bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analyses of trends and survival in patients with urothelial versus nonurothelial bladder carcinoma: National Cancer Database (NCDB) analysis.
Authors: Aragon-Ching Jeanny B. , Trump Donald L. , Wang Hongkun 
Published: March 2019

402 Background: Bladder cancer is estimated to occur in 81,190 patients in 2018 with estimated death in 17,240. Urothelial cancers make up the majority of cancers but non-urothelial cancers are known to have more aggressive phenotype with worse survival. We have demonstrated previously that non-urothelial histologic subtypes have worse survival outcomes compared to urothelial cancers in a population-based analysis (Aragon-Ching J et al.; J Clin Oncol 36, 2018 (suppl 6S: abstr 425). Methods: The primary objective of this review is to gather data on trends and differences between urothelial versus non-urothelial histologies (squamous, sarcomatoid, small cell or neuroendocrine, adenocarcinoma) and compare the demographics, disease characteristics (incidence of metastases, stage presentation, etc), and survival according to the NCDB. Results: Data from diagnosis in year 2004 – 2013 were extracted from the NCDB. A total of 76,858 and 5560 patients were included for urothelial and non-urothelial, respectively. More men were diagnosed with urothelial carcinoma (75%) and non-urothelial carcinoma (61%) than women. The median age was 71 years and 69 years of age, respectively for urothelial and non-urothelial. Majority were Caucasian at 91% and 86%, respectively though there seemed to be more African-Americans in the non-urothelial (11%) compared to 6% in the urothelial cohorts. More patients were diagnosed with higher stages of III and IV in the non-urothelial group (62%) compared to 36% in the urothelial group, although the sites of metastases in the brain, bone or liver were fairly equivalent for both urothelial and non-urothelial cohorts. Median survival time from diagnosis was better in the urothelial compared to non-urothelial arms [69.91 (69.39 – 70.54) vs 64.53 (61.5 – 67.45 months), p-value < 0.001]. Conclusions: Non-urothelial cancers have distinct demographics different from non-urothelial cancers. Patients often present at a higher stage and survival appears to fare worse than urothelial cancers. Further studies to refine treatment options to optimize treatment outcomes are an area of increased unmet need.
Carcinomas of the renal pelvis, ureters, and urinary bladder arise by similar carcinogenic pathways: A pathoepidemiological analysis.
Authors: Nizam Amanda , Henson Donald , Aragon-Ching Jeanny B. 
Published: March 2019

403 Background: Urothelial carcinomas comprise the most common malignant tumors in the urinary tract. Kidney epithelial cancers, on the other hand, have a different pathoepidemiologic incidence and characteristics. We report a population-based analysis of the histopathology of upper and lower urinary tract cancers as an approach to exploring the relationship of tumors that share similar morphologic phenotypes. Our results depend on observations made 65 years ago that age of diagnosis and age specific incidence rates generated straight lines when plotted as logarithms. Methods: Data from 2000 through 2014 from the SEER Program were used to calculate incidence rates of renal, renal pelvis, ureter and urinary bladder cancers. Graphic plots of the epidemiologic patterns were analyzed relating to incidence and age-specific rates of these upper and lower tract carcinomas. The graphic analysis included evaluation of age frequency density plots and double logarithmic plots (log-log) of age-specific incidence rates and age at diagnosis. Results: Cancers of the kidney are initially more frequent than cancers of the urinary bladder, but after age 60, cancers of the bladder become more common with age-specific rates rapidly rising in all age groups. The age frequency density plot for renal cancers peaks earlier, around age 60, indicating a potentially different tumorigenic process. While the log-log plots reveal near parallel proportional rate patterns for cancers of the renal pelvis, ureters, and urinary bladder, while the rate for the cancer of the kidney was not parallel on inspection. Similar slopes indicate that cancer incidence is increasing at near similar rates regardless of the incidence of each cancer. Thus, the percentage change per unit time for cancers of the renal pelvis, ureters, and bladder is comparable. Conclusions: Tumors that arise from the renal pelvis, ureters, and urinary bladder are pathogenically related and share a common carcinogenic field based on pathoepidemiologic analyses.
Prostate cancer-related quality of life and risk for anxiety and depression.
Authors: McManus Shauna , Olson Julie , Miller Melissa F. , Clark Kelly , Stein Kevin 
Published: March 2019

41 Background: Due to side effects of invasive treatments, prostate cancer (PC) patients face long-term quality of life (QoL) concerns and enduring psychosocial distress. We explored how QoL is linked to distress among a national sample of men with PC. Methods: 214 men with PC enrolled in the Cancer Support Community’s Cancer Experience Registry. Participants provided demographic/clinical background and completed the Prostate Cancer-Related QoL Scales, covering 6 QoL domains ( urinary control, sexual intimacy, sexual confidence, masculine self-esteem, cancer control, and treatment regret). Psychosocial distress was captured by CancerSupportSource, a 25-item tool with 2-item depression and anxiety screening subscales. Scores ≥3 indicate risk for clinically significant depression or anxiety respectively, and signal need for referral and further assessment. We examined bivariate correlations between demographic/clinical background, QoL, and prevalence of ‘risk for clinically significant anxiety and depression’, and used logistic regression to calculate odds of anxiety and depression risk by QoL, adjusting for demographic/clinical variables. Results: Participants were 93% White; mean ( SD) age=64 (12) years; mean ( SD) years since diagnosis=4.3 (4.9); 25% had metastatic disease. 54% underwent radiation; 55% surgery. 40% were at risk for clinically significant anxiety; 35% depression. Poorer QoL scores for sexual intimacy, sexual confidence, masculine self-esteem, cancer control, and treatment regret were bivariately associated with anxiety ( p<.05) and depression ( p<.001) risk. In logistic regression, poorer perceived cancer control predicted anxiety risk (R2=.44; OR=0.97; p<.01). Lower masculine self-esteem predicted depression risk (R2=.68; OR=0.88; p<.05). Conclusions: Questioning treatment efficacy and worrying about disease progression (i.e., lower perceived cancer control) predicts greater likelihood of anxiety risk. Lower masculine self-esteem predicts odds of depression risk. These findings elucidate the ways that PC patients’ perceptions of advancing disease and diminishing masculinity are linked to distress, thus identifying areas for psycho-educational and supportive interventions.
FGFR3 mutation as a prognostic indicator in patients with urothelial carcinoma: A systematic review and meta-analysis.
Authors: Khalid Sidra , Basulaiman Bassam Mohammed , Emack Jeff , Booth Christopher M. , Hernandez-Barajas David , Duran Ignacio , Smoragiewicz Martin , Amir Eitan , Vera-Badillo Francisco 
Published: March 2019

411 Background: Mutations in the fibroblast growth factor receptor-3 (FGFR3) have been implicated in urothelial tumorigenesis. The role of FGFR3 inhibitors in urothelial carcinoma is being explored in clinical trials. Here we explore the association between FGFR3 mutations and survival in urothelial carcinoma. Methods: We conducted a systemic review of electronic databases to identify studies published 1985-2018. Studies were included if they described the associated between FGFR3 mutations and outcomes of non-muscle invasive (NMI) and muscle invasive (MI) urothelial carcinomas. We used a composite endpoint of progression-free and recurrence-free survival (PRFS). Analysis was performed in Revman software. Hazard ratios (HR) and the 95% confidence intervals (CI) were obtained and entered; and then weighted and pooled in a meta-analysis with random effect modelling. The statistical tests were two sided. Results: Twelve retrospective and prospective studies comprising a total of 2162 patients were included. Analysis was done for two groups. The first group, included 1651 patients with NMI urothelial carcinomas; 886 (53.6%) of these had FGFR3 mutation. Compared to FGFR3 wild type, FGFR3 mutation did not influence PRFS (HR = 1.01, CI = 0.79-1.29, p = 0.95); I2 42%. In the second analysis, 511 patients with NMI and MI urothelial carcinomas were evaluated; 30% (n = 151) of which had FGFR3 mutation. In this group, FGFR3 mutation was not associated with PRFS (HR = 1.46, CI = 0.45-4.71, p = 0.53); I2 90%. Conclusions: Our meta-analysis does not show an association between FGFR3 mutation status and PRFS in urothelial carcinoma. [Table: see text]
Outcomes of patients following dose-dense neoadjuvant chemotherapy for muscle-invasive bladder cancer: Implications for organ-sparing strategies.
Authors: Dumont Clement , Gauthier Helene , Mongiat-Artus Pierre , Masson-Lecomte Alexandra , Desgrandchamps Francois , Culine Stephane 
Published: March 2019

426 Background: Locoregional management of muscle-infiltrating bladder cancer (MIBC) after neoadjuvant chemotherapy (NAC) is controversial, because of both the morbidity of radical cystectomy (RC). Bladder preservation may be feasible after complete tumor response. Methods: This single-center retrospective study included 120 MIBC patients (stages ypT2-4aN0-3M0) treated between 2011 and 2017 with up to 6 cycles of neoadjuvant dose-dense Methotrexate, Vinblastin, Doxorubicin and Cisplatin (DD-MVAC). The primary outcome was relapse-free survival (RFS) depending on pathological findings on RC specimens, classified as either pathological complete response (pCR: ypT0N0/x), residual organ-confined disease (yOCD: ypTa/is/1/2N0/x), residual non-organ-confined disease (yNOCD: ypT≥3Nany or ypTanyN1-3). Secondary objectives included the rate of pCR in RC patients, the rate of ypT0 in the intention-to-treat population, and RFS in ypT0 patients according to locoregional management. Results: After a median number of 5 cycles of NAC, RC was performed in 75% of the patients, concurrent radiochemotherapy (CRC) in 11% and cystoscopic surveillance (CS) in 8%. In the intention-to-treat population, the ypT0 rate was 47%. Among 90 patients who underwent RC, 49% achieved pCR, 16% had yOCD and 34% yNOCD. Median follow-up in RC patients alive at last follow-up was 40 months. Three-year RFS was 86% in RC patients with pCR, 69% in patients with yOCD and 21% in patients with yNOCD (p < 0.0001). Outcomes were similar between ypT0 patients treated with either RC or CRC/CS (3-year RFS: 81% vs 100%, p = 0.20). Limitations to this study included its restrospective design and the lower number of patients treated with CRC/CS. Conclusions: Patients reaching ypT0 after dose-dense NAC show improved prognosis regardless of locoregional treatment. Patients with yOCD are frequently cured by RC, as opposed to patients with yNOCD. Prospective trials are needed to compare upfront cystectomy and bladder-sparing management in patients with both pCR or yNOCD.
Prognostic value of genomic alterations in DNA damage response (DDR) genes in relapsed/advanced bladder cancer (BCa).
Authors: Yin Ming , Grivas Petros , Folefac Edmund , Clinton Steven K. , Emamekhoo Hamid , Holder Sheldon L. , Drabick Joseph J. , Woo Michele Sue-Ann , Vasekar Monali K. , Pal Sumanta K. , Joshi Monika 
Published: March 2019

427 Background: DDR defects play an important role in tumorigenesis, progression, treatment response and outcomes of BCa. We previously showed DDR mutations were associated with better prognosis in relapsed/advanced (TxN2-3M0-1) BCa. In this study, we aimed to update and validate our findings in 3 independent datasets. Methods: 81 BCa patients (pts) who had FoundationOne tumor tissue genomic sequencing (315 cancer-related genes) were used as discovery dataset. Validation dataset 1 consisted of additional 91 pts with FoundationOne test. Validation dataset 2 consisted of 129 relapsed/advanced pts from TCGA BCa cohort. Overall survival (OS) was measured from time of initial BCa diagnosis to death or last follow-up. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI). Logistic regression analysis was performed to calculate odds ratio (OR) and 95% CI. A panel of 32 DDR genes (excluding ATM) were used for analyses because ATM mutation was a negative prognostic factor in our prior study. Results: DDR mutations were present in 76.5% (62/81), 40.7% (37/91) and 51.2% (66/129) pts of the 3 datasets. They were associated with longer OS (adjHR = 0.39, 95% CI 0.21–0.73, p = 0.003) in the discovery dataset, which were confirmed in two validation datasets (Validation 1: adjHR = 0.51, 95% CI 0.26–1.03, p = 0.059; Validation 2: adjHR = 0.62, 95% CI 0.39–0.97, p = 0.038). There was a trend for longer OS with increased number of DDR mutations in individual pts. Pts carrying ≥3 DDR mutations had the best prognosis (data not shown). In 144 cisplatin or carboplatin-treated pts pooled from the 3 cohorts, pts with DDR mutations were more likely to have objective response (OR = 1.81, 95% CI 0.85–3.92 for any DDR mutations; OR = 3.65, 95% CI 0.91–14.7 for ≥3 DDR mutations) and longer overall survival (HR = 0.61, 95% CI 0.38–0.98 for any DDR mutations; HR = 0.49, 95% CI 0.19–1.27 for ≥3 DDR mutations). Conclusions: DDR mutations (excluding ATM gene and especially ≥3) correlated with better outcomes in relapsed/advanced BCa. Further exploration of the deleterious nature and functional impact of alterations is critical along with prospective validation in ongoing trials.
Clinical outcomes of muscle-invasive bladder cancer patients with hydronephrosis treated with tetra-modality bladder sparing therapy incorporating consolidative partial cystectomy.
Authors: Kijima Toshiki , Fukuda Shohei , Fukushima Hiroshi , Moriyama Shingo , Uehara Sho , Yasuda Yosuke , Yoshida Soichiro , Yokoyama Minato , Ishioka Junichiro , Matsuoka Yoh , Saito Kazutaka , Fujii Yasuhisa 
Published: March 2019

430 Background: Trimodality bladder sparing therapy has become an accepted treatment for selected patients with muscle-invasive bladder cancer (MIBC). As the presence of hydronephrosis may reduce complete response rate and survival in trimodality therapy, some investigators deem hydronephrosis as a contraindication for bladder sparing. We have developed a tetra-modality bladder sparing therapy (TeMT) consisting of maximal transurethral resection (TUR), induction chemoradiotherapy (CRT), and partial cystectomy (PC) (Koga et al, BJU Int 2012). TeMT which enables surgical consolidation of the original MIBC site, including uretero-vesical anastomosis if necessary, may provide more chance of bladder sparing for patients with hydronephrosis. Methods: In total, 151 patients with cT2-3N0M0 MIBC (median age 69 years, female/male = 33/118, cT2/3 = 100/51) entered tetra-modality bladder-sparing protocol. After maximal TUR and CRT (40 Gy + cisplatin), response was evaluated via cytology, imaging, and tumor-site rebiopsy. Consolidative PC was performed in complete responders, while radical cystectomy was recommended for others. Extension of ipsilateral intrapelvic ureter in pretreatment computed tomography was graded following the Society for Fetal Urology grading system, then patients with grade 2-3 were classified as with hydronephrosis. Response rate to CRT, MIBC recurrence-free survival, and cancer-specific survival (CSS) were compared between patients with or without hydronephrosis. Results: Hydronephrosis was found in 19 patients (14%), and was associated with lower response rate to CRT (42% in hydronephrosis vs 77% in normal, p = 0.03). On an intent-to-treat basis, patients with hydronephrosis (n = 19) had lower 5-yr CSS than those without it (n = 132) (62% vs 85%, p < 0.01). Among the 106 patients who underwent PC as per protocol, patients with (n = 9) and without hydronephrosis (n = 97) had comparable 5-yr MIBC recurrence-free survival (100% vs 97%, p = 0.11) and CSS (100% vs 93%, p = 0.46). Conclusions: Patients with hydronephrosis should not necessarily be excluded from tetra-modality bladder sparing therapy.
Association between stromal/TGF-β/EMT gene expression signature and response to pembrolizumab monotherapy in cisplatin-ineligible patients with locally advanced (unresectable) or metastatic urothelial carcinoma.
Authors: Grivas Petros , Castellano Daniel E. , O'Donnell Peter H. , Cristescu Razvan , Frenkl Tara L. , Keefe Stephen Michael , Loboda Andrey , Souza Sandra C. , Ma Hua , Snyder Alex , Zhang Chunsheng , Albright Andrew , Lunceford Jared , Balar Arjun Vasant 
Published: March 2019

433 Background: PD-L1 immunohistochemistry and an 18-gene T cell–inflamed gene expression profile (GEP) are associated with response to anti–PD-1/PD-L1 therapy across tumor types, including urothelial carcinoma. A gene expression signature representing convergent biology related to stromal/EMT/TGF-β pathways was developed and prespecified for testing for association with pembrolizumab response in urothelial carcinoma patients treated on the KEYNOTE-052 trial (NCT02335424). Methods: KEYNOTE-052 was a single-arm phase 2 trial of pembrolizumab in cisplatin-ineligible patients with previously untreated, advanced urothelial carcinoma. Primary objective of this analysis was to assess the association between the Stromal/EMT/TGF-β signature and outcomes (best overall response [BOR], PFS, OS) as an independent biomarker and to understand its potential prognostic/predictive role beyond the T cell–inflamed GEP score or PD-L1 assessed using combined positive score (CPS). Cox regression models for PFS and OS and a logistic regression model for BOR evaluated associations between Stromal/EMT/TGF-β signature and outcomes adjusting for ECOG performance status (PS) and level of the GEP or CPS (1-sided P value). Results: RNA-Seq data from baseline tumor specimens were available for 187/370 patients on KEYNOTE-052. Lower Stromal/EMT/TGF-β score was associated with favorable BOR rate ( P < 0.001), PFS ( P < 0.001), and OS ( P = 0.002) after adjustment for ECOG PS and GEP (which remained significant at the 0.05 level in all cases). The patterns indicated a very consistent downward trend in the distribution of the Stromal/EMT/TGF-β score for responders versus nonresponders, regardless of GEP. In models that adjusted for both ECOG PS and PD-L1 CPS, the Stromal/EMT/TGF-β score remained significant (BOR rate, P = 0.002; PFS, P = 0.013; OS, P = 0.029). Conclusions: Higher Stromal/EMT/TGF-β signature was associated with resistance to pembrolizumab independently of GEP or PD-L1 in urothelial carcinoma patients on the KEYNOTE-052 trial. Clinical trial information: NCT02335424.
Impact of concurrent medications on outcomes with PD1/PD-L1 inhibitors for metastatic urothelial carcinoma.
Authors: Agarwal Archana , Pond Gregory Russell , Curran Catherine , Nassar Amin , Nuzzo Pier Vitale , Kumar Vivek , McGregor Bradley Alexander , Wei Xiao X. , Harshman Lauren Christine , Choueiri Toni K. , Kilbridge Kerry L. , Sonpavde Guru 
Published: March 2019

435 Background: The impact of concurrent medications (meds) on outcomes with PD1/PD-L1 inhibitors in metastatic urothelial carcinoma (mUC) is unclear. We investigated whether candidate concurrent meds (NSAIDS [N], metformin [M], antibiotics [A], statins [S] and corticosteroids [C]) have an association with outcomes in mUC patients (pts) receiving a PD1/PD-L1 inhibitor. We hypothesized that A and C compromise outcomes, while N, M and S improve outcomes. Methods: Data from mUC pts who received PD1/PD-L1 inhibitors at the Dana-Farber Cancer Institute (DFCI) was obtained. The concurrent medication was required to be administered within 1 month before starting to anytime during PD1/PD-L1 inhibitor therapy. A Cox regression analysis was done to study the association of variables with response and survival. Results: Data was available for 101 pts with mUC who received atezolizumab [n = 52], pembrolizumab [n = 39], nivolumab [n = 9] and durvalumab [n = 1]. Prior platinum had been administered in 74 pts (73.2%), 25 were chemonaive (24.8%) and prior therapy status was unknown in 2 pts (2%). The concurrent meds were N (n = 30), M (n = 7), A (n = 26), S (n = 33) and C (n = 12). The median survival was 57.9 weeks. Response was seen in 26 pts [25.7%]. A was associated with a lower probability of response (11.5%) than those not on A (30.7%), and worse survival (HR = 1.93, 95% CI 1.93 – 3.42, P = 0.024). Pts who received neither A nor C, one of them or both had a response rate (RR) of 30.6%, 20% and 0%, and median survival of 65.3, 53.1 and 14.9 weeks, respectively (HR = 3.02, 95% CI = 1.34-6.83, p = 0.027). Pts who did not receive N, M and S (n = 52) exhibited a median OS of 39.6 weeks, while those who received ≥1 of these meds (n = 49) exhibited a median survival of 160.3 weeks (p = NS). The study is limited by the retrospective design and modest sample size. Conclusions: In this hypothesis-generating study, concurrent antibiotics or corticosteroids compromised outcomes in mUC pts receiving a PD1/PD-L1 inhibitor and receiving both further compromised outcomes. The numerically higher survival with concurrent N, M or S did not attain statistical significance, but requires further study in larger datasets.
Correlation of myeloid-derived suppressor cells (MDSC) with pathologic complete response (pCR), recurrence free survival (RFS), and overall survival (OS) in patients with urothelial carcinoma (UC) undergoing cystectomy.
Authors: Fallah Jaleh , Diaz-Montero C. Marcela , Rayman Patricia A. , Wei Wei (Auston) , Sheng Iris Yeong- Fung , Finke James , Kim Jin Sub , Pavicic Paul G. , Dann Priscilla , Company Donna , Stephenson Andrew J. , Campbell Steven , Haber Georges-Pascal , Lee Byron H , Mian Omar Y. , Gilligan Timothy D. , Rini Brian I. , Garcia Jorge A. , Grivas Petros , Ornstein Moshe Chaim 
Published: March 2019

437 Background: MDSCs play an important role in maintaining a tumor immunosuppressive microenvironment. The association of circulating levels of MDSCs with pCR (pT0N0) and outcomes was investigated in patients (pts) with non-metastatic UC undergoing cystectomy. Methods: Peripheral blood samples from pts with non-metastatic UC was collected. MDSCs were measured in freshly purified peripheral blood mononuclear cells, using flow cytometry. Total (T) MDSC was defined as CD33+/HLADR-. T-MDSC subtypes were polymorphonuclear (PMN-MDSC: CD15+/CD14-), monocytic (M-MDSC: CD15-/CD14+], and uncommitted (UC-MDSC: CD15-/CD14-]. MDSC populations were presented as % of live nucleated blood cells. Wilcoxon rank sum test was used to compare MDSCs between pCR groups. Kaplan-Meier and log-rank test were used to analyze RFS and OS. Results: MDSC data were available for 124 pts (106 male, 18 female), median age 68, 28 (23%) never smokers, 93 (75%) pure UC. Thirty four pts (27%) received intravesical BCG; 49 (39%) received neoadjuvant chemotherapy (NAC); 22 (19%) had pCR (pT0N0) following surgery. PMN-MDSC was the dominant subtype (42%) and frequency of UC-MDSC and M-MDSC was 40% and 17%, respectively. Circulating levels of T-MDSC and PMN-MDSC were significantly lower in pCR patients than those in non-pCR patients (Table). Sixteen deaths were observed and 21 pts recurred after surgery. The median follow-up time of patients alive was 18.7 months (range 0.3-42.4). The median OS or RFS of all patients was not reached. One-year and two-year OS rates were 94% and 83%, respectively. One-year and two-year RFS rates were 82% and 69%, respectively. There was no association between MDSC subtypes with OS or RFS. Conclusions: Total- and PMN-MDSC subtypes in blood were significantly correlated with pCR in pts with non-metastatic UC who undergo cystectomy. The relatively short follow-up may impact the association with RFS and OS; additional follow-up is needed. [Table: see text]