Metastatic Urothelial Bladder Cancer Research Articles

Efficacy of cytoreductive radical cystectomy in metastatic urothelial bladder cancer based on site and number of metastases

BackgroundRecent studies have highlighted the overall survival (OS) benefit of cytoreductive radical cystectomy (CRC) in metastatic bladder cancer (mBCa). Cytoreductive surgery has been established in other urologic cancers. However, the efficacy of CRC and optimal criteria for patient selection in mBCa is unclear. This study investigated the oncologic efficacy of CRC, particularly emphasizing the location and number of metastasis sites as a predictor of survival and treatment response. MethodsA retrospective analysis of cT2-4N0-3M1 mBCa patients treated with multiagent chemotherapy between 2004 and 2019 was conducted using the National Cancer Database. Patients were classified by additional treatment with CRC or conservative local treatment (CLT), consisting of transurethral resection of bladder tumor, radiation, or no local treatment and propensity score (PS) matched. Kaplan-Meier analysis and multivariate Cox Proportional Hazards model assessed the effect of CRC or CLT on OS within the matched cohort and in four subgroups (1) patients with only distant lymph node (LN) metastasis vs. any organ metastasis, (2) patients with single metastasis vs. multiple metastases. Sensitivity analysis estimated the influence of unmeasured confounders on CRC OS benefit. ResultsPropensity matching yielded 247 and 251 patients treated with CRC and CLT, respectively. Median OS in patients who received CRC was greater than that of patients treated with CLT (20.4 months vs. 12.0 months, P < 0.001). CRC was associated with reduced mortality risk in patients with only distant LN metastases (HR = 0.545, P = 0.039), any organ metastasis (HR = 0.421, P < 0.001), and single visceral metastasis (HR = 0.483, P = 0.002). However, CRC did not significantly improve OS in patients with multiple metastases (HR = 0.501, P = 0.064). ConclusionThese findings demonstrate an OS benefit of CRC with multiagent chemotherapy and pinpoint multiple visceral metastases as a potential contraindication for CRC. Although limited by the influence of unmeasured confounders, these findings may inform future prospective investigations into CRC.

Enfortumab vedotin as a salvage option as 5th line therapy for metastatic urothelial bladder cancer

Abstract A 67-year-old female patient with a muscle-invasive, non-metastatic urothelial bladder cancer (UC) (pT2 G3 cN0 cM0) developed metachronous metastases within 6 months after radical cystectomy with ileal conduit urinary diversion. After a good primary response to platinum-based chemotherapy, treatment was switched to the immune checkpoint inhibitor (ICI) pembrolizumab due to progressive disease. Subsequently the patient underwent selective internal radiotherapy (SIRT) of the liver and received vinflunine as well as a re-challenge with pembrolizumab. Two years after the initial diagnosis, rapid disease progression ultimately led to a switch to 5th line therapy with enfortumab vedotin (EV), which had only been approved in the United States at that time. The antibody-drug conjugate was well tolerated by the patient after dose reduction to 1.0 mg/ kg body weight. Simultaneous irradiation of newly occurring precardiac, hepatic and cerebral metastases were necessary. After 10 months of therapy with EV, tumour regression was observed accompanied with good symptom control. The presented case illustrates the efficacy and tolerability of EV in a heavily pre-treated patient with metastatic UC (mUC).

Treatment patterns, survival, and healthcare utilisation and costs in patients with locally advanced and metastatic bladder cancer in Denmark 2015–2020

Background Treatment patterns in locally advanced and metastatic urothelial bladder cancer (La/mUBC) is changing, but little is known about current treatment patterns, survival, and costs of these patients. Our aim was to describe treatment patterns, survival, and healthcare utilisation/costs in Danish La/mUBC patients in a routine clinical care setting. Methods Registry-based nationwide cohort study including all bladder cancer patients aged 18 years or older with a La/mUBC tumour in the pathology register and a concomitant bladder cancer diagnosis in the Danish National Patient Registry in the period 2015–2020. We categorised the patients according to (1) La/mUBC at time of first bladder cancer diagnosis (de novo La/mUBC) and (2) non-invasive or localised muscle-invasive bladder cancer at time of diagnosis which had progressed to La/mUBC. All patients were included at date of pathology-confirmed La/mUBC. Follow-up ended 30 September 2022. Results We identified 1278 patients (69% men) with La/mUBC and no other previous cancer. Of these, 212 (17%) had de novo La/mUBC, while 1066 (83%) had progressed to La/mUBC. Median age was 72 years. Patients were followed for a median of 13.0 months (interquartile range 4.7;32.0). During follow-up, 651 (51%) patients started first-line treatment, of these, 285 progressed to second-line treatment, and 112 also started third-line treatment. Median survival was 13.0 months from La/mUBC diagnosis, 12.1 months from start of first-line treatment, 9.8 months from start of second-line treatment, and 8.6 months from start of third-line treatment. The mean number of days admitted to hospital was 3.47, 3.97, and 4.07 per month following initiation of first-line, second-line, and third-line treatment, respectively. Conclusion Patients with La/mUBC have a poor prognosis, and in routine clinical care only around half of the patients received systemic anti-cancer treatment suggesting an unmet need for novel treatments. The overall costs only increased slightly from first to third-line treatment.

Erdafitinib in the Treatment of Metastatic Urothelial Carcinoma.

A Hispanic man, aged 42 years, was diagnosed with stage IV metastatic urothelial bladder cancer (MUBC) with nonregional lymphadenopathies and lung, bone, and skin involvement. He received first-line treatment with gemcitabine and cisplatin for 6 cycles, achieving a partial response (PR). Next, he received immunotherapy maintenance with avelumab for 4 months until disease progression. A next-generation sequencing test of paraffin-embedded tumor tissue identified a fibroblast growth factor receptor 3 (FGFR3) S249C missense mutation.

Short-course treatment after complete response to pembrolizumab in metastatic urothelial bladder cancer: a case series.

Background: The optimal duration of treatment for metastatic patients who achieve a complete response with immune checkpoint inhibitors is unknown. Methods: The outcome for sixmetastatic bladder cancer patients who received short course of pembrolizumab is reported. Results: A median number of sevencycles of pembrolizumab was given. After a median follow-up of 38months, progressive disease was confirmed in three patients. All patients relapsed in lymph nodes and underwent pembrolizumab rechallenge: oneachieved a complete response, another a partial response. Conclusion: Our case series paves the way for discontinuation of pembrolizumab in patients who achieve a complete response since threeout of six patients remain free of disease after 3-year follow-up. Prospective studies are required to confirm our results.

PD36-09 TIME TRENDS IN SYSTEMIC TREATMENTS AND SURVIVAL IN PATIENTS WITH METASTATIC UROTHELIAL BLADDER CANCER: OUTCOMES IN THE ERA OF IMMUNOTHERAPY

You have accessJournal of UrologyCME1 Apr 2023PD36-09 TIME TRENDS IN SYSTEMIC TREATMENTS AND SURVIVAL IN PATIENTS WITH METASTATIC UROTHELIAL BLADDER CANCER: OUTCOMES IN THE ERA OF IMMUNOTHERAPY Harshit Garg, Mukund Bhandari, Monica Sridhar, Onika Noel, Furkan Dursun, Michael Liss, Dharam Kaushik, Robert Svatek, Chethan Ramamurthy, and Ahmed Mansour Harshit GargHarshit Garg More articles by this author , Mukund BhandariMukund Bhandari More articles by this author , Monica SridharMonica Sridhar More articles by this author , Onika NoelOnika Noel More articles by this author , Furkan DursunFurkan Dursun More articles by this author , Michael LissMichael Liss More articles by this author , Dharam KaushikDharam Kaushik More articles by this author , Robert SvatekRobert Svatek More articles by this author , Chethan RamamurthyChethan Ramamurthy More articles by this author , and Ahmed MansourAhmed Mansour More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003334.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The management of metastatic urothelial carcinoma of the urinary bladder has been revolutionized with the advent of immune-checkpoint inhibitors (ICI). However, the survival outcomes in metastatic bladder cancer over the past decade with improvements in systemic therapies have not been studied. The aim of the study is to investigate the time trends in treatment strategies and overall survival (OS) in patients with metastatic urothelial cancer of the bladder. METHODS: Using the recently updated National Cancer Database, patients with newly diagnosed metastatic urothelial cancer of the urinary bladder between 2014-2019 were included. We analyzed changes in the first-line systemic treatment and the changes in the 1-year OS using cox multivariable regression and Kaplan Meier analysis. The OS analysis was censored at 1-year to account for possible bias due to shorter follow-up in most recent years. RESULTS: Overall, 10,965 patients met the inclusion criteria with 9,229 receiving systemic chemotherapy and 1,666 patients receiving systemic immunotherapy. The use of immunotherapy increased from 2.3% (9/391) in 2007 to 36.5% (484/1325) to 2019 (p<0.001) and the use of systemic chemotherapy decreased from 98.2% (270/275) in 2004 to 63.5% (841/1325) in 2019 (p<0.001). (Figure 1a). The median and 1-year OS of the entire cohort increased from 9.9 months and 38.6% in 2004 to 12.5 months and 50.8% in 2018 respectively (p<0.001) (Figure 1b). From 2009 to 2018, the 1-y OS improved gradually from 38.3% to 53.6% in systemic chemotherapy and 44.4% to 46.3% in the systemic immunotherapy group. (Figure 1c) The improvement in systemic chemotherapy arm could be potentially attributed to increased use of second line immunotherapy in this cohort. CONCLUSIONS: The use of immunotherapy as first-line therapy has substantially increased over the past years. The median OS in metastatic bladder cancer has also improved over the past 15 years, possibly because of the advent of immune-checkpoint therapy. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e983 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Harshit Garg More articles by this author Mukund Bhandari More articles by this author Monica Sridhar More articles by this author Onika Noel More articles by this author Furkan Dursun More articles by this author Michael Liss More articles by this author Dharam Kaushik More articles by this author Robert Svatek More articles by this author Chethan Ramamurthy More articles by this author Ahmed Mansour More articles by this author Expand All Advertisement PDF downloadLoading ...

Enfortumab Vedotin in metastatic bladder cancer: a case report of durable clinical efficacy in a pretreated patient.

Metastatic urothelial bladder cancer is associated with high mortality rates. The advent of immunocheckpoint inhibitors (ICIs), with the approval of pembrolizumab in second line treatment, has changed the treatment landscape and improved clinical outcomes of patients. Until recently, subsequent lines of therapy have been limited to single-agents chemotherapy, poor efficacy and relevant toxicities. Recent studies in pretreated urothelial bladder cancer have led to the approval in clinical practice of enfortumab vedotin, demonstrating better clinical efficacy compared with the standard of care. Herein we report a case of a 57-year-old male patient with metastatic bladder cancer, who had unsatisfactory responses to first-line chemotherapy and subsequent second-line immunotherapy. Based on robust data of efficacy and safety from clinical trials, we treated the patient with enfortumab vedotin as third-line therapy. An initial adverse event, probably not strictly related to the drug, led to temporarily discontinuation of enfortumab vedotin and subsequent administration with a dose reduction. Despite this, the drug induced a first partial response on most of the metastatic sites and a complete response on lung and pelvic metastases was subsequently observed. Of note, responses were durable, with good tolerability and improvement in cancer-associated symptoms, such as pain.

Consolidative Radiotherapy for Metastatic Urothelial Bladder Cancer Patients with No Progression and with No More than Five Residual Metastatic Lesions Following First-Line Systemic Therapy: A Retrospective Analysis.

Patients who received first-line therapy for the treatment of metastatic urothelial bladder cancer (mUBC) and who were progression-free following treatment with no more than five residual metastases were retrospectively identified through the database of four Comprehensive Cancer Centers, between January 2005 and December 2018. Among them, patients who received subsequent definitive radiotherapy (of EQD2Gy > 45Gy) to the bladder and residual metastases were included in the consolidative group (irradiated (IR) group), and the other patients were included in the observation group (NIR group). Progression-free survival (PFS) and overall survival (OS) were determined from the start of the first-line chemotherapy using the Kaplan-Meier method. To prevent immortal time bias, a Cox model with time-dependent covariates and 6-month landmark analyses were performed to examine OS and PFS. A total of 91 patients with at least stable disease following first-line therapy and with no more than five residual metastases were analyzed: 51 in the IR group and 40 in the NIR group. Metachronous metastatic disease was more frequent in the NIR group (19% vs. 5%, p = 0.02); the median number of metastases in the IR group vs. in the NIR group was 2 (1-9) vs. 3 (1-5) (p = 0.04) at metastatic presentation, and 1 (0-5) vs. 2 (0-5) (p = 0.18) after completion of chemotherapy (residual lesions), respectively. Two grade 3 toxicities (3.9%) and no grade 4 toxicity were reported in the IR group related to radiotherapy. With a median follow up of 85.9 months (95% IC (36.7; 101.6)), median OS and PFS were 21.7 months (95% IC (17.1; 29.7)) and 11.1 months (95% IC (9.9; 14.1)) for the whole cohort, respectively. In multivariable analysis, consolidative radiotherapy conferred a benefit in both PFS (HR = 0.49, p = 0.007) and OS (HR = 0.47, p = 0.015) in the whole population; in the landmark analysis at 6 months, radiotherapy was associated with improved OS (HR = 0.48, p = 0.026), with a trend for PFS (HR = 0.57, p = 0.082). Consolidative radiotherapy for mUBC patients who have not progressed after first-line therapy and with limited residual disease seems to confer both OS and PFS benefits. The role of consolidative radiotherapy in the context of avelumab maintenance should be addressed prospectively.

Impact of systemic treatments on overall survival in metastatic urothelial bladder cancer: A time-trend analysis

Impact of systemic treatments on overall survival in metastatic urothelial bladder cancer: A time-trend analysis

Immune Checkpoint Inhibitors in Urothelial Carcinoma (Literature Review)

Bladder cancer is globally considered as one of the most aggressive neoplasms. Traditionally, first-line therapy for metastatic urothelial carcinoma has remained unchanged over the past decades and has been based on combinations of cisplatin. Unfortunately, almost all patients eventually progress and die from bladder cancer, despite the initial response associated with cisplatin-based combinations. Immune checkpoint inhibitors are becoming an increasingly widely used therapeutic option in many solid tumors. In bladder cancer, a high level of programmed death-ligand is determined by rapidly progressive and aggressive tumors and unsatisfactory survival rates. Although checkpoint inhibitors are effective in metastatic urothelial bladder cancer, only a small proportion of treated patients receive a clear benefit, while a large number of patients experience significant side effects and toxicity without improving quality of life or surviving. None of the available biomarkers at this point was associated with response rates. There is evidence of an correlation between PD-L1 expression, the efficacy of immune checkpoint inhibitors, and treatment outcomes in patients with bladder cancer. A major paradigm shift in bladder cancer medicine has followed the FDA approval of avelumab, pembrolizumab, durvalumab, atezolizumab, and nivolumab for the treatment of patients with metastatic urothelial carcinoma previously treated with chemotherapy. Combining classical clinicopathological parameters with data obtained via information technology, together with genomic profiling, could be the future of personalized therapy for bladder cancer.

89Zirconium-labelled girentuximab (89Zr-TLX250) PET in patients with urothelial cancer (ZiPUP): A phase I trial of a novel staging modality for urothelial carcinoma.

TPS4609 Background: Bladder cancer is a lethal disease with a rising incidence. The current standard imaging modalities for staging are either CT of the chest, abdomen and pelvis or FDG PET/CT. However, there are issues with using these modalities for staging. CT is known to have relatively low sensitivity for detecting low volume metastatic disease, while FDG is predominantly renally excreted and therefore has intense activity in the urinary tract, which limits its utility to detect bladder or upper tract lesions, or nodal metastases in close proximity to the urinary tract. Zirconium-89-Girentuximab (89Zr-TLX250) may have utility in the accurate staging of bladder and urothelial cancer, with less renal excretion as compared to FDG, however this has not previously been investigated. ZipUp is an investigator initiated trial. South Metropolitan Health Service WA is the trial sponsor. The study received funding and study drug support from Telix Pharmaceuticals Methods: ZiPUP is a single-arm, phase I trial examining the feasibility, safety, and utility of 89Zr-TLX250 PET/CT in patients either undergoing pre-operative staging of urothelial carcinoma or bladder cancer for curative intent, or with known metastatic urothelial carcinoma or bladder cancer. All participants will undergo 89Zr-TLX250 PET/CT and will need to have undergone recent FDG PET/CT for means of comparison. This trial aims to recruit 10 participants undergoing staging and 10 participants with known metastatic disease. The primary endpoint is effectiveness by assessing sensitivity and specificity in detecting lymph node metastases compared to FDG PET/CT; secondary endpoints are safety, tolerability, and feasibility. The first patient was enrolled in this single site study and the study is expected to be completed by December 2022. If 89Zr-TLX250 PET/CT is proven to be feasible, safe, and effective in staging urothelial cancer, it could improve the appropriate selection of treatment for patients with metastatic or primary urothelial carcinoma or bladder cancer. Clinical trial information: NCT05046665.

Educational webcast series targeted to the interprofessional bladder cancer care team improves clinician knowledge, confidence, and competence.

e23002 Background: There are an estimated &gt;81,000 new cases of metastatic urothelial bladder cancer (mUBC) diagnosed in the U.S each year, resulting in more than 17,000 deaths. mUBC has been shown to be susceptible to immune checkpoint inhibitors (ICIs), and beyond currently approved first and second line indications, these agents are being studied in bladder-sparing regimens and for high risk NMIBC patients who are BCG-unresponsive. Needs assessments demonstrate educational gaps involved in medication selection, dosing, and immune-related adverse event management as barriers to immunotherapy use by the interprofessional bladder cancer care team. The webcast series, “Key Issues for the Advanced Bladder Cancer Care Clinic: Incorporating Immunotherapy into your Community-Based Urology Practice” was designed specifically for the interprofessional team of bladder cancer clinicians to address unmet educational needs by focusing on the communities where the significant majority of patients are diagnosed, evaluated, and managed. Methods: Four online activities were designed to target urology and uro-oncology community physicians, physician assistants, nurse practitioners, nurses, and pharmacists focused on ICI therapies for bladder cancer, with a focus on the role of the team. Learning and confidence change were objectively assessed by analyzing pre- and post-test results before and after the educational activities. Statistical testing between pre- and post-tests were conducted via chi square analysis with a priori significance set at 0.05. Results: Evaluations were collected from N=706 participants. Knowledge advancements, as determined by significant ( P&lt;0.05) increases in correct responses, were observed in several specific topic areas: recognition of ongoing clinical trials (29% pre-test vs. 69% post-test) biomarkers and treatment selection (43% pre-test vs. 81% post-test) logistical concerns for patients initiating ICIs (60% pre-test vs. 80% post-test) Participant self-reported mean confidence scores increased with statistical significance in implementation of appropriate immunotherapy and in recognizing and mitigating irAEs from pre- to post-test ( P&lt;0.05). Conclusions: As the treatment paradigm for bladder cancer continuously evolves, all members of the oncology healthcare team must be equipped to evolve with it to ensure optimal patient care. This analysis shows that online accredited education can significantly improve the knowledge and confidence of the interprofessional bladder cancer care team in multiple areas surrounding the effective and appropriate use of ICIs.

Errata corrige: Significance of interventional radiology in liver transplantation

The KEYWORDS of this article on page 87 as listed are first-line treatment, metastatic urothelial bladder cancer, maintenance immunotherapy. Keywords have been corrected to: transplantation, chemoembolization, radioembolization, ablation.

Life expectancy in metastatic urothelial bladder cancer patients according to race/ethnicity.

to compare observed overall survival vs age-adjusted lifetable (LT) derived life expectancy (LE) in metastatic urothelial bladder cancer (MBCa) patients according to race/ethnicity. We identified Caucasian, African American, Hispanic/Latino and Asian metastatic urothelial bladder cancer patients from 2004 to 2011 within the Surveillance, Epidemiology and End Results database. Social Security Administration tables were used to compute 5year LE. LT-derived LE was compared to observed overall survival OS. Additionally, we relied on Poisson regression plots to display cancer-specific mortality (CSM) relative to other-cause mortality (OCM) for each race/ethnicity. Overall, 2286 MBCa patients were identified. Of those, 1800 (79%) were Caucasian vs 212 (9.3%) African American vs 189 (8.3%) Hispanic/Latino vs 85 (3.7%) Asians. The median age at diagnosis was 71years for Asians vs 70 for Caucasians vs 67 for Hispanic/Latinos vs 67 for African Americans. African Americans showed the biggest difference between observed OS and LT-predicted LE at five years (-83.8%), followed by Hispanic/Latinos (-81%), Caucasians (-77%) and Asian patients (-69%). In Poisson regression plots, Hispanic/Latinos displayed the highest cancer-specific mortality rate (88%), while African/Americans showed the highest other cause mortality rate (12%). Conversely, Asian patients displayed the lowest CSM rate (83%) and second lowest OCM rate (7%). African Americans showed the least favorable survival profile in MBCa, despite being youngest at diagnosis. Contrarily, Asians displayed the best survival profile in MBCa, despite being oldest at diagnosis.

MP03-10 LIFE EXPECTANCY IN METASTATIC UROTHELIAL BLADDER CANCER PATIENTS ACCORDING TO RACE/ETHNICITY

You have accessJournal of UrologyCME1 May 2022MP03-10 LIFE EXPECTANCY IN METASTATIC UROTHELIAL BLADDER CANCER PATIENTS ACCORDING TO RACE/ETHNICITY Francesco Chierigo, Christoph Würnschimmel, Rocco Simone Flammia, Benedikt Horlemann, Gabriele Sorce, Benedikt Hoeh, Zhe Tian, Fred Saad, Markus Graefen, Michele Gallucci, Alberto Briganti, Francesco Montorsi, Felix K.H. Chun, Shahrokh F. Shariat, Guglielmo Mantica, Maro Borghesi, Nazareno Suardi, Carlo Terrone, and Pierre I. Karakiewicz Francesco ChierigoFrancesco Chierigo More articles by this author , Christoph WürnschimmelChristoph Würnschimmel More articles by this author , Rocco Simone FlammiaRocco Simone Flammia More articles by this author , Benedikt HorlemannBenedikt Horlemann More articles by this author , Gabriele SorceGabriele Sorce More articles by this author , Benedikt HoehBenedikt Hoeh More articles by this author , Zhe TianZhe Tian More articles by this author , Fred SaadFred Saad More articles by this author , Markus GraefenMarkus Graefen More articles by this author , Michele GallucciMichele Gallucci More articles by this author , Alberto BrigantiAlberto Briganti More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Felix K.H. ChunFelix K.H. Chun More articles by this author , Shahrokh F. ShariatShahrokh F. Shariat More articles by this author , Guglielmo ManticaGuglielmo Mantica More articles by this author , Maro BorghesiMaro Borghesi More articles by this author , Nazareno SuardiNazareno Suardi More articles by this author , Carlo TerroneCarlo Terrone More articles by this author , and Pierre I. KarakiewiczPierre I. Karakiewicz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002515.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To compare observed overall survival vs age-adjusted life-table (LT) derived life expectancy (LE) in metastatic urothelial bladder cancer (MBCa) patients according to race/ethnicity. METHODS: We identified Caucasian, African American, Hipanic/Latino and Asian metastatic urothelial bladder cancer patients from 2004 to 2011 within the Surveillance, Epidemiology and End Results database to. Social Security Administration tables were used to compute five-year LE. LT-derived LE was compared with observed overall survival OS. Additionally, we relied on Poisson regression plots to display cancer-specific mortality (CSM) relative to other-cause mortality (OCM) for each race/ethnicity. RESULTS: Overall, 2,286 MBCa patients were identified. Of those, 1,800 (79%) were Caucasian vs 212 (9.3%) African American vs 189 (8.3%) Hispanic/Latino vs 85 (3.7%) Asians. The median age at diagnosis was 71 years for Asians vs 70 for Caucasians vs 67 for Hispanic/Latinos vs 67 for African Americans. African Americans showed the biggest difference between observed OS and LT-predicted LE at five years (-83.8%), followed by Hispanic/Latinos (-81%), Caucasians (-77%) and Asian patients (-69%). In Poisson regression plots, Hispanic/Latinos displayed the highest cancer-specific mortality rate (88%), while African/Americans showed the highest other cause mortality rate (12%). Conversely, Asian patients displayed the lowest CSM rate (83%) and second-lowest OCM rate (7%). CONCLUSIONS: African Americans showed the least favorable survival profile in MBCa, despite being youngest at diagnosis. Contrarily, Asians displayed the best survival profile in MBCa, despite being oldest at diagnosis. Source of Funding: no funding © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e23 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Francesco Chierigo More articles by this author Christoph Würnschimmel More articles by this author Rocco Simone Flammia More articles by this author Benedikt Horlemann More articles by this author Gabriele Sorce More articles by this author Benedikt Hoeh More articles by this author Zhe Tian More articles by this author Fred Saad More articles by this author Markus Graefen More articles by this author Michele Gallucci More articles by this author Alberto Briganti More articles by this author Francesco Montorsi More articles by this author Felix K.H. Chun More articles by this author Shahrokh F. Shariat More articles by this author Guglielmo Mantica More articles by this author Maro Borghesi More articles by this author Nazareno Suardi More articles by this author Carlo Terrone More articles by this author Pierre I. Karakiewicz More articles by this author Expand All Advertisement PDF DownloadLoading ...

Anti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naïve or experienced for immune checkpoint blockade

BackgroundThis phase 1b study (NCT02323191) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of colony-stimulating factor-1 receptor-blocking monoclonal antibody (mAb) emactuzumab in combination with the programmed cell death-1 ligand (PD-L1)-blocking...

Fibroblast Growth Factor Inhibitors for Treating Locally Advanced/Metastatic Bladder Urothelial Carcinomas via Dual Targeting of Tumor-Specific Oncogenic Signaling and the Tumor Immune Microenvironment.

Locally advanced or metastatic urothelial bladder cancer (a/m UBC) is currently treated using platinum-based combination chemotherapy. Immune checkpoint inhibitors (ICIs) are the preferred second-line treatment options for cisplatin-eligible a/m UBC patients and as first-line options in cisplatin-ineligible settings. However, the response rates for ICI monotherapy are modest (~20%), which necessitates the exploration of alternative strategies. Dysregulated activation of fibroblast growth factor receptor (FGFR) signaling enhances tumor proliferation, survival, invasion, angiogenesis, and immune evasion. The recent U.S. Food and Drug Administration approval of erdafitinib and the emergence of other potent and selective FGFR inhibitors (FGFRis) have shifted the treatment paradigm for patients with a/m UBC harboring actionable FGFR2 or FGFR3 genomic alterations, who often have a minimal-to-modest response to ICIs. FGFRi–ICI combinations are therefore worth exploring, and their preliminary response rates and safety profiles are promising. In the present review, we summarize the impact of altered FGFR signaling on a/m UBC tumor evolution, the clinical development of FGFRis, the rationale for FGFRi–ICI combinations, current trials, and prospective research directions.

Immune Checkpoint Inhibitors in Urothelial Bladder Cancer: State of the Art and Future Perspectives.

Bladder cancer (BC) is the most common malignancy of the genitourinary tract, with high morbidity and mortality rates. Until recently, the treatment of locally advanced or metastatic urothelial BC was based on the use of chemotherapy alone. Since 2016, five immune checkpoint inhibitors (ICIs) have been approved by the Food and Drug Administration (FDA) in different settings, i.e., first-line, maintenance and second-line treatment, while several trials are still ongoing in the perioperative context. Lately, pembrolizumab, a programmed death-1 (PD-1) inhibitor, has been approved for Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC), using immunotherapy at an early stage of the disease. This review investigates the current state and future perspectives of immunotherapy in BC, focusing on the rationale and results of combining immunotherapy with other therapeutic strategies.

Consolidative radiotherapy for metastatic urothelial bladder cancer patients without progression and with no more than three residual metastatic lesions following first line systemic therapy: A prospective randomized comparative phase II trial (BLAD RAD01/GETUG-AFU V07).

TPS4588 Background: Consolidative local treatment of the primary tumor in the treatment of metastatic malignancies has shown promising results in several types of tumors, mostly relying on the seed-and-soil theory. Furthermore, the local treatment of the residual metastases following systemic treatment is a promising approach, in part due to the high incidence of progression at prior sites of disease in patients who had initially responded to chemotherapy. To date, no prospective data exists on such consolidative approach in metastatic urothelial bladder cancer (mUBC). The phase II trial BLAD-RAD01 GETUG-AFU V07 was designed to investigate the role of local consolidative radiotherapy in patients with limited mUBC and without progression following the initial phase of first-line systemic therapy. Methods: This is a phase II, multicenter, randomized open-label and comparative study. Patients with mUBC (excluding brain and liver metastases), without progression following standard first-line systemic therapy according to RECIST v1.1, and with no more than 3 residual metastatic lesions on 18FDG-PET scanner and/or contrast-enhanced CT-scanner are eligible for the study. After the completion of systemic treatment, an estimated 130 patients will be randomized in a 1:1 ratio between consolidative local treatment (pelvic radiotherapy +/- previous transurethal resection of bladder tumor, associated with stereotactic body radiotherapy (SBRT) to the residual metastases) plus standard of care (arm B) and standard of care only (arm A). Stratification is performed based upon: the center, the ECOG performance status, the administration of immunotherapy or not, the number of residual metastatic lesions and the imaging modality for assessment of the number of residual lesions. To date, standard of care for this population is maintenance treatment with avelumab. Radiotherapy regimens consist in conventionally fractionated (64Gy in 32 fractions) or hypofractionated (55Gy in 20 fractions) irradiation of the bladder, optional pelvic nodes irradiation, and 3 to 5 fractions of 6 to 18 Gy in SBRT for metastases, depending on the location. The main objective is to detect an increase in 20-month overall survival rate following chemotherapy from 50% (based upon the JAVELIN 100 trial) to 66%; this corresponds to a hazard ratio of 0.6. A total of 83 events are necessary for 85% power to detect this difference if it is true using a one-sided logrank test at the 10% of significance. Target difference, type I and II error rates are relaxed and compatibles with recommendations for comparative phase II trials. Key secondary endpoints are progression free survival, safety and quality of life. To date, one patient has been enrolled and eight centers are open for accrual. Clinical trial information: NCT04428554.

Role of consolidative radiotherapy for metastatic urothelial bladder cancer patients without progression and with no more than five residual metastatic lesions following first line systemic therapy: A retrospective analysis.

454 Background: Consolidative local treatment of the primary tumor and metastases in the treatment of metastatic malignancies has shown promising results in several types of primary tumors. The aim of this study is to assess consolidative radiotherapy to the bladder and to residual metastases among metastatic urothelial bladder cancer with no progression following first line systemic therapy, hypothesizing an increase in overall survival and in progression free survival. Methods: Between January 2005 and December 2018, patients who received standard first-line chemotherapy for the treatment of metastatic urothelial bladder cancer (mUBC) were retrospectively identified through the database of four Comprehensive Cancer Centers in France. Among them, patients with no disease progression following chemotherapy and with no more than 5 residual metastases were analyzed: patients who received subsequent radiotherapy (of EQD2Gy &gt; 50Gy) to the bladder and residual metastases were included in the consolidative group (RT group), and the other patients were included in the observation group (OBS group). PFS and OS were determined from the start of the first-line chemotherapy using the Kaplan-Meier method. To account for the delay from chemotherapy initiation to consolidative radiotherapy, a Cox model with time-dependant covariates, and a 6-month landmark analyses were performed to examine OS and PFS. Results: A total of 91 patients with at least stable disease following chemotherapy and with no more than 5 residual metastases were analyzed: 51 in the RT group and 40 in the OBS group. Metachronous metastatic disease (following definitive treatment of localized UBC) was more frequent in the OBS group (19% vs 5%, p = 0.02); the median number of metastases in the RT group vs in the OBS group was: 2 (1-9) vs 3 (1-5) (p = 0.04) at metastatic presentation, and 1 (0-5) vs 2 (0-5) (p = 0.18) after completion of chemotherapy (residual lesions), respectively. Two grade 3 toxicities (3.9%) and no grade 4 toxicity were reported in the RT group. With a median follow up of 85.9 months (95% IC [36.7; 101.6]), median OS and PFS were 21.7 months (95% IC [17.1; 29.7]) and 11.1 months (95% IC [9.9; 14.1]) for the whole cohort, respectively. In multivariable analysis: consolidative RT in comparison with observation was associated with improved OS in both the standard analysis (HR = 0.47, p = 0.015) and in the 6-month landmark analysis (HR = 0.48, p = 0.026); and with improved PFS only in the standard analysis (HR = 0.49, p = 0.007). Conclusions: Consolidative radiotherapy for mUBC patients who have not progressed after chemotherapy and with limited residual disease seems to confer both OS and PFS advantage. Prospective data in that field with addition of avelumab are needed.