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Background: Bladder cancer with divergent differentiation (BCDD) comprises a heterogenous group of tumors with a poor prognosis, and differential expression of nectin‐4 and programmed death ligand‐1 (PD‐L1) has been reported in BCDD. Importantly, nectin‐4 expression in bladder cancer is associated with response to enfortumab vedotin, and PD‐L1 expression is associated with responses to immune checkpoint inhibitors (ICIs). Methods: The authors conducted a retrospective review identifying 117 patients with advanced or metastatic BCDD who were treated at Winship Cancer Institute from 2011 to 2021. They performed immunohistochemistry staining for nectin‐4 and PD‐L1 expression by histologic subtype as well as genomic analysis of these patients, including RNA sequencing, whole‐exome sequencing, and fusion detection analysis as well as a subgroup genomic analysis of patients with BCDD who received ICIs. Results: The results indicated that nectin‐4 expression was highest in the groups who had the squamous and plasmacytoid subtypes, whereas the group that had the sarcomatoid subtype (70.8%) had the highest proportion of PD‐L1–positive patients. Genomic analysis yielded several key findings, including a 50% RB1 mutation rate in patients who had small cell BCDD, targetable PIK3CA mutations across multiple subtypes of BCDD, and significantly higher expression of TEC in responders to ICIs. Conclusions: In this study, the authors identified clinically relevant data on nectin‐4 and PD‐L1 expression in patients with rare bladder tumors. They also identified several novel findings in the genomic analysis that highlight the role of precision medicine in this population of patients. Larger, prospective studies are needed to validate these hypothesis‐generating data. In this study, the authors performed a retrospective analysis focused on the histologic and genomic characterization of bladder cancer with divergent differentiation. The results indicated that nectin‐4 expression was highest in patients with squamous and plasmacytoid differentiation, whereas patients who had sarcomatoid differentiation (70.8%) had the highest proportion of programmed death ligand‐1–positive disease, and several novel findings were identified in the genomic analysis that have potential clinical implications for these patients with rare tumors. [ABSTRACT FROM AUTHOR]

Background: Poor comprehension of prostate cancer (PCa) medical terms can create barriers to PCa treatment discussions. The authors measured comprehension of PCa terms and its relationship to health literacy in a group of Black men who were newly diagnosed with PCa. They examined whether tailoring communication with alternative colloquial words would be helpful and acceptable. Methods: Patients were recruited from urology clinics (N = 152). After they met with their providers to discuss PCa treatment options, they participated in an educational supplement delivered as a structured interview. The supplement tailored PCa treatment information by allowing men to choose between colloquial and medical terms for genitourinary (GU) function. Health literacy was measured using the Rapid Estimate of Adult Literacy in Medicine, and comprehension of common PCa terms was assessed using published methods. Pearson correlation was used to estimate the association between health literacy and comprehension of PCa terms. Spearman rank correlation (r) was used to assess the relation between the total number of medical terms preferred (range, 0–10) and Rapid Estimate of Adult Literacy in Medicine scores (range, 0–66). Results: Most patients (62%) had low health literacy, which was strongly correlated with their understanding of PCa terms (r = 0.526; p <.001). Poor comprehension of many PCa terms established the need to use alternative language for GU function (only 20% knew the word incontinence). There was a statistically significant positive association between the number of medical terms preferred and health literacy (r = 0.358; p <.001). A majority of patients (91%) preferred a mixture of medical and colloquial terms. Conclusions: Tailoring communications with colloquial terms for GU function was preferred by most patients regardless of health literacy. Poor comprehension of common prostate cancer terms for genitourinary function creates health literacy barriers to treatment discussions. Tailoring medical terms with alternative colloquial words preferred by patients was helpful regardless of health literacy. [ABSTRACT FROM AUTHOR]

Background: The 2018 Leibovich prognostic model for nonmetastatic renal cell carcinoma (RCC) combines clinical, surgical, and pathologic factors to predict progression‐free survival (PFS) and cancer‐specific survival (CSS) for patients with clear cell (ccRCC), papillary (pRCC), and chromophobe (chRCC) histology. Despite high accuracy, <1% of the original cohort was Black. Here, the authors examined this model in a large population with greater Black patient representation. Methods: By using a prospectively maintained RCC institutional database, patients were assigned Leibovich model risk scores. Survival outcomes included 5‐year and 10‐year PFS and CSS. Prognostic accuracy was determined using area under the curve (AUC) analysis and calibration plots. Black patient subanalyses were conducted. Results: In total, 657 (29%) of 2295 patients analyzed identified as Black. Declines in PFS and CSS were observed as scores increased. Discrimination for ccRCC was strong for PFS (AUC: 5‐year PFS, 0.81; 10‐year PFS, 0.78) and for CSS (AUC: 5‐year CSS, 0.82; 10‐year CSS, 0.74). The pRCC AUC for PFS was 0.74 at 5 years and 0.71 at 10 years; and the AUC for CSS was 0.74 at 5 years and 0.70 at 10 years. In chRCC, better performance was observed for CSS (AUC at 5 years, 0.75) than for PFS (AUC: 0.66 at 5 years; 0.55 at 10 years). Black patient subanalysis revealed similar‐to‐improved performance for ccRCC at 5 years (AUC: PFS, 0.79; CSS, 0.87). For pRCC, performance was lower for PFS (AUC at 5 years, 0.63) and was similar for CSS (AUC at 5 years, 0.77). Sample size limited Black patient 10‐year and chRCC analyses. Conclusions: The authors externally validated the 2018 Leibovich RCC prognostic model and found optimal performance for ccRCC, followed by pRCC, and then chRCC. Importantly, the results were consistent in this large representation of Black patients. Plain Language Summary: In 2018, a model to predict survival in patients with renal cell carcinoma (kidney cancer) was introduced by Leibovich et al.This model has performed well; however, Black patients have been under‐represented in examination of its performance.In this study, 657 Black patients (29%) were included, and the results were consistent.This work is important for making sure the model can be applied to all patient populations. The authors examined and externally validated the 2018 Leibovich prognostic model for nonmetastatic renal cell carcinoma in a large population with greater Black patient representation. The results indicated optimal performance of the model across all histologies and were consistent among Black patients. [ABSTRACT FROM AUTHOR]

Background: This study was aimed at assessing the associations of sarcopenia, muscle density, adiposity, and inflammation with overall survival (OS) after cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma. Methods: In all, 158 patients undergoing CN from 2001 to 2014 had digitized preoperative imaging for tissue segmentation via Slice‐O‐Matic software (version 5.0) at the mid‐L3 level. The skeletal muscle index was calculated with the skeletal muscle area (cm2) normalized for height (m2), and the skeletal muscle density (SMD) was calculated with average Hounsfield units. Adiposity was measured with the cross‐sectional area (cm2) of visceral, subcutaneous, and intramuscular adiposity compartments and was similarly normalized for height. The average fat density was obtained in Hounsfield units. OS was estimated with the Kaplan‐Meier method. Associations between body composition, inflammation metrics, and relevant clinicopathology and OS were assessed with univariable and multivariate Cox analyses. Results: Seventy‐six of the 158 patients (48%) were sarcopenic. Sarcopenia was associated with elevated neutrophil to lymphocyte ratios (NLRs; P =.02), increased age (P =.001), lower body mass indices (P =.009), greater modified Motzer scores (P =.019), and lower SMD (P =.006). The median OS was 15.0 and 29.4 months for sarcopenic and nonsarcopenic patients, respectively (P =.04). Elevated inflammation (NLR or C‐reactive protein), in addition to sarcopenia, was independently associated with OS, with an elevated NLR ≥ 3.5 and sarcopenia associated with the poorest OS at 10.2 months. No associations were observed between measurements of muscle density or adiposity and OS. Conclusions: Sarcopenia and measures of high systemic inflammation are additively associated with inferior OS after CN and may be of use in preoperative risk stratification. Lay Summary: Body composition and sarcopenia (a deficiency in skeletal musculature) have been shown to affect outcomes in cancer.We found that sarcopenic patients had poor survival in comparison with nonsarcopenic patients in the setting of metastatic renal cell carcinoma (mRCC).Patients with both elevated inflammation and sarcopenia had the poorest survival.Sarcopenia is an objective measure of nutrition that can assist in therapeutic counseling and decision‐making for individualized treatment in mRCC. Sarcopenia and measures of high systemic inflammation are additively associated with inferior overall survival after cytoreductive nephrectomy. This may be of use in preoperative risk stratification. [ABSTRACT FROM AUTHOR]

Background: Body composition and inflammation are gaining importance for prognostication in cancer. This study investigated the individual and combined utility of the preoperative skeletal muscle index (SMI) and the modified Glasgow Prognostic Score (mGPS) for estimating postoperative outcomes in patients with localized renal cell carcinoma (RCC) undergoing nephrectomy.Methods: The authors performed a retrospective review of 352 patients with localized RCC. SMI was measured via computed tomography or magnetic resonance imaging. Patients met the criteria for sarcopenia by body mass index- and sex-stratified thresholds. Multivariable and Kaplan-Meier analyses of associations of sarcopenia and mGPS with overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival (CSS) were performed. Variables were analyzed independently and combined into risk groups: low risk (nonsarcopenic, low mGPS), medium risk (sarcopenia only), medium risk (inflammation only), and high risk (sarcopenic, high mGPS). Receiver operating characteristic (ROC) curves were used to analyze risk groups in comparison with the Stage, Size, Grade, and Necrosis (SSIGN) score and the modified International Metastatic RCC Database Consortium (IMDC) score.Results: The majority of the patients were at stage pT3 (63%), 39.5% of the patients were sarcopenic, and 19.3% had an elevated mGPS at the baseline. The median follow-up time was 30.4 months. Sarcopenia and mGPS were independently associated with worse OS (hazard ratio for sarcopenia, 1.64; P = .006; hazard ratio for mGPS, 1.72; P = .012), CSS, and RFS. Risk groups had an increasing association with worse RFS (P = .015) and CSS (P = .004) but not OS (P = .087). ROC analyses demonstrated a higher area under the curve for risk groups in comparison with the SSIGN and IMDC scores at 5 years.Conclusions: Sarcopenia and an elevated mGPS were associated with worse clinical outcomes in this study of patients with localized RCC. This has implications for preoperative prognostication and treatment decision-making.Lay Summary: Kidney cancer is a disease with a wide variety of outcomes. Among patients undergoing surgical removal of the kidney for cancer that has not spread beyond the kidney, many are cured, but some experience recurrence. Physicians are seeking ways to better predict who is at risk for recurrence or death from kidney cancer. This study has evaluated body composition and markers of inflammation before surgery to predict the risk of recurrence or death after surgery. Specifically, low muscle mass and an elevated inflammation score (the modified Glasgow Prognostic Score) have been associated with an increased likelihood of recurrence of kidney cancer and death. [ABSTRACT FROM AUTHOR]