3%), and respiratory failure (3.9%). Elevated frailty index (HFRS ≥5) was identified in 22% of patients. Frailty was associated with higher 30-day readmission rates (18.0% vs 9.5%, P < .01), which held on multivariate modeling (odds ratio [OR], 1.59 [95% CI, 1.37-1.85]). Frail patients spent more days in the hospital (8.2 vs 6.8, P = .02) and incurred more charges across hospital stays ($275,000 vs $188,000, P < .01). Patients >75 years old (OR, 1.26 [1.03-1.55]) and patients with electrolyte abnormalities (OR, 1.25 [1.07-1.46] were significantly more likely to be readmitted. CONCLUSION: In this head and neck cancer surgical population, HFRS significantly predicted unplanned readmission. HFRS is a potential risk stratification tool and should be compared with other methods and explored in other cancer populations. Beyond the challenge of identifying at-risk patients, future work should explore potential interventions aimed at mitigating readmission.

Evaluating Prostate-Specific Antigen Screening for Young African American Men With Cancer.

BACKGROUND: Despite higher risks associated with prostate cancer, young African American men are poorly represented in prostate-specific antigen (PSA) trials, which limits proper evidence-based guidance. We evaluated the impact of PSA screening, alongside primary care provider utilization, on prostate cancer outcomes for these patients. METHODS: We identified African American men aged 40-55 years, diagnosed with prostate cancer between 2004 and 2017 within the Veterans Health Administration. Inverse probability of treatment-weighted propensity scores were used in multivariable models to assess PSA screening on PSA levels higher than 20, Gleason score of 8 or higher, and metastatic disease at diagnosis. Lead-time adjusted Fine-Gray regression evaluated PSA screening on prostate cancer-specific mortality (PCSM), with noncancer death as competing events. All statistical tests were 2-sided. RESULTS: The cohort included 4726 patients. Mean age was 51.8 years, with 84-month median follow-up. There were 1057 (22.4%) with no PSA screening prior to diagnosis. Compared with no screening, PSA screening was associated with statistically significantly reduced odds of PSA levels higher than 20 (odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.49 to 0.63; P < .001), Gleason score of 8 or higher (OR = 0.78, 95% CI = 0.69 to 0.88; P < .001), and metastatic disease at diagnosis (OR = 0.50, 95% CI = 0.39 to 0.64; P < .001), and decreased PCSM (subdistribution hazard ratio = 0.52, 95% CI = 0.36 to 0.76; P < .001). Primary care provider visits displayed similar effects. CONCLUSIONS: Among young African American men diagnosed with prostate cancer, PSA screening was associated with statistically significantly lower risk of PSA levels higher than 20, Gleason score of 8 or higher, and metastatic disease at diagnosis and statistically significantly reduced risk of PCSM. However, the retrospective design limits precise estimation of screening effects. Prospective studies are needed to validate these findings.

Association of Health-Care System and Survival in African American and Non-Hispanic White Patients With Bladder Cancer.

BACKGROUND: African American patients with bladder cancer have inferior outcomes compared with non-Hispanic White (White) patients. We hypothesize that access to health care is a primary determinant of this disparity. We compared outcomes by race for patients with bladder cancer receiving care within the predominant hybrid-payer health-care model of the United States captured in the Surveillance, Epidemiology, and End Results (SEER) database with those receiving care within the equal-access model of the Veterans' Health Administration (VHA). METHODS: African American and White patients diagnosed with bladder cancer were identified in SEER and VHA. Stage at presentation, bladder cancer-specific mortality (BCM), and overall survival (OS) were compared by race within each health-care system. RESULTS: The SEER cohort included 122 449 patients (93.7% White, 6.3% African American). The VHA cohort included 36 322 patients (91.0% White, 9.0% African American). In both cohorts, African American patients were more likely to present with muscle-invasive disease and metastases, but the differences between races were statistically significantly smaller in VHA. In SEER multivariable models, African American patients had worse BCM (hazard ratio [HR] = 1.22, 95% confidence interval [CI] = 1.15 to 1.29) and OS (HR = 1.26, 95% CI = 1.20 to 1.31). In contrast within the VHA, African American patients had similar BCM (HR = 0.97, 95% CI = 0.88 to 1.07) and OS (HR = 0.99, 95% CI = 0.93 to 1.05). CONCLUSIONS: In this study of contrasting health-care models, receiving medical care in an equal-access system was associated with reduced differences in stage at presentation and eliminated disparities in survival outcomes for African American patients with bladder cancer. Our findings highlight the importance of reducing financial barriers to care to notably improve health equity and oncologic outcomes for African American patients.

Impact of underlying malignancy on emergency department utilization and outcomes.

PURPOSE: Cancer patients frequently utilize the emergency department (ED) for a variety of diagnoses both related to and unrelated to their cancer, yet ED outcomes for cancer patients are not well documented. This study sought to define risks and identify predictors for inpatient admission and hospital mortality among cancer patients presenting to the ED. PATIENTS AND METHODS: We utilized the National Emergency Department Sample to identify patients with and without a diagnosis of cancer presenting to the ED between January 2016 and December 2018. We used multivariable mixed-effects logistic regression models to assess the influence of cancer on outcomes of hospital admission after the ED visit and hospital mortality for the whole patient cohort and individual presenting diagnoses. RESULTS: There were 340 million weighted ED visits, of which 8.3 million (2.3%) were associated with a cancer diagnosis. Compared to non-cancer patients, patients with cancer had an increased risk of inpatient admission (64.7% vs. 14.8%; p < 0.0001) and hospital mortality (4.6% vs. 0.5%; p < 0.0001). For each of the top 15 presenting diagnoses, cancer patients had increased risks of hospitalization (odds ratio [OR] range 2.0-13.2) or death (OR range 2.1-14.4). Although our dataset does not contain reliable estimation of stage, cancer site was the most robust individual predictor associated with the risk of hospitalization or death compared to other clinical or system-related factors. CONCLUSIONS: Cancer patients in the ED have high risks for hospital admission and death when compared to patients without cancer. Cancer patients represent a distinct population and may benefit from cancer-specific risk stratification or focused interventions to improve outcomes.

Prognostic Utility of Pretreatment Neutrophil-Lymphocyte Ratio in Advanced Larynx Cancer.

PURPOSE: Neutrophil-lymphocyte ratio has been explored as a prognosticator in several cancer types, but its association with larynx cancer outcomes is not well known. We aimed to identify an optimal NLR cutoff point and examine the prognostic utility of this biomarker in patients with locoregionally advanced larynx cancer treated with curative intent. METHODS: In the Veterans Affairs' (VA) national database, we identified patients with locoregionally advanced (T3-4N0-3M0) laryngeal squamous cell carcinoma diagnosed between 2000 and 2017 and treated with curative intent. NLR cutoff points were calculated using Contal/O'Quigley's method. Outcomes of larynx cancer-specific survival (CSS), overall survival (OS), and non-larynx cancer survival (NCS) were evaluated in multivariable Cox and Fine-Gray models. RESULTS: In 1047 patients, the optimal pretreatment NLR cutoff was identified as 4.17 - 722 patients with NLR ⩽ 4.17, 325 patients with NLR > 4.17. The elevated NLR cohort had a higher proportion of T4 disease (39.4% vs 28.4%), node positive disease (52.3% vs 43.1%), and surgical treatment (43.7% vs 35.2%). In multivariable analysis, NLR > 4.17 was independently associated with worse OS (HR 1.31, 95% CI 1.12-1.54, P = .001) and worse CSS (HR 1.46, 95% CI 1.17-1.83, P < .001), but not with NCS (HR 0.94, 95% CI 0.75-1.18, P = .58). CONCLUSION: In locoregionally advanced larynx cancer treated with curative intent, we identified elevated NLR to be associated with inferior OS and CSS. Further prospective studies are needed to investigate pretreatment NLR and our identified 4.17 cutoff as a potential larynx cancer-specific marker for this high risk population.

Evaluating the clinical trends and benefits of low-dose computed tomography in lung cancer patients.

BACKGROUND: Despite guideline recommendations, utilization of low-dose computed tomography (LDCT) for lung cancer screening remains low. The driving factors behind these low rates and the real-world effect of LDCT utilization on lung cancer outcomes remain limited. METHODS: We identified patients diagnosed with non-small cell lung cancer (NSCLC) from 2015 to 2017 within the Veterans Health Administration. Multivariable logistic regression assessed the influence of LDCT screening on stage at diagnosis. Lead time correction using published LDCT lead times was performed. Cancer-specific mortality (CSM) was evaluated using Fine-Gray regression with non-cancer death as a competing risk. A lasso machine learning model identified important predictors for receiving LDCT screening. RESULTS: Among 4664 patients, mean age was 67.8 with 58-month median follow-up, 95% CI = [7-71], and 118 patients received ≥1 screening LDCT before NSCLC diagnosis. From 2015 to 2017, LDCT screening increased (0.1%-6.6%, mean = 1.3%). Compared with no screening, patients with ≥1 LDCT were more than twice as likely to present with stage I disease at diagnosis (odds ratio [OR] 2.16 [95% CI 1.46-3.20]) and less than half as likely to present with stage IV (OR 0.38 [CI 0.21-0.70]). Screened patients had lower risk of CSM even after adjusting for LDCT lead time (subdistribution hazard ratio 0.60 [CI 0.42-0.85]). The machine learning model achieved an area under curve of 0.87 and identified diagnosis year and region as the most important predictors for receiving LDCT. White, non-Hispanic patients were more likely to receive LDCT screening, whereas minority, older, female, and unemployed patients were less likely. CONCLUSIONS: Utilization of LDCT screening is increasing, although remains low. Consistent with randomized data, LDCT-screened patients were diagnosed at earlier stages and had lower CSM. LDCT availability appeared to be the main predictor of utilization. Providing access to more patients, including those in diverse racial and socioeconomic groups, should be a priority.

Active surveillance for intermediate-risk prostate cancer in African American and non-Hispanic White men.

BACKGROUND: The safety of active surveillance (AS) for African American men compared with non-Hispanic White (White) men with intermediate-risk prostate cancer is unclear. METHODS: The authors identified patients with modified National Comprehensive Cancer Network favorable ("low-intermediate") and unfavorable ("high-intermediate") intermediate-risk prostate cancer diagnosed between 2001 and 2015 and initially managed with AS in the Veterans Health Administration database. They analyzed definitive treatment, disease progression, metastases, prostate cancer-specific mortality (PCSM), and all-cause mortality by using cumulative incidences and multivariable competing-risks (disease progression, metastasis, and PCSM) or Cox (all-cause mortality) regression. RESULTS: The cohort included 1007 men (African Americans, 330 [32.8%]; Whites, 677 [67.2%]) followed for a median of 7.7 years; 773 (76.8%) had low-intermediate-risk disease, and 234 (23.2%) had high-intermediate-risk disease. The 10-year cumulative incidences of definitive treatment were not significantly different (African Americans, 83.5%; 95% confidence interval [CI], 78.5%-88.7%; Whites, 80.6%; 95% CI, 76.6%-84.4%; P = .17). Among those with low-intermediate-risk disease, there were no significant differences in the 10-year cumulative incidences of disease progression (African Americans, 46.8%; 95% CI, 40.0%-53.3%; Whites, 46.9%; 95% CI, 42.1%-51.5%; P = .91), metastasis (African Americans, 7.1%; 95% CI, 3.7%-11.8%; Whites, 10.8%; 95% CI, 7.6%-14.6%; P = .17), or PCSM (African Americans, 3.8%; 95% CI, 1.6%-7.5%; Whites, 3.8%; 95% CI, 2.0%-6.3%; P = .69). In a multivariable regression including the entire cohort, African American race was not associated with increased risks of definitive treatment, disease progression, metastasis, PCSM, or all-cause mortality (all P > .30). CONCLUSIONS: Outcomes in the Veterans Affairs Health System were similar for African American and White men treated for low-intermediate-risk prostate cancer with AS.

Salvage Following Transoral Laser Microsurgery for Early Glottic Cancer in National Veteran Database.

OBJECTIVES: Transoral laser microsurgery (TLM) is commonly utilized for early glottic cancer and offers favorable oncologic and functional outcomes. However, the survival implications of salvage therapy for recurrent or persistent disease have not been definitively characterized. STUDY DESIGN: Retrospective, national database cohort study. METHODS: Data were extracted from Veterans Health Affairs (VHA) Informatics and Computing Infrastructure (VINCI) concerning the TLM-based management of T1-T2 glottic squamous cell carcinoma patients between 2000 and 2017. Patients were characterized as either requiring TLM-only, or in cases of persistent or recurrent local disease, TLM plus change in treatment modality (radiotherapy, chemoradiotherapy, or open surgery). Predictors of overall survival (OS), cancer-specific survival (CSS), and salvage-free survival were evaluated via Cox and Fine-Gray models. RESULTS: About 553 patients (70.9% T1a, 13.4% T1b, 15.7% T2) were included, with a median follow-up time of 74.5 months. The need for non-TLM salvage increased along with more advanced disease (11.7% T1a, 29.7% T1b, 32.2% T2). Compared to patients with T1a disease, those with T1b and T2 tumors initially treated with TLM had a significantly higher probability of receiving non-TLM salvage (T1b: HR 2.70, 95% CI: 1.61-4.54; T2: HR 3.02, 95% CI: 1.88-4.84). In a multivariable model, receipt of non-TLM salvage was not a significant predictor of either OS (HR = 0.91, 95% CI: 0.62-1.33, P = .624) or CSS (HR 1.21 95% CI 0.51-2.86, P = .667). CONCLUSION: The majority of patients with early glottic cancer that are managed with TLM do not require additional salvage therapy. When non-TLM salvage was required, there was no decrement in OS or CSS. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2766-2772, 2021.