Neoadjuvant chemotherapy followed by concomitant chemoradiation with gemcitabine in muscle invasive bladder cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4541-4541
Author(s):  
Abdul Mateen ◽  
Allah Rakha Adil ◽  
Quratul Ain Hashmi ◽  
Arif Moin Duraishi ◽  
Famya Abdullah
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Urinary Bladder Cancer ◽  
Disease Recurrence ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
End Point ◽  
Muscle Invasive

4541 Background: Urinary bladder cancer is one of the most prevelent genitourinay cancer in Pakistan. It is especially common in population that consumes smokeless tobacco. Advanced stage at diagnosis is usual presentaion due to illiteracy, poverty and lack of primary health facilities. The study was aimed to optimize treatment of muscle invasive bladder cancer in poor resource country. Methods: A total of 65 patients were enrolled for the study. All patients had muscle invasive disease on transurethral resection. Patients were to in stage range from T2-3, N0 and M0 to be selected. The patients were planned for gemcitabine and cisplatinum (GC) every three weeks in a dose of 1000 mg/m² and 40 mg/m² on D1 and D8 of each cycle respectively. Ultrasonography was performed to assess for any bladder mass at this point. The patients with no visible tumor were planned for whole bladder external radiotherapy (ERT) along with weekly gemcitabine 100 mg/m². A total of 63 Gray (Gy) was planned with 1.8 Gy per fraction and five fractions a week. Gemcitabine was given on 1st day of every week during whole course of ERT.Treatment interruptions were allowed depending upon chemotherapy and ERT related toxicity. Primary end point was to assess disease free survival (DFS) while overall survival was also assessed as a secondary end point. Results: 54 patients (83%) were available for assessment to treatment and to assess DFS and OS. Rest of the patients 11/65 (17%) were excluded from the analysis due to inability to complete the treatment. Five patients (8%) showed disease recurrence during treatment and were switched to other treatment. 11 patients (20%) showed bowel, 15 patients (28%) showed bladder and 8 patients (15%) showed hematological related grade 1-2 toxicity. Four year DFS and OS were 43% and 52% respectively. Mean and median DFS (year) were 3.16±0.36 (95% confidence interval [CI] 2.91 to 3.42) and 2.68±0.54 (95% CI 2.41 to 2.93) respectively. Mean and median OS (year) were 3.95±0.43 (95% CI 3.67 to 4.21) and 3.55±0.31 (95% CI 3.37 to 3.76) respectively. Conclusions: Neoadjuvant chemotherapy with GC followed by concomitant CRT using gemcitabine is an excellent choice for bladder preservation in poor resource countries.

scholarly journals Circulating Tumor DNA Analyses Predict Disease Recurrence in Non-Muscle-Invasive Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jinghua Zhang ◽  
Daofeng Dai ◽  
Junqiang Tian ◽  
Lifeng Li ◽  
Jing Bai ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Size ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Circulating Tumor Dna ◽  
Targeted Sequencing ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive ◽  
Tumor Dna

Circulating tumor DNA (ctDNA) can be a prognostic biomarker for non-muscle-invasive bladder cancer (NMIBC); however, targeted sequencing has not been performed to detect ctDNA in NMIBC. We applied targeted sequencing based on an 861-gene panel to determine mutations in tumor tissue DNA and plasma ctDNA in 82 NMIBC patients receiving transurethral resection (TUR) of bladder followed by immunotherapy. We detected 476 and 165 somatic variants in tumor DNA from 82 NMIBC patients (100%) and ctDNA from 54 patients (65.85%), respectively. Patients with high heterogeneity in tumor DNA had a significantly shorter disease-free survival than those with low heterogeneity. Tumor-derived alterations were detectable in plasma of 43 patients (52.44%). The concordance of somatic variants between tumor DNA and plasma ctDNA were higher in patients with T1 stage (p < 0.0001) and tumor size ≥3 cm (p = 0.0002). Molecular tumor burden index (mTBI) in ctDNA positively correlated with larger tumor size (p = 0.0020). A higher mTBI was an independent predictor of recurrence after TUR of bladder followed by immunotherapy. Analysis of ctDNA based on targeted sequencing is a promising approach to predict disease recurrence for NMIBC patients receiving TUR of bladder followed by immunotherapy.

Using radiologic response to predict prognosis in patients with muscle-invasive bladder cancer undergoing carboplatin-based neoadjuvant chemotherapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 361-361
Author(s):  
Shingo Hatakeyama ◽  
Hayato Yamamoto ◽  
Akiko Okamoto ◽  
Atsushi Imai ◽  
Takahiro Yoneyama ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Multivariate Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Contrast Enhanced Ct ◽  
Muscle Invasive

361 Background: Prognosis and tumor responses of carboplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer (MIBC) are not well documented. To assess the usefulness of carboplatin-based neoadjuvant chemotherapy, we examined the correlation between radiological responses and pathologic down staging on radical cystectomy (RCx) specimens, disease free survival (DFS), and overall survival (OS). Methods: Between March 2005 and June 2013, we performed carboplatin-based neoadjuvant chemotherapy followed by radical cystectomy in 115 patients with T2-4NxM0 MIBC. After diagnostic TUR biopsy, all participants received two courses of Gemcitabine plus Carboplatin therapy. Baseline and post chemotherapy tumor size from contrast enhanced CT were reviewed. The patients were divided in two groups between responders (CR+PR), and non-responders (SD+PD). RCx and bilateral pelvic lymphadenectomy were performed approximately within a month after cessation of chemotherapy. DFS and OS distributions within radiologic response subgroups were estimated with the Kaplan-Meier method and compared using the log-rank test. To evaluate independent predictor for DFS and OS, age, gender, performance status, pathological T and N stage, down-staging, tumor grade, renal function, and radiological responses were applied by Cox-regression multivariate analysis. Results: No significant differences were observed in patient backgrounds between the groups. Radiologic responses were observed in 75 (65%) patients with 69±24% decrease in responder group, whereas tumor response was 2.8±14% in non-responders. The rate of pathological down staging to <pT2 was 37 (49%) in responders, 5 (13%) in non-responders group. Radiologic response was a strong predictor of DFS and OS. A 5-year advantages of DFS and OS in responders vs. non-responders were 88% and 86% vs. 64% and 69%, respectively (P=0.021 and P=0.013). Multivariate analysis showed radiologic response was the independent factor for DFS and OS. Conclusions: Radiological response post carboplatin-based neoadjuvant chemotherapy is associated with OS in patients with MIBC.

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.

scholarly journals A Muscle-Invasive Bladder Cancer Patient With High Tumor Mutational Burden and RB1 Mutation Achieved Bladder Preservation Following Chemotherapy Combined With Immunotherapy: A Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Chuanzhen Cao ◽  
Zhichao Fu ◽  
Yueping Liu ◽  
Aiping Zhou ◽  
Jianfei Wang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Invasive Bladder Cancer ◽  
Adjuvant Chemoradiotherapy ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
Trimodality Therapy ◽  
Muscle Invasive ◽  
Bladder Sparing

Neoadjuvant chemotherapy followed by radical cystectomy is the standard of care for patients diagnosed with muscle-invasive bladder cancer (MIBC). However, urinary diversion following radical cystectomy significantly reduces patient quality of life. In addition, patients who significantly respond to neoadjuvant chemotherapy have a strong will to preserve the bladder. Bladder-sparing therapy has become a research focus worldwide. Although the bladder-sparing regimen, referred to as trimodality therapy (TMT), has been accepted, the efficacy of immunotherapy combined with chemotherapy for bladder preservation in patients with MIBC has not yet been published. We describe the case of a 50-year-old male presented intermittent macrohematuria and was diagnosed with bladder urothelial carcinoma by diagnostic transurethral resection of bladder tumor (TURBt) with clinical stage IIIA (cT3bN0M0). A complete response was achieved after four courses of neoadjuvant chemotherapy combined with pembrolizumab. Then, we performed a second TURBt plus randomized biopsy by cystoscopy. The pathology indicated no tumor in the bladder. Adjuvant chemoradiotherapy and immunotherapy were subsequently performed. Imaging examinations, cystoscopy and urine tumor DNA (utDNA) levels were used for surveillance after treatment. Finally, the patient achieved bladder preservation and had remained cancer-free for 19 months at the last follow-up on February 20, 2021. This is the first published case study to describe neoadjuvant chemotherapy plus pembrolizumab followed by concurrent chemoradiotherapy as a novel bladder-sparing regimen and successfully achieved a promising outcome.

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.

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