bluuebunny/crossref_metadata_2025_split huggingface dataset:
Approaches to immune checkpoint inhibitor (ICI) maintenance therapy in metastatic urothelial cancer (mUC): A qualitative analysis of oncology providers in the United States.
Authors: Grivas Petros , Huber Caroline , Pawar Vivek , Roach Meaghan , May Suepattra Grace , Desai Isha , Chang Jane , Bharmal Murtuza 
Published: March 2021

407 Background: Avelumab first-line (1L) maintenance therapy for patients (pts) with advanced/mUC that has not progressed with platinum-containing chemotherapy was recently approved in the US based on improved overall survival seen in the JAVELIN Bladder 100 trial. However, provider perspectives regarding 1L maintenance therapy in mUC have not been reported. Methods: We performed a qualitative interview study with US oncologists and oncology nurses treating pts with mUC in academic and community practices. Telephone interviews were conducted in August 2020 using a semi-structured discussion guide to explore decision-making processes about treatment for pts with mUC and perspectives about ICI maintenance therapy in the 1L setting. The latter was defined as either 1) ICI for pts who achieve disease control with platinum-containing chemotherapy (Regimen A) or 2) ICI + chemotherapy followed by ICI (Regimen B). Thematic analysis identified key determinants and clinical considerations associated with ICI maintenance therapy in mUC. Results: Results for 18 oncologists (mean age 51.3 yrs [SD 9]; 11% female; 55% with >15 yrs in practice; 39% academic) and 18 oncology nurses (mean age 43.8 yrs [SD 11.1]; 94% female; 34% with >15 yrs in practice; 50% academic) are reported. Cisplatin- and carboplatin-based chemotherapy regimens were the most commonly administered 1L treatments, with ICI monotherapy reserved only for frail (i.e., comorbid and/or elderly) pts. All oncologists recommended 4-6 cycles of 1L chemotherapy. Providers reported different perspectives about the maintenance approaches. Those who expressed a preference for Regimen A (oncologists, 66.6%; nurses, 71.4%) cited potentially less toxicity as a key factor driving their choice. Providers who preferred Regimen B cited the perceived potential for deeper and more durable responses based on previous experience with this maintenance approach in other tumors as a driver of their choice. For Regimen A, providers universally did not recommend a treatment break between chemotherapy and ICI maintenance because of concerns about progression. Frequency of administration was not cited as a driver of treatment decisions for either maintenance approach; instead, providers prioritized survival and tolerability. Responses were generally consistent between oncologists and nurses. Conclusions: Overall, providers adhered to new guidelines for 1L treatment of mUC (NCCN and ESMO) and expressed receptivity toward Regimen A. Although few providers had experience with this new regimen, most preferred it vs ICI + chemotherapy followed by ICI in 1L mUC. Our findings highlight the need to increase provider awareness of Regimen A, i.e., avelumab maintenance in pts with response or stable disease with 1L chemotherapy as a standard of care in advanced/mUC, which has Level I evidence.
Safety and efficacy outcomes in immune checkpoint inhibitor (ICI)-treated metastatic urothelial carcinoma (mUC) patients (pts) requiring treatment interruption (TI) due to immune-related adverse events (irAEs).
Authors: Nizam Amanda , Sheng Iris Yeong- Fung , Allman Kimberly D. , Martin Allison , Gilligan Timothy D. , Gupta Shilpa , Ornstein Moshe Chaim 
Published: March 2021

411 Background: Most patients (pts) with metastatic urothelial carcinoma (mUC) will receive immune checkpoint inhibitors (ICI) at some point during treatment. As such, understanding of immune-mediated toxicity is integral to optimal patient management. We describe the clinical characteristics, treatment, and outcomes of ICI-treated mUC pts who experienced irAEs requiring treatment interruption (TI). Methods: ICI-treated mUC pts who developed > grade 2 (per CTCAEv5) irAEs leading to >2 week TI were retrospectively reviewed. Patient-, disease-, treatment-, and toxicity-related data were evaluated. Toxicity was graded per CTCAEv5. Time to treatment interruption (TTI), treatment-free interval (TFI), time to next treatment (TTNT), and duration of response (DoR) were assessed descriptively. Results: Of 200 ICI-treated mUC pts, 18 (9%) experienced irAEs necessitating TI. 12 (43%) were male; median age at diagnosis was 72.5 (range, 45-80); 15 (83%) had KPS > 80. 8 (44%) had pure UC histology, 14 (78%) had prior cystectomy or nephroureterectomy, and 11 (61%) received platinum-based chemotherapy in the perioperative setting. 4 (22%) received 1L platinum-based Tx for mUC. ICI therapy was distributed evenly between atezolizumab (50%, n = 9) and pembrolizumab (50%, n = 9). Median TTI was 6.5 months (mos) (range, 1-19). The most common irAEs were dermatitis (22%, n = 4), colitis (17%, n = 3), and transaminitis (17%, n = 3); the majority were grade 2 (72%, n = 13). No grade 4/5 events occurred. 14 pts (78%) were treated with methylprednisolone and/or prednisone. Median initial prednisone-equivalent steroid dose was 45 mg/day (range, 30-1,250) with a median steroid duration of 42 days (range, 4-198). ICI were held and later re-challenged in 10 pts (56%), permanently discontinued in 7 pts (39%), and transitioned to a subsequent Tx in 1 pt (5%). Of 10 pts re-challenged with ICI, 7 (70%) experienced an irAE upon re-challenge (4 with recurrent irAEs, 3 with new irAEs); ICI was permanently discontinued in 3 of these pts. For pts receiving subsequent Tx, median TFI was 1 month (range, 0-12) and median TTNT was 5 mos (range, 2-31). Median DoR among all pts with initial response to ICI therapy was 15.5 mos (range, 2-52). Of 7 pts who permanently discontinued ICI and received no further Tx, 6 (86%) demonstrated an ongoing sustained therapy response with median DoR of 22.5 mos (range, 12-52). Conclusions: In this cohort, ICI-treated mUC pts who developed irAEs requiring treatment interruption had a high rate of subsequent irAEs upon ICI re-challenge. Importantly, pts who discontinue ICI due to irAE can have durable responses off treatment, consistent with data from other cancers.
Trends over time in survival in patients with urothelial carcinoma in the real-world: A multicenter analysis.
Authors: Samnani Sunil , Veitch Zachary William Neil , Kaiser Jeenan , Stecca Carlos , Alqaisi Husam , North Scott A. , Sridhar Srikala S. , Alimohamed Nimira S. 
Published: March 2021

412 Background: Patients with muscle-invasive bladder cancer (MIBC) historically have poor long-term outcomes, with nearly 50% developing metastatic disease. Similarly, patients with metastatic urothelial carcinoma (mUC) have had median overall survivals of less than 2 years. Novel therapies have been implemented over time in attempts to improve outcomes. This study evaluates trends in survival over time in patients with MIBC and mUC treated in the real-world setting. Methods: Retrospective data was collected from two major cancer centres in Alberta and the Princess Margaret Cancer Centre in Ontario, Canada. Consecutive patients treated with platinum-based chemotherapy between 01/2005 and 01/2018 who had confirmed MIBC or mUC were evaluated. Patients were excluded if they had been treated as part of a clinical trial in the first-line setting. Patients were categorized based on year of diagnosis at presentation: time period 1 (T1) diagnosed between 01/2005 and 12/2011, and time period 2 (T2) diagnosed between 01/2012 and 12/2018. The co-primary endpoints were disease-free survival (DFS) for MIBC, progression-free survival (PFS) for mUC, and overall survival (OS) for both. Results: 572 patients were included, 196 (78% male; median age 63.8 years) had MIBC and 376 (76% male; median age 68.4 years) were treated for mUC. Amongst patients with MIBC, 33% (65) were treated in T1 and 67% (131) in T2. Median DFS and OS were significantly improved in T2 compared to T1 for patients with MIBC (Table). On multivariate analysis, earlier year of diagnosis and ECOG status ≥2 was independently associated with poor outcomes (p=0.016 and p=0.008, respectively). Amongst patients with mUC, 205 (55%) were treated in T1 and 171 (45%) in T2. Median PFS and OS did not significantly improve over time in patients with mUC from T1 to T2 (Table). Conclusions: In this real-world analysis, outcomes for patients with MIBC have significantly improved over time. This is likely attributed to standardization of perioperative chemotherapy protocols and improvements in surgical techniques. Similar improvements have not yet been demonstrated for patients with mUC during the two time periods. However, novel therapies (eg. immunotherapy) were only approved in 2017. Future analysis may explore the reasons for improvement in patients with MIBC and will evaluate outcomes in mUC patients treated from 2017 onwards. CI= confidence interval, HR= hazard ratio. [Table: see text]
Urethral recurrence following radical cystectomy: Risk factors and outcomes.
Authors: Khanna Abhinav , Zganjar Andrew , Shah Paras , Tollefson Matthew K. , Karnes R. Jeffrey , Sharma Vidit , Tarrell Robert F. , Thapa Prabin , Thompson R. Houston , Frank Igor , Boorjian Stephen A. 
Published: March 2021

416 Background: Urethral recurrence (UR) has been reported to occur in up to 5% of patients following radical cystectomy (RC). Debate continues regarding the utility of screening for UR after RC. Moreover, oncologic outcomes of patients with UR remain incompletely described, and reports have been limited by small cohort sizes. Herein, we evaluated risk factors for UR as well as cancer-specific survival (CSS) and overall survival (OS) among patients with UR. Methods: We reviewed our institutional RC registry to identify patients with UR following RC. Logistic regression was used to assess risk factors for UR. Kaplan-Meier and Cox proportional hazard regression were used to compare outcomes in those with UR diagnosis prompted by symptoms versus those with asymptomatic UR diagnosed on surveillance cytology. Results: Overall, 2930 patients underwent RC from 1980-2018, with a median post-operative follow-up of 4.9 years (IQR 1.6-11.0), of whom 144 (4.9%) were subsequently diagnosed with UR. Prostatic urethral involvement at RC (odds ratio [OR] 5.75 [3.67-9.01], p < 0.0001) and higher pT-stage (OR 3.57 [2.07-6.14], p < 0.0001) were associated with an increased risk of UR, whereas receipt of continent urinary diversion (OR 0.34 [0.20-0.58], p < 0.0001) was associated with a decreased risk of UR. A total of 72/144 (50%) patients were diagnosed with UR based on symptoms, and 104/144 (72.2%) patients with UR underwent subsequent urethrectomy. Patients with symptomatic recurrence had higher tumor stage on urethrectomy than those with asymptomatic recurrence (≥pT2 in 13.1% vs 3.1%, p = 0.007). At a median follow-up of 2.6 years (IQR 1.0-7.1) after UR, 68 of the patients with UR died of urothelial carcinoma. Kaplan-Meier analyses suggest longer median overall and cancer-specific survival for patients with UR detected by cytology than those presenting with symptoms (p = 0.05 for both). On multivariable analyses, patients who experienced UR had significantly increased risk of cancer-specific (hazard ratio [HR] 1.93 [95% confidence interval 1.50-2.50), p < 0.0001) and all-cause mortality (HR 1.34 [1.13-1.65], p = 0.001). Conclusions: Approximately 5% of patient undergoing RC experience UR, with higher pT-stage and prostatic urethral involvement increasing the risk of UR. Asymptomatic detection of UR was associated with lower pathologic stage at urethrectomy as well as longer cancer-specific and overall survival, supporting urethral surveillance after RC.
The effect of antibiotic use within 30 days of initiation of immune checkpoint inhibitor (ICI) efficacy in patients with metastatic urothelial carcinoma (mUC) in real-world setting.
Authors: Gupta Shilpa , Khan Mohammad Siddique , Radakovich Nathan , Wei Wei , Ornstein Moshe Chaim , Gilligan Timothy D. , Mian Omar Y. , Dawsey Scott 
Published: March 2021

417 Background: There is emerging evidence that patients (pts) treated with immune-checkpoint inhibitors (ICIs) may have a poorer response in the setting of antibiotic use (ABx), possibly due to negative impact on gut microbiota. Our group previously demonstrated that Abx use 60 days before or 60 days in mUC pts after initiation of ICI therapy did not have a significant impact on overall survival (OS) in real-world setting. We now studied the effect of Abx use within 30 days of initiation of ICI on OS in the same cohort of mUC patients. Methods: We performed a retrospective analysis of adult pts with mUC treated at the Cleveland Clinic between 2015 and 2020. Pts included in the study received at least 2 cycles of ICI therapy with either atezolizumab or pembrolizumab. Statistical analysis included study of OS in weeks using the Kaplan Meier method and rank log test, Fischer’s exact test, and Kruskal-Wallis test. Results: A total of 115 pts that received ICI therapy were included. 57 pts received atezolizumab and 58 pts received pembrolizumab. 38 pts (33%) received antibiotics and 77pts (67%) did not. The most commonly used Abx used were Cephalosporins (27%), Penicillins/Carbapenems (25%), Flouroquinolones (23%), and Bactrim (11%). 18 pts received Abx within 30 days before initiation of ICI, 13 pts received Abx within 30 days after initiation of ICI, and 7 pts received Abx before and after initiation of ICI. There was no statistical difference in OS in the group of pts that received Abx 30 days prior to initiation of ICI with median OS of 5.95 months (95% CI 3.22-13.67, p=0.0695) compared to 12.39 months (95% CI 10.09 – 18.6) in those who did not receive Abx. Similarly, there was no statistical difference in OS in the group of pts that received Abx 30 days after initiation of ICI with median OS of 5.09 months (95% CI 2.53-22.57, p=0.2339) compared to 12.02 months (95% CI 8.6`-17.02 Table). Conclusions: In our single institution study of mUC patients receiving ICI treatment, the use of Abx did not affect the OS. Although there was a trend for better OS seen in pts who did not receive Abx, it was not statistically significant (Table). Due to the limitations of a retrospective analysis and small sample size, further studies are warranted taking into account other factors that may affect gut microbiota in mUC pts. [Table: see text]
Alignment and discordances in perceptions and experiences of shared decision making (SDM) among bladder cancer (BC) patients and their care team.
Authors: Chamie Karim , Psutka Sarah P. , Patel Taral , Bupathi Manojkumar , Farris Breanne Y , Crawford Rebecca R , Carter Jeffrey D. , Sapir Tamar 
Published: March 2021

420 Background: To align BC treatment with patient goals, it is vital that healthcare providers (HCPs) engage their patients (pts) in SDM for treatment planning. We assessed alignment and discordances on aspects of SDM among BC pts and their urology and oncology teams. Methods: Between 05/2020 and 06/2020, surveys were administered to 53 pts with BC (48% female, mean age 68 years) and 23 HCPs, as part of in-clinic and virtual collaborative patient education sessions across 5 US-based practices. Surveys were designed to assess perceptions, preferences, and experiences with regard to SDM during BC care. Results: Survey findings indicated key alignments and discordances in pts’ reported experience and HCPs’ perceptions of the use of SDM in BC care. HCPs and pts identified the same top 2 patient goals for BC care: 1) preventing progression/recurrence (61% pts, 48% HCPs) and 2) maintaining quality of life (35% pts, 78% HCPs). When asked to identify patient’s top challenges for pts in BC care, both pts and HCPs indicated post-treatment aspects as the top challenge, though pts indicated managing side effects/serious worry about side effects from treatment as the top challenge (22%); whereas, HCPs were split evenly between managing side effects from treatment (26%) and managing life changes as a result of urinary diversion (26%). HCPs overestimated the effect that fatigue and worry had on pts capacity for SDM: only 9% of pts indicated worry or fatigue as a barrier to SDM, but 65% of HCPs indicated this as a likely barrier. Furthermore, the patient experience of SDM differed from HCP perception of SDM (Table); for some aspects of SDM, such as explaining different treatment options, explaining pros/cons of treatment options, and overall involvement in treatment decisions, fewer HCPs indicated that these aspects of SDM always or usually occurred as compared to pts. Conclusions: These findings reveal important alignments and discordances between pts and HCPs with regard to BC care and SDM, which may inform future bladder cancer and SDM initiatives. [Table: see text]
The association of malnutrition and sarcopenia with geriatric assessment impairment and outcomes in patients with bladder cancer undergoing cystectomy.
Authors: Gurjar Megan Seema , Osterman Chelsea K. , Nyrop Kirsten A. , Bjurlin Marc , Tan Hung-Jui , Nielsen Matthew E. , Wallen Eric M. , Milowsky Matthew I. , Muss Hyman B. , Smith Angela B. 
Published: March 2021

423 Background: Malnutrition and sarcopenia are linked to decreased functional status in older adults with malignancy, but their effect on geriatric assessment (GA) impairment in patients with bladder cancer (BC) undergoing radical cystectomy (RC) is unknown. We investigated the association between malnutrition and sarcopenia with GA impairment and postoperative outcomes. Methods: Patients with BC undergoing RC between 2012 – 2019 were enrolled in a prospective cohort study of GA before RC. Malnutrition was evaluated by a dietitian pre-RC per the Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition diagnostic criteria. Sarcopenia, defined by a skeletal muscle index of < 52.4 cm2/m2 in males and < 38.5 cm2/m2 in females, was determined using SliceOmatic software to analyze pre-RC CT images at the L3 vertebra. Patients with vs without malnutrition and those with vs without sarcopenia were compared using Fisher’s exact and Wilcoxon rank sum tests. Results: Of 73 patients, 59 had GA + nutrition evaluation and 51 had GA + sarcopenia assessment (overall median age 68 [IQR 62-74], 76% male). The prevalence of malnutrition was 7% and sarcopenia was 63%. A numerically greater proportion of patients with malnutrition or sarcopenia were impaired on ≥ 1 GA measure compared to those without malnutrition (100% vs 78%, p=0.57) or sarcopenia (78% vs 68%, p=0.52), although this was not statistically significant (Table). Median hospital length of stay (LOS) was increased for patients with vs without sarcopenia (4 vs 5 days, p=0.005). Post-RC complication rate was similar for patients with vs without malnutrition (100% vs 75%, p=0.56) and patients with vs without sarcopenia (81% vs 74%, p=0.73), but malnourished patients were more likely to have Clavien-Dindo grade 3+ complications than those without malnutrition (100% vs 27%, p = 0.009). Conclusions: In our cohort of patients with BC undergoing RC, those with malnutrition or sarcopenia may have an increased rate of impairment on GA compared to those without malnutrition or sarcopenia. Sarcopenia was associated with increased LOS while malnutrition was associated with increased major complications. Our results are limited by small sample size, and future work is needed to elucidate whether addressing these modifiable factors improves functional status and postoperative outcomes. Research Sponsor: U.S. National Institutes of Health[Table: see text]
Impact of angiotensin inhibitors on pathologic complete response with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC).
Authors: Thomas Jonathan , Pond Gregory Russell , Curran Catherine , Freeman Dory , Ravi Praful , Mossanen Matthew , Preston Mark A. , Steele Graeme S. , Mantia Charlene , McGregor Bradley Alexander , Jain Rakesh K. , Sonpavde Guru 
Published: March 2021

432 Background: The renin-angiotensin system (RAS) is involved in regulation of angiogenesis, cell proliferation, desmoplasia and immunosuppression. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) may have antitumor effects partly by inhibiting transforming growth factor (TGF)-β, a major resistance mechanism in bladder cancer. Methods: Patients (pts) with muscle invasive bladder cancer (MIBC) treated or not treated with ACEi/ARB while receiving preceding radical cystectomy (RC) were assessed for pathologic complete response (pCR) defined as pT0N0 and overall survival (OS). Pathologic features, performance status, clinical stage, type and number of cycles of NAC, and presence of grade ≥3 toxicities were collected retrospectively. The Kaplan-Meier method was used to estimate overall survival (OS). Logistic and Cox regression was used to explore factors potentially prognostic for pCR and OS respectively. Results: 187 patients received NAC followed by RC. The mean age at the time of NAC was 65. 71% were male and 29% were female. Of the 187 patients, 61% received Cisplatin/Gemcitabine and 28.3% received dose dense MVAC. Of patients receiving NAC, 53 (28%) had a pCR. The 5-year OS was 64%. There were 41 (21.9%) patients taking an ACEi and 24 (12.8%) patients taking an ARB at the start of NAC. Of the 41 patients who took an ACEi, 17 (41.5%) had a pCR; of the 146 patients who did not take an ACEi, 36 (24.7%) had a pCR. ACEi intake during NAC was the only factor associated with pCR on multivariable analysis (odds ratio of 2.17 [95% CI 1.05-4.48] p = 0.037). pCR was the only factor shown to be associated with significantly improved OS (Hazard Ratio 0.18 [95% CI 0.07-0.45] p = < 0.001). After adjusting for pCR, ACEi was not significantly prognostic of OS (HR = 1.12, 95% CI = 0.60 to 2.09, p = 0.72). ARB intake while receiving NAC was not associated with pCR or OS. Conclusions: ACEi intake was associated with significantly increased pCR in patients with MIBC receiving NAC, and pCR was the only significant factor associated with OS. We hypothesize that ACEi may augment the activity of NAC and increase pCR, which translates to improved OS. ACEi intake was not associated with improvement in OS potentially due to competing causes of mortality in patients requiring ACEi. Our data requires validation.