bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival outcomes associated with different palliative systemic therapies (PSTs) in patients with metastatic bladder cancer (mBC).
Authors: Vafaei-Nodeh Saba , Beigi Arshia , Huang Longlong , Mimmack Gillian , Sun Shaun Zheng , Ko Jenny J. 
Published: February 2020

450 Background: Cisplatin-based (Cis) chemotherapy (C) is considered standard first-line regimen for treating mBC. In individuals medically unfit for Cis, carboplatin-based (Cb) regimens may be considered. Alternative PSTs include immunotherapy (I) as first or second-line treatments. The purpose of this study is to investigate current trends and clinical outcomes of PSTs in patients with mBC. Methods: A retrospective analysis was conducted on patients initially diagnosed with bladder cancer from Sep 2014 to Dec 2016 and had de novo or recurrent mBC. Kaplan-Meier method and Log-Rank test were used to compare survival outcomes among patients receiving different PSTs. Results: In 273 patients, 123 (45.1%) had de novo and 150 (54.9%) had recurrent disease. The median overall survivals (mOS) were 5.3 (95% CI: 3.7-8.2) and 6.5 months (95% CI 5.1-8.9), respectively (p=0.54). Patients received one of the following: C (23.1%), I (6.2%), C followed by I (C/I, 10.6%), and no treatment (NT, 60.1%). The mOS were 9.5 (95% CI: 7.1-12.5), 9.2 (95% CI: 6.1 - not estimable (NE)), 23.9 (95% CI: 16.30-NE), and 3.5 months (95% CI: 3.03-4.30), respectively. Each treatment group had a longer mOS than the NT group (p<0.01 in all three pairwise comparisons). Additionally, patients receiving C/I had a longer mOS than those receiving either C or I (p<0.001 and p=0.0497, respectively). The mOS were not statistically different between C vs I (p=0.2649). In patients receiving any C, 50.0% received Gemcitabine (G) plus Cis and 30.4% received G plus Cb. The mOS were 11.0 (95% CI: 8.7-19.7) and 14.4 months (95% CI:10.7-19.2), respectively, which were not significantly different (p=0.36). Conclusions: Despite the general preference for G plus Cis over Cb, this study showed that G plus Cb as a PST may be a comparable and efficacious treatment. While C currently remains the preferred initial line of PST, patients receiving I had similar survival outcomes to the C group despite many of the patients having Cis ineligibility. Real-world mOS of 2 years in patients who receive both C and I is unprecedented and indicates efficacy of PST. This study provides further evidence for immunotherapy as first or second-line regimen in treating mBC.
Proposal of a new subcategory of the pT3 classification: Effects of tumor location and subclassification of renal pelvic pT3 to predict the prognosis of pelvic carcinoma more accurately than the current TNM classification.
Authors: Sano Tomoyasu , Hattori Ryohei , Yamada Shin , Kamihira Osamu , Kobayashi Hiroaki , Tsuji Yoshikazu , Sassa Naoto , Gotoh Momokazu , Tsuzuki Toyonori 
Published: February 2020

455 Background: Whether pT3 urothelial carcinoma of the renal pelvis (UCRP) and urothelial carcinoma of the ureter (UCU) show the same prognosis or not remains controversial.This study aims to reveal whether the prognosis of pT3 UCRP shows similar to those of pT3 UCU. Methods: We retrospectively evaluated 954 patients who underwent nephroureterectomy between 1983 and 2017 at our institutions.None of the patients received neoadjuvant therapy.All HE slides for each patient were reviewed by a single genitourinary pathologist (TT).pT3 UCRP was subdivided pT3a (urothelial carcinomas that extend only to the renal medulla) and pT3b (urothelial carcinomas that extend to the renal cortex and/or peripelvic adipose tissue) according to the criteria previously we proposed.Fine and Gray model was developed to predict the reccurence-free survival (RFS) and cancer-specific survival (CSS). Results: Overall, 954 patients were eligible for this study, 493 of whom were pT3 with only renal pelvis and 461 of whom were pT3 with only ureter. A total of 202 cases were pT3 UCRP and 146 were pT3 UCU. The pT3 subclassification of UCRP resulted in 79 pT3a and 120 pT3b cases.No significant difference was found in the 5-yr RFS and 5-yr CSS between pT3a UCRP and pT2 UCRP and pT2 UCU. (RFS; pT3a UCRP vs pT2 UCRP: HR = 1.19 p = 0.74; pT3a UCRP vs pT2 UCU HR = 0.88, p = 0.72, CSS;pT3a UCRP vs. pT2 UCRP: HR = 0.69; p = 0.56; pT3a UCRP vs. pT2 UCU: HR = 0.66, p = 0.31) The RFS rate was significantly higher in the pT3a UCRP than that of pT3b, (pT3a vs pT3b: HR = 2.59, p = 0.0038) and so was the CSS rate. (pT3a vs. pT3b: HR = 3.1 p = 0.001) In fine and gray model analysis for RFS, pT stage, lymph node metastasis, WHO/ISUP grade, lymphovascular invasion were independently associated with tumor recurrence, whereas pT stage, lymph node metastasis, operation method, histologic type, lymphovascular invasion, gross type, adjuvant chemotherapy were independently associated with cancer mortality. Conclusions: Subclassifying pT3 UCRP into pT3a and pT3b was useful in determining the prognosis of different patients.The pT3b UCRP showed similar outcome compared to those of UCU.
Micropapillary urothelial carcinoma (mpUC): A comparative analysis of oncologic outcomes compared to conventional urothelial carcinoma (CUC).
Authors: Diamantopoulos Leonidas Nikolaos , Khaki Ali Raza , Gadzinski Adam John , Winters Brian , Vakar-Lopez Funda , Tretiakova Maria S. , Gore John L. , Schade George R. , Psutka Sarah P. , Hsieh Andrew Caleb , Lee John Kyung , Yezefski Todd , Schweizer Michael Thomas , Cheng Heather H. , Yu Evan Y. , Lin Daniel W. , Montgomery Robert B. , Grivas Petros , Wright Jonathan L. 
Published: February 2020

459 Background: MpUC is a rare variant associated with adverse outcomes. We describe our institutional experience and compare clinicopathologic features and survival between patients with mpUC and CUC. Methods: Patients with mpUC or CUC at radical cystectomy (RC) or transurethral resection of bladder tumor were identified from a retrospective institutional RC database. Clinicopathologic/treatment data were extracted and compared using T-test and χ2 test. Recurrence free survival (RFS) and overall survival (OS) from RC to first recurrence or death were estimated using the KM method. Factors identified as significant in univariable (UVA) Cox regression analysis for OS were included in multivariable analysis (MVA). Results: 64 consecutive patients with mpUC and 457 with CUC were identified (2003 - 2018); 36 (56%) and 188 (41%) received neoadjuvant chemotherapy (NAC). MpUC had higher incidence of pT3/4 (41% vs. 28%) or pN+ disease (39% vs. 17%), carcinoma in-situ (52% vs. 24%) and lymphovascular invasion (LVI, 39% vs. 16%) at RC, compared to CUC (all p < 0.05). Rates of ypT0N0 after NAC were comparable between groups (25% vs. 35%, p = 0.26). Median follow-up was 62 months (95% CI 55.4 – 68.3). 5-year RFS was 24% (mpUC) vs. 58% (CUC), p = 0.001. 5-year OS was 40% (mpUC) vs. 69% (CUC), p = 0.001. MpUC histology was not independently associated with OS after adjusting for pT stage, node ratio (# nodes +/ # nodes removed) and ECOG status (Table). Conclusions: Patients with mpUC presented with advanced stage at RC, while they showed inferior RFS and OS, when compared to CUC. However, rates of pathologic response to NAC were comparable to CUC and mpUC was not associated with OS in MVA. Further studies are needed to define the optimal management of this variant. [Table: see text]
Outcomes of urothelial carcinoma patients with central nervous system metastases.
Authors: Andrews Erik , Curran Catherine , Grivas Petros , Diamantopoulos Leonidas Nikolaos , Kanesvaran Ravindran , Wang Jue , Jain Rohit K. , Tandon Ankita , Drakaki Alexandra , Sonpavde Guru 
Published: February 2020

468 Background: Urothelial carcinoma (UC) metastatic to the central nervous system (CNS) is extremely rare. Given the lack of systematic data regarding outcomes in UC metastatic to the CNS, we conducted a retrospective multicenter study to more broadly characterize outcomes. Methods: Patients (pts) diagnosed with metastatic UC to the CNS were identified from collaborating institutions. Data were collected for demographics, clinical and pathological variables. Descriptive statistics were reported to examine tumor regression, time to treatment discontinuation or failure (TTF), and overall survival (OS). Results: 39 pts with UC metastatic to the CNS were evaluable from 6 institutions. The ECOG-PS ranged from 0-4 (median 2), the median age was 67 (range 39-82), and 8 (20.5%) were female. The histology consisted of pure urothelial, mixed predominant urothelial, and mixed predominant non-urothelial in 26 (66.7%), 8 (20.5%), and 5 (12.8%) pts, respectively. The sites of CNS metastases (mets) were the brain, meninges, and a combination of CNS sites in 37 (95%), 1 (2.5%) and 1 (2.5%) pts, respectively. 33 (84.6%) pts received radiation therapy (RT) to their mets and 6 (15.4%) did not. Of 16 pts who received systemic therapy (ST), cisplatin-based chemotherapy, non-cisplatin based chemotherapy, and PD-1/L1 inhibitors were administered in 6 (37.5%), 5 (31.25%), and 5 (31.25%) pts, respectively. The overall median TTF and OS were 90 and 154 days (d). The median OS for pts who had ST compared to those who did not was 193.5 (n=12) versus 71 (n=17) d. The median OS for pts who had RT compared to those who did not was 92 (n=25) versus 15.5 (n=4) d. The median OS for pts who received neither ST nor RT, compared to pts receiving both, was 12 (range 7-19) versus 232 (n=11) d. Best response to systemic therapy PR, CR, SD and PD were seen in 2 (12.5%), 1 (6.25%), 1 (6.25%) and 12 (75%) pts, respectively. For the 5 pts who received RT only, best response PR and PD were seen in 2 (40%) and 3 (60%) pts, respectively. Conclusions: Pts with UC metastatic to the CNS present with a poor performance status and have outcomes that are dismal and appear worse than those with metastases to other organs. A combination of systemic and radiation therapy might achieve improved outcomes in selected pts.
Efficacy of neoadjuvant chemotherapy followed by resection in primary and secondary muscle-invasive bladder cancer (MIBC).
Authors: An Josiah , Sanchez Kevin , Mott Sarah L. , Garje Rohan 
Published: February 2020

497 Background: Neoadjuvant chemotherapy followed by cystectomy in MIBC is associated with improved survival compared to cystectomy alone. Recent retrospective studies indicated that secondary MIBC (non-MIBC progressed to MIBC) had worse outcome with cisplatin based neoadjuvant chemotherapy when compared to primary MIBC. To further evaluate this observation, we queried our database to assess the differential response and determine if prior use of intravesical therapy diminishes the effect of cisplatin based neoadjuvant chemotherapy. Methods: A total of 387 patients diagnosed with T2-4 or N0-3 and M0 from 2000-2018 and underwent cystectomy were retrospectively chart reviewed for demographics, treatment and outcomes at University of Iowa Holden Comprehensive Cancer Center. Cox regression models were utilized to assess differences in recurrence-free survival (RFS) and overall survival (OS). Time was calculated from cystectomy to recurrence or death due to any cause for RFS and OS, respectively. Results: Of the 387 patients, 324 patients had primary MIBC and 63 had secondary MIBC. Median follow up was 25.8 months. Intravesical therapy was administered to 98% (62/63) of secondary MIBC patients. Neoadjuvant chemotherapy was administered to 38% (122/324) of primary MIBC patients and 21% (13/63) of secondary MIBC patients. NAC had no difference in response rates (CR and PR) for primary vs secondary MIBC (p=0.73). Additionally, there was no difference between the primary and secondary MIBC with regards to RFS (p=0.54) and OS (p=0.12) on univariate analysis. The effect of neoadjuvant chemotherapy did not differ based on prior use of intravesical therapy in terms of RFS (p=0.61) or OS (p=0.40). Additionally, neoadjuvant chemotherapy irrespective of prior use of intravesical therapy was not associated with RFS (p=0.66) or OS (p=0.15). Conclusions: Prior intravesical therapy was not associated with differential efficacy of neoadjuvant chemotherapy in secondary MIBC when compared to primary MIBC.
Association of an immune gene signature with pathologic response and outcome after neoadjuvant pembrolizumab (pembro), compared to neoadjuvant chemotherapy (NAC), in muscle-invasive bladder cancer (MIBC).
Authors: Necchi Andrea , Raggi Daniele , Briganti Alberto , Farè Elena , Giannatempo Patrizia , Marandino Laura , Bianchi Marco , Gallina Andrea , Salonia Andrea , Gandaglia Giorgio , Fossati Nicola , Capitanio Umberto , Montorsi Francesco , Boormans Joost L. , Liu Yang , de Jong Joep , Black Peter C. , Dittamore Ryan , Davicioni Elai , Gibb Ewan 
Published: February 2020

533 Background: In the PURE01 study (NCT02736266), neoadjuvant pembro resulted in 42% pathologic complete responses (pT0) in patients (pts) with MIBC. In this study, we investigated immune transcriptome signatures and molecular subtyping as potential predictors of pembro efficacy. Methods: Pts enrolled in the PURE01, which is still recruiting pts in its amended design, had predominant urothelial carcinoma histology and stage cT≤4N0 MIBC. Biomarker analyses included transcriptome profiling for 78 pts. A cisplatin-based NAC cohort of 140 cT≤4N0 MIBC pts was used for comparison. The association of Immune190, immune hallmark RNA signatures and molecular subtypes (TCGA, Consensus classifier, Genomic subtyping classifier [GSC]) was evaluated with respect to pT0 and recurrence-free survival (RFS). Multivariable logistic regression analyses (MVA) were used adjusting for the clinical T-stage and gender. Results: The Immune190 signature was significant for pT0 on MVA (OR: 1.54, 95%CI: 1.1-2.3, p=0.02) in the PURE01 cohort, but not in NAC cohort (OR: 0.96, 95%CI: 0.8-1.2, p=0.73). The hallmarks for IFN-γ (OR: 1.10, 95%CI: 1-1.2, p=0.007) and IFN-α response (OR: 1.07, 95%CI: 1-1.1, p=0.009) were also associated with pT0 for PURE01, but not for NAC (IFN-γ: OR: 0.99, 95%CI: 0.9-1.1, p=0.846 and INF-α: OR: 0.99, 95%CI: 0.95-1.04, p=0.806). In PURE-01, patients with Immune190 scores >0.35 had 100% 2-y RFS vs 80% of those with ≤0.35; no difference was observed in NAC pts, as well as for the other hallmarks in both groups. The neuroendocrine (NE)-like subtype had the worst 2-y RFS in all three subtyping models (33%, p<0.01) whereas the GSC Claudin-low subtype had the best outcome with no recurrences within 24 months. The other subtypes had RFS ranging from 75-86% in TCGA, 53-89% in Consensus, and 74-92% in the GSC. Conclusions: We found RNA Immune190 signature was reliably associated with response and outcome after neoadjuvant pembro. Molecular subtyping revealed special subtypes with outlier outcomes. These data suggest RNA profiling may provide a potential tool for personalizing the neoadjuvant therapy approach. Clinical trial information: NCT02736266.
BCG shortage: Reassessing the clinical viability of Bacillus Calmette-Guerin (BCG) after reconstitution.
Authors: Brooks Nathan , Nagaraju Supriya , Matulay Justin T. , Han Xiang-Yang , Kamat Ashish M. 
Published: February 2020

534 Background: To address the current worldwide shortage of BCG, the AUA and SUO recommend reducing the dose to 1/3rd vial and enabling 3 patients to be treated in one setting. The manufacturer states that BCG must be used immediately after reconstitution, despite literature in the bacteriological world suggesting that M. Bovis might be viable for longer than a few hours. Herein we sought to study the viability of BCG after re-constitution at time points relevant to clinical practice. Methods: TICE BCG from separate lots was reconstituted per the manufacturer’s guidance and stored at 4 °C without light exposure. At predetermined time points, BCG was inoculated on Selective Middlebrook 7H11 agar in triplicate and incubated at 37°C with 5% CO2. M. smegmatis served as a positive control and un-inoculated media was incubated for 2 weeks as a negative control. CFUs were assessed between 3 and 4 weeks from plating. Acid-fast staining confirmed the presence of BCG. Data was analyzed as the mean of replicated experiments and compared to the reference (Time 0) using Student’s T-tests. Results: No significant difference in CFUs was observed for BCG between 0 and 8 hours after reconstitution (Table). Colony forming units significantly declined starting 24 hours after reconstitution, though the magnitude of this difference was less than 10 fold (which falls within the range of CFUs listed for the vial by manufacturer). Viability remained constant for both lots analyzed. Conclusions: Given the recurrent shortages of BCG, split dosing may become a clinical necessity. This often presents logistic quandaries since the manufacturer recommends each vial must be used within 2 hours. We have shown that the viability of TICE BCG is unaltered at least 8 hours after reconstitution and only begins to decline at 24 hours after reconstitution. This should allow pharmacists and physicians administering BCG more leeway in scheduling patients for split dose therapy. [Table: see text]
Development of a composite biomarker-based calculator to predict the probability of pathologic complete response (pT0) after neoadjuvant pembrolizumab (pembro) in muscle invasive bladder cancer (MIBC).
Authors: Necchi Andrea , Meeks Joshua J. , Bandini Marco , Fall Leigh Ann , Raggi Daniele , Briganti Alberto , Farè Elena , Giannatempo Patrizia , McLaughlin Kimberly A. , Das Arighno , Marandino Laura , Gallina Andrea , Salonia Andrea , Gandaglia Giorgio , Fossati Nicola , Ross Jeffrey S. , Montorsi Francesco , Dittamore Ryan , Davicioni Elai , Gibb Ewan 
Published: February 2020

539 Background: The PURE01 study (NCT02736266) evaluates the use of pembro before radical cystectomy (RC) in MIBC. We assessed selected individual and combined biomarkers for predicting pT0 response after pembro, and developed a tool that may be used as an aid for clinical decision-making. Methods: Patients (pts) enrolled in the PURE01 were clinical (c) stage T≤4aN0M0 MIBC. Analysis to date included a comprehensive genomic profiling (FoundationONE assay), programmed cell-death-ligand-1 (PD-L1) combined positive score assessment (CPS, Dako 22C3 antibody) and whole transcriptome (Decipher assay) and RNA-seq profiling of pre/post therapy samples. Multivariable logistic regression analyses (MVA) evaluated baseline cT-stage and biomarkers in association with pT0 response. Corresponding coefficients were used to develop a risk calculator based on the tumor mutational burden (TMB), CPS, Immune190 signature score, and cT-stage. Decision-curve analysis was performed. Results: Complete biomarker data was available for 84 pts. Increasing TMB, CPS, and Immune190 scores showed a linear positive correlation with the pT0 probability in logistic regression (p=0.02, p=0.004, p=0.02). The c-index of the risk calculator was 0.79. Decision-curve analysis found the net-benefit of the model was higher than the “treat-all” option within the clinically-meaningful threshold probabilities of achieving a pT0 of 40-60%. Within this range, adding the Immune190 score improved the model over TMB and CPS. A significant decrease in median TMB values was observed (p=0.005) in 24 matched RC, versus a non-significant change in median CPS in 38 matched RC. Molecular subtyping switching was observed in 20/31 matched cases (64.5%), most frequently to the luminal-infiltrated subtype (80%). Conclusions: The study presents the first composite biomarker-based pT0 probability calculator for optimal pt selection. Pending validation, the model may be used to recommend neoadjuvant pembro to very selected MIBC pts. The observed changes in biomarker features in post-therapy samples may have an impact on future adjuvant strategies. Clinical trial information: NCT02736266.
Veterans affairs (VA) prostate cancer treatment (Tx) sequencing (VAPCaTS): A real-world study.
Authors: Freedland Stephen J. , De Hoedt Amanda M. , DerSarkissian Maral , Chang Rose , Satija Ambika , Nguyen Catherine , Park Suna , Aillaud Aurore , Drea Edward Joseph , Duh Mei S. , Polascik Thomas J. , Szatrowski Ted P. 
Published: February 2020

54 Background: Limited real-world data are available on tx sequence for patients (pts) with metastatic hormone-sensitive PC (mHSPC) treated with androgen deprivation therapy (ADT) plus docetaxel (D) or abiraterone (A) who progress to metastatic castrate-resistant prostate cancer (mCRPC). Methods: VA electronic medical records were used to retrospectively analyze 240 men treated for mHSPC with ADT and D (n=208; selected to be overrepresented) from 07/2014-08/2018 or ADT and A (n=32) from 12/2016-09/2018 and receiving at least one tx after progressing to mCRPC. Results: For D and A cohorts respectively, median age at mHSPC diagnosis was 65.2 and 70.8 yrs; 62% and 77% were white; 98% and 100% had bone metastases (mets), 40% and 34% had lymph node mets, 21% and 16% had lung mets, and 20% and 6% had liver mets; median follow-up after ADT start was 2.2 and 1.4 yrs. Pts in D and A cohorts had 56% and 36% low, 33% and 45% intermediate, and 11% and 19% high Halabi risk scores at mCRPC, respectively. Among all pts, max mCRPC tx lines was 6; 106 (44%) had only one line, 71 (30%) had two lines, and 63 (26%) pts had ≥ three lines. Across all mCRPC tx lines, 71 (30%) received a taxane at some point (47 D, 40 cabazitaxel [C]). Txs for first and second line mCRPC are shown in the Table. For D pts who received androgen-receptor targeted agents (ARTA) as first mCRPC tx and received any second mCRPC tx, 70 (62%) were treated with back-to-back ARTA. For A pts, 25 (78%) received back-to-back ARTA as first mCRPC tx. Conclusions: Most pts received ARTA as first mCRPC tx, and a large proportion of pts were treated with back-to-back ARTA. Longer follow-up is needed to assess which sequences are associated with optimal outcomes.[Table: see text]
Prognostic value of hypoxia gene expression in bladder cancer patients.
Authors: Chang Hyun , Lee Seung-Hyun , Koo Taeryool , Kim Moon Ho , Sung Soo-Yoon 
Published: February 2020

548 Background: The prognostic value of hypoxia in bladder cancer remains unknown. We aimed to evaluate the potential role of hypoxia gene signature as prognostic factors in bladder cancer patients. Methods: We investigated the hypoxia gene signature and clinicopathologic features of The Cancer Genome Atlas (TCGA) bladder urothelial carcinoma (n = 408) using the Kaplan-Meier survival curves and multivariate Cox regression analyses. The clinicopathologic data and the processed data of hypoxia gene signature were obtained from TCGA Bladder urothelial carcinoma database. Results: Hypoxia gene signature score was significantly associated with overall survival (OS) and progression-free survival (PFS). Higher score resulted in shorter OS and PFS in Kaplan-Meier survival curves with Log-rank test ( P < 0.01 and P <0.05, respectively). In multivariate analysis containing clinical prognostic variables, higher hypoxia gene signature score predicted poor OS (adjusted HR= 1.58, 95% CI 1.15 - 2.19; P <0.01). Conclusions: Hypoxia gene signature was an independent prognostic factor in bladder cancer. Prospective studies are needed to evaluate the prognostic role of hypoxia in bladder cancer patients.