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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.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has left patients with current or past history of cancer facing disparate consequences at every stage of the cancer trajectory. This comprehensive review offers a landscape analysis of the current state of the literature on COVID-19 and cancer, including the immune response to COVID-19, risk factors for severe disease, and impact of anticancer therapies. We also review the latest data on treatment of COVID-19 and vaccination safety and efficacy in patients with cancer, as well as the impact of the pandemic on cancer care, including the urgent need for rapid evidence generation and real-world study designs. SIGNIFICANCE: Patients with cancer have faced severe consequences at every stage of the cancer journey due to the COVID-19 pandemic. This comprehensive review offers a landscape analysis of the current state of the field regarding COVID-19 and cancer. We cover the immune response, risk factors for severe disease, and implications for vaccination in patients with cancer, as well as the impact of the COVID-19 pandemic on cancer care delivery. Overall, this review provides an in-depth summary of the key issues facing patients with cancer during this unprecedented health crisis.

The application of induced pluripotent stem cells (iPSCs) in advanced therapies is increasing at pace, but concerns remain over their clinical safety profile. We report the first-ever application of doggybone DNA (dbDNA) vectors to generate human iPSCs. dbDNA vectors are closed-capped linear double-stranded DNA gene expression cassettes that contain no bacterial DNA and are amplified by a chemically defined, current good manufacturing practice (cGMP)-compliant methodology. We achieved comparable iPSC reprogramming efficiencies using transiently expressing dbDNA vectors with the same iPSC reprogramming coding sequences as the state-of-the-art OriP/EBNA1 episomal vectors but, crucially, in the absence of p53 shRNA repression. Moreover, persistent expression of EBNA1 from bacterially derived episomes resulted in stimulation of the interferon response, elevated DNA damage, and increased spontaneous differentiation. These cellular activities were diminished or absent in dbDNA-iPSCs, resulting in lines with a greater stability and safety potential for cell therapy., Graphical abstract, Thornton et al. have applied novel doggybone cDNA technology to generate transiently maintained gene delivery vectors containing no bacterial motifs to generate induced pluripotent stem cells (iPSCs). When compared to episomal OriP/EBNA1, our vectors generated safer, more stable colonies at an equivalent efficiency.

BACKGROUND This study was done to determine the representation of minorities, women, and the elderly in National Cancer Institute (NCI) clinical trials. METHODS This is an analysis in the NCI Clinical Data Update System. Patients were evaluated in breast, colorectal, lung, and prostate cancer trials from 2000 to 2019. Representation in a trial was determined by race/ethnicity, sex, and age. Secondarily, the change in trial participation by multivariable analysis by comparing years 2000 through 2004 to 2015 through 2019 was evaluated. RESULTS The cohort included 242,720 participants: 197,320 Non-Hispanic White (81.3%), 21,190 Black (8.7%), 11,587 Hispanic (4.8%), and 6880 Asian/Pacific Islander (2.8%). Black and Hispanic patients were underrepresented for colorectal (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.50-0.67; P < .001 and OR, 0.74; 95% CI, 0.64-0.87; P < .001, respectively), lung (OR, 0.83; 95% CI, 0.76-0.91; P < .001 and 0.66; 95% CI, 0.57-0.77; P < .001, respectively), and prostate cancer trials (OR, 0.85; 95% CI, 0.79-0.92; P < .001 and OR, 0.58; 95% CI, 0.51-0.66; P < .001) between 2015 and 2019. The odds of participation in 2015 to 2019 increased among Black patients in breast (OR, 2.19; 95% CI, 2.07-%2.32; P < .001), lung (OR, 1.54; 95% CI, 1.38-1.73; P < .001), and prostate cancer trials (OR, 1.14; 95% CI, 1.04-1.26; P < .001). The odds of participation in a trial among Hispanic patients increased for breast (OR, 3.32; 95% CI, 3.09-3.56; P < .001), colorectal (OR, 2.46; 95% CI, 2.04-2.96; P < .001), lung (OR, 3.88; 95% CI, 3.20-4.69; P < .001), and prostate cancer (OR, 1.70; 95% CI, 1.42-2.04; P = .005). CONCLUSIONS This study identified that Black and Hispanic patients remain underrepresented in trials, but in recent years, participation has increased. These findings indicate that minority participation has increased over time, but further efforts are needed.

Issues Relapse is a theoretical construct and empirical object of inquiry. It is unclear how relapse is operationalised with regard to the various phases in substance use disorders (SUD). The aim was to investigate relapse operationalisations in SUDs studies after short- and long-term abstinence and remission, recovery and slip/lapse. Approach Systematic review using the following databases: Epistemonikos, Cochrane Central Register of Controlled Trials (CENTRAL and DARE), MEDLINE, EMBASE, Google Scholar, CINAHL, Web of Science and PsycINFO. Search returned 3426 articles, with 276 meeting the following inclusion criteria: empirical study published in English in a peer-reviewed journal; samples meet diagnostic criteria for dependence syndrome or moderate–severe drug use disorder or alcohol use disorder; reports relapse, abstinence, recovery, remission, slip or lapse. Review protocol registration: PROSPERO (CRD42020154062). Key Findings Thirty-two percent of the studies had no definition of ‘relapse’. Most relapse operationalisations were defined according to measure (26%), time (17%), use (26%) and amount and frequency (27%). Of the 16 studies with a follow-up duration of up to 2 years, one (6%) contained a definition of ‘long-term abstinence’. Of the 64 studies with a follow-up duration of more than 2 years, four (6%) contained a definition of ‘long-term abstinence’. Of those, one (2%) mentioned ‘early relapse’ and one (2%) mentioned ‘late relapse’. Implications Future research is needed to explore the possible difference between early and late relapse. Moreover, working to increase consensus on relapse operationalisations in SUD research is warranted. Conclusions We identified no consensus on relapse operationalisations nor agreement on the differentiation between early and late relapse. The clinical utility of current relapse operationalisations seems low and may compromise knowledge accumulation about relapse and implementation of research into treatment.

Germline testing is becoming increasingly relevant in prostate cancer (PCa) screening, prognosis, and management. A subset of patients with PCa harbor pathogenic/likely pathogenic variants (P/LPVs) in genes mediating DNA-repair processes, and these P/LPVs have implications for cancer screening, treatment, and cascade testing. As a result, it is recommended that all men with high-risk localized and metastatic PCa undergo routine germline testing. As more PCa patients undergo germline testing, it is important that clinicians and genetics experts recognize current disparities in germline testing rates among racial/ethnic minorities in the United States. The reasons for these disparities are multiple and require similarly manifold consideration to close the germline testing gap and reduce inequities in PCa screening, management, and treatment.

Background Little is known regarding the rate and clinical outcomes of asymptomatic carriers of SARS‐CoV‐2 among patients with cancer. Detection of asymptomatic carriers is important in this population given the use of myelosuppressive and immunomodulating therapies. Understanding the asymptomatic carrier rate will help to develop mitigation strategies in this high‐risk cohort. Methods Retrospective cohort analysis of an asymptomatic screening protocol which required patients receiving infusional anti‐cancer therapy to undergo a symptom/exposure screen and SARS‐CoV‐2 PCR testing 24–96 h prior to their infusion. The primary outcome of this analysis was the rate of asymptomatic SARS‐CoV‐2 infection. Secondary outcomes included the rate of COVID‐19‐related hospitalization and mortality and delays in oncologic therapy. Results Among a cohort of 2691 cancer patients who underwent asymptomatic screening, 1.6% (N = 43/2691) of patients were found to be SARS‐CoV‐2 positive on asymptomatic screening. 11.6% (N = 5/43) of the cohort ultimately developed COVID‐19‐related symptoms. Four patients required hospitalization for complications of COVID‐19 infection. No patient died from COVID‐related complications. 97.7% (N = 42/43) had their anti‐cancer therapy delayed or deferred with a median delay of 21 days (range: 7–77 days). Conclusions Overall, among a cohort of active cancer patients receiving anti‐cancer therapy, an asymptomatic SARS‐CoV2 PCR‐based screening protocol detected a small cohort of asymptomatic carriers. The majority of these patients remained asymptomatic on long‐term follow‐up and outcomes were much more favorable compared to previously described outcomes of cancer patients with symptomatic COVID‐19 infection., Little is known about the rate of asymptomatic SARS‐CoV‐2 carriers among cancer patients. Here, we examined a cohort of active cancer patients who underwent asymptomatic SARS‐CoV‐2 PCR screening prior to their infusion therapy. We found a low rate of asymptomatic carriers (1.6%) among this cohort and this asymptomatic cohort had favorable longterm infectious outcomes.

In the United States of America (USA), prostate cancer (PC) is the most common cancer in men and the second cause of cancer mortality. Black men (BM) have a higher incidence and worse mortality when compared to white men (WM). We compared trends in PC mortality in the USA by race and state from 1999 to 2019.We extracted PC mortality data from the Centers for Disease Control (CDC) WONDER database using the International Classification of Diseases (ICD) 10 code C61. Age-Standardized Mortality Rates (ASMR) were divided into racial groups and reported by year and state. Due to the lack of available data in many states, analyses were conducted only for WM and BM using Joinpoint regression for trend comparisons.Between 1999-2019, ASMR decreased at the national level in Black (-44.6%), Asian (-44.8%), White (-31.8%), and American Indian or Alaskan native men (-19.0%). ASMR decreased in all states for both races. The greatest drop in ASMR was in Kentucky (-47.0%) for WM and Delaware (-57.8%) for BM. In 2019, ASMRs in BM (13.4/100 000) were significantly higher than WM (7.3/100 000), American Indian or Alaskan Native (3.2/100 000), and Asian men (3.2/100 000) (p 0.001). The highest ASMRs were in Nebraska (33.5/100 000) for BM and Alaska (11/100 000) for WM.During the last 20 years, the PC mortality rate dropped in all states for all races, suggesting an advancement in management strategies. Although a higher decrease in ASMR was observed in BM, ASMR remain higher among BM. ASMRs were also found to be increasing in many states post USPSTF guideline change (2012), indicating a need for more education around optimized prostate cancer screening.

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, recurrent, and metastatic disease. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. These NCCN Guidelines Insights summarizes much of the panel's discussions for the 4.2022 and 1.2023 updates to the guidelines regarding systemic therapy for metastatic prostate cancer.

OBJECTIVES: To compare clinical outcomes with programmed-death ligand-1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation therapy (RT) prior to developing metastatic disease. PATIENTS AND METHODS: We performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first-line and second-line or greater [second-plus line]). Logistic regression was used to compare ORR, while Kaplan–Meier analysis and Cox regression were used for PFS and OS. Multivariable models were adjusted for known prognostic factors. RESULTS: We included 562 patients (first-line: 342 and second-plus line: 220). There was no difference in outcomes based on prior locoregional treatment among those treated with first-line ICIs. In the second-plus-line setting, prior RS was associated with higher ORR (adjusted odds ratio 2.61, 95% confidence interval [CI]1.19–5.74]), longer OS (adjusted hazard ratio [aHR] 0.61, 95% CI 0.42–0.88) and PFS (aHR 0.63, 95% CI 0.45–0.89) vs no prior RS. This association remained significant when type of prior locoregional treatment (RS and RT) was modelled separately. CONCLUSION: Prior RS before developing advanced disease was associated with better outcomes in patients with aUC treated with ICIs in the second-plus-line but not in the first-line setting. While further validation is needed, our findings could have implications for prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include the study’s retrospective nature, lack of randomization, and possible selection and confounding biases.

PURPOSE Cediranib, a pan-vascular endothelial growth factor receptor inhibitor, suppresses expression of homologous recombination repair (HRR) genes and increases sensitivity to poly-(ADP-ribose) polymerase inhibition in preclinical models. We investigated whether cediranib combined with olaparib improves the clinical outcomes of patients with prostate cancer. METHODS Patients with progressive metastatic castration-resistant prostate cancer (mCRPC) were randomly assigned 1:1 to arm A: cediranib 30 mg once daily plus olaparib 200 mg twice daily or arm B: olaparib 300 mg twice daily alone. The primary end point was radiographic progression-free survival (rPFS) in the intention-to-treat patients. The secondary end points were rPFS in patients with HRR-deficient and HRR-proficient mCRPC. RESULTS In the intention-to-treat set of 90 patients, median rPFS was 8.5 (95% CI, 5.4 to 12.0) and 4.0 (95% CI, 3.2 to 8.5) months in arms A and B, respectively. Cediranib/olaparib significantly improved rPFS versus olaparib alone (hazard ratio [HR], 0.617; 95% CI, 0.392 to 0.969; P = .0359). Descriptive analyses showed a median rPFS of 10.6 (95% CI, 5.9 to not assessed [NA]) and 3.8 (95% CI, 2.33 to NA) months (HR, 0.64; 95% CI, 0.272 to 1.504) among patients with HRR-deficient mCRPC, and 13.8 (95% CI, 3.3 to NA) and 11.3 (95% CI, 3.8 to NA) months (HR, 0.98; 95% CI, 0.321 to 2.988) among patients with BRCA2-mutated mCRPC in arms A and B, respectively. The incidence of grades 3-4 adverse events was 61% and 18% in arms A and B, respectively. CONCLUSION Cediranib combined with olaparib improved rPFS compared with olaparib alone in men with mCRPC. This combination was associated with an increased incidence of grades 3-4 adverse events. BRCA2-mutated subgroups treated with olaparib with or without cediranib were associated with a numerically longer median rPFS.

BackgroundT2-weighted MRI is standard for detecting clinically significant prostate cancer (csPCa) by identifying visible lesions that stand out from the background prostate.PurposeTo determine whether patients with csPCa have abnormalT2-weighted signal in non-lesion, background prostate tissue (BP).MethodsThis retrospective study included two patient cohorts who underwent 3T MRI examination for suspected csPCa. Median (urine-normalized)T2-weighted signal was computed for BP and compared between patients with and without csPCa. csPCa discrimination performance ofT2-weighted BP signal was evaluated using area under receiver operating characteristic curves (AUC).T2andS0(a proxy for proton density) were computed and compared between patients with and without csPCa.T2was also recomputed using larger buffers around csPCa lesions. csPCa discrimination performance was compared between two predictors: Restriction Spectrum Imaging (RSI)C1and RSIC1normalized by global prostate medianT2-weighted signal.ResultsCohort 1: 46 patients (age: 64±10 years). Cohort 2: 151 patients (65±8 years). Urine-normalizedT2-weighted signal was systematically lower in BP of subjects with csPCa (p≤0.034) and indicated the presence of cancer (cohort 1: AUC=0.80; cohort 2: AUC=0.68). BPT2was significantly lower in csPCa patients (p≤0.011), whileS0was not (p≥0.30). BPT2measurements were stable to within 5% with buffers from 0 to 30 mm around visible lesions. csPCa discrimination improved with incorporation of BPT2-weighted signal (cohort 1: AUC=0.72 for RSIC1alone, versus 0.81 with BPT2-weighted signal; cohort 2: AUC=0.63 versus 0.76).ConclusionLowerT2-weighted signal in BP suggests the presence of csPCa.

Recipients of solid organ transplants (SOTs) have unique risks for infections, but providers are often hesitant to apply the principles of antimicrobial stewardship to this patient population due to perceived excess risk. The methods of implementation science may move the field forward to simultaneously improve patient outcomes and patient safety.Perspective piece on implementation science in SOT patients.Herein, we provide explanation of implementation science as it relates to SOT patients. In addition, we provide examples of how implementation science can be applied to antimicrobial stewardship in SOT patients.Implementation science may offer insights and solutions to the challenges of implementing evidence-based antimicrobial stewardship interventions in patients with SOT, including uptake of new practices and the de-implementation of outdated or low-value practices.