Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer.

PURPOSE: Lutetium-177 [177Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24 h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [177Lu]Lu-PSMA-617. METHODS: In this retrospective study, 68 men with progressive mCRPC treated with [177Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [177Lu]Lu-PSMA-617infusion (mean ± SD: 1.8 ± 0.6 h, range 1.1-4.9 h). Quantitative analysis of [177Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [177Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUVmax and SUVmean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates. RESULTS: 56 patients (means age 76.2 ± 8.1 years, range: 60-93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~ 12 min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [177Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0-15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had > 30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P = 0.008) and PSA-PFS (median 6 months vs. 1 months, P < 0.001). However, changes in SUVmax or SUVmean did not correlate with PSA-PFS or OS. CONCLUSION: We successfully implemented same-day post-therapy SPECT/CT after [177Lu]Lu-PSMA-617 infusions. Quantitation of 1-2 h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC.

Clinical characteristics, racial inequities, and outcomes in patients with breast cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) cohort study.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This 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. Results: 1383 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. Conclusions: Using 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. Funding: This 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 number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.

Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors.

BACKGROUND: Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors. METHODS: This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia. Overall survival and progression-free survival were estimated using the Kaplan-Meier method. Objective response rates were determined per Response Evaluation Criteria in Solid Tumours 1.1 criteria. Treatment-related adverse events were graded per the Common Terminology Criteria for Adverse Events, version 5.0. Two-sided statistical tests were used for comparisons. RESULTS: Among 92 patients, 8 (8.7%) were Asian, 6 (6.5%) were Black, and 24 (29%) were Hispanic and/or Latinx. Median (interquartile range) age was 62 (53-70) years. In all, 83 (90%) had metastatic penile squamous cell carcinoma, and 74 (80%) had received at least second-line treatment. Most patients received pembrolizumab monotherapy (n = 26 [28%]), combination nivolumab-ipilimumab with or without multitargeted tyrosine kinase inhibitors (n = 23 [25%]), or nivolumab (n = 16 [17%]) or cemiplimab (n = 15 [16%]) monotherapies. Median overall and progression-free survival were 9.8 months (95% confidence interval = 7.7 to 12.8 months) and 3.2 months (95% confidence interval = 2.5 to 4.2 months), respectively. The objective response rate was 13% (n = 11/85) in the overall cohort and 35% (n = 7/20) in patients with lymph node-only metastases. Visceral metastases, Eastern Cooperative Oncology Group (ECOG) performance status of 1 or higher, and a higher neutrophil/lymphocyte ratio were associated with worse overall survival. Treatment-related adverse events occurred in 27 (29%) patients, and 9.8% (n = 9) of the events were grade 3 or higher. CONCLUSIONS: Immune checkpoint inhibitors are active in a subset of patients with penile squamous cell carcinoma. Future translational studies are warranted to identify patients more likely to derive clinical benefit from immune checkpoint inhibitors.

Response and Outcomes of Maintenance Avelumab After Platinum-Based Chemotherapy (PBC) in Patients With Advanced Urothelial Carcinoma (aUC): "Real World" Experience.

BACKGROUND: Platinum-based chemotherapy (PBC) followed by avelumab switch maintenance in nonprogressors is standard first line (1L) treatment for advanced urothelial carcinoma (aUC). We describe clinical features and outcomes in a "real-world' cohort treated with avelumab maintenance for aUC. MATERIALS AND METHODS: This was a retrospective cohort study of patients (pts) who received 1L switch maintenance avelumab after no progression on PBC for aUC. We calculated progression-free survival (PFS) and overall survival (OS) from initiation of maintenance avelumab. We also described OS and PFS for specific subsets using Cox regression and observed response rate (ORR). RESULTS: A total of 108 pts with aUC from 14 sites treated with maintenance avelumab were included. There was a median of 6 weeks1-30 from end of PBC to avelumab initiation; median follow-up time from avelumab initiation was 8.8 months (1-42.7). Median [m]PFS was 9.6 months (95%CI 7.5-12.1) and estimated 1-year OS was 72.5%. CR/PR (vs. SD) to 1L PBC (HR = 0.33, 95% CI 0.13-0.87) and ECOG PS 0 (vs. ≥1), (HR = 0.15, 95% CI 0.05-0.47) were associated with longer OS. The presence of liver metastases was associated with shorter PFS (HR = 2.32, 95% CI 1.17-4.59). ORR with avelumab maintenance was 28.7% (complete response 17.6%, partial response 11.1%), 29.6% stable disease, 26.9% progressive disease as best response (14.8% best response unknown). CONCLUSIONS: Results seem relatively consistent with findings from JAVELIN Bladder100 trial and recent "real world" studies. Prior response to platinum-based chemotherapy, ECOG PS 0, and absence of liver metastases were favorable prognostic factors. Limitations include the retrospective design, lack of randomization and central scan review, and possible selection/confounding biases.

Patient-reported distress at a cancer center during the COVID-19 pandemic.

Assessments of health-related quality of life (HRQOL) are conducted by health systems to improve patient-centered care. Studies have shown that the COVID-19 pandemic poses unique stressors for patients with cancer. This study investigates change in self-reported global health scores in patients with cancer before and during the COVID-19 pandemic. In this single-institution retrospective cohort study, patients who completed the Patient-Reported Outcomes Measurement Information System (PROMIS) at a comprehensive cancer center before and during the COVID-19 pandemic were identified. Surveys were analyzed to assess change in the global mental health (GMH) and global physical health (GPH) scores at different time periods (pre-COVID: 3/1/5/2019-3/15/2020, surge1: 6/17/2020-9/7/2020, valley1: 9/8/2020-11/16/2020, surge2: 11/17/2020-3/2/2021, and valley2: 3/3/2021-6/15/2021). A total of 25,192 surveys among 7209 patients were included in the study. Mean GMH score for patients before the COVID-19 pandemic (50.57) was similar to those during various periods during the pandemic: surge1 (48.82), valley1 (48.93), surge2 (48.68), valley2 (49.19). Mean GPH score was significantly higher pre-COVID (42.46) than during surge1 (36.88), valley1 (36.90), surge2 (37.33) and valley2 (37.14). During the pandemic, mean GMH (49.00) and GPH (37.37) scores obtained through in-person were similar to mean GMH (48.53) and GPH (36.94) scores obtained through telehealth. At this comprehensive cancer center, patients with cancer reported stable mental health and deteriorating physical health during the COVID-19 pandemic as indicated by the PROMIS survey. Modality of the survey (in-person versus telehealth) did not affect scores.

Role of Underlying Liver Pathology in the Development of Immune-Related Hepatitis: A Case-Control Study.

BACKGROUND: Immune-related hepatitis (irH) is a serious immune-related adverse event (IRAE) that may result in morbidity, immune checkpoint inhibitor (ICI) therapy interruption and, rarely, mortality. The impact of underlying liver pathology, including liver metastasis, on the incidence of irH remains poorly understood. OBJECTIVES: We hypothesized that the presence of underlying liver pathology increased the risk of irH in patients with cancer treated with ICI. PATIENTS AND METHODS: We conducted a retrospective case-control study of irH in patients with cancer receiving first ICI treatment from 2016-2020. Provider documented cases of ≥ grade 2 irH were identified and control matched in a 2:1 ratio based on age, sex, time of ICI initiation, and follow-up time. Conditional logistic regression was used to estimate the relationship between irH and liver metastasis at ICI initiation. RESULTS: Ninety-seven cases of irH were identified, 29% of which had liver metastases at time of ICI initiation. Thirty-eight percent of patients developed grade 2, 47% grade 3, and 14% grade 4 irH. When adjusted for covariates/confounders, the presence of liver metastasis was associated with increased odds of irH (aOR 2.79 95% CI 1.37-5.66, p = 0.005). The presence of liver metastases did not correlate with irH grade or rate of irH recurrence after ICI rechallenge. CONCLUSIONS: Presence of liver metastases increased the odds of irH in patients with first-time ICI therapy. Limitations include the retrospective nature, moderate sample size, possible selection bias and confounding. Our findings are hypothesis-generating and warrant external validation as well as tissue and circulating biomarker exploration.

Clinical Characteristics, Racial Inequities, and Outcomes in Patients with Breast Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Cohort Study.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This 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. Results: 1,383 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. Conclusions: Using 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.

Sarcomatoid Urothelial Carcinoma Is Associated With Limited Response to Neoadjuvant Chemotherapy and Poor Oncologic Outcomes After Radical Cystectomy.

INTRODUCTION: To examine oncologic outcomes and response to neoadjuvant chemotherapy (NAC) in patients with sarcomatoid urothelial carcinoma (SUC) treated with radical cystectomy (RC). MATERIALS AND METHODS: We retrospectively queried our institutional database (2003-18) and Surveillance, Epidemiology, and End Results (SEER)-Medicare (2004-2015) for patients with cT2-4, N0-2, M0 SUC and conventional UC (CUC) treated with RC. Clinicopathologic characteristics were described using descriptive statistics (t test, χ2-test and log-rank-test for group comparison). Overall (OS) and recurrence-free-survival (RFS) after RC were estimated with the Kaplan Meier method and associations with OS were evaluated with Cox proportional hazards models. RESULTS: We identified 38 patients with SUC and 287 patients with CUC in our database, and 190 patients with SUC in SEER-Medicare. In the institutional cohort, patients with SUC versus CUC had higher rates of pT3/4 stage (66% vs. 35%, P < 0.001), lower rates of ypT0N0 (6% vs. 35%, P = .02), and worse median OS (17.5 vs. 120 months, P < .001). Further, patients with SUC in the institutional versus SEER-Medicare cohort had similar median OS (17.5 vs. 21 months). In both cohorts, OS was comparable between patients with SUC undergoing NAC+RC vs. RC alone (17.5 vs. 18.4 months, P = .98, institutional cohort; 24 vs. 20 months, P = .56, SEER cohort). In Cox proportional hazards models for the institutional RC cohort, SUC was independently associated with worse OS (HR 2.3, CI 1.4-3.8, P = .001). CONCLUSION: SUC demonstrates poor pathologic response to NAC and worse OS compared with CUC, with no OS benefit associated with NAC. A unique pattern of rapid abdominopelvic cystic recurrence was identified.

Geriatric assessment in the older adult with genitourinary cancer: A narrative review.

Genitourinary (GU) cancers including bladder, prostate, and kidney cancers affect older adults with a higher prevalence compared to younger adults. GU cancer treatment is associated with poorer outcomes in older adults compared to their younger counterparts. To better identify and support older adults receiving cancer care, oncologic societies recommend the use of a geriatric assessment (GA) to guide management. However, little is known about the implementation and usefulness of the GA in older adults with GU cancers. We performed a narrative review to investigate the utility of the GA in older adults with GU cancers and propose strategies to optimize the real-world use of the GA. Here, we describe a framework to incorporate GA into the routine cancer care of older adults with GU cancers and provide several implications for future research.

Treatment Rechallenge With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma.

OBJECTIVES: To examine patient and disease characteristics, toxicity, and clinical outcomes for patients with advanced urothelial carcinoma (aUC) who are rechallenged with immune checkpoint inhibitor (ICI)-based therapy. PATIENTS AND METHODS: In this retrospective cohort, we included patients treated with ICI for aUC after having prior ICI treatment. Endpoints included the evaluation of radiographic response and disease control rates with first and second ICI courses, outcomes based on whether there was a change in ICI class (anti-PD-1 vs. anti-PD-L1), and assessment of the reasons for ICI discontinuation. RESULTS: We identified 25 patients with aUC from 9 institutions who received 2 separate ICI courses. ORR with first ICI and second ICI were 39% and 13%, respectively. Most patients discontinued first ICI due to progression (n = 19) or treatment-related toxicity (n = 4). Thirteen patients received non-ICI treatment between the first and second ICI, and 12 patients changed ICI class (anti-PD-1 vs. anti-PD-L1) at rechallenge. Among 10 patients who changed ICI class, 8 (80%) had progressive disease as best response with second ICI, while among 12 patients re-treated with the same ICI class, only 3 (25%) had progressive disease as best response at the time of rechallenge. With second ICI, most patients discontinued treatment due to progression (n = 18) or patient preference (n = 2). CONCLUSIONS: A proportion of patients with aUC rechallenged with ICI-based regimens may achieve disease control, supporting clinical trials in that setting, especially with ICI-based combinations. Future studies are needed to validate our results and should also focus on identifying biomarkers predictive of benefit with ICI rechallenge.

Use of Machine Learning and Lay Care Coaches to Increase Advance Care Planning Conversations for Patients With Metastatic Cancer.

PURPOSE: Patients with metastatic cancer benefit from advance care planning (ACP) conversations. We aimed to improve ACP using a computer model to select high-risk patients, with shorter predicted survival, for conversations with providers and lay care coaches. Outcomes included ACP documentation frequency and end-of-life quality measures. METHODS: In this study of a quality improvement initiative, providers in four medical oncology clinics received Serious Illness Care Program training. Two clinics (thoracic/genitourinary) participated in an intervention, and two (cutaneous/sarcoma) served as controls. ACP conversations were documented in a centralized form in the electronic medical record. In the intervention, providers and care coaches received weekly e-mails highlighting upcoming clinic patients with < 2 year computer-predicted survival and no prior prognosis documentation. Care coaches contacted these patients for an ACP conversation (excluding prognosis). Providers were asked to discuss and document prognosis. RESULTS: In the four clinics, 4,968 clinic visits by 1,251 patients met inclusion criteria (metastatic cancer with no prognosis previously documented). In their first visit, 28% of patients were high-risk (< 2 year predicted survival). Preintervention, 3% of both intervention and control clinic patients had ACP documentation during a visit. By intervention end (February 2021), 35% of intervention clinic patients had ACP documentation compared with 3% of control clinic patients. Providers' prognosis documentation rate also increased in intervention clinics after the intervention (2%-27% in intervention clinics, P < .0001; 0%-1% in control clinics). End-of-life care intensity was similar in intervention versus control clinics, but patients with ≥ 1 provider ACP edit met fewer high-intensity care measures (P = .04). CONCLUSION: Combining a computer prognosis model with care coaches increased ACP documentation.

Racial Diversity and Reporting in United States Food and Drug Administration Registration Trials for Thoracic Malignancies from 2006 to 2020.

There is significant racial disparity in thoracic malignancies in terms of epidemiology and outcomes. We analyzed race reporting and racial diversity in the registration trials of drugs approved by the FDA for thoracic malignancies from 2006 to 2020. We found a significant under-representation of non-white participants in FDA drug registration trials in thoracic malignancies. Furthermore, though almost all trials report some race information, FDA guidelines are not universally followed. There is a disproportionate disease burden of lung cancer in under-represented race communities, and clinical trials should prioritize racial diversity and inclusion efforts.

Considerations in the reliability and fairness audits of predictive models for advance care planning.

Multiple reporting guidelines for artificial intelligence (AI) models in healthcare recommend that models be audited for reliability and fairness. However, there is a gap of operational guidance for performing reliability and fairness audits in practice. Following guideline recommendations, we conducted a reliability audit of two models based on model performance and calibration as well as a fairness audit based on summary statistics, subgroup performance and subgroup calibration. We assessed the Epic End-of-Life (EOL) Index model and an internally developed Stanford Hospital Medicine (HM) Advance Care Planning (ACP) model in 3 practice settings: Primary Care, Inpatient Oncology and Hospital Medicine, using clinicians' answers to the surprise question ("Would you be surprised if [patient X] passed away in [Y years]?") as a surrogate outcome. For performance, the models had positive predictive value (PPV) at or above 0.76 in all settings. In Hospital Medicine and Inpatient Oncology, the Stanford HM ACP model had higher sensitivity (0.69, 0.89 respectively) than the EOL model (0.20, 0.27), and better calibration (O/E 1.5, 1.7) than the EOL model (O/E 2.5, 3.0). The Epic EOL model flagged fewer patients (11%, 21% respectively) than the Stanford HM ACP model (38%, 75%). There were no differences in performance and calibration by sex. Both models had lower sensitivity in Hispanic/Latino male patients with Race listed as "Other." 10 clinicians were surveyed after a presentation summarizing the audit. 10/10 reported that summary statistics, overall performance, and subgroup performance would affect their decision to use the model to guide care; 9/10 said the same for overall and subgroup calibration. The most commonly identified barriers for routinely conducting such reliability and fairness audits were poor demographic data quality and lack of data access. This audit required 115 person-hours across 8-10 months. Our recommendations for performing reliability and fairness audits include verifying data validity, analyzing model performance on intersectional subgroups, and collecting clinician-patient linkages as necessary for label generation by clinicians. Those responsible for AI models should require such audits before model deployment and mediate between model auditors and impacted stakeholders.

Immunotherapy for Urothelial Carcinoma: Focus on Clinical Utility of Nivolumab.

Over the past decade, the emergence of immune checkpoint inhibitors has brought about significant change to the treatment landscape of bladder cancer. Nivolumab is an immune checkpoint inhibitor that has shown favorable results resulting in FDA approval for treatment of platinum-refractory locally advanced or metastatic urothelial carcinoma. More recently, it was the first (and only) immune checkpoint inhibitor to receive FDA approval for the treatment of urothelial carcinoma in the adjuvant setting after radical surgery. Multiple trials are now actively underway to further understand the nuances in which immune checkpoint inhibitors such as nivolumab can be beneficial. In this review, we explore the development of nivolumab in terms of its mechanism of action, its growing indications in the treatment of urothelial carcinoma, and potential future directions for clinical trials. Immune checkpoint inhibitors are a promising treatment for bladder cancer, but further work is needed to continue to improve outcomes for patients.

Demographics, Outcomes, and Risk Factors for Patients with Sarcoma and COVID-19: A CCC19-Registry Based Retrospective Cohort Study.

BACKGROUND: Patients with sarcoma often require individualized treatment strategies and are likely to receive aggressive immunosuppressive therapies, which may place them at higher risk for severe COVID-19. We aimed to describe demographics, risk factors, and outcomes for patients with sarcoma and COVID-19. METHODS: We performed a retrospective cohort study of patients with sarcoma and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) registry (NCT04354701) from 17 March 2020 to 30 September 2021. Demographics, sarcoma histologic type, treatments, and COVID-19 outcomes were analyzed. RESULTS: of 281 patients, 49% (n = 139) were hospitalized, 33% (n = 93) received supplemental oxygen, 11% (n = 31) were admitted to the ICU, and 6% (n = 16) received mechanical ventilation. A total of 23 (8%) died within 30 days of COVID-19 diagnosis and 44 (16%) died overall at the time of analysis. When evaluated by sarcoma subtype, patients with bone sarcoma and COVID-19 had a higher mortality rate than patients from a matched SEER cohort (13.5% vs 4.4%). Older age, poor performance status, recent systemic anti-cancer therapy, and lung metastases all contributed to higher COVID-19 severity. CONCLUSIONS: Patients with sarcoma have high rates of severe COVID-19 and those with bone sarcoma may have the greatest risk of death.

Cancer Therapy Approval Timings, Review Speed, and Publication of Pivotal Registration Trials in the US and Europe, 2010-2019.

Importance: Ensuring patients have access to safe and efficacious medicines in a timely manner is an essential goal for regulatory agencies, one which has particular importance in oncology because of the substantial unmet need for new therapies. The 2 largest regulatory agencies, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have pivotal global roles, and their recommendations and approvals are frequently followed by other national regulators. Objective: To compare market authorization dates for new oncology therapies approved in the US and Europe over the past decade and to examine and contrast the regulatory activities of the FDA and EMA in the approval of new cancer medicines. Design, Setting, and Participants: This cross-sectional study reviewed the FDA and EMA regulatory databases to identify new oncology therapies approved in both the US and Europe from 2010 to 2019, and characterization of the timings of regulatory activities. Statistical analysis was performed from January to April 2022. Main Outcomes and Measures: Regulatory approval date, review time, submission of market authorization application, accelerated approval or conditional marketing authorization status and proportion of approvals prior to peer-reviewed publication of pivotal trial results. Results: In total, 89 new concomitant oncology therapies were approved in the US and Europe from 2010 to 2019. The FDA approved 85 oncology therapies (95%) before European authorization and 4 therapies (5%) after. The median (IQR) delay in market authorization for new oncology therapies in Europe was 241 (150-370) days compared with the US. The median (IQR) review time was 200 (155-277) days for the FDA and 426 (358-480) days for the EMA. Sixty-four new licensing applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA. Thirty-five oncology therapies (39%) were approved by the FDA prior to pivotal study publication, whereas only 8 (9%) by the EMA. Conclusion and Relevance: In this cross-sectional study, new oncology therapies were approved earlier in the US than Europe. The FDA received licensing applications sooner and had shorter review times. However, more therapies were approved prior to licensing study publication, leaving uncertainty for practitioners regarding clinical utility and safety of newly approved therapies.

Long term cost comparisons of radical cystectomy versus trimodal therapy for muscle-invasive bladder cancer.

BACKGROUND: Earlier studies on the cost of muscle-invasive bladder cancer treatments are limited to short-term costs of care. We determined the 2- and 5-year costs associated with trimodal therapy (TMT) vs. radical cystectomy (RC). METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Total Medicare costs at 2 and 5 years following RC vs. TMT were compared using inverse probability of treatment-weighted propensity score models. RESULTS: A total of 2,537 patients aged 66 to 85 years were diagnosed with clinical stage T2-4a muscle-invasive bladder cancer. Total median costs for patients that received no definitive treatment(s) were $73,780 and $88,275 at 2-and 5-years. Costs were significantly higher for TMT than RC at 2-years ($372,839 vs. $191,363, Median Difference $127,815, Hodges-Lehmann Estimate (H-L) 95% Confidence Interval (CI), $112,663-$142,966) and 5-years ($424,570 vs. $253,651, Median Difference $124,466, H-L 95% CI, $105,711-$143,221). TMT had higher outpatient costs than RC (2-years: $318,221 vs. $100,900; 5-years: $367,092 vs. $146,561) with significantly higher costs with radiology, medications, pathology/laboratory, and other professional services. RC had higher inpatient costs than TMT (2-years: $62,240 vs. $33,631, Median Difference $-29,174, H-L 95% CI, $-32,364-$-25,984; 5-years: $75,499 vs. $45,223, Median Difference $-29,843, H-L 95% CI, $-33,905-$-25,781). CONCLUSIONS AND RELEVANCE: The excess spending associated with trimodal therapy vs. radical cystectomy was largely driven by outpatient expenditures. The relatively high long-term trimodal therapy costs are prime targets for cost containment strategies to optimize future value-based care.