872 External validation of disease-free survival at 2 or 3 years as a surrogate and new primary endpoint for patients undergoing radical cystectomy for muscle invasive urothelial carcinoma of the bladder

2012 ◽  
Vol 11 (1) ◽  
pp. e872-e872a
Author(s):  
H.M. Fritsche ◽  
M. May ◽  
M. Burger ◽  
P. Nuhn ◽  
W. Otto ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Radical Cystectomy ◽  
Primary Endpoint ◽  
External Validation ◽  
Disease Free Survival ◽  
Free Survival ◽  
Carcinoma Of The Bladder ◽  
Muscle Invasive ◽  
Disease Free

scholarly journals LGALS4 as a Prognostic Factor in Urothelial Carcinoma of Bladder Affects Cell Functions

2019 ◽  
Vol 18 ◽  
pp. 153303381987660 ◽  
Author(s):  
Yu Ding ◽  
Qifeng Cao ◽  
Chen Wang ◽  
Huangqi Duan ◽  
Haibo Shen
Keyword(s):  
Urothelial Carcinoma ◽  
Survival Curve ◽  
Disease Free Survival ◽  
Hub Genes ◽  
Free Survival ◽  
Polymerase Chain ◽  
Carcinoma Of The Bladder ◽  
Bladder Cells ◽  
And Migration ◽  
Disease Free

Background: To identify the hub genes related to urothelial carcinoma of the bladder prognosis and to understand their underlying mechanism. Methods: The expression profiles of 18 pairs of urothelial carcinoma of the bladder patient tissue and paired adjacent tissue obtained from the Cancer Genome Atlas were performed. Weighted gene coexpression network analysis was employed to screen gene modules and hub genes with significant differential expressions in urothelial carcinoma of the bladder. The hub genes expression in urothelial carcinoma of the bladder tissues was validated by reverse transcription-quantitative polymerase chain reaction. The overall survival curve and disease-free survival curve of prognostic factor ( LGALS4) were plotted using the Kaplan-Meier method. Furthermore, LGALS4 messenger RNA and protein expression were also assessed in 2 urothelial carcinoma of the bladder cell lines (T24 and 5637) by quantitative reverse transcription–polymerase chain reaction and Western blot. The functions of urothelial carcinoma of the bladder cells with transfected pcDNA3.1- LGALS4 were identified through MTT assay, plate clone formation assay, flow cytometry, and cell migration experiments. Results: LGALS4 was the hub gene of pink module and it was related to prognosis. Higher LGALS4 expression predicted higher probabilities of overall survival and disease-free survival. Overexpression of LGALS4 in urothelial carcinoma of the bladder cells suppressed cell viability and migration but induced apoptosis. Conclusion: LGALS4 played a critical role in the progression of urothelial carcinoma of the bladder and held a promise to be the biomarker for diagnosis and treatment of urothelial carcinoma of the bladder. It predicted good prognosis of urothelial carcinoma of the bladder and restrained the growth and migration of urothelial carcinoma of the bladder cells.

Feasibility and efficacy of gemcitabine and carboplatin neoadjuvant chemotherapy in muscle-invasive bladder cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16100-e16100
Author(s):  
T. Koie ◽  
H. Yamamoto ◽  
A. Okamoto ◽  
S. Hatakeyama ◽  
A. Momose ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Objective Response ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive ◽  
Disease Free

e16100 Background: The neoadjuvant M-VAC followed by radical cystectomy for muscle-invasive bladder cancer has improved survival compared to radical cystectomy alone. Nevertheless, M-VAC has been associated with severe toxicity. The objective of this retrospective study was to evaluate the objective response rate, the impact on overall survival, disease-free survival, disease-free survival and toxicity adverse events of gemcitabine and carboplatin (GC) neoadjuvant chemotherapy in patients with locally advanced bladder cancer. Methods: We reviewed the clinical and pathological data of 140 patients who underwent radical cystectomy and bilateral pelvic lymphadenectomy for T2N0M0 to T4aN0M0 bladder cancer at our institution between January 2001 and August 2008. Seventy patients were treated with neoadjuvant GC followed by cystectomy between March 2005 and August 2008 (GC group), and 70 patients were treated with cystectomy alone between January 2001 and May 2007 (cystectomy alone group). In the GC group, the patients received 2 courses of GC therapy consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. The primary endpoint was the objective response rate, and the secondary endpoints were overall survival, cancer-specific survival, disease free survival, and toxicity. Results: Fifteen patients (23.8%) had a complete response and 26 patients (41.3%) had a partial response in the GC group. At a mean follow-up period of 26.7 months, the overall survival was 85.0% in the GC group and 47.8% in the cystectomy alone group (p = 0.003). The cancer-specific survival was 78.4% in the GC group and 44.6% in the cystectomy alone group (p = 0.0018). The disease-free survival was 82.9% in the GC group and 35.7% in the cystectomy alone group (p = 0.0001). Hematologic toxicities were the main adverse events. Grade 3/4 neutropenia occurred in 26 patients (37.1%) and thrombocytopenia in 15 (21.4%). There was no grade 3/4 gastrointestinal toxicity and no renal function abnormalities. Conclusions: Although this is not a randomized study, the GC neoadjuvant therapy followed by radical cystectomy is feasible and may be associated with improved survival among patients with muscle-invasive bladder cancer. A randomized trial is warranted. No significant financial relationships to disclose.

Tracking minimal residual disease with urine tumor DNA in muscle-invasive bladder cancer after neoadjuvant chemotherapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16514-e16514
Author(s):  
Kevin Chen ◽  
Pradeep S Chauhan ◽  
Ramandeep K Babbra ◽  
Wenjia Feng ◽  
Nadja Pejovic ◽  
...  
Keyword(s):  
Radical Cystectomy ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Driver Mutations ◽  
Free Survival ◽  
Treatment Responses ◽  
Muscle Invasive ◽  
Bladder Sparing ◽  
Disease Free ◽  
Tumor Dna

e16514 Background: Standard-of-care for muscle-invasive bladder cancer (MIBC) consists of neoadjuvant chemotherapy (NAC) followed by radical cystectomy. The inability to noninvasively assess minimal residual disease (MRD) after NAC limits our ability to offer bladder-sparing treatment. We perform urine tumor DNA (utDNA) analysis to identify pathologic complete response (pCR) at the time of cystectomy in patients receiving NAC. Methods: We applied CAPP-Seq to urine cell-free DNA samples acquired on the day of radical cystectomy from 19 MIBC patients treated with NAC. utDNA variant-calling was performed without prior tumor mutational knowledge using a panel of 49 consensus driver genes mutated in MIBC. The utDNA level for each patient was represented by the duplex-supported non-silent driver mutation with the highest variant allele fraction (vAF) after removing germline variants. We also serially tracked utDNA variants in two patients before, during, and after NAC. Results: Comparing patients with residual disease detected in their cystectomy specimen ( n = 10) to those who achieved a pCR ( n = 9), median utDNA levels were 2.4% vs. 0%, respectively ( P = 0.006). Using an optimal utDNA threshold to define MRD detection, positive utDNA MRD was highly correlated with the absence of pCR ( P = 0.003). Analysis of two patients’ serial urine samples revealed utDNA dynamics that were consistent with treatment responses in real-time. In one patient who ultimately achieved a pCR, four non-silent driver mutations were detectable pre-NAC, including ERCC2 N238S (7.8% vAF) associated with increased chemosensitivity. One week after starting NAC, ERCC2 N238S increased by 1.6-fold in urine, as did PIK3CA E726K which increased by 8.4-fold. Four weeks post-NAC, however, all mutations previously detected in this patient’s urine became undetectable, consistent with the patient’s pCR and long-term disease-free survival. Conversely, another patient harbored two non-silent driver mutations in PLEKHS1 (1.9% vAF) and KMT2D (4.9% vAF) pre-NAC. One week after starting NAC, both mutations decreased dramatically by 8.0- and 4.3-fold, respectively. By three weeks post-NAC, however, these mutations progressively increased by 5.2-fold on average, which correlated with a lack of pCR as well as post-treatment disease progression. Two newly detected non-silent driver mutations in ARID1A and ERBB2 also emerged on NAC and persisted following completion of chemotherapy , likely reflecting the development of treatment resistance. Conclusions: utDNA MRD after NAC but before radical cystectomy for MIBC correlated significantly with pathologic response, which could help personalize patient selection for bladder-sparing treatments in the future. Serial monitoring of utDNA variants during NAC can reveal dynamic mutational changes that reflect real-time treatment responses as well as ultimate disease-free survival.

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