scholarly journals Stromal marker fibroblast activation protein drives outcome in T1 non-muscle invasive bladder cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257195
Author(s):  
Tim Muilwijk ◽  
Murat Akand ◽  
Sofie Daelemans ◽  
Koen Marien ◽  
Yannick Waumans ◽  
...  

Fibroblast activation protein-α (FAP) is a transmembrane peptidase and a surrogate marker for cancer-associated fibroblasts (CAFs). FAP has been linked to worse prognosis and therapy resistance in several cancers. We hypothesised that FAP might have a prognostic 3biomarker potential to stratify patients with high-grade (HG) T1 non-muscle-invasive bladder cancer (NMIBC). We selected 30 patients with HG T1 NMIBC that progressed to ≥T2 disease which were pair-matched based on CUETO progression score variables with 90 patients that did not progress. After revision a final cohort of 86 patients was retained. Slides were stained for FAP, the luminal marker GATA3 and the basal marker CK5. All HG T1 tumour regions of interest (ROIs) within each patient were annotated, analysed and scored using image analysis software. FAP expression in HG T1 ROIs was significantly higher in progressors vs. non-progressors and was prognostic for recurrence-free survival, progression-free survival, cancer-specific survival, and overall survival. FAP expression in HG T1 ROIs remained strongly prognostic for these outcomes in a bivariable model corrected for adequate BCG per FDA definition. Expression of GATA3 and CK5 did not differ between progressors vs. non-progressors, and were not prognostic for these outcomes. FAP might serve as an easily applicable prognostic biomarker to risk-stratify patients with HG T1 NMIBC if these results are prospectively validated in a larger series.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 516-516
Author(s):  
Hiroaki Matsumoto ◽  
Kazuhiro Nagao ◽  
Sho Ozawa ◽  
Masahiro Samoto ◽  
Junichi Mori ◽  
...  

516 Background: Radical cystectomy is still the standard treatment for muscle-invasive bladder cancer (MIBC), while the patients with MIBC are not always appropriate candidates due to multiple comorbidities. We establish novel treatment strategy by trimodal treatment. Methods: The regimen was gemcitabine 300 mg/m2, and cisplatin 30mg/m2 in day 1 and concomitant irradiation 2Gy/Fr, 5 fraction per week. Irradiation was administered to whole pelvis up to 30Gy, then boost to true pelvis until total 48Gy to 54Gy. Extensive transurethral resection (TURBT) was performed and we confirmed pathological stage ≥T2. TURBT was also performed after chemoradiotherapy to evaluate the pathological response to treatment. This study was approved in our institutional review board (ID: H23-89) and the information was opened on UMIN (ID: UMIN000006363). We analyzed their treatment efficacy and survival. Results: The patients were 29 men and 9 women, median age was 76.5 y.o. and median follow up was 23 months (1 - 112). Clinical stage T2, T3, T4, N1 and N2 were 23, 10, 5, 4, 2 cases, respectively. The 2- and 5-year metastatic-free survival (MFS), bladder-recurrence free survival (bRFS), cancer-specific survival (CSS), and overall survival (OS) rates after treatment were 91.7 and 84.0%, 59.7 and 42.6%, 87.3 and 87.3%, and 87.3 and 81.8%, respectively. Salvage cystectomy was performed 3 patients and they were still alive. CR rate was 78.9% and overall response rate was 92.1%. cT stage and valiant histology was not associated with treatment response. The patients achieved CR had significant good prognosis in CSS (p=0.0149) and OS (p=0.0149) compared with non-responders. In cox hazard model, CR achievement was significant prognostic factors for OS (p =0.0015, HR 6.804e+26, 95% CI 56.94-1.631e+86). Patients were able to receive 3 to 5 cycle GC radiation and any grade 3 or more adverse event was 7 (18.4%) cases. no treatment related death was recorded. Conclusions: In selected patients, GC radiation for MIBC may provide good oncological outcomes as bladder preservation strategy.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Makito Miyake ◽  
◽  
Kota Iida ◽  
Nobutaka Nishimura ◽  
Tatsuki Miyamoto ◽  
...  

Abstract Background To explore possible solutions to overcome chronic Bacillus Calmette–Guérin (BCG) shortage affecting seriously the management of non-muscle invasive bladder cancer (NMIBC) in Europe and throughout the world, we investigated whether non-maintenance eight-dose induction BCG (iBCG) was comparable to six-dose iBCG plus maintenance BCG (mBCG). Methods This observational study evaluated 2669 patients with high- or highest-risk NMIBC who treated with iBCG with or without mBCG during 2000–2019. The patients were classified into five groups according to treatment pattern: 874 (33%) received non-maintenance six-dose iBCG (Group A), 405 (15%) received six-dose iBCG plus mBCG (Group B), 1189 (44%) received non-maintenance seven−/eight-dose iBCG (Group C), 60 (2.2%) received seven−/eight-dose iBCG plus mBCG, and 141 (5.3%) received only ≤5-dose iBCG. Recurrence-free survival (RFS), progression-free survival, and cancer-specific survival were estimated and compared using Kaplan–Meier analysis and the log-rank test, respectively. Propensity score-based one-to-one matching was performed using a multivariable logistic regression model based on covariates to obtain balanced groups. To eliminate possible immortal bias, 6-, 12-, 18-, and 24-month conditional landmark analyses of RFS were performed. Results RFS comparison confirmed that mBCG yielded significant benefit following six-dose iBCG (Group B) in recurrence risk reduction compared to iBCG alone (groups A and C) before (P < 0.001 and P = 0.0016, respectively) and after propensity score matching (P = 0.001 and P = 0.0074, respectively). Propensity score-matched sequential landmark analyses revealed no significant differences between groups B and C at 12, 18, and 24 months, whereas landmark analyses at 6 and 12 months showed a benefit of mBCG following six-dose iBCG compared to non-maintenance six-dose iBCG (P = 0.0055 and P = 0.032, respectively). There were no significant differences in the risks of progression and cancer-specific death in all comparisons of the matched cohorts. Conclusions Although non-maintenance eight-dose iBCG was inferior to six-dose iBCG plus mBCG, the former might be an alternative remedy in the BCG shortage era. To overcome this challenge, further investigation is warranted to confirm the real clinical value of non-maintenance eight-dose iBCG.


2015 ◽  
Vol 33 (12) ◽  
pp. 1959-1964 ◽  
Author(s):  
Peter Rubenwolf ◽  
Christian Thomas ◽  
Stefan Denzinger ◽  
Arndt Hartmann ◽  
Maximilian Burger ◽  
...  

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 294-294
Author(s):  
Andrew J. Lightfoot ◽  
Benjamin N. Breyer ◽  
Henry M. Rosevear ◽  
Badrinath Konety ◽  
Michael A. O'Donnell

294 Background: Combination chemotherapy is the standard of care for neoadjuvant, adjuvant, and metastatic bladder cancer due to increased efficacy when compared to monotherapy. We report our experience with sequential intravesical combination chemotherapy using gemcitabine and mitomycin C (MMC) for non-muscle invasive bladder cancer (NMIBC). Methods: We performed a multi-institutional retrospective review of 47 consecutive patients who received 6 weekly treatments with sequential gemcitabine (1g) and mitomycin C (40mg) chemotherapy for NMIBC. Thirty patients received treatment at University of Iowa, 14 at UCSF and 3 at University of Minnesota. Results: A total 47 patients (median age 70, range 32-85; 36 males, 11 females) previously failing a median of 2 intravesical treatments were reviewed. The complete response (CR), 1-year recurrence-free survival (1-RFS) and 2-year recurrence-free survival (2-RFS) for all patients was 68%, 48% and 38%, respectively. In all, 14 of 47 patients (30%) remain free of recurrence with a median time to followup of 26 months (range 6-80 months). The median time to recurrence for all patients who recurred was 4 months (range 1-33 months). Ten patients required cystectomy. Conclusions: Sequential intravesical combination chemotherapy using gemcitabine and MMC appears to be a useful treatment for patients with a history of NMIC which has failed BCG or other intravesical therapy, in addition to patients with intermediate and high-risk disease.


2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 296-296
Author(s):  
Michael S. Cookson ◽  
Christine Francis Lihou ◽  
Samira Q. Harper ◽  
Thomas Li ◽  
Surya Chitra ◽  
...  

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.


2018 ◽  
Vol 104 (6) ◽  
pp. 434-437
Author(s):  
Hakan Türk ◽  
Sıtkı Ün ◽  
Ahmet Cinkaya ◽  
Hilmi Kodaz ◽  
Murtaza Parvizi ◽  
...  

Introduction: Radical cystectomy (RC) is the main treatment option for patients with muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC), which carry the highest risk of progression. In this study, we investigated the effect of time from transurethral resection of the bladder (TUR-B) to cystectomy on lymph node positivity, cancer-specific survival and overall survival in patients with MIBC. Methods: The records were reviewed of 530 consecutive patients who had RC and pelvic lymphadenectomy procedures with curative intent performed by selected surgeons between May 2005 and April 2016. Our analysis included only patients with transitional cell carcinoma of the bladder; we excluded 23 patients with other types of tumor histology. Results: Patients who underwent delayed RC were compared with patients who were treated with early RC; both groups were similar in terms of age, gender, T stage, tumor grade, tumor differentiation, lymph node status and metastasis status. However, when both groups were compared for disease-free survival and overall survival, patients of the early-RC group had a greater advantage. Conclusions: The optimal time between the last TUR-B and RC is still controversial. A reasonable time for preoperative preparation can be allowed, but long delays, especially those exceeding 3 months, can lead to unfavorable outcomes in cancer control.


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