bluuebunny/crossref_metadata_2025 huggingface dataset:
A retrospective study of primitive neuroectodermal tumor (PNET) of the kidney in a tertiary cancer center in India.
Authors: Menon Nandini Sharrel , Kalra Devanshi , Prabhash Kumar , Noronha Vanita , Menon Santosh , Bakshi Ganesh , Prakash Gagan , Pal Mahendra , Laskar Siddhartha , Khanna Nehal Rishi , Agrawal Archi , Joshi Amit
Published: March 2021

361

Background: Primitive neuroectodermal tumours (PNET) of the kidney are rare tumours with aggressive behaviour. This study was conducted to review the diagnosis and management of patients with renal PNET at our centre. Methods: This was a retrospective study conducted at a tertiary cancer care centre in Mumbai, India. The demographic and clinical data of 17 patients treated by the uro-oncology services were retrieved from electronic medical records. Descriptive analysis was performed for baseline characteristics.Overall & progression-free survival was determined using the Kaplan Meier method. Cox regression was used for multivariate analysis. Results: There were 12 male and 5 female patients in this cohort with a median age of 27 years. At diagnosis 2 patients had metastatic disease and 15 patients had non-metastatic disease. Median follow up in this cohort was 22 months (range 2-30 months). Presenting complaints were hematuria, abdominal pain, flank pain, fever, bone pain, and incidentally detected renal mass. All patients were Mic -2 positive and 13 were FLI-1 positive on immunohistochemistry. Fourteen patients underwent radical nephrectomy. One (5.9%) patient received both neoadjuvant and adjuvant chemotherapy, 8 (47.1%) received adjuvant and 2 (11.8%) received palliative chemotherapy upfront. Eight patients received adjuvant radiation to the renal bed.There was disease progression in12 patients,10 of 15 patients with non metastatic disease at diagnosis eventually developed metastasis.The median progression free survival (PFS) was 10.55 months.The pathological feature that was associated with a shorter PFS was tumor size ⩾10 cm(p = 0.044).The median overall survival was 20.04 months (95% CI 9.49 -not reached). The presence of metastasis and treatment received significantly impacted overall survival (OS). Median OS in patients with non-metastatic disease was not reached versus 14.1 months in those with metastatic disease (p = .019).The median OS in patients treated with multimodality approach was 20.11 months. Patients did not undergo surgery had a median OS of 5.45 months (p < .001) and those who did not receive any chemotherapy had a median OS of 4.57 months (p = .024).Thus, patients who received multimodality treatment had better outcomes. Conclusions: PNET kidney is an aggressive tumor which should be treated with a multimodality approach. Tumor size ⩾10 cm was an adverse prognostic factor.
Androgen deprivation therapy and risk of SARS-CoV-2 infection in men with prostate cancer: A University of California (UC) Health System registry study.
Authors: Kwon Daniel , Vashisht Rohit , Borno Hala , Aggarwal Rahul Raj , Small Eric Jay , Butte Atul , Huang Franklin W.
Published: March 2021

37

Background: SARS-CoV-2 entry into host cells is facilitated by the transmembrane protease TMPRSS2. TMPRSS2 expression can be modulated by the androgen receptor. It is unclear whether androgen deprivation therapy (ADT) may partially protect from SARS-CoV-2 infection. Methods: A retrospective registry study of adult men with prostate cancer who underwent testing for SARS-CoV-2 in the UC Health System between February 1, 2020 and October 6, 2020 was performed. The University of California Health COVID Research Data Set (UC CORDS), which includes electronic health data of all patients who underwent testing for SARS-CoV-2 at 5 UC academic medical centers (UC Davis, UC Irvine, UC Los Angeles, UC San Diego, and UC San Francisco) and 12 affiliated hospitals across California, was used. Association of SARS-CoV-2 infection and receipt of ADT (GnRH agonist or antagonist) within 90 days of COVID testing was determined using the Chi-Squared test. Analyses (Chi-Squared or Fisher’s exact tests) were also performed in race/ethnicity subgroups. Results: Overall, 2,948 men with prostate cancer who underwent SARS-CoV-2 testing were identified, of whom 59 (2.0%) tested positive. Of the 2,948 men, 2,124 (72%) were White; 219 (7%) Black or African-American; 182 (6%) Asian or Native Hawaiian/Pacific-Islander; 176 (6%) Other race; and 247 (8%) Unknown race. There were 235 (8%) Hispanic or Latino men. Among the 444 men who received ADT in the entire cohort, 7 (1.6%) tested positive, and among the 2,504 men who did not receive ADT, 52 (2.1%) tested positive (OR 0.76, 95% CI 0.34-1.67, P = 0.49). No statistically significant association between ADT and SARS-CoV-2 positivity was found within race or ethnicity subgroups. Conclusions: No association between the use of ADT and the risk of testing positive for SARS-CoV-2 was identified in this study of a diverse patient population in the University of California Health System medical centers and hospitals. In this setting of an overall low prevalence of SARS-CoV-2 infection, thus far, there is no strong evidence of a protective benefit of ADT.
Paternity, relationship, sexual activity and fertility in testicular cancer (TC) survivors (TCS): Results from a single institution observational prospective study.
Authors: Bimbatti Davide , Pierantoni Francesco , Maruzzo Marco , Deppieri Filippo Maria , Msaki Aichi , Gatti Maura , Dionese Michele , Lai Eleonora , Marino Dario , Basso Umberto , Zagonel Vittorina
Published: March 2021

380

Background: TC represents 1% of male neoplasms but it is the most common in young adults. Interdisciplinary management with chemotherapy, radiotherapy and surgery has led to a 10-year relative survival rate of up to 95%. These treatments (Tx) have short- and long-term side effects. While sexual dysfunction can reduce fertility, psychosocial distress can create relationship problems and finally affect the ability to procreate. Methods: From February 2020, we submitted a series of questionnaires to all the patients (pts) currently followed-up at the Istituto Oncologico Veneto free from TC recurrence for at least 2 years from the last Tx. International Index of Erectile Function (IIEF-15) and Premature Ejaculation Diagnostic Tool (PEDT) were used. We also set up a questionnaire to investigate paternity and family status. Data about disease and treatments were collected from medical records. Results: 84 TCS completed the questionnaires, clinical data are reported in the table below. 29,8% of pts fathered children before diagnosis with a strong correlation with older age at diagnosis (45,4 vs 30,8 years, p<0,001). After Tx, 14 pts had children: 9 of which naturally, 2 out 6 were successful via assisted reproductive technology (ART) (including one patient that received high-dose chemotherapy and stem cell transplantation), 3 via adoption. 89,3% of pts had stable relationships. Of pts who did not have children: 13,1% claimed to be due to lack of a partner, 39,3% claimed to be unready, while 14,3% had tried unsuccessfully to conceive. While 28,6% pts claim to currently have fertility issues, only 8,3% of pts reported to have these issues before diagnosis. 70,2% of pts performed a spermiogram after Tx, 10 pts had spermatogenic impairment. Higher rate of sexual dysfunction after Tx was detected by questionnaires while only 4 pts claimed to have had a pre-existing issue prior to TC diagnosis. PEDT shows that 38,1% had premature ejaculation and that in 22,6% this issue is highly probable. IIEF confirms a high rate of erectile dysfunction (14,3% severe and 10,7% mild or moderate). No correlations were identified between sexual dysfuntion and previous Tx. Conclusions: Most TCS had not planned fatherhood while 16,7% had children after Tx and 14.3% tried unsuccessfully to conceive. ART and adoption is possible but challenging and little used. PEDT and IIEF found high rates of sexual dysfunction but no association with previous Tx were found. [Table: see text]
Validation of testicular germ cell tumor (GCT) staging in nationwide cancer registries.
Authors: Badia Rohit R , Wong Daniel , Ghandour Rashed , Chertack Nathan , Meng Xiaosong , Hutchinson Ryan C. , Margulis Vitaly , Lotan Yair , Madrigales Alejandra , Woldu Solomon L. , Bagrodia Aditya
Published: March 2021

383

Background: Nationwide cancer registries such as the National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results (SEER) rely on accurate data from institutional tumor registries to formulate hypotheses and report outcomes and treatment patterns for patients with cancer. We evaluated the accuracy of our institutional registry for testicular germ cell tumors (GCT) by comparing data abstracted by urologists with data abstracted by our tumor registry. Methods: We performed a retrospective review of patients receiving initial diagnosis and treatment for testicular cancer at our hospital system from 2005-2016. We reviewed registrar coding for American Joint Committee on Cancer clinical staging, overall composite stage grouping, and first-line treatment and compared it with urologist-reviewed staging at the time of diagnosis. Results: Paired staging from registry and urologist was available for 80 patients. T, N, M, and S-staging were accurate for 90%, 81%, 94%, and 54% of records, respectively. Composite staging and first-line treatment were concordant for 39% and 90% of patients, respectively. A separate review of 33 Stage IS patients per registry for composite staging revealed only 15% concordance. Conclusions: We identified significant inconsistencies with data abstracted by our institutional tumor registry for patients with testicular cancer, most notably with regards to S and composite stage. An educational intervention to improve abstraction by registry led to increased concordance. Assuming similar discrepancies may exist at other institutions and for other cancer types, caution should be used when interpreting NCDB and SEER cancer staging data. This sheds light on the need for improved clarification of staging guidelines, dynamic institutional internal auditing, and training reform within cancer registries.
Localized testicular germ cell tumor (TGCT) surveillance: A Delphi consensus study.
Authors: DA Silva Angélique , Flechon Aude , Culine Stephane , Coquan Elodie , Thiery Vuillemin Antoine , Planchamp François , Murez Thibaut , Mejean Arnaud , Pasquier David , Fizazi Karim , Joly Florence
Published: March 2021

384

Background: Stage I testicular germ cell tumor (TGCT) has excellent cure rates and surveillance is fully included in patient’s management, particularly during the first years of follow-up. Surveillance guidelines differ between the academic societies, with different recommendations concerning clinical and imaging frequency de-escalation and long term follow-up. We evaluated surveillance practice and schedules followed by French specialists and set up a DELPHI method to obtain a consensual surveillance program with an optimal schedule for patients with localized TGCT. Methods: An online survey on surveillance practice of stage I TGCT based on clinical-cases was conducted among urologists, radiotherapists and oncologists. Results were compared to AFU, ESMO and EAU guidelines. Then a panel of experts assessed surveillance proposals following a formal consensus method (DELPHI method). Statements were drafted after analysis of the previous survey and systematic literature review, with 2 successive rounds to reach a consensus. Results: Survey and DELPHI were conducted between July 2018 and May 2019. Sixty-one (12.2%) participated to the survey (69% oncologists, 15% urologists, 16% radiotherapists). For the first 5 years of follow-up we observed 30 to 50% of adherence to AFU’s guidelines, 20 to 36% of adherence to ESMO’s guidelines and 6 to 45% of practices not corresponding to any of the guidelines depending on clinical situations. Only 25% of practitioners stopped surveillance after the 5th year, as recommended. No physician followed the ESMO guidelines of de-escalation chest imaging. For the Delphi study, a panel of 32 experts (78% oncologists, 16% urologists, 6% radiotherapists) was asked about 38 statements. Consensus was reached for 26 statements concerning clinico-biological surveillance modalities and end of surveillance after the 5th year of follow-up. For seminoma, abdominal ultrasound was proposed as an option to the abdominopelvic (AP) scan for the 4th year of follow-up. No consensus was reached regarding de-escalation of chest imaging. Conclusions: The survey proved that French TGCT specialists do not follow current guidelines. With DELPHI method, a consensus was obtained for frequency of clinico-biological surveillance, discontinuation of surveillance after the 5th year and stop of AP scan on the 4th year of follow-up for seminoma. Questions remains concerning type and frequency of chest imaging.
Comprehensive genomic profiling (CGP) in patients with relapsed/refractory germ cell tumors (GCT).
Authors: Akel Reem , Anouti Bilal , Kern Sean , Cary Clint , Masterson Timothy A. , Jacob Joseph M , Bratslavsky Gennady , Danziger Natalie , Pavlick Dean , Hanna Nasser H. , Einhorn Lawrence H. , Ross Jeffrey S. , Adra Nabil
Published: March 2021

388

Background: Understanding the genetic alterations in patients with relapsed/refractory GCT (rrGCT) could delineate the pathogenesis of cisplatin resistance. Our study uses CGP to characterize genomic alterations (GA) in refractory GCT and correlate with clinical outcomes. Methods: 432 patients with rrGCT were seen at Indiana University between Jan 2016 to Sep 2019 of whom 52 patients underwent CGP using a hybrid-capture based commercial assay to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and reported as mutations/Mb and microsatellite instability (MSI) was determined on 114 loci. PDL1 expression was determined by IHC (DAKO 22C3 antibody). Results: All patients relapsed after first-line cisplatin-based combination chemotherapy. Median age at diagnosis was 33 (range 15-68). Primary site of GCT was testicular in 85% and mediastinum in 8%. 6 patients had pure seminoma and 46 had non-seminoma. Platinum refractory disease, defined as serologic or radiographic progression within 4 weeks of first-line chemotherapy comprised 23% of patients. The primary tumor was used for sequencing in 6 cases (12%) and non-primary tumor metastatic site (lymph node, lung, liver, brain, omentum) in 46 cases (88%). The most common GA in the entire cohort were FGF6 (27%), FGF23 (27%), KDM5A (27%), CCND2 (27%), KRAS (18%), TP53 (14%), KIT (8%), APC (8%), ZNF217 (6%), MUTYH (6%), AURKA (6%), NRAS (6%), EGFR (6%), CTNNB1 (6%), GNAS (6%). Most common alterations for testicular primary tumors were FGF6, FGF23, KDM5A, CCND2, KRAS, TP53, KIT. For non-testicular primary GCT, most common GA were APC, TP53, EGFR. Most common GA for non-seminoma were FGF6, FGF23, KDM5A, CCND2, KRAS, TP53, APC. Most common GA for pure seminoma was KIT. Potentially targetable genomic alterations were found in 17 patients (33%). 10 of 17 patients (59%) tested had PDL1 score ≥1% and 3 patients had PDL1 ≥50%. Median TMB was 3.5 mutations/MB. There were 4 patients (8%) with TMB ≥ 10 mutations/Mb and 2 patients (4%) with TMB ≥ 20 mutations/Mb. 1 of 48 patients (2%) evaluated for MSI had MSI-High status. Isochromosome 12p was detected in the majority of samples where it was tested. Outcomes with GA-directed therapy will be presented at the conference. Conclusions: CGP can reveal potential therapeutic targets in patients with rrGCT including EGFR, ERBB3, KIT, and MET. Consistent with reported clinical trials in rrGCT, biomarkers predicting response to immune checkpoint blockade are uncommon with most patients having low TMB, absence of MSI-H status, and low expression of PDL1.
A multicenter, retrospective study on impact of immunotherapy in urothelial carcinoma with bone metastases (Meet-Uro01 Study).
Authors: Giannatempo Patrizia , Marandino Laura , Raggi Daniele , Pierantoni Francesco , Maruzzo Marco , Lipari Helga , Banna Giuseppe Luigi , De Giorgi Ugo , Naglieri Emanuele , Buti Sebastiano , Stellato Marco , Vignani Francesca , Roviello Giandomenico , Veccia Antonello , Losanno Tania , Mucciarini Claudia , Pignata Sandro , Necchi Andrea , Di Maio Massimo
Published: March 2021

401

Background: Considerable numbers of patients (pts) with metastatic urothelial carcinoma (mUC) (approximately 25-47%) develop bone metastases (BoM). Their impact on the efficacy of immunotherapy (IO) is not yet sufficiently investigated. We developed a national collaboration on this issue, with the aim to assess the effect of BoM on survival outcomes of immunotherapy-treated pts in a large retrospective cohort. Methods: Data on pts diagnosed with mUC and treated between 07/14 and 08/20 with single-agent immunotherapy (IO) after failure of at least 1 previous line of chemotherapy (CT) for advanced disease, or (neo-)adjuvant CT within 12 months were retrospectively collected across 14 centers. PFS and OS were analyzed using the Kaplan-Meier method. Cox regression analysis was performed evaluating potential prognostic factors for OS and PFS. Each factor was evaluated in univariable (UV) and multivariable (MVA) analysis. Results: A total of 208 evaluable pts treated with single-agent immunotherapy (anti PD-1 n=42; anti PD-L1 n=166) were identified, including 122 without BoM (59% BoM-) and 86 (41%) BoM+. 13% of pts had progressed within 12 months after (neo-)adjuvant CT and 79% after a previous line of platinum-based CT for advanced disease (cisplatin 42.8%; carboplatin 36.5%). The presence of BoM negatively affected performance status (PS) of patients at baseline (ECOG PS 0/1/2 in 58% / 37% / 5% in BoM- vs 38% / 52% / 9% in BoM+; p=0.017). Other baseline characteristics were comparable. BoM+ showed shorter PFS (median 2.0 vs 2.6 months, HR 1.76 [95%CI, 1.31-2.37], p<0.001) and OS (median 3.9 vs 7.8 months, HR 1.59 [95%CI, 1.15-2.20], p=0.005) than BoM-. Probability of being alive was 62% vs 40% after 6 months, 38% vs 23% after 1 year and 24% vs 13% after 2 years, in BoM- and BoM+ respectively. Within each Bellmunt score, PFS and OS of BoM+ pts were shorter compared to BoM-. Both BoM and higher Bellmunt risk score were significantly associated with shorter PFS and OS in UV and MV analyses (Table). Conclusions: Patients with mUC treated with single-agent immunotherapy for BoM+ advanced disease have a dismal prognosis compared with BoM-. Further research is needed to understand the mechanism behind these clinical outcomes. [Table: see text]
Immune checkpoint inhibitors (ICI) in advanced upper tract and lower tract urothelial carcinoma (UC): A comparison of outcomes.
Authors: Esagian Stepan M. , Khaki Ali Raza , Carril-Ajuria Lucia , Park Joseph J. , Bilen Mehmet Asim , Stewart Tyler Francis , Santos Victor Sacristan , Jain Jayanshu , Morales-Barrera Rafael , Devitt Michael Edward , Hoimes Christopher J. , Shreck Evan , Tripathi Abhishek , Zakopoulou Roubini , Rodriguez-Vida Alejo , Drakaki Alexandra , Kumar Vivek , Msaouel Pavlos , Koshkin Vadim S , Grivas Petros
Published: March 2021

406

Background: Despite anatomical and biological differences, upper and lower tract UC (UTUC; LTUC) are usually managed similarly. Modern era clinical trial data comparing their outcomes with ICI are conflicting. We hypothesized that response and outcomes would be similar in patients (pts) with advanced UTUC and LTUC. Methods: We performed a retrospective cohort study collecting demographic, clinicopathologic, treatment, and outcome data for pts with advanced UC receiving ICI (2013-2020) across 24 centers (US; Europe). We compared objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) between pts with UTUC and LTUC. Uni- / multi- variable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Stratified subgroup analyses were performed according to histology (pure, mixed) and line of treatment (first-line, subsequent). Results: A total of 984 pts were identified, and 707, 717, and 738 were included in ORR, OS, and PFS analyses, respectively. After exclusions, the UTUC group comprised of 130 pts (vs. 616 in LTUC) with median age 71 (40-92) (vs. 70 [32-93]), 62% men (vs. 76%), 41% never smokers (vs. 29%), 62% with history of prior radical surgery for primary tumor (vs. 52%), and 29% with liver metastases (vs. 18%). Table shows results of ORR, OS, and PFS analyses. In the overall population, pts with UTUC and LTUC receiving ICI had comparable ORR, OS, and PFS. Pts with mixed-histology UTUC had significantly lower ORR (adjusted OR 0.20, 95%CI 0.05-0.91) and shorter PFS (adjusted HR 1.66, 95%CI: 1.06-2.59) vs. mixed-histology LTUC. Conclusions: Pts with advanced UTUC and LTUC receiving ICI have similar response and outcomes, except for pts with mixed-histology UTUC vs LTUC. Subset analysis of primary tumor location in ongoing clinical trials can validate our data, while biomarker work is ongoing. [Table: see text]
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.
Impact of subsequent therapy on survival in KEYNOTE-361: Pembrolizumab (pembro) plus chemotherapy (chemo) or pembro alone versus chemo as first-line therapy for advanced urothelial carcinoma (UC).
Authors: Alva Ajjai Shivaram , Csőszi Tibor , Ozguroglu Mustafa , Matsubara Nobuaki , Geczi Lajos , Cheng Susanna Y. , Fradet Yves , Oudard Stephane , Vulsteke Christof , Morales-Barrera Rafael , Flechon Aude , Gunduz Seyda , Loriot Yohann , Rodriguez-Vida Alejo , Mamtani Ronac , Yu Evan Y. , Nam Kijoeng , Imai Kentaro , Homet Moreno Blanca , Powles Thomas
Published: March 2021

439

Background: The phase III KEYNOTE-361 study examined the efficacy and safety of 1L pembro + chemo or pembro alone vs chemo for pts with advanced UC. The PFS and OS benefit of pembro + chemo vs chemo did not reach statistical significance; no further formal tesing was done. We present an exploratory analysis of OS by subsequent therapy in KEYNOTE-361 (NCT02853305) to assess how 1L and 2L therapy selection affected survival outcomes; no formal comparisons were conducted. Methods: OS was estimated for pts by whether they received subsequent therapy, and by whether subsequent therapy included an anti–PD-(L)1 agent. Results: 351 pts were randomized to pembro + chemo, 307 pts to pembro, and 352 pts to chemo. As of Apr 29, 2020, the median (range) time from randomization to data cutoff was 31.7 (22.0-42.3) mo. 124/351 pts (35%) in the pembro + chemo arm, 126/307 pts (41%) in the pembro arm, and 215/352 pts (61%) in the chemo arm received any subsequent therapy. Similar rates of subsequent therapy (pembro + chemo: 32%; pembro: 43%; chemo: 59%) were observed for pts who experienced progressive disease (PD) by blinded independent central review (BICR). A higher rate of pts (169/352 [48%]) in the chemo arm received subsequent anti–PD-(L)1 therapy than in either the pembro + chemo arm (23/351 [7%]) or pembro arm (14/307 [5%]). Due to the small pt numbers, pts in the pembro + chemo or pembro arms who received subsequent anti−PD-(L)1 were not considered further. This analysis included all pts who received 2L therapy (465/1010 pts [46%]); the rate of 2L therapy was similar in pts with PD by BICR (274/615 [45%]). Chemo agents alone or in combination, specifically carboplatin, cisplatin, docetaxel, doxorubicin, gemcitabine, and paclitaxel, were the most commonly received subsequent therapies for pts who did not receive anti–PD-(L)1 in 2L. Pts who received 1L chemo followed by subsequent anti–PD-(L)1 had longer mOS (19.1 mo [95% CI 16.2-22.2]) than pts with 1L pembro followed by 2L therapy not including an anti−PD-(L)1 agent (16.0 mo [95% CI 11.8-19.2]) (Table). Conclusions: In this exploratory analysis, favorable survival outcomes were observed for pts who received 1L chemo followed by anti–PD-(L)1 compared with pts who received 1L pembro followed by 2L therapy not including an anti–PD-(L)1 agent. These data underline the continued importance of immunotherapy as 2L therapy for advanced UC. Clinical trial information: NCT02853305 . Research Sponsor: Merck & Co., Inc[Table: see text]