Differential effects of obesity on perioperative outcomes in renal cell carcinoma patients based on race and ethnicity and neighborhood-level socioeconomic status.

Background: Obesity is a well-established risk factor of renal cell carcinoma (RCC), however the impact of obesity on surgical outcomes for racial and ethnic minority patients with RCC is unclear. This study investigated whether a higher body mass index (BMI) or obesity (BMI ≥30 kg/m2) was associated with worse perioperative outcomes and if there were heterogeneous effects based on race, ethnicity, and neighborhood-level socioeconomic factor. Methods: In this single-center cross-sectional study, medical records of patients who underwent partial or radical nephrectomy between 2010 and 2022 were retrospectively reviewed. Logistic regression analysis was performed to assess associations of BMI and perioperative outcomes [ischemia time, estimated blood loss (EBL), and length of hospital stay]. Results: A total of 432 patients, including 49.8% non-Hispanic White (NHW), 35.0% Hispanic, and 6.9% American Indian (AI) patients, were included. Median [interquartile range (IQR)] BMI was 30.2 (26.3-35.2) kg/m2, and Hispanic (31.5) and AI (32.5) patients had higher median BMI than NHW (29.1) patients (P=0.006). Median ischemia time, EBL, and length of hospital stay were 18.5 (IQR, 15.0-22.4) minutes, 150 (IQR, 75.0-300.0) mL, and 3 (IQR, 2-5) days. BMI ≥35 kg/m2 was associated with a longer ischemia time [>18.5 minutes; odds ratio (OR), 5.17; 95% confidence interval (CI): 1.81-14.76; P=0.002], and the association was stronger in NHW than Hispanic patients (BMI continuous OR, 1.13; 95% CI: 1.04-1.22; P=0.004 in NHW and OR, 1.07; 95% CI: 0.98-1.17; P=0.12 in Hispanics). Class I and II/III obese patients had over two-fold increased odds of a larger EBL (>150 mL) than patients with normal weight (OR, 2.17; 95% CI: 1.03-4.59; P=0.04 for class I and OR, 2.24; 95% CI: 1.04-4.84; P=0.04 for class II/III obese patients). This association was stronger in patients from neighborhoods with high social deprivation index (SDI) and in NHW patients (BMI ≥30 vs. <30 kg/m2, OR, 3.53; 95% CI: 1.57-7.97; P=0.002 in high SDI neighborhoods and OR, 2.38; 95% CI: 1.10-5.14; P=0.03 in NHW). BMI was not associated with a longer hospital stay. Conclusions: In this study, obesity increased likelihood of worse perioperative outcomes, and the associations varied based on race and ethnicity and neighborhood-level socioeconomic factors.

AR loss in prostate cancer stroma mediated by NF-κB and p38-MAPK signaling disrupts stromal morphogen production.

Androgen Receptor (AR) activity in prostate stroma is required to maintain prostate homeostasis. This is mediated through androgen-dependent induction and secretion of morphogenic factors that drive epithelial cell differentiation. However, stromal AR expression is lost in aggressive prostate cancer. The mechanisms leading to stromal AR loss and morphogen production are unknown. We identified TGFß1 and TNFα as tumor-secreted factors capable of suppressing AR mRNA and protein expression in prostate stromal fibroblasts. Pharmacological and RNAi approaches identified NF-κB as the major signaling pathway involved in suppressing AR expression by TNFα. In addition, p38α- and p38δ-MAPK were identified as suppressors of AR expression independent of TNFα. Two regions of the AR promoter were responsible for AR suppression through TNFα. FGF10 and Wnt16 were identified as androgen-induced morphogens, whose expression was lost upon TNFα treatment and enhanced upon p38-MAPK inhibition. Wnt16, through non-canonical Jnk signaling, was required for prostate basal epithelial cell survival. These findings indicate that stromal AR loss is mediated by secreted factors within the TME. We identified TNFα/TGFß as two possible factors, with TNFα mediating its effects through NF-κB or p38-MAPK to suppress AR mRNA transcription. This leads to loss of androgen-regulated stromal morphogens necessary to maintain normal epithelial homeostasis.

Evaluating the definition and distribution of spring ephemeral wildflowers in eastern North America.

PREMISE: The herbaceous layer accounts for the majority of plant biodiversity in eastern North American forests, encompassing substantial variation in life history strategy and function. One group of early-season herbaceous understory species, colloquially referred to as spring ephemeral wildflowers, are ecologically and culturally important, but little is known about the prevalence and biogeographic patterns of the spring ephemeral strategy. METHODS: We used observations collected by the Global Biodiversity Information Facility (GBIF) to quantify the ephemerality of 559 understory forb species across eastern North America and classify them according to a continuous ephemerality index (ranging from 0 = never ephemeral to 1 = always ephemeral). We then used this information to model where ephemeral forbs were most common across the landscape with the goal of identifying geographic and environmental drivers important to their distributions and ranges. RESULTS: Only 3.4% of all understory wildflower species were spring ephemerals in all parts of their range, and 18.4% (103 species) were ephemeral in at least part of their range. Spring ephemerals peaked in absolute species richness and relative proportion at mid latitudes. CONCLUSIONS: Spring ephemeral phenology is an important shade-avoidance strategy for a large segment of the total understory species in temperate deciduous forests. In North America, the strategy is relatively most important for forest understories at mid latitudes. The definitions of spring ephemerality we provide here serve as an important ecological context for conservation priorities and to evaluate responses of this biodiverse group to future environmental change.

Neighborhood social vulnerability and disparities in time to kidney cancer surgical treatment and survival in Arizona.

BACKGROUND: Hispanics and American Indians (AI) have high kidney cancer incidence and mortality rates in Arizona. This study assessed: (1) whether racial and ethnic minority patients and patients from neighborhoods with high social vulnerability index (SVI) experience a longer time to surgery after clinical diagnosis, and (2) whether time to surgery, race and ethnicity, and SVI are associated with upstaging to pT3/pT4, disease-free survival (DFS), and overall survival (OS). METHODS: Arizona Cancer Registry (2009-2018) kidney and renal pelvis cases (n = 4592) were analyzed using logistic regression models to assess longer time to surgery and upstaging. Cox-regression hazard models were used to test DFS and OS. RESULTS: Hispanic and AI patients with T1 tumors had a longer time to surgery than non-Hispanic White patients (median time of 56, 55, and 45 days, respectively). Living in neighborhoods with high (≥75) overall SVI increased odds of a longer time to surgery for cT1a (OR 1.54, 95% CI: 1.02-2.31) and cT2 (OR 2.32, 95% CI: 1.13-4.73). Race and ethnicity were not associated with time to surgery. Among cT1a patients, a longer time to surgery increased odds of upstaging to pT3/pT4 (OR 1.95, 95% CI: 0.99-3.84). A longer time to surgery was associated with PFS (HR 1.52, 95% CI: 1.17-1.99) and OS (HR 1.63, 95% CI: 1.26-2.11). Among patients with cT2 tumor, living in high SVI neighborhoods was associated with worse OS (HR 1.66, 95% CI: 1.07-2.57). CONCLUSIONS: High social vulnerability was associated with increased time to surgery and poor survival after surgery.

The Invasion of Galinsoga quadriradiata into High Elevations Is Shaped by Variation in AMF Communities.

Mountain ranges have been previously suggested to act as natural barriers to plant invasion due to extreme environmental conditions. However, how arbuscular mycorrhizal fungi (AMF) affect invasion into these systems has been less explored. Here, we investigated how changes in AMF communities affect the performance of Galinsoga quadriradiata in mountain ranges. We performed a greenhouse experiment to study the impact of inoculations of AMF from different elevations on the performance and reproduction of invaders and how competition with native plants changes the effects of invader-AMF interactions. We found strong evidence for a nuanced role of AMF associations in the invasion trajectory of G. quadriradiata, with facilitative effects at low elevations and inhibitory effects at high elevations. Galinsoga quadriradiata performed best when grown with inoculum collected from the same elevation but performed worst when grown with inoculum collected from beyond its currently invaded range, suggesting that AMF communities can help deter invasion at high elevations. Finally, the invasive plants grown alone experienced negative effects from AMF, while those grown in competition experienced positive effects, regardless of the AMF source. This suggests that G. quadriradiata lowers its partnerships with AMF in stressful environments unless native plants are present, in which case it overpowers native plants to obtain AMF support during invasion. Finally, our results indicate that invader-AMF interactions can inhibit invasive range expansion at high elevations, and biotic interactions, in addition to harsh environmental conditions, make high-elevation mountain ranges natural barriers against continued invasion.

Gemcitabine as first-line therapy for high-grade non-muscle invasive bladder cancer: results from a tertiary center in the contemporary BCG-shortage era.

Background: To evaluate the safety profile and efficacy of intravesical gemcitabine as first-line adjuvant therapy for non-muscle invasive bladder cancer (NMIBC) in the setting of ongoing Bacillus Calmette-Guérin (BCG) shortage. Methods: We performed an institutional, retrospective review of patients treated with intravesical gemcitabine induction and maintenance therapy from March 2019 to October 2021. Patients with intermediate or high-risk NMIBC who were BCG-naïve or experienced a high-grade (HG) recurrence after 12 months since the last dose of BCG were included in the analysis. The primary endpoint was complete response (CR) rate at the 3-month visit. Secondary endpoints were recurrence-free survival (RFS) and assessment of adverse events. Results: A total of 33 patients were included. All had HG disease and 28 (84.8%) were BCG-naive. The median follow-up was 21.4 months (range, 4.1-39.4). Tumor stages were cTa in 39.4%, cT1 in 54.5%, and cTis in 6.1% of patients. Most patients (90.9%) were in the AUA high-risk category. The 3-month CR was 84.8%. Among patients who achieved CR with adequate follow-up, 86.9% (20/23) remained disease-free at 6 months. The 6-month and 12-month RFS were 87.2% and 76.5%, respectively. The estimated median RFS was not reached. Approximately 78.8% of patients were able to complete full induction. Common adverse events (incidence ≥10%) included dysuria and fatigue/myalgia. Conclusions: Intravesical gemcitabine for intermediate and high-risk NMIBC in areas where BCG supply is limited was safe and feasible at short-term follow-up. Larger prospective studies are needed to better ascertain the oncologic efficacy of gemcitabine.

Clear cell renal cell carcinoma molecular variations in non-Hispanic White and Hispanic patients.

BACKGROUND: The United States is becoming increasingly diverse, but few molecular studies have assessed the progression of clear cell renal cell carcinoma (ccRCC) in diverse patient populations. This study examined ccRCC molecular variations in non-Hispanic White (NHW) and Hispanic patients and their effect on the association of gene expression with high-grade (Grade 3 or 4) ccRCC and overall mortality. METHODS: A total of 156 patients were included in VHL sequencing and/or TempO-Seq analysis. DESeq2 was used to identify the genes associated with high-grade ccRCC. Logistic regression analysis was performed to assess whether race and ethnicity was associated with high/moderate impact VHL somatic mutations and the ccA/ccB subtype. Cox regression analysis was performed to assess association of molecular subtype and gene expression with overall mortality. RESULTS: NHWs had moderate or high impact mutations in the VHL gene at a higher frequency than Hispanics (40.2% vs. 27.4%), while Hispanics had a higher frequency of the ccA subtype than NHWs (61.9% vs. 45.8%). ccA was more common in patients with BMI≥35 (65.2%) than in those with BMI < 25 (45.0%). There were 11 differentially expressed genes between high- and low-grade tumors. The Haptoglobin (HP) gene was most significantly overexpressed in high- compared to low-grade ccRCC in all samples (p-adj = 1.7 × 10-12 ). When stratified by subtype, the 11 genes were significantly differentially expressed in the ccB subtype, but none of them were significant after adjusting for multiple testing in ccA. Finally, patients with the ccB subtype had a significantly increased risk of overall mortality (HR 4.87; p = 0.01) compared to patients with ccA, and patients with high HP expression and ccB, had a significantly increased risk of mortality compared to those with low HP expression and ccA (HR 6.45, p = 0.04). CONCLUSION: This study reports ccRCC molecular variations in Hispanic patients who were previously underrepresented.

Targeting NEDDylation is a Novel Strategy to Attenuate Cisplatin-induced Nephrotoxicity.

Although cisplatin remains a backbone of standard-of-care chemotherapy regimens for a variety of malignancies, its use is often associated with severe dose-limiting toxicities (DLT). Notably, 30%-40% of patients treated with cisplatin-based regimens are forced to discontinue treatment after experiencing nephrotoxicity as a DLT. New approaches that simultaneously prevent renal toxicity while improving therapeutic response have the potential to make a major clinical impact for patients with multiple forms of cancer. Here, we report that pevonedistat (MLN4924), a first-in-class NEDDylation inhibitor, alleviates nephrotoxicity and synergistically enhances the efficacy of cisplatin in head and neck squamous cell carcinoma (HNSCC) models. We demonstrate that pevonedistat protects normal kidney cells from injury while enhancing the anticancer activity of cisplatin through a thioredoxin-interacting protein (TXNIP)-mediated mechanism. Cotreatment with pevonedistat and cisplatin yielded dramatic HNSCC tumor regression and long-term animal survival in 100% of treated mice. Importantly, the combination decreased nephrotoxicity induced by cisplatin monotherapy as evidenced by the blockade of kidney injury molecule-1 (KIM-1) and TXNIP expression, a reduction in collapsed glomeruli and necrotic cast formation, and inhibition of cisplatin-mediated animal weight loss. Inhibition of NEDDylation represents a novel strategy to prevent cisplatin-induced nephrotoxicity while simultaneously enhancing its anticancer activity through a redox-mediated mechanism. Significance: Cisplatin therapy is associated with significant nephrotoxicity, which limits its clinical use. Here we demonstrate that NEDDylation inhibition with pevonedistat is a novel approach to selectively prevent cisplatin-induced oxidative damage to the kidneys while simultaneously enhancing its anticancer efficacy. Clinical evaluation of the combination of pevonedistat and cisplatin is warranted.

Wildflower phenological escape differs by continent and spring temperature.

Temperate understory plant species are at risk from climate change and anthropogenic threats that include increased deer herbivory, habitat loss, pollinator declines and mismatch, and nutrient pollution. Recent work suggests that spring ephemeral wildflowers may be at additional risk due to phenological mismatch with deciduous canopy trees. The study of this dynamic, commonly referred to as "phenological escape", and its sensitivity to spring temperature is limited to eastern North America. Here, we use herbarium specimens to show that phenological sensitivity to spring temperature is remarkably conserved for understory wildflowers across North America, Europe, and Asia, but that canopy trees in North America are significantly more sensitive to spring temperature compared to in Asia and Europe. We predict that advancing tree phenology will lead to decreasing spring light windows in North America while spring light windows will be maintained or even increase in Asia and Europe in response to projected climate warming.

Impacts of Neighborhood Characteristics and Surgical Treatment Disparities on Overall Mortality in Stage I Renal Cell Carcinoma Patients.

Racial/ethnic minority groups in the United States have high renal cell carcinoma (RCC) mortality rates. This study assessed surgical treatment disparities across racial/ethnic groups and impacts of neighborhood socioeconomic characteristics on surgical treatments and overall mortality. Stage I RCC patients diagnosed between 2004 and 2016 from National Cancer Database were included (n = 238,141). We assessed differences in associations between race/ethnicity and treatment patterns using logistic regression and between race/ethnicity and overall mortality using Cox regression with and without neighborhood characteristics in the regression models. When compared to non-Hispanic Whites (NHWs), American Indians/Alaska Natives and non-Hispanic Blacks (NHBs) were more likely not to receive surgical care and all racial/ethnic minority groups had significantly increased odds of undergoing radical rather than partial nephrectomy, even after adjusting for neighborhood characteristics. Including surgical treatment and neighborhood factors in the models slightly attenuated the association, but NHBs had a significantly increased risk of overall mortality. NHBs who underwent radical nephrectomy had an increased risk of mortality (HR 1.15, 95% CI: 1.08-1.23), but not for NHBs who underwent partial nephrectomy (HR 0.92, 95% CI: 0.84-1.02). Neighborhood factors were associated with surgical treatment patterns and overall mortality in both NHBs and NHWs. Neighborhood socioeconomic factors may only partly explain RCC disparities.

Renal Cell Carcinoma Surgical Treatment Disparities in American Indian/Alaska Natives and Hispanic Americans in Arizona.

American Indians/Alaska Natives (AI/AN) and Hispanic Americans (HA) have higher kidney cancer incidence and mortality rates compared to non-Hispanic Whites (NHW). Herein, we describe the disparity in renal cell carcinoma (RCC) surgical treatment for AI/AN and HA and the potential association with mortality in Arizona. A total of 5111 stage I RCC cases diagnosed between 2007 and 2016 from the Arizona Cancer Registry were included. Statistical analyses were performed to test the association of race/ethnicity with surgical treatment pattern and overall mortality, adjusting for patients' demographic, healthcare access, and socioeconomic factors. AI/AN were diagnosed 6 years younger than NHW and were more likely to receive radical rather than partial nephrectomy (OR 1.49 95% CI: 1.07-2.07) compared to NHW. Mexican Americans had increased odds of not undergoing surgical treatment (OR 1.66, 95% CI: 1.08-2.53). Analysis showed that not undergoing surgical treatment and undergoing radical nephrectomy were statistically significantly associated with higher overall mortality (HR 1.82 95% CI: 1.21-2.76 and HR 1.59 95% CI: 1.30-1.95 respectively). Mexican Americans, particularly U.S.-born Mexican Americans, had an increased risk for overall mortality and RCC-specific mortality even after adjusting for neighborhood socioeconomic factors and surgical treatment patterns. Although statistically not significant after adjusting for neighborhood-level socioeconomic factors and surgical treatment patterns, AI/AN had an elevated risk of mortality.

Digital image analysis using video microscopy of human-derived prostate cancer vs normal prostate organoids to assess migratory behavior on extracellular matrix proteins.

The advent of perpetuating living organoids derived from patient tissue is a promising avenue for cancer research but is limited by difficulties with precise characterization. In this brief communication, we demonstrate via time-lapse imaging distinct phenotypes of prostate organoids derived from patient material- without confirmation of cellular identity. We show that organoids derived from histologically normal tissue more readily spread on a physiologic extracellular matrix (ECM) than on pathologic ECM (p<0.0001), while tumor-derived organoids spread equally on either substrate (p=0.2406). This study is an important proof-of-concept to defer precise characterization of organoids and still glean information into disease pathology.

The long noncoding RNA H19 regulates tumor plasticity in neuroendocrine prostate cancer.

Neuroendocrine (NE) prostate cancer (NEPC) is a lethal subtype of castration-resistant prostate cancer (PCa) arising either de novo or from transdifferentiated prostate adenocarcinoma following androgen deprivation therapy (ADT). Extensive computational analysis has identified a high degree of association between the long noncoding RNA (lncRNA) H19 and NEPC, with the longest isoform highly expressed in NEPC. H19 regulates PCa lineage plasticity by driving a bidirectional cell identity of NE phenotype (H19 overexpression) or luminal phenotype (H19 knockdown). It contributes to treatment resistance, with the knockdown of H19 re-sensitizing PCa to ADT. It is also essential for the proliferation and invasion of NEPC. H19 levels are negatively regulated by androgen signaling via androgen receptor (AR). When androgen is absent SOX2 levels increase, driving H19 transcription and facilitating transdifferentiation. H19 facilitates the PRC2 complex in regulating methylation changes at H3K27me3/H3K4me3 histone sites of AR-driven and NEPC-related genes. Additionally, this lncRNA induces alterations in genome-wide DNA methylation on CpG sites, further regulating genes associated with the NEPC phenotype. Our clinical data identify H19 as a candidate diagnostic marker and predictive marker of NEPC with elevated H19 levels associated with an increased probability of biochemical recurrence and metastatic disease in patients receiving ADT. Here we report H19 as an early upstream regulator of cell fate, plasticity, and treatment resistance in NEPC that can reverse/transform cells to a treatable form of PCa once therapeutically deactivated.

National trends and survival outcomes of penile squamous cell carcinoma based on human papillomavirus status.

BACKGROUND: There are no series evaluating penile squamous cell carcinoma (pSCC) based on human papillomavirus (HPV) infection. Herein, we present national registry data on clinical and survival outcomes for pSCC based on HPV status. METHODS: We performed a retrospective review of 1224 pSCC patients with known HPV staining from the National Cancer Database. Patients with cM1 disease, those who did not receive treatment, or had missing follow-up data were excluded. Logistic regression identified factors associated with locally aggressive disease. Univariable, multivariable, and inverse probability of treatment weighting (IPTW)-Cox proportional hazard modeling were used to assess hazard ratios (HR) associated with overall survival (OS). RESULTS: After exclusion criteria, we identified 825 cases of which 321 (38.9%) were HPV positive. The HPV-positivity rate did not significantly change by year. HPV-positive patients were younger, had lower Charlson-Deyo performance score, and resided in areas with both lower median household income and lower school education completion. HPV-positive tumors presented with lower American Joint Committee on Cancer clinical T-stage (cT), poorer differentiation, lower rates of lymphovascular invasion (LVI), but more node-positive disease (cN+). For those who underwent lymph node surgery, there were no differences in final pathologic stage, upstaging, or presence of extranodal extension. Only tumor differentiation, LVI, and performance score were independent predictors for locally aggressive disease. HPV status was not a predictor of OS (IPTW-HR:0.89, p = 0.13). CONCLUSIONS: In the largest series evaluating pSCC based on HPV status, HPV-positive tumors were associated with lower cT stages, less LVI, but more cN + disease. More studies on prognostic factors are needed, and time may still be immature to use HPV information for risk stratification.

Racial and Ethnic Disparities in Preoperative Surgical Wait Time and Renal Cell Carcinoma Tumor Characteristics.

Racial/ethnic minority groups have a disproportionate burden of kidney cancer. The objective of this study was to assess if race/ethnicity was associated with a longer surgical wait time (SWT) and upstaging in the pre-COVID-19 pandemic time with a special focus on Hispanic Americans (HAs) and American Indian/Alaska Natives (AIs/ANs). Medical records of renal cell carcinoma (RCC) patients who underwent nephrectomy between 2010 and 2020 were retrospectively reviewed (n = 489). Patients with a prior cancer diagnosis were excluded. SWT was defined as the date of diagnostic imaging examination to date of nephrectomy. Out of a total of 363 patients included, 34.2% were HAs and 8.3% were AIs/ANs. While 49.2% of HA patients experienced a longer SWT (≥90 days), 36.1% of Non-Hispanic White (NHW) patients experienced a longer SWT. Longer SWT had no statistically significant impact on tumor characteristics. Patients with public insurance coverage had increased odds of longer SWT (OR 2.89, 95% CI: 1.53-5.45). Public insurance coverage represented 66.1% HA and 70.0% AIs/ANs compared to 56.7% in NHWs. Compared to NHWs, HAs had higher odds for longer SWT in patients with early-stage RCC (OR, 2.38; 95% CI: 1.25-4.53). HAs (OR 2.24, 95% CI: 1.07-4.66) and AIs/ANs (OR 3.79, 95% CI: 1.32-10.88) had greater odds of upstaging compared to NHWs. While a delay in surgical care for early-stage RCC is safe in a general population, it may negatively impact high-risk populations, such as HAs who have a prolonged SWT or choose active surveillance.

The dispersal-related traits of an invasive plant Galinsoga quadriradiata correlate with elevation during range expansion into mountain ranges.

Detecting shifts in trait values among populations of an invasive plant is important for assessing invasion risks and predicting future spread. Although a growing number of studies suggest that the dispersal propensity of invasive plants increases during range expansion, there has been relatively little attention paid to dispersal patterns along elevational gradients. In this study, we tested the differentiation of dispersal-related traits in an invasive plant, Galinsoga quadriradiata, across populations at different elevations in the Qinling and Bashan Mountains in central China. Seed mass-area ratio (MAR), an important seed dispersal-related trait, of 45 populations from along an elevational gradient was measured, and genetic variation of 23 populations was quantified using inter-simple sequence repeat (ISSR) markers. Individuals from four populations were then planted in a greenhouse to compare their performance under shared conditions. Changing patterns of seed dispersal-related traits and populations genetic diversity along elevation were tested using linear regression. Mass-area ratio of G. quadriradiata increased, while genetic diversity decreased with elevation in the field survey. In the greenhouse, populations of G. quadriradiata sourced from different elevations showed a difference response of MAR. These results suggest that although rapid evolution may contribute to the range expansion of G. quadriradiata in mountain ranges, dispersal-related traits will also likely be affected by phenotypic plasticity. This challenges the common argument that dispersal ability of invasive plants increases along dispersal routes. Furthermore, our results suggest that high-altitude populations would be more effective at seed dispersal once they continue to expand their range downslope on the other side. Our experiment provides novel evidence that the spread of these high-altitude populations may be more likely than previously theorized and that they should thus be cautiously monitored.

Nephrectomy Delay of More than 10 Weeks from Diagnosis Is Associated with Decreased Overall Survival in pT3 RCC.

In this study, we aimed to evaluate the impact of surgical wait time (SWT) on outcomes of patients with renal cell carcinoma (RCC), and to investigate risk factors associated with prolonged SWT. Using the National Cancer Database, we retrospectively reviewed the records of patients with pT3 RCC treated with radical or partial nephrectomy between 2004 and 2014. The cohort was divided based on SWT. The primary outcome was 5-year overall survival (OS). Logistic regression analysis was used to investigate the risk factors associated with delayed surgery. Cox proportional hazards models were fitted to assess relations between SWT and 5-year OS after adjusting for confounding factors. A total of 22,653 patients were included in the analysis. Patients with SWT > 10 weeks had higher occurrence of upstaging. Using logistic regression, we found that female patients, African-American or Spanish origin patients, treatment in academic or integrated network cancer center, lack of insurance, median household income of <$38,000, and the Charlson-Deyo score of ≥1 were more likely to have prolonged SWT. SWT > 10 weeks was associated with decreased 5-year OS (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.15-1.33). This risk was not markedly attenuated after adjusting for confounding variables, including age, gender, race, insurance status, Charlson-Deyo score, tumor size, and surgical margin status (adjusted HR, 1.13; 95% CI, 1.04-1.24). In conclusion, the vast majority of patients underwent surgery within 10 weeks. There is a statistically significant trend of increasing SWT over the study period. SWT > 10 weeks is associated with decreased 5-year OS.