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This summary provides the results of a study of two treatments for cancer, enfortumab vedotin and pembrolizumab, that were studied together against locally advanced or metastatic urothelial cancer (la/mUC), a cancer that occurs most commonly in the bladder. In the 45 patients studied, around 16% did have serious side effects, but most side effects were manageable. Twenty-four percent of patients, however, stopped the study treatment because of their side effects. Within about 2 months of starting treatment, most patients' (73%) tumors were smaller and stayed smaller, on average, for more than 2 years. The combination of enfortumab vedotin plus pembrolizumab is a new treatment option for patients with locally advanced or metastatic urothelial cancer when they cannot receive the typical treatment, cisplatin. Advanced or metastatic urothelial cancer is a type of cancer where the cancer has already spread outside of the bladder or urinary tract. [ABSTRACT FROM AUTHOR]

Prostate cancer relies on signaling through the androgen receptor (AR) for maintenance and progression; and androgen-deprivation therapy remains a cornerstone of treatment for advanced prostate cancer. An effective clinical classification of prostate cancer should account for the extent of the disease as well as the mechanisms that are driving the growth of the tumor. The previous terms hormone-sensitive and hormone-refractory described response to treatment. It has become clear that these terms do not reflect the mechanism of disease relapse; however over the last decade there has been a better understanding of androgen-receptor mediated signaling effects and incomplete suppression of androgens in prostate cancer. The Prostate Cancer Clinical Trials Working Group 2 (PCWG2) now recommends addressing the spectrum of clinical states based on castration status as this ligand-centered terminology can more accurately describe the patients’ disease, and ultimately provides a useful framework for patient management and drug development. Optimized use of androgen-deprivation therapy, low molecular weight inhibitors of adrenal androgen biosynthesis, and new AR antagonists are promising new therapeutics that can further define the meaning of castrate state. As hormone resistance is redefined to include patients that are refractory to treatments that ablate adrenal and in situ tumoral androgens, a meaningful new clinical state in patients will be forged. We propose a model for incorporating these patients into the current PCWG2 conceptualization of the disease. [ABSTRACT FROM PUBLISHER]

BACKGROUND. Patients undergoing immune checkpoint inhibitor (ICI) therapy may present to the emergency department (ED) with a wide range of immune-related adverse events. OBJECTIVE. The purpose of our study was to evaluate chest CT findings in patients receiving ICI therapy presenting to the ED and to explore these findings' associations with clinical parameters. METHODS. This retrospective study included 136 patients (75 men, 61 women; mean age, 65 ± 12 [SD] years) receiving ICI therapy who underwent chest CT at 163 ED visits between 2011 and 2018. Two radiologists independently reviewed chest CT examinations for various findings and resolved discrepancies by consensus. Clinical parameters, including survival at last available follow-up, were recorded. Chest CT findings were summarized, and interreader agreement was evaluated using kappa coefficients. Associations between CT findings and clinical parameters were explored using Fisher exact, chi-square, Wilcoxon, and Kruskal-Wallis tests. RESULTS. A total of 62.5% of patients had primary lung cancer; 52.9% received nivolumab monotherapy, and 30.1% received pembrolizumab monotherapy. A total of 55.8% of ED visits occurred within 60 days after ICI initiation. The most common CT findings were worsening lung tumor burden (60.1%), new consolidation unrelated to tumor (30.1%), new or worsening pleural effusion (23.9%), and ICI-associated pneumonitis (12.9%). The most common CT pneumonitis pattern was radiation recall pneumonitis (6/21, 28.6%). A total of 78.5% of ED visits with chest CT resulted in hospitalization; 66.9% of patients subsequently died. Survival was worse for patients with, versus without, worsening tumor (72.2% vs 49.1% of patients deceased vs alive at follow-up, p = .006) and for patients with, versus without, pleural effusion (39.2% vs 17.5% of patients deceased vs alive at follow-up, p = .04). Kappa values for interreader agreement of evaluated chest CT findings ranged from 0.66 (worsening tumor burden) to 1.00 (numerous findings). CONCLUSION. Most ED chest CT examinations in patients receiving ICI therapy exhibited worsening lung tumor burden, which was associated with worse survival. New consolidation and ICI-associated pneumonitis (most commonly radiation recall pneumonitis) were also commonly detected in the ED setting. CLINICAL IMPACT. Understanding pathologies detected on chest CT in patients undergoing ICI therapy who present to the ED may guide radiologists in interpreting such imaging.

Background: While immune checkpoint inhibitors (ICIs) are approved in the first-line (1L) setting for cisplatin-unfit patients with programmed death-ligand 1 (PD-L1)-high tumors or for platinum (cisplatin/carboplatin)-unfit patients, response rates remain modest and outcomes vary with no clinically useful biomarkers (except for PD-L1)., Objective: We aimed to develop a prognostic model for overall survival (OS) in patients receiving 1L ICIs for advanced urothelial cancer (aUC) in a multicenter cohort study., Design, Setting, and Participants: Patients treated with 1L ICIs for aUC across 24 institutions and five countries (in the USA and Europe) outside clinical trials were included in this study., Outcome Measurements and Statistical Analysis: We used a stepwise, hypothesis-driven approach using clinician-selected covariates to develop a new risk score for patients receiving ICIs in the 1L setting. Demographics, clinicopathologic data, treatment patterns, and OS were collected uniformly. Univariate Cox regression was performed on 18 covariates hypothesized to be associated with OS based on published data. Variables were retained for multivariate analysis (MVA) if they correlated with OS (p < 0.2) and were included in the final model if p < 0.05 on MVA. Retained covariates were assigned points based on the beta coefficient to create a risk score. Stratified median OS and C-statistic were calculated., Results and Limitations: Among 984 patients, 357 with a mean age of 71 yr were included in the analysis, 27% were female, 68% had pure UC, and 13% had upper tract UC. Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases were significant prognostic factors on MVA and were included in the risk score. C index for new 1L risk score was 0.68 (95% confidence interval 0.65-0.71). Limitations include retrospective nature and lack of external validation., Conclusions: We developed a new 1L ICI risk score for OS based on data from patients with aUC treated with ICIs in the USA and Europe outside of clinical trials. The score components highlight readily available factors related to tumor biology and treatment response. External validation is being pursued., Patient Summary: With multiple new treatments under development and approved for advanced urothelial carcinoma, it can be difficult to identify the best treatment sequence for each patient. The risk score may help inform treatment discussions and estimate outcomes in patients treated with first-line immune checkpoint inhibitors, while it can also impact clinical trial design and endpoints. TAKE  HOME MESSAGE: A new risk score was developed for advanced urothelial carcinoma treated with first-line immune checkpoint inhibitors. The score assigned Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases each one point, with a higher score being associated with worse overall survival., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Metastatic castration-resistant prostate cancer (mCRPC) remains a terminal diagnosis with an aggressive disease course despite currently approved therapeutics. The recent successful development of poly ADP-ribose polymerase (PARP) inhibitors for patients with mCRPC and mutations in DNA damage repair genes has added to the treatment armamentarium and improved personalized treatments for prostate cancer. Other promising therapeutic agents currently in clinical development include the radiotherapeutic 177-lutetium-prostate-specific membrane antigen (PSMA)-617 targeting PSMA-expressing prostate cancer and combinations of immunotherapy with currently effective treatment options for prostate cancer. Herein, we have highlighted the progress in systemic treatments for mCRPC and the promising agents currently in ongoing clinical trials.

Immune checkpoint inhibitor (ICI)-associated myocarditis is a rare but potentially fatal complication associated with development of other immune-related adverse events (irAEs). Troponin levels, ECG, echocardiography, and cardiac MR can assist with the diagnosis of this rare albeit serious adverse effect related to immunotherapy. In this case report, we present the clinical and radiological features of myocarditis in three patients presenting with acute symptoms while receiving therapy with ICIs. Blood troponin and ECG were abnormal in all three myocarditis cases. Initial echocardiography was abnormal in two patients with reduced left ventricular ejection fraction (LVEF). The third patient demonstrated an initially normal LVEF with subsequent transient decrease in LVEF on follow-up echocardiogram. Cardiac MR was abnormal in three cases with areas of mid-myocardial/epicardial delayed enhancement. All patients experienced additional irAEs. One patient died shortly after myocarditis diagnosis, one was made comfort care due to poor clinical status, and one improved with steroid treatment.

Objective: The purpose of this article is to provide a primer for radiologists outlining the modern systemic therapies used in melanoma brain metastases, including tyrosine kinase inhibitors and immune checkpoint inhibitors. The role of radiologic treatment response evaluation will be discussed from the standpoint of both modern systemic therapies and more traditional treatments., Conclusion: Understanding the role of systemic treatments in melanoma brain metastases is critical for oncologic imaging interpretation in this unique patient population.

Background: The identification of prognostic and/or predictive biomarkers for response to immune checkpoint inhibitors (ICI) could help guide treatment decisions., Objective: We assessed changes in programmed cell death-1 (PD1)/PD1 ligand (PDL1) expression in key immunomodulatory cell subsets (myeloid-derived suppressor cells [MDSC]; cytotoxic T lymphocytes [CTL]) following ICI therapy and investigated whether these changes correlated with outcomes in patients with metastatic urothelial carcinoma (mUC)., Patients and Methods: Serial peripheral blood samples were collected from ICI-treated mUC patients. Flow cytometry was used to quantify PD1/PDL1 expression on MDSC (CD33 + HLADR - ) and CTL (CD8 + CD4 - ) from peripheral blood mononuclear cells. MDSC were grouped into monocytic (M)-MDSC (CD14 + CD15 - ), polymorphonuclear (PMN)-MDSC (CD14 - CD15 + ), and immature (I)-MDSC (CD14 - CD15 - ). Mixed-model regression and Wilcoxon signed-rank or rank-sum tests were performed to assess post-ICI changes in immune biomarker expression and identify correlations between PD1/PDL1 expression and objective response to ICI., Results: Of 41 ICI-treated patients, 26 received anti-PDL1 (23 atezolizumab/3 avelumab) and 15 received anti-PD1 (pembrolizumab) therapy. Based on available data, 27.5% had prior intravesical Bacillus Calmette-Guérin therapy, 42% had prior neoadjuvant chemotherapy, and 70% had prior cystectomy or nephroureterectomy. Successive doses of anti-PDL1 correlated with decreased percentage of PDL1 + (%PDL1 + ) M-MDSC, while doses of anti-PD1 correlated with decreased %PD1 + M- and I-MDSC. Although pre-treatment %PD1 + CTL did not predict response, a greater %PD1 + CTL within 9 weeks after ICI initiation correlated with objective response., Conclusions: Treatment with ICI correlated with distinct changes in PD1/PDL1-expressing peripheral immune cell subsets, which may predict objective response to ICI. Further studies are required to validate immune molecular expression as a prognostic and/or predictive biomarker for long-term outcomes in mUC.

Background: Myeloid derived suppressor cells (MDSC) are heterogeneous immunosuppressive cells with potential predictive and prognostic roles in cancer. The association between MDSC, clinicopathologic factors, and pathologic response in patients with bladder urothelial carcinoma (UC) was explored., Methods: Peripheral blood or tissue were collected from patients with UC undergoing definitive surgery. MDSCs levels were measured in peripheral blood mononuclear cells and fresh tumor tissue. MDSCs were identified by flow cytometry and defined as total MDSC (T-MDSC) CD33+/HLADR-. From this population, 3 subsets were identified: polymorphonuclear-MDSC (PMN-MDSC) defined as CD33+/HLADR-/CD15+/CD14-, monocytic-MDSC (M-MDSC) defined as CD33+/HLADR-/CD15-/CD14+, and immature-MDSC (I-MDSC) defined as CD33+/HLADR-/CD15-/CD14-. MDSC populations were presented as % of live nucleated blood cells. Spearman correlations (r) and Wilcoxon rank sum test were used to assess correlations between MDSC populations, clinicopathologic factors, and pathologic complete response (pCR)., Results: 85 patients scheduled to undergo cystectomy from February 2015 through Dec 2016 were included. All patients had blood drawn for analysis and 23 patients had residual tumor tissue collected for analysis at the time of surgery. Of these 85, 74 (87%) were men with a median age at diagnosis of 68 (range: 44-87). Pure UC was the most common histology (75%); 28 (35%) patients had prior treatment with intravesical therapy and 36 (42%) were treated with neoadjuvant chemotherapy, primarily gemcitabine plus cisplatin (n = 24). On surgical pathology, 18 (21%) of the patients had pCR, 11 (13%) had positive lymph nodes, and 20 patients (24%) had lymphovascular invasion. Statistically significant associations were found between circulating MDSC levels and pCR rates (P<0.01), absolute neutrophil-lymphocyte ratio (P = 0.008), and histology (P = 0.01). Tumor % M-MDSCs were negatively associated with lymphovascular invasion (P = 0.04). There were no significant correlations between peripheral blood mononuclear cells and tumor MDSC subtypes., Conclusions: Blood and tissue MDSC levels correlate with several clinicopathologic factors and may predict for pCR. Future studies are needed to highlight the role of MDSC in predicting long-term outcomes and to determine the clinical implications of these findings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To assess the national utilization of partial nephrectomy (PN) for T1a renal masses across different racial groups by hospital type. Although clinical guidelines recommend PN for small renal masses (SRMs), racial disparities persist in the use of PN. High-volume and academic hospitals have been associated with greater use of PN for SRMs. However, it is unknown whether racial disparities persist in the use of PN across different types of hospitals., Methods: Using the National Cancer Database, we identified patients with localized T1a renal cancer (≤4 cm) from 1998 to 2011. The primary outcome was receipt of PN among patients surgically treated for SRMs. Multivariable logistic regression analyses were used to assess for racial differences in treatment with PN stratified by hospital characteristics., Results: Among 118,207 patients diagnosed with clinical T1a renal masses, 36.5% underwent PN (n = 43,134). Overall, a greater proportion of white patients underwent PN (37.3%) compared with African-American (32.4%) and Hispanic (33.7%) patients with SRMs (P <.001). When stratified by hospital type, disparities persisted in the use of PN; African-American patients had lower adjusted odds ratios for being treated with PN when treated at comprehensive community cancer (odds ratio: 0.90; P = .003) and academic (odds ratio: 0.65; P <.001) hospitals compared with white patients., Conclusions: In this population-based cohort, we found that racial disparities persist across all types of hospitals in the use of PN for SRMs. Further research is needed to identify, and target for intervention, the factors contributing to racial disparities in the surgical management of SRMs., (Copyright © 2016 Elsevier Inc. All rights reserved.)