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A myriad of organ-specific complications have been observed with COVID-19. While racial/ethnic minorities have been disproportionately burdened by this disease, our understanding of the unique risk factors for complications among a diverse population of cancer patients remains limited. This is a multi-institutional, multi-ethnic cohort study evaluating COVID-19 complications among cancer patients. Patients with an invasive cancer diagnosis and confirmed SARS-CoV-2 infection were identified from March to November 2020. Demographic and clinical data were obtained and a multivariate logistic regression was employed to evaluate the impact of demographic and clinical factors on COVID-19 complications. The study endpoints were evaluated independently and included any complication, sepsis, pulmonary complications and cardiac complications. A total of 303 patients were evaluated, of whom 48% were male, 79% had solid tumors, and 42% were Hispanic/Latinx (Hispanic). Malignant hematologic cancers were associated with a higher risk of sepsis (OR 3.93 (95% CI 1.58-9.81)). Male patients had a higher risk of sepsis (OR 4.42 (95% CI 1.63-11.96)) and cardiac complications (OR 2.02 (95% CI 1.05-3.89)). Hispanic patients had a higher odds of any complication (OR 2.31 (95% CI 1.18-4.51)) and other race was associated with a higher odds of cardiac complications (OR 2.41 (95% CI 1.01-5.73)). Clinically, fever, cough, and ≥2 co-morbidities were independently significantly associated with any complication. This analysis evaluated covariates that can significantly predict a myriad of complications among a multi-ethnic cohort of cancer patients. The conclusions drawn from this analysis elucidate a mechanistic understanding of differential illness severity from COVID-19.

e17010 Background: Approximately 12% of patients (pts) with metastatic PCa (mPCa) identified by conventional imaging harbor DDRv. The increased use of PSMA PET has identified a group of pts with extra-prostatic PCa which is not apparent on conventional imaging and for whom the frequency of germline DDRv testing remains unknown. Methods: A single-institution retrospective analysis of patients with PCa detected by PSMA PET who had also undergone germline genetic testing was undertaken. Data collected included PSA level at time of PSMA PET imaging, stage/Gleason score at diagnosis (dx), rationale for germline testing, castration status, and whether the metastatic disease identified on PSMA PET represented de novo or recurrent mPCa. Germline sequencing results were evaluated for 16 DNA damage repair genes: ATM, ATR, BAP1, BARD1, BRCA1, BRCA2, BRIP1, CHEK2, GEN1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51C, and RAD51D. The frequency of DDRv was evaluated in groups defined by PSMA imaging results: localized (N0M0), Node-Positive (N+M0), metastatic (M+) PCa. Results: Of 795 PCa pts who underwent germline testing and 2101 PCa pts who underwent PSMA PET imaging, 386 had undergone both, and constitute the study cohort. In the study cohort the distribution of PCa extent identified by PSMA PET was: 81/386 (21.0%) N0M0; 76/386 (19.7%) N+M0; 229/386 (59.3%) M+. There were no statistically significant differences in the prevalence of DDRv with regards to age, Gleason score at dx, PSA at time of imaging, castration status at time of imaging, rationale for germline testing, or if metastatic, whether de novo or recurrent. The distribution of DDRv is shown in the table. There were no statistically significant differences between groups. Conclusions: The overall frequency of pathogenic germline DDRv in PCa pts who had undergone PSMA PET imaging was 4.66%, considerably lower than what has been reported in men with mPCa detected with conventional imaging. The presence or absence of extra-prostatic PCa detected by PSMA PET imaging did not appear to affect the frequency of DDRv. Validation of these findings in other cohorts will be important to guide recommendations for germline genetic testing in the growing group of PCa pts undergoing PSMA PET imaging. [Table: see text]

BackgroundLimited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations.MethodsThis is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity.Results1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status.ConclusionsUsing one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients.FundingThis study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication.Clinical trial numberCCC19 registry is registered on ClinicalTrials.gov, NCT04354701.

BackgroundEnfortumab vedotin (EV) is an antibody-drug conjugate approved for patients with treatment-refractory advanced urothelial carcinoma (aUC), however data on biomarkers of response is lacking.MethodsWe retrospectively identified all aUC patients at our institution who received EV monotherapy and had next-generation sequencing (NGS) data available. Patients were considered responders if they had a complete response or partial response on restaging scans during treatment. Observed response rate (ORR) was evaluated by local investigator and compared between responders and non-responders using Chi-squared test. A univariable analysis was conducted using the Cox proportional hazard test to assess for associations between baseline characteristics and most common somatic alterations (in ≥10% of patients) with patient survival outcomes [progression-free survival (PFS) and overall survival (OS)]. Somatic alterations were then individually evaluated in separate multivariate models while accounting for patient and clinical characteristics using Cox regression models.ResultsAmong 29 patients treated with EV monotherapy, 27 had available NGS data. Median age was 70, 24 (83%) were men, 19 (62%) were Caucasian, 15 (52%) had pure urothelial histology and 22 (76%) had primary tumor in the bladder. ORR was 41%, and PFS and OS for the overall cohort were 5.1 months and 10.2 months. Responders were enriched among patients with TP53, KDM6A and MDM2 alterations. Patients with these alterations, as well as those with composite TP53/MDM2 alterations (alterations in either TP53 or MDM2), also had increased ORR with EV treatment compared to patients without these alterations. In the univariable analysis, baseline albumin level ≥ 3.0g/dL and presence of composite TP53/MDM2 alterations were associated with a prolonged OS. Baseline ECOG 0/1, TP53 alterations and TP53/MDM2 alterations were associated with a prolonged PFS. In the multivariable analysis, TP53 and TP53/MDM2 alterations were genomic markers predictive of improved PFS after accounting for the relevant clinical characteristics.ConclusionIn this single-center retrospective analysis of aUC patients treated with EV, presence of TP53 or MDM2 somatic alterations, lower ECOG PS scores (ECOG 0 or 1) and higher albumin levels (≥3 g/dL) were associated with improved outcomes with EV treatment. Prospective and external validation of these findings in larger cohorts is warranted.

BackgroundEarly progression on first-line (1L) platinum-based therapy or between therapy lines may be a surrogate of more aggressive disease and poor outcomes in advanced urothelial carcinoma (aUC), but its prognostic role regarding immune checkpoint inhibitor (ICI) response and survival is unclear. We hypothesized that shorter time until start of second-line (2L) ICI would be associated with worse outcomes in aUC.Patients and methodsWe performed a retrospective multi-institution cohort study in patients with aUC treated with 1L platinum-based chemotherapy, who received 2L ICI. Patients receiving switch maintenance ICI were excluded. We defined time to 2L ICI therapy as the time between the start of 1L platinum-based chemotherapy to the start of 2L ICI and categorized patients a priori into 1 of 3 groups: less than 3 months versus 3-6 months versus more than 6 months. We calculated overall response rate (ORR) with 2L ICI, progression-free survival (PFS) and overall survival (OS) from the start of 2L ICI. ORR was compared among the 3 groups using multivariable logistic regression, and PFS, OS using cox regression. Multivariable models were adjusted for known prognostic factors.ResultsWe included 215, 215, and 219 patients in the ORR, PFS, and OS analyses, respectively, after exclusions. ORR difference did not reach statistical significance between patients with less than 3 months versus 3-6 months versus more than 6 months to 2L ICI. However, PFS (HR 1.64; 95% CI 1.02-2.63) and OS (HR 1.77; 95% CI 1.10-2.84) was shorter among those with time to 2L ICI less than 3 months compared to those who initiated 2L ICI more than 6 months.ConclusionAmong patients with aUC treated with 2L ICI, time to 2L ICI less than 3 months was associated with lower, but not significantly different ORR, but shorter PFS and OS compared to 2L ICI more than 6 months. This highlights potential cross resistance mechanisms between ICI and platinum-based chemotherapy.

ObjectivesTo 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 methodsWe 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.ResultsWe 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.ConclusionPrior 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.

BackgroundSites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI.MethodsWe identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd+ line.ResultsWe identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd+ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd+ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant.ConclusionBone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.

BackgroundThe risks associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated illness, coronavirus disease 2019 (COVID-19), among patients with a cancer diagnosis have not been fully characterized. This study leverages data from a multi-institutional cohort study, the University of California Cancer COVID Consortium, to evaluate outcomes associated with SARS-CoV-2 infection among patients with cancer.MethodsClinical data were collected from March to November 2020 and included patient demographics, cancer history and treatment, SARS-CoV-2 exposure and testing, and COVID-19 clinical management and outcomes. Multivariate ordinal logistic regression permitting unequal slopes was used to evaluate the impact of demographic, disease, and treatment factors on SARS-CoV-2 related hospitalization, intensive care unit (ICU) admission, and mortality.FindingsAmong all evaluated patients (n = 303), 147 (48%) were male, 118 (29%) were older adults (≥65 years old), and 104 (34%) were non-Hispanic white. A subset (n = 63, 21%) had hematologic malignancies and the remaining had solid tumors. Patients were hospitalized for acute care (n = 79, 26%), ICU-level care (n = 28, 9%), or died (n = 21, 7%) due to COVID-19. Patients with ≥2 comorbidities were more likely to require acute care (odds ratio [OR] 2.09 [95% confidence interval (CI), 1.23-3.55]). Cough was identified as a significant predictor of ICU hospitalization (OR 2.16 [95% CI, 1.03-4.57]). Importantly, mortality was associated with an active cancer diagnosis (OR 3.64 [95% CI, 1.40-9.5]) or advanced age (OR 3.86 [95% CI, 1.2-12.44]).InterpretationThis study observed that patients with active cancer or advanced age are at an increased risk of death from COVID-19. These study observations can inform risk counseling related to COVID-19 for patients with a cancer diagnosis.

Patients with B-lymphoid malignancies have been consistently identified as a population at high risk of severe COVID-19. Whether this is exclusively due to cancer-related deficits in humoral and cellular immunity, or whether risk of severe COVID-19 is increased by anticancer therapy, is uncertain. Using data derived from the COVID-19 and Cancer Consortium (CCC19), we show that patients treated for B-lymphoid malignancies have an increased risk of severe COVID-19 compared with control populations of patients with non-B-lymphoid malignancies. Among patients with B-lymphoid malignancies, those who received anticancer therapy within 12 months of COVID-19 diagnosis experienced increased COVID-19 severity compared with patients with non-recently treated B-lymphoid malignancies, after adjustment for cancer status and several other prognostic factors. Our findings suggest that patients recently treated for a B-lymphoid malignancy are at uniquely high risk for severe COVID-19.SignificanceOur study suggests that recent therapy for a B-lymphoid malignancy is an independent risk factor for COVID-19 severity. These findings provide rationale to develop mitigation strategies targeted at the uniquely high-risk population of patients with recently treated B-lymphoid malignancies. This article is highlighted in the In This Issue feature, p. 171.

BackgroundImmune checkpoint inhibitors (ICI) improve overall survival (OS) in patients with locally advanced, unresectable, or metastatic urothelial carcinoma (aUC), but response rates can be modest. We compared outcomes between patients with and without prior intravesical Bacillus Calmette-Guerin (BCG), who received ICI for aUC, hypothesizing that prior intravesical BCG would be associated with worse outcomes.Patients and methodsWe performed a retrospective cohort study across 25 institutions in US and Europe. We compared observed response rate (ORR) using logistic regression; progression-free survival (PFS) and OS using Kaplan-Meier and Cox proportional hazards. Analyses were stratified by treatment line (first line/salvage) and included multivariable models adjusting for known prognostic factors.ResultsA total of 1026 patients with aUC were identified; 614, 617, and 638 were included in ORR, OS, PFS analyses, respectively. Overall, 150 pts had history of prior intravesical BCG treatment. ORR to ICI was similar between those with and without prior intravesical BCG exposure in both first line and salvage settings (adjusted odds radios 0.55 [P= .08] and 1.65 [P= .12]). OS (adjusted hazard ratios 1.05 [P= .79] and 1.13 [P= .49]) and PFS (adjusted hazard ratios 1.12 [P= .55] and 0.87 [P= .39]) were similar between those with and without intravesical BCG exposure in first line and salvage settings.ConclusionPrior intravesical BCG was not associated with differences in response and survival in patients with aUC treated with ICI. Limitations include retrospective nature, lack of randomization, presence of selection and confounding biases. This study provides important preliminary data that prior intravesical BCG exposure may not impact ICI efficacy in aUC.

IntroductionTumor mutational burden (TMB) and APOBEC mutational signatures are potential prognostic markers in patients with advanced urothelial carcinoma (aUC). Their utility in predicting outcomes to specific therapies in aUC warrants additional study.MethodsWe retrospectively reviewed consecutive UC cases assessed with UCSF500, an institutional assay that uses hybrid capture enrichment of target DNA to interrogate 479 common cancer genes. Hypermutated tumors (HM), defined as having TMB ≥10 mutations/Mb, were also assessed for APOBEC mutational signatures, while non-HM (NHM) tumors were not assessed due to low TMB. The logrank test was used to determine if there were differences in overall survival (OS) and progression-free survival (PFS) among patient groups of interest.ResultsAmong 75 aUC patients who had UCSF500 testing, 46 patients were evaluable for TMB, of which 19 patients (41%) had HM tumors and the rest had NHM tumors (27 patients). An additional 29 patients had unknown TMB status. Among 19 HM patients, all 16 patients who were evaluable for analysis had APOBEC signatures. HM patients (N=19) were compared with NHM patients (N=27) and had improved OS from diagnosis (125.3 months vs 35.7 months, p=0.06) but inferior OS for patients treated with chemotherapy (7.0 months vs 13.1 months, p=0.04). Patients with APOBEC (N=16) were compared with remaining 56 patients, comprised of 27 NHM patients and 29 patients with unknown TMB, showing APOBEC patients to have improved OS from diagnosis (125.3 months vs 44.5 months, p=0.05) but inferior OS for patients treated with chemotherapy (7.0 months vs 13.1 months, p=0.05). Neither APOBEC nor HM status were associated with response to immunotherapy.ConclusionsIn a large, single-institution aUC cohort assessed with UCSF500, an institutional NGS panel, HM tumors were common and all such tumors that were evaluated for mutational signature analysis had APOBEC signatures. APOBEC signatures and high TMB were prognostic of improved OS from diagnosis and both analyses also predicted inferior outcomes with chemotherapy treatment.

BackgroundThe frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and coronavirus disease 2019 (COVID-19), a high-risk group for coinfection.MethodsWe included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, using data from the COVID-19 and Cancer Consortium (CCC19, NCT04354701). We captured coinfections within ±2 weeks from diagnosis of COVID-19, identified factors cross-sectionally associated with risk of coinfection, and quantified the association of coinfections with 30-day mortality.ResultsAmong 8765 patients (hospitalized or not; median age, 65 years; 47.4% male), 16.6% developed coinfections: 12.1% bacterial, 2.1% viral, 0.9% fungal. An additional 6.4% only had clinical diagnosis of a coinfection. The adjusted risk of any coinfection was positively associated with age >50 years, male sex, cardiovascular, pulmonary, and renal comorbidities, diabetes, hematologic malignancy, multiple malignancies, Eastern Cooperative Oncology Group Performance Status, progressing cancer, recent cytotoxic chemotherapy, and baseline corticosteroids; the adjusted risk of superinfection was positively associated with tocilizumab administration. Among hospitalized patients, high neutrophil count and C-reactive protein were positively associated with bacterial coinfection risk, and high or low neutrophil count with fungal coinfection risk. Adjusted mortality rates were significantly higher among patients with bacterial (odds ratio [OR], 1.61; 95% CI, 1.33-1.95) and fungal (OR, 2.20; 95% CI, 1.28-3.76) coinfections.ConclusionsViral and fungal coinfections are infrequent among patients with cancer and COVID-19, with the latter associated with very high mortality rates. Clinical and laboratory parameters can be used to guide early empiric antimicrobial therapy, which may improve clinical outcomes.

BackgroundExercise may improve clinical and quality of life outcomes for men with prostate cancer. No randomized controlled trials (RCTs) have examined the feasibility, safety, and acceptability of remote exercise training in men with metastatic castrate-resistant prostate cancer (mCRPC).MethodsWe conducted a pilot RCT (1:1:1 aerobic or resistance exercise 3x/week or usual care) to determine the feasibility, safety, and acceptability of remotely monitored exercise over 12 weeks in 25 men with mCRPC. A prescribed exercise program was based on baseline testing including high- and moderate-intensity aerobic exercise or resistance exercise completed at a local exercise facility. Feasibility was based on attendance, adherence, and tolerance; safety on adverse events; and acceptability on participant interviews.ResultsBetween March 2016 and March 2020, 25 patients were randomized (8 aerobic, 7 resistance, and 10 control). Twenty-three men (82%) completed the 12-week study. Men who completed the remote intervention attempted 90% and 96% of prescribed aerobic and resistance training sessions, respectively, and 86% and 88% of attempted sessions were completed as or more than prescribed. We observed changes in performance tests that corresponded with the exercise prescription. No safety concerns were identified. Ninety percent of participants interviewed were satisfied with the program and would recommend it to others.ConclusionsRemotely monitored exercise training is feasible, safe, and acceptable in men with mCRPC; there was no difference in these outcomes by mode of exercise. Through this research, we provide direction and rationale for future studies of exercise and clinical outcomes in patients with metastatic prostate cancer.

PurposeEnfortumab vedotin (EV) is an antibody-drug conjugate (ADC) targeting NECTIN4 (encoded by the PVRL4/NECTIN4 gene) approved for treatment-refractory metastatic urothelial cancer. Factors that mediate sensitivity or resistance to EV are unknown. In this study, we sought to (i) examine heterogeneity of NECTIN4 gene expression across molecular subtypes of bladder cancer and (ii) determine whether NECTIN4 expression mediates EV sensitivity or resistance.Experimental designMolecular subtyping and NECTIN4 expression data from seven muscle-invasive bladder cancer clinical cohorts (n = 1,915 total specimens) were used to assess NECTIN4 expression across molecular subtypes. The outcome of the transcriptomic analysis was relative NECTIN4 expression in the consensus molecular subtypes of bladder cancer. Expression of NECTIN4 was validated in bladder cancer cell lines. NECTIN4 was stably overexpressed or knocked down in basal and luminal bladder cancer cell lines and EV drug sensitivity assays were performed, as measured by cell proliferation and clonogenic assays.ResultsNECTIN4 expression is heterogenous across molecular subtypes of bladder cancer and significantly enriched in luminal subtypes. NECTIN4 expression is positively correlated with luminal markers GATA3, FOXA1, and PPARG across all cohorts. NECTIN4 expression is both necessary and sufficient for EV sensitivity in luminal and basal subtypes of urothelial bladder cancer cells. Downregulation of NECTIN4 leads to EV resistance.ConclusionsSensitivity to EV is mediated by expression of NECTIN4, which is enriched in luminal subtypes of bladder cancer. These findings may have implications for biomarker development, patient selection, and the inclusion of molecular subtyping in ongoing and future EV clinical trials.See related commentary by Teo and Rosenberg, p. 4950.

BackgroundImmune checkpoint inhibitors (ICI) can achieve durable responses in a subset of patients with locally advanced or metastatic urothelial carcinoma (aUC). The use of tumor genomic profiling in clinical practice may help suggest biomarkers to identify patients most likely to benefit from ICI.MethodsWe undertook a retrospective analysis of patients treated with an ICI for aUC at a large academic medical center. Patient clinical and histopathological variables were collected. Responses to treatment were assessed for all patients with at least one post-baseline scan or clear evidence of clinical progression following treatment start. Genomic profiling information was also collected for patients when available. Associations between patient clinical/genomic characteristics and objective response were assessed by logistic regression; associations between the characteristics and progression-free survival (PFS) and overall survival (OS) were examined by Cox regression. Multivariable analyses were performed to identify independent prognostic factors.ResultsWe identified 119 aUC patients treated with an ICI from December 2014 to January 2020. Genomic profiling was available for 78 patients. Overall response rate to ICI was 29%, and median OS (mOS) was 13.4 months. Favorable performance status at the start of therapy was associated with improved OS (HR 0.46, p=0.025) after accounting for other covariates. Similarly, the presence of a TERT promoter mutation was an independent predictor of improved PFS (HR 0.38, p=0.012) and OS (HR 0.32, p=0.037) among patients who had genomic profiling available. Patients with both a favorable performance status and a TERT promoter mutation had a particularly good prognosis with mOS of 21.1 months as compared with 7.5 months in all other patients (p=0.03).ConclusionsThe presence of a TERT promoter mutation was an independent predictor of improved OS in a cohort of aUC patients treated with an ICI who had genomic data available. Most of the clinical and laboratory variables previously shown to be prognostic in aUC patients treated with chemotherapy did not have prognostic value among patients treated with an ICI. Genomic profiling may provide important prognostic information and affect clinical decision making in this patient population. Validation of these findings in prospective patient cohorts is needed.

PurposeThe response to the COVID-19 pandemic has affected the management of patients with cancer. In this pooled retrospective analysis, we describe changes in management patterns for patients with cancer diagnosed with COVID-19 in two academic institutions in the San Francisco Bay Area.Materials and methodsAdult and pediatric patients diagnosed with COVID-19 with a current or historical diagnosis of malignancy were identified from the electronic medical record at the University of California, San Francisco, and Stanford University. The proportion of patients undergoing active cancer management whose care was affected was quantified and analyzed for significant differences with regard to management type, treatment intent, and the time of COVID-19 diagnosis. The duration and characteristics of such changes were compared across subgroups.ResultsA total of 131 patients were included, of whom 55 were undergoing active cancer management. Of these, 35 of 55 (64%) had significant changes in management that consisted primarily of delays. An additional three patients not undergoing active cancer management experienced a delay in management after being diagnosed with COVID-19. The decision to change management was correlated with the time of COVID-19 diagnosis, with more delays identified in patients treated with palliative intent earlier in the course of the pandemic (March/April 2020) compared with later (May/June 2020) (OR, 4.2; 95% CI, 1.03 to 17.3; P = .0497). This difference was not seen among patients treated with curative intent during the same timeframe.ConclusionWe found significant changes in the management of cancer patients with COVID-19 treated with curative and palliative intent that evolved over time. Future studies are needed to determine the impact of changes in management and treatment on cancer outcomes for patients with cancer and COVID-19.

Introduction: Consultation audio recordings improve patient decision‐making but are underutilized. Patient‐administered recording apps on mobile devices may increase access, but implementation has not been evaluated. Methods: We conducted a single‐arm study delivering education, coaching, and reminders for patients to record their appointment using a mobile recording app. Patients had progressive, advanced prostate cancer and an upcoming appointment where the option of docetaxel would be discussed. We used the RE‐AIM framework for evaluation. Reach was the proportion of patients who participated. Effectiveness was change in informed decision‐making pre‐ vs. post‐appointment. We used a questionnaire evaluating patient knowledge about docetaxel (0%–100% correct) and the decisional conflict scale‐informed subscale (0 = feels extremely uninformed to 100 = extremely informed) to compare means using the paired t‐test. Adoption was the proportion of providers agreeing to be recorded. Implementation was coordinator adherence to intervention delivery. We conducted semistructured interviews with patients, caregivers, and providers to assess barriers, facilitators, and suggestions for recording implementation. Results: Of 102 patients approached, 50 (49%) patients participated. Mean age was 75 years, 38 (76%) were Non‐Hispanic White, and 43 (86%) had telehealth appointments. Knowledge increased from 44.7% to 49.5% (p = 0.019), particularly about palliative care (42% answering correctly to 60%, p = 0.035). Decisional conflict‐informed subscale increased from 48.9 to 70.9 (p < 0.001). Forty‐three patients (85%) made a recording, of whom 33 (77%) reported the recording helped treatment decision‐making. All 17 providers agreed to be recorded. Coordinator adherence was high. Multi‐level barriers, suggestions, and facilitators mostly related to intervention complexity and stakeholder compatibility. Conclusion: Patient‐administered audio recordings had a positive effect on decision‐making, particularly for palliative care awareness. For broader implementation, efforts should focus on revising institutional policies; teaching patients or caregivers to use existing recording functions on their devices; leveraging artificial intelligence for transcription and summarization; and integrating recording into telehealth technology and electronic patient portals. Trial Registration:https://clinicaltrials.gov/study/NCT05127850 [ABSTRACT FROM AUTHOR]

Background: [177Lu]Lu–PSMA‐617 (177Lu‐PSMA‐617) plus protocol‐permitted standard of care (SOC) prolonged overall survival (OS) and radiographic progression‐free survival (rPFS) versus SOC in patients with prostate‐specific membrane antigen (PSMA)–positive metastatic castration‐resistant prostate cancer (mCRPC) in the phase 3 VISION study, in addition to beneficial effects on symptomatic skeletal events (SSEs) and health‐related quality of life (HRQOL). Methods: Post hoc analyses used the full analysis set from the VISION study (N = 831) overall and by randomized treatment arm (177Lu‐PSMA‐617 plus SOC, n = 551; SOC, n = 280). Correlations were determined between OS and rPFS and between rPFS or OS and time to SSE or to worsening HRQOL (Functional Assessment of Cancer Therapy–Prostate [FACT‐P] and 5‐level EQ‐5D [EQ‐5D‐5L]). Correlation analyses used an iterative multiple imputation copula‐based approach (correlation coefficients [rho] of <0.3 were defined as weak, ≥0.3 and <0.5 as mild, ≥0.5 and <0.7 as moderate, and ≥0.7 as strong). Results: In the overall population, rPFS correlated strongly with OS (rho, ≥0.7). Correlations between rPFS or OS and time to SSE without death were weak or mild. Time to worsening in the FACT‐P total score and emotional and physical well‐being domains correlated mildly or moderately with rPFS and moderately with OS. Correlation coefficients for time‐to‐worsening EQ‐5D‐5L scores were mild to moderate for both rPFS and OS. Correlation coefficients were similar between treatment arms. Conclusions: In this analysis of the VISION study, rPFS correlated strongly with OS but not with time to SSE or worsening HRQOL. These findings require further investigation. In patients with metastatic castration‐resistant prostate cancer participating in the VISION randomized phase 3 trial, radiographic progression‐free survival correlated strongly with overall survival but not with time to a first symptomatic skeletal event or worsening health‐related quality of life or pain. There were no clear or consistent differences in the strengths of correlation between the two treatment groups ([177Lu]Lu‐PSMA‐617 plus protocol‐permitted standard of care vs. standard of care alone). [ABSTRACT FROM AUTHOR]

Purpose: 68Ga-PSMA-11 is recommended for the selection of patients for treatment in the package insert for 177Lu-PSMA-617. We aimed to compare imaging properties and post-treatment outcomes from radioligand therapy (RLT) of patients selected with 68Ga-PSMA-11 and 18F-DCFPyL. Methods: We retrospectively evaluated 80 patients undergoing PSMA RLT, who had pretreatment imaging using either 68Ga-PSMA-11 or 18F-DCFPyL. For both groups, we compared the biodistribution and lesion uptake and the PSA response to treatment. Results: Both agents had comparable biodistribution. Patients initially imaged with 18F-DCFPyL had a higher PSA response (66% vs. 42%), and more patients had a PSA50 response (72% vs. 43%) compared to patients imaged with 68Ga-PSMA-11. Conclusion: 18F-DCFPyL and 68Ga-PSMA-11 had comparable biodistribution and lesion uptake. Patients imaged with 18F-DCFPyL demonstrated clinical benefit to PSMA RLT comparable to those imaged with 68Ga-PSMA-11, and either agent can be used for screening patients. [ABSTRACT FROM AUTHOR]