Molecular subtyping of metastatic urothelial bladder cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 326-326
Author(s):  
Charlotte Ackerman ◽  
Sanjeev Mariathasan ◽  
Dorothee Nickles ◽  
Alfonso Gomez De Liano Lista ◽  
Akhila Ganeshi Wimalasingham ◽  
...  

326 Background: TCGA molecular sybtyping is established in metastatic urothelial bladder cancer (UBC). It remains unclear if it is of prognostic importance with chemotherapy in metastatic UBC. Data into immune therapy suggests TCGA subtyping is predictive to response. Methods: Archival formalin-fixed paraffin embedded (FFPE) tissue were analysed from 170 patients that had consented into a clinical trial (NCT00949455) after first line chemotherapy for metastatic disease. Gene expression levels were quantified by NanoString technology. Molecular subtypes were assigned according to The Cancer Genome Atlas (TCGA) subtypes. Clinical information was available for all patients and analysis on individual genes were explored. Results: 170 patients were analysed, 75% male. 107 (64%) patients received cisplatin based first-line chemotherapy, with 36% receiving carboplatin based regimen. Median overall survival (OS) was 15.73 months [95% CI: 13.87-17.58], and median progression free survival (PFS) was 10.71 months [95% CI: 8.97-12.45]. Samples were initially clustered into luminal (n=109) and basal (n=61) subtypes. Response to first line chemotherapy occurred in all subtypes but was shown to be significantly higher in the luminal subtype versus the basal subtype [58% vs 20%, p=0.01]. PFS was superior in luminal subtypes [11.8 months vs 8.9 months, p=0.005]. Exploratory analysis showed that luminal II subtype had the best outcome for OS [20.3 months, p=0.03] compared to the other subtypes. Outcomes with other genes including immune markers were explored. TCGA outcomes can be summarised in the table. Conclusions: In metastatic urothelial cancer, TCGA subclassifying influences outcome of patients post chemotherapy. [Table: see text]

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 454-454
Author(s):  
Amélie Aboudaram ◽  
Leonor Chaltiel ◽  
Damien Pouessel ◽  
Pierre Graff-Cailleaud ◽  
Nicolas Benziane ◽  
...  

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 > 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.


2016 ◽  
Vol 34 (15_suppl) ◽  
pp. TPS4574-TPS4574 ◽  
Author(s):  
Thomas Powles ◽  
Matt D. Galsky ◽  
Daniel Castellano ◽  
Michiel Simon Van Der Heijden ◽  
Daniel Peter Petrylak ◽  
...  

2021 ◽  
Vol 93 (2) ◽  
pp. 143-147
Author(s):  
Lampros Mitrakas ◽  
Stavros Gravas ◽  
Foteini Karasavvidou ◽  
Ioannis Zachos ◽  
Anastasios Karatzas ◽  
...  

Objective: To conduct a prospective study of the potential prognostic role of endothelin-1 (ET-1) in a cohort of primary high-grade non-muscle-invasive urothelial bladder cancer patients, who were treated with adjuvant intravesical Bacillus Calmette-Guérin (BCG). Material and methods: Patients with primary high-grade nonmuscle- invasive urothelial bladder cancer, who received postoperatively induction and maintenance BCG therapy, were prospectively included. Recurrence and progression were histologically proven. Immunohistochemical staining for ET-1 was assessed. Epidemiological, pathological and clinical parameters as well as the expression of ET-1 in tumor specimens were statistically analyzed for recurrence, progression, recurrence-free survival (RFS) and progression-free survival (PFS). Results: ET-1 associates significantly with recurrence (p = 0.000), progression (p = 0.000), RFS (p = 0.000) and PFS (p = 0.000). The patient’s age is also significant for recurrence (p = 0.003, OR = 1.273 95% CI: 1.086-1.492) and RFS (p = 0.013). Conclusions: ET-1 seems to deteriorate prognosis in patients suffering from primary high-grade non-muscle-invasive urothelial bladder cancer, who are treated with adjuvant BCG instillations. Furthermore, the patient’s age associates with an increased likelihood for recurrence.


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