scholarly journals Survival of patients with metastatic bladder cancer in the Russian Federation: results of a multicenter registry study URRU

2021 ◽  
Vol 17 (3) ◽  
pp. 102-109
Author(s):  
I. V. Tsimafeyeu ◽  
G. N. Alekseeva ◽  
V. V. Petkau ◽  
R. A. Zukov ◽  
M. S. Mazhbich ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Progressive Disease ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Novel Treatments ◽  
Common Drug ◽  
Metastatic Bladder Cancer ◽  
Anonymized Data ◽  
The Russian Federation ◽  
Multicenter Registry

Background. Data on the overall survival (OS) of patients with metastatic bladder cancer (BCa) is rarely published.The objective of the URRU register study is to assess OS and collect information on the administration of different treatments in patients with metastatic BCa in routine clinical practice in Russia.Materials and methods. Patients were retrospectively identified in 9 oncology centers in different regions of Russia and included in the study if they were diagnosed with metastatic BCa between January 2017 and January 2018. We collected anonymized data online, including demographic characteristics of patients, details of their therapy, and outcomes.Results. This study included 246 patients. Their mean age upon the diagnosis of metastatic BCa was 72 years with 60.6 % of patients over 70 years of age. The proportion of males was 74.8 %. The histological subtype of BCa (urothelial carcinoma, etc.) was identified in 70.3 % of cases. Ninety-two patients (37.4 %) received pharmacotherapy. The most common treatment option was chemotherapy (76 %); the most common drug combination was gemcitabine and cisplatin (41.3 %). Immunotherapy was used in 19.6 % of patients; 13.6 % of participants received more than two lines of therapy. Three-year OS rate was 10.6 %; median OS was 7 months (95 % confidence interval (CI) 5.4-8.6). Patients receiving systemic therapy demonstrated significantly longer survival than those receiving no therapy (21 months; 95 % CI 17.38-24.62 vs 3 months; 95 % CI 1.79-4.22; p <0.0001). Patients receiving immunotherapy had better survival than individuals receiving chemotherapy (median OS 34.5 months vs 18 months; p = 0.003).Conclusion. The survival rates in the URRU study were relatively low, which can be attributed to the fact that only one-third of patients received pharmacotherapy and very few patients received immunotherapy. Second and subsequent lines of therapy were rarely used in patients with progressive disease. The implementation of novel treatments, including immune checkpoint inhibitors, will increase the survival of BCa patients.

Survival trends among patients with metastatic bladder cancer in the United States.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 306-306
Author(s):  
Binay Kumar Shah ◽  
Rakesh Mandal
Keyword(s):  
United States ◽  
Bladder Cancer ◽  
Survival Rates ◽  
Age Groups ◽  
Stage Iv ◽  
Relative Survival ◽  
The United States ◽  
Ajcc Stage ◽  
Metastatic Bladder Cancer ◽  
Z Value

306 Background: The chemotherapy regimens for metastatic bladder cancer (MBC) have evolved over the last two decades. Due to favorable toxicity profile, a combination of cisplatin and gemcitabine is widely used for the treatment of MBC since 2000. It is unclear if the survival trend in MBC has changed over last two decades. This study was conducted to evaluate the relative survival rates for patients with MBC in the United States during 1991-1999 and 2000-2008. Methods: We used the Surveillance, Epidemiology, and End Results (SEER*Stat) program to analyze 6-month and 12-month relative survival rates of AJCC stage-IV bladder cancer patients included in the SEER database. We used Z-test in the SEER*Stat program to compare relative survival rates among cohorts of patients categorized by race, gender, and age groups (<60 and ≥60 years). Results: The dataset comprised 9,819 and 986 patients with AJCC stage-IV bladder cancer among Caucasians and African Americans (AA), respectively. Among Caucasian men (<60 years), 6-month survival rates were 85.4±1.7% (n=442) and 77.9±1.3% (n=1,117) for 1991-1999 and 2000-2008, respectively. Similarly, 12-month survival rates in this group were 68.6±2.2% (n=442) and 60.4±1.5% (n=1,117) for 1991-1999 and 2000-2008, respectively. Thus, both 6-month and 12-month survival rates in 2000-2008 were lower among young Caucasians; and the differences were statistically significant when compared to 1991-1999 (6-month: Z-value = -3.205, p=0.001; 12-month: Z-value= -2.984, p=0.003). The survival rates among AA were not statistically significant. Conclusions: In young Caucasian patients (<60 years) with MBC, 6- month and 12-month relative survival rates were lower for the period 2000-2008 compared to 1991-1999. Further studies may be required to evaluate factors responsible for decreased survival rates among this population.

Bladder cancer rapid autopsy: A mechanism for collecting metastatic tumor tissue and establishing xenograft models of metastatic disease.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 478-478 ◽  
Author(s):  
Hung-Ming Lam ◽  
Funda Vakar-Lopez ◽  
Andrew Caleb Hsieh ◽  
Eva Corey ◽  
Robert B. Montgomery ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Carcinoma ◽  
Checkpoint Inhibitors ◽  
Metastatic Tumor ◽  
Clinical History ◽  
Multiple Tumor ◽  
Treatment Information ◽  
Metastatic Bladder Cancer ◽  
Biological Studies ◽  
Rapid Autopsy

478 Background: Patients with metastatic bladder cancer have a poor prognosis with a median survival of only 9-15 months. Understanding the biology of metastatic bladder cancer has been historically difficult due to a paucity of specimens and models that recapitulate human disease. We established a bladder cancer rapid autopsy program to systemically acquire metastases, and build patient-derived xenograft (PDX) and organoid models for biological studies. Methods: Patients with metastatic bladder cancer were consented and a rapid autopsy was performed 2-6 hours after death to allow acquisition of normal and metastasis specimens. Frozen and formalin-fixed and paraffin embedded specimens were collected and pathological evaluation was performed on each specimen. Additionally, tumors were implanted subcutaneously into SCID mice to establish PDXs. Once PDXs were developed, PDXs were dissociated for companion organoid culture. Clinical history and treatment information was documented for each patient. Results: We have performed 10 bladder cancer rapid autopsies to date, and have acquired 105 metastatic and 45 normal specimens. The pathological subtypes of patients include urothelial cell carcinoma (5/10), squamous cell carcinoma (3/10), and plasmacytoid variant of urothelial carcinoma (2/10). The cohort has been treated BCG only (1/10), chemotherapy (3/10), and chemotherapy and immune checkpoint inhibitors (6/10). The leading site of metastasis was the liver (7/10) and lung (7/10), followed by lymph node (5/10), bone (5/10), intestine (4/10), and omentum (2/10). Half (5/10) of the patients had extensive liver metastases that allow acquisition of multiple tumor foci. For the first time, PDX and organoids from two independent metastases (omentum – CoCaB 14.1 and liver –CoCaB 14.2) from the same patient were successfully developed. Conclusions: This bladder cancer rapid autopsy program provides an important volume of metastatic tumor specimens for study. Importantly, the first bladder cancer PDX derived from metastasis has been developed. The availability of metastatic bladder cancer specimens, PDXs, and organoids will allow biological studies of advanced disease.

scholarly journals Immune checkpoint inhibitors for metastatic bladder cancer

2017 ◽  
Vol 6 (S4) ◽  
pp. S720-S732
Author(s):  
Marta Cubelli ◽  
Vincenzo Di Nunno ◽  
Karim Rihawi ◽  
Francesco Massari
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Metastatic Bladder Cancer

Circulating cellular biomarkers associated with delayed time to progression among bladder cancer patients treated with immune checkpoint inhibitors.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 398-398
Author(s):  
Vadim S Koshkin ◽  
Terence W. Friedlander ◽  
Patricia Li ◽  
Joseph Schonhoft ◽  
Rachel Krupa ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Significant Trend ◽  
Response To Treatment ◽  
Time To Progression ◽  
Metastatic Bladder Cancer ◽  
Delayed Time

398 Background: Circulating tumor cells (CTCs) are an important emerging biomarker in bladder cancer that allow for a minimally invasive assessment of tumor activity and response to treatment. Characterization of CTC and other single cell populations associated with improved clinical outcomes can help guide treatment recommendations for patients with metastatic bladder cancer. Methods: Patients with metastatic bladder cancer who received treatment with anti-PD-1 or anti-PD-L1 agents were enrolled in this study. Patient response to treatment was assessed by treating physicians according to RECIST v1.1. Blood samples were prospectively collected from patients prior to the initiation of therapy and then while on treatment and shipped to Epic Sciences for processing. All nucleated cells were subjected to immunofluorescent (IF) staining and CTC and leukocyte identification by fluorescent scanners using algorithmic analysis. Kaplan-Meier analysis was utilized to compare time to progression of patients whose CTC and leukocyte values were above and below several pre-determined parameters. Results: A total of 27 patients (median age 74 years, 70% male) were enrolled in this study and were treated with anti-PD-1/PD-L1 agents pembrolizumab (n=15), atezolizumab (n=11), or nivolumab (n=1). For 20 patients who had evaluable responses, objective response rate (ORR) was 2/20 (10%), all partial responses; another 5/20 (35%) had stable disease. Increased CD4% (>8% of total leukocytes) was associated with delayed time to progression (TTP) (p=0.002) whereas increased baseline total CTCs (>2) had a statistically non-significant trend towards shorter TTP (p=0.09). Baseline CD8%, CD4/CD8 ratio and CTC PD-L1 status were not associated with TTP. Conclusions: In a preliminary analysis among metastatic bladder cancer patients treated with immune checkpoint inhibitors, patients with an increased baseline CTC count had a statistically non-significant trend towards shorter TTP whereas increased baseline CD4 cells had an association with delayed TTP. This prospective study is ongoing, and the results will be further validated in larger patient cohorts.

scholarly journals The current status of checkpoint inhibitors in metastatic bladder cancer

2016 ◽  
Vol 33 (7) ◽  
pp. 629-635 ◽  
Author(s):  
Omar Fahmy ◽  
Mohd Ghani Khairul-Asri ◽  
Arnulf Stenzl ◽  
Georgios Gakis
Keyword(s):  
Bladder Cancer ◽  
Checkpoint Inhibitors ◽  
Current Status ◽  
Metastatic Bladder Cancer

scholarly journals Therapeutically actionable PAK4 is amplified, overexpressed and involved in bladder cancer progression

2019 ◽  
Author(s):  
Darshan S. Chandrashekar ◽  
Balabhadrapatruni V. S. K. Chakravarthi ◽  
Alyncia D. Robinson ◽  
Joshua C. Anderson ◽  
Sumit Agarwal ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Protein Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Disease Incidence ◽  
Treatment Options ◽  
Survival Rates ◽  
Kinase Assay ◽  
Elevated Expression

AbstractMuscle-invasive bladder carcinomas (MIBCs) are aggressive genitourinary malignancies. Disease incidence and survival rates vary based on aggressiveness and treatment options. Metastatic urothelial carcinoma of the bladder is generally incurable by current chemotherapy and leads to early mortality. For a minority (∼20%) of patients, T-cell checkpoint inhibitors provide durable benefits following prior platinum therapy. Recent studies have identified molecular subtypes of MIBCs with different sensitivities to frontline therapy, suggesting heterogeneity in these tumors and pointing to the importance of molecular characterization of MIBCs to provide effective treatment. We have performed multi-omic profiling of the kinome to identify therapeutic targets that are overexpressed in a subset of BLCAs. Our analyses revealed amplification and overexpression of P21 (RAC1) activated kinase 4 (PAK4) in a subset of BLCAs. For these tumors, multiplex kinase assay profiling identified corresponding PAK4 target substrates. By performing experiments using cultured bladder cancer cells, we confirmed the role of PAK4 in BLCA cell proliferation and invasion. Furthermore, our studies showed that a PAK4 inhibitor was effective in curtailing growth of BLCA cells. Transcriptomic analyses identified elevated expression of another kinase, Protein Tyrosine Kinase 6 (PTK6), upon treatment with a PAK4 inhibitor. Similarly, RNA interference of PAK4 led to elevated expression of PTK6. Treatment with a combination of kinase inhibitors (vandetanib and dasatinib) showed enhanced sensitivity compared to either drug alone. Thus, PAK4 may be therapeutically actionable for a subset of MIBC patients with amplified and/or overexpressed PAK4 in their tumors. Our results also indicate that combined inhibition of PAK4 and PTK6 may overcome resistance to PAK4. These observations warrant clinical investigations with selected BLCA patients.

The association of access to systemic therapy and overall survival in metastatic bladder cancer in Russia: An analysis of URRU register.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 88-88
Author(s):  
Vladislav Petkau ◽  
Galina Alekseeva ◽  
Ruslan Zukov ◽  
Mikhail Mazhbich ◽  
Galina Statsenko ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Metastatic Disease ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Cancer Center ◽  
Metastatic Bladder Cancer ◽  
Number Of Patients ◽  
Geographical Regions

88 Background: Social, economic and community disadvantages are well-described for metastatic bladder cancer (mBC) in different geographical regions. For the first time in Russian Federation we investigated treatment options and survival disparities for patients with mBC including urothelial cancer in URRU register. Methods: Patients were retrospectively identified at 9 cancer centers in southern, central, and eastern regions of Russia (Astrakhan, Ekaterinburg, Ivanovo, Khabarovsk, Krasnoyarsk, Moscow, Omsk, Rostov-on-Don, Vladivostok). Patients were included in the study if histologically confirmed mBC was diagnosed between January 2017 and January 2018 and they had at least one visit to the cancer center during the follow-up period. Anonymised data were collected by online registry. The outcomes of interest were overall survival (OS), patient characteristics and treatment patterns. Results: 246 adult patients were included in the study for analysis. Mean number of patients in one region per year was 31. All patients had metastatic disease. Median age at diagnosis of mBC was 72 (37-99) years (with 60.6% of patients aged ≥70 years). Patients were predominantly male (75%), histological subtype of BC (urothelial carcinoma, etc.) was determined in 70.32%. 92 (37.4%) patients received systemic therapy for mBC. Despite the approved checkpoint inhibitors for mBC in 2017-2018 in Russia the main treatment option was chemotherapy (n=70; 76%). Multivariate analysis by adjusting demographic and cancer variables showed that non-receipt of systemic therapy was independently associated with higher odds of death (Odds Ratio=3.1, confidence interval (CI)=1.89 to 5.18). Median OS (21 months; 95% CI 17.38-24.62) of patients who received systemic therapy was significantly longer than that of patients who did not received the therapy (3 months; 95% CI 1.79-4.22; p<0.0001). Patients receiving immunotherapy had better survival outcomes comparing to chemotherapy (median OS 34.5 vs. 18 months, p=0.003). Conclusions: In Russia only one third of patients with mBC received systemic therapy for metastatic disease which affected OS. Consistent with other studies these results indicate that patients should have access to novel therapies.

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