Postchemotherapy AKR1B10 expression correlates with disease-free survival in muscle-invasive bladder cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 319-319
Author(s):  
Yasuhiro Hashimoto ◽  
Takuya Koie ◽  
Hayato Yamamoto ◽  
Atsushi Imai ◽  
Shingo Hatakeyama ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Chemotherapy Group ◽  
Intensity Score ◽  
Muscle Invasive ◽  
Disease Free

319 Background: AKR1B10 is a member of the aldo-keto reductase superfamily of NAD(P)H-dependent oxidoreductases.AKR1B10 is considered to contribute to cell proliferation and chemo-resistance. In the present study, we examined whether AKR1B10 expression correlates with disease free survival in bladder cancer specimens. Methods: The cohort includes consecutive 57 patients with muscle-invasive bladder cancer who received neoadjuvant chemotherapy followed by radical cystectomy. All patients received two cycles of neoadjuvant chemotherapy with gemcitabine plus carboplatin. Bladder cancer specimens were obtained at pre- and post-neoadjuvant chemotherapy, which were subjected to quantitative real-time PCR and immunohistochemistry to evaluate AKR1B10 expression. Intensity scoring for immunohistochemistry was categorized using a 4-graded scoring system according to a previously published method, with positive cells for each specific marker expressed as a percentage of the total number of cells as follows: 0%–10% = 0; 11%–30% = 1; 31%–70% = 2; 71%–100% = 3. Results: AKR1B10 mRNA expression was significantly higher in the post-chemotherapy groups than in the pre-chemotherapy groups (p < 0.001). The average immunohistochemical intensity score in the pre-chemotherapy group was 0.83 ± 1.08, compared to a significantly higher average intensity score of 2.03 ± 1.03 in the post-chemotherapy group (p < 0.001) Disease free survival of the post-chemotherapy AKR1B10(+) patients (61.2%) was significantly lower than that of AKR1B10(−) patients (100%) (log-rank test: p = 0.039). Conclusions: Although the present study is small and preliminary, post-chemotherapy AKR1B10 expression may have a predictive potential for response of chemotherapy and disease recurrence after definitive therapy for muscle-invasive bladder cancer. Further study is warranted to elucidate its clinical significance.

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.

1057 POST-CHEMOTHERAPY AKR1B10 EXPRESSION CORRELATES WITH DISEASE FREE SURVIVAL IN MUSCLE-INVASIVE BLADDER CANCER

2012 ◽  
Vol 187 (4S) ◽  
Author(s):  
Yasuhiro Hashimoto ◽  
Takuya Koie ◽  
Hayato Yamamoto ◽  
Atsushi Imai ◽  
Shingo Hatakeyama ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive ◽  
Disease Free

The Role of Partial Cystectomy in the Treatment of Muscle-Invasive Bladder Cancer

2005 ◽  
Vol 72 (2) ◽  
pp. 215-223
Author(s):  
P. Tombolini ◽  
M. Ruoppolo ◽  
G. Dormia ◽  
E. Dormia
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
Free Survival ◽  
Muscle Invasive ◽  
Bladder Sparing ◽  
Disease Free

Partial cystectomy has been widely performed in the treatment of muscle-invasive bladder cancer in the 1960s and 70s. During the 1970s and 80s a more aggressive surgical approach was advocated by urologists. However, major complications occurred in 4–25% of patients undergoing radical cystectomy and urinary diversion. The overall survival in patients managed by radical cystectomy has increased during the last decades, but disease-free survival remains the same. This procedure allows excellent loco-regional tumor control, but not changes in the timing of distant metastases and in the failure to control the disease. Recently, multimodal strategies in sparing bladder surgery have been proposed. Neoadjuvant chemotherapy, with or without irradiation, allows bladder sparing surgery in selected patients. A literature review demonstrates a later recurrence in the preserved bladder ranging from 40–75%. One-third of these recurrences required cystectomy and 15–20% of cases with bladder preservation experienced disease progression and died of cancer within 2 yrs. Only 40 and 20% of T2-T3 bladder cancer patients are alive and disease-free at 5 and 10 yrs of follow-up, respectively. In our experience, in selected patients, disease-free survival, overall survival, time to progression and final bladder preservation rate was higher compared to other patients. Bladder sparing in selected patients, i.e. single non-recurrent neoplasm, favorable site, no prostatic or urethral involvement, complete response to neoadjuvant chemotherapy, no P53 overexpression, no previous BCG-failure, is a feasible approach. Cystectomy, possibly with neobladder tailoring, is currently, the standard therapy for muscle-invasive bladder cancer. A better understanding of bladder tumor disease is necessary to choose the optimal treatment and to control each individual patient.

Effectiveness and safety of valrubicin in non–muscle-invasive bladder cancer following reintroduction: Results from a medical chart review study.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 296-296
Author(s):  
Michael S. Cookson ◽  
Christine Francis Lihou ◽  
Samira Q. Harper ◽  
Thomas Li ◽  
Surya Chitra ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Concomitant Medication ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
The United States ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

296 Background: Valrubicin was approved in the United States in 1998, removed from the market in 2002 because of manufacturing issues, and reintroduced in 2009. We report secondary outcomes and concomitant medication use from a US multicenter, observational, retrospective study. Methods: Medical records of adult patients with non–muscle-invasive bladder cancer (NMIBC) who used valrubicin were abstracted (March–September 2011). Kaplan-Meier analyses were performed for disease-free survival (DFS), progression-free survival (PFS), worsening-free survival (WFS), cystectomy-free survival (CFS), and time to cystectomy. Results: 113 patients (mean age, 73.7 years) received intravesical valrubicin (median, 6 instillations [range, 2–18]). 107 patients (94.7%) received >3 instillations; 97 (85.8%) completed the full course of therapy (≥6 instillations). DFS was 51.6% (95% CI, 40.9%–61.3%) at 3 months, 30.4% (95% CI, 20.4%–41.1%) at 6 months, and median DFS was 3.5 months (95% CI, 2.5–4.0). PFS was 97.6% (95% CI, 90.9%–99.4%) at 3 months, 87.2% (95% CI, 75.4%–93.5%) at 6 months, and median PFS was 18.2 months (95% CI, 17.2–19.0). WFS was 47.4% (95% CI, 37.2%–57.0%) at 3 months and 28.1% (95% CI, 18.8%–38.2%) at 6 months. CFS was 98.0% (95% CI, 92.2%–99.5%) at 3 months and 93.7% (95% CI, 85.2%–97.4%) at 6 months. Median CFS was not reached; only 13.3% of patients underwent radical cystectomy after starting valrubicin. 56 patients (49.6%) experienced ≥1 local adverse reaction; the most common were hematuria and pollakiuria (both 17.7%), micturition urgency (15.9%), and bladder spasm (14.2%). 55 patients (48.7%) used ≥1 concomitant medication for local adverse reactions; the most commonly used were urinary antispasmodics (21.2%), fluoroquinolones (14.2%), and other urologicals (14.2%). Conclusions: In patients with NMIBC treated with intravesical valrubicin, median DFS and PFS were 3.5 and 18.2 months, respectively, and median CFS was not reached as only 13% of patients underwent radical cystectomy. Valrubicin was well tolerated, and most patients received the full course of 6 instillations. Funding: Research and abstract were supported by Endo Pharmaceuticals Inc.

scholarly journals Prospects for the use of the method of intravesical hyperthermic chemotherapy in the treatment of patients with non-muscle invasive bladder cancer

2021 ◽  
pp. 22-27
Author(s):  
Roman Chystiakov
Keyword(s):  
Bladder Cancer ◽  
Therapy Group ◽  
Disease Free Survival ◽  
Intravesical Chemotherapy ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Hyperthermic Chemotherapy ◽  
Bcg Therapy ◽  
Muscle Invasive ◽  
Disease Free

The aim: to compare disease-free survival time (DFS) in high-risk non-muscle-invasive bladder cancer patients treated with adjuvant hyperthermic intravesical chemotherapy and standard BCG therapy. Materials and methods: patients were divided into 2 groups. Group 1 (control) included patients who received adjuvant therapy after TURB with BCG vaccine (BCG therapy group; n=50), group 2 (study group) included patients (HIVEC® therapy group; n=46 ), who received adjuvant intravesical chemotherapy using a Combat BRS HIVEC® device for local hyperthermia. Results: median follow-up was 23 months (range 4 - 36). Tumor recurrence was reported in 19 patients receiving intravesical BCG therapy and in 8 patients receiving intravesical hyperthermic chemotherapy. The incidence of DFS in patients receiving chemohyperthermy was statistically higher than in patients receiving BCG therapy (log-rank test result: p=0.029). Conclusions: The method of hyperthermic intravesical chemotherapy significantly increased the 2-year disease-free survival rate - 82.6 % versus 62 % BCG therapy group (p=0.025). Its use in the future will allow increasing the frequency of organ-preserving treatment of patients with primary and recurrent muscular-non-invasive bladder tumors

scholarly journals Construction of an Immune-Associated Gene-Based Signature in Muscle-Invasive Bladder Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Chengquan Shen ◽  
Ting Xu ◽  
Yefeng Sun ◽  
Liping Wang ◽  
Zhijuan Liang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Survival Analysis ◽  
Risk Score ◽  
Disease Free Survival ◽  
Differentially Expressed ◽  
Invasive Bladder Cancer ◽  
Prognostic Signature ◽  
Muscle Invasive Bladder Cancer ◽  
Free Survival ◽  
Muscle Invasive

Background. In recent years, immune-associated genes (IAGs) have been documented as having critical roles in the occurrence and progression of muscle-invasive bladder cancer (MIBC). Novel immune-related biomarkers and a robust prognostic signature for MIBC patients are still limited. The study is aimed at developing an IAG-based signature to predict the prognosis of MIBC patients. Methods. In the present study, we identified differentially expressed IAGs in MIBC by using transcriptomics data from The Cancer Genome Atlas (TCGA) database and proteomics data from our samples. We further constructed an IAG-based signature and evaluated its prognostic and predictive value by survival analysis and nomogram. Tumor Immune Estimation Resource (TIMER) was applied to explore the correlation between the IAG-based signature and immune cell infiltration in the microenvironment of MIBC. Results. A total of 22 differentially expressed IAGs were identified, and 2 IAGs (NR2F6 and AHNAK) were used to establish a prognostic signature. Subsequently, survival analysis showed that high-risk scores were significantly correlated with poor overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of MIBC patients. A prognostic nomogram was constructed by integrating clinical factors with the IAG-based signature risk score. In addition, the IAG-based signature risk score was positively associated with the infiltration of macrophages and dendritic cells in MIBC. Conclusions. We constructed and verified a novel IAG-based signature, which could predict the prognosis of MIBC and might reflect the status of the immune microenvironment of MIBC. Further studies in more independent clinical cohorts and further experimental exploration of the prognostic IAG-based signature are still needed.

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