scholarly journals Tumor budding correlates with tumor invasiveness and predicts worse survival in pT1 non-muscle-invasive bladder cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Markus Eckstein ◽  
Charlotte Kimmel ◽  
Johannes Bruendl ◽  
Florian Weber ◽  
Stefan Denzinger ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Lamina Propria ◽  
Growth Pattern ◽  
Invasive Bladder Cancer ◽  
Tumor Budding ◽  
Muscle Invasive Bladder Cancer ◽  
Tumor Invasiveness ◽  
Bcg Therapy ◽  
Invasion Pattern ◽  
Muscle Invasive

AbstractTumor budding is defined as a single cell or a cluster of up to 5 tumor cells at the invasion front. Due to the difficulty of identifying patients at high risk for pT1 non-muscle-invasive bladder cancer (NMIBC) and the difficulties in T1 substaging, tumor budding was evaluated as a potential alternative and prognostic parameter in these patients. Tumor budding as well as growth pattern, invasion pattern and lamina propria infiltration were retrospectively evaluated in transurethral resection of the bladder (TURB) specimens from 92 patients with stage pT1 NMIBC. The presence of tumor budding correlated with multifocal tumors (p = 0.003), discontinuous invasion pattern (p = 0.039), discohesive growth pattern (p < 0.001) and extensive lamina propria invasion (p < 0.001). In Kaplan–Meier analysis, tumor budding was associated with significantly worse RFS (p = 0.005), PFS (p = 0.017) and CSS (p = 0.002). In patients who received BCG instillation therapy (n = 65), the absence of tumor budding was associated with improved RFS (p = 0.012), PFS (p = 0.011) and CSS (p = 0.022), with none of the patients suffering from progression or dying from the disease. Tumor budding is associated with a more aggressive and invasive stage of pT1 NMIBC and a worse outcome. This easy-to-assess parameter could help stratify patients into BCG therapy or early cystectomy treatment groups.

scholarly journals Rapamycin enhances BCG-specific γδ T cells during intravesical BCG therapy for non-muscle invasive bladder cancer: a randomized, double-blind study

2021 ◽  
Vol 9 (3) ◽  
pp. e001941
Author(s):  
Niannian Ji ◽  
Neelam Mukherjee ◽  
Ryan M Reyes ◽  
Jonathan Gelfond ◽  
Martin Javors ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cells ◽  
Γδ T Cells ◽  
Percentage Change ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Double Blind ◽  
Bcg Therapy ◽  
Intravesical Bcg ◽  
Muscle Invasive

BackgroundAlthough intravesical BCG is the standard treatment of high-grade non-muscle invasive bladder cancer (NMIBC), response rates remain unsatisfactory. In preclinical models, rapamycin enhances BCG vaccine efficacy against tuberculosis and the killing capacity of γδ T cells, which are critical for BCG’s antitumor effects. Here, we monitored immunity, safety, and tolerability of rapamycin combined with BCG in patients with NMIBC.MethodsA randomized double-blind trial of oral rapamycin (0.5 or 2.0 mg daily) versus placebo for 1 month was conducted in patients with NMIBC concurrently receiving 3 weekly BCG instillations (NCT02753309). The primary outcome was induction of BCG-specific γδ T cells, measured as a percentage change from baseline. Post-BCG urinary cytokines and immune cells were examined as surrogates for local immune response in the bladder. Secondary outcomes measured were adverse events (AEs) and tolerability using validated patient-reported questionnaires.ResultsThirty-one patients were randomized (11 placebo, 8 rapamycin 2.0 mg, and 12 rapamycin 0.5 mg). AEs were similar across groups and most were grade 1–2. One (12.5%) patient randomized to 2.0 mg rapamycin was taken off treatment due to stomatitis. No significant differences in urinary symptoms, bowel function, or bother were observed between groups. The median (IQR) percentage change in BCG-specific γδ T cells from baseline per group was as follows: −26% (−51% to 24%) for placebo, 9.6% (−59% to 117%) for rapamycin 0.5 mg (versus placebo, p=0.18), and 78.8% (−31% to 115%) for rapamycin 2.0 mg (versus placebo, p=0.03). BCG-induced cytokines showed a progressive increase in IL-8 (p=0.02) and TNF-α (p=0.04) over time for patients on rapamycin 2.0 mg, whereas patients receiving placebo had no significant change in urinary cytokines. Compared with placebo, patients receiving 2.0 mg rapamycin had increased urinary γδ T cells at the first week of BCG (p=0.02).ConclusionsFour weeks of 0.5 and 2.0 mg oral rapamycin daily is safe and tolerable in combination with BCG for patients with NMIBC. Rapamycin enhances BCG-specific γδ T cell immunity and boosts urinary cytokines during BCG treatment. Further study is needed to determine long-term rapamycin safety, tolerability and effects on BCG efficacy.

Tumor Budding: Prognostic Value in Muscle-invasive Bladder Cancer

Urology ◽  
2019 ◽  
Vol 130 ◽  
pp. 93-98 ◽  
Author(s):  
Laura Lorenzo Soriano ◽  
Guzmán Ordaz Jurado ◽  
José Luis Pontones Moreno ◽  
Sara Villarroya Castillo ◽  
Soraya Hernández Girón ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Prognostic Value ◽  
Invasive Bladder Cancer ◽  
Tumor Budding ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

S1605: Phase II trial of atezolizumab in BCG-unresponsive non-muscle invasive bladder cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4591-TPS4591 ◽  
Author(s):  
Parminder Singh ◽  
Tangen Catherine ◽  
Seth P. Lerner ◽  
David McConkey ◽  
Melissa Plets ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Invasive Bladder Cancer ◽  
Type I ◽  
Muscle Invasive Bladder Cancer ◽  
Primary Endpoints ◽  
Bcg Therapy ◽  
Muscle Invasive

TPS4591 Background: Radical cystectomy is the standard of care for patients with BCG-unresponsive high risk non-muscle invasive bladder cancer (NMIBC). Based on the reported efficacy of atezolizumab in metastatic urothelial carcinoma and the known expression of PD-L1 expression in NMIBC after BCG therapy, this trial will evaluate the activity of atezolizumab in BCG-unresponsive high risk NMIBC. Methods: This is a single arm phase II trial testing systemic atezolizumab (1200 mg IV) every 3 weeks for one year in 135 patients with BCG-unresponsive high risk NMIBC. The study will enroll 70 patients with CIS (with or without concomitant Ta/T1) and 65 with Ta/T1 only. Patients with CIS at baseline will undergo mandatory repeat biopsy at 6 months, and all other patients only for suspected recurrence. Patients with persistent CIS, high grade Ta/T1 recurrence or progression to muscle invasive or metastatic disease will be taken off treatment. The co-primary endpoints are: (1) complete response (CR) at 6 months in the CIS subgroup, and (2) event-free survival (EFS) at 18 months in the overall population. A hierarchical approach will be used to test the two co-primary endpoints. Secondary endpoints include duration of CR as well as progression-free, cystectomy-free, bladder cancer-specific and overall survival in all patients. Response will be correlated to expression of PD-L1 and CD8 by IHC, and to molecular subtypes and immune signatures by RNA-sequencing. Results: If ≥28 (40%) CIS patients respond, the agent will be considered promising. This design has a significance level of 4.6%, and a power of 96%. If the lower bound of the 90% confidence interval of the 18-month EFS excludes 20%, the investigators will conclude the regimen significantly improves EFS relative to historical data (type I error rate 0.05 and statistical power 0.93). Conclusion:Successful completion of this trial could lead to a new treatment paradigm for patients with BCG-unresponsive high risk NMIBC. Funding: NIH/NCI grants: CA180888, CA180819, CA180820, CA180821, and CA180863. Clinical trial information: NCT02844816.

The DEAL trial: A diet and exercise intervention in (pre)-diabetics during treatment for non-muscle invasive bladder cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 473-473
Author(s):  
Woodson Smelser ◽  
Vassili Glazyrine ◽  
Brian Barnes ◽  
Abigail Stanley ◽  
Misty Bechtel ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Dietary Intervention ◽  
Exercise Intervention ◽  
Invasive Bladder Cancer ◽  
Laboratory Evaluation ◽  
Diabetic Patients ◽  
High Grade ◽  
Muscle Invasive Bladder Cancer ◽  
Bcg Therapy ◽  
Muscle Invasive

473 Background: Patients with diabetes are at greater risk for bladder cancer (BC) as well as disease recurrence and progression. Even after controlling for clinical and pathologic risk factors, DM confers a 2x greater risk of recurrence and 9x greater risk of progression. We hypothesize that utilizing a carbohydrate restricted (CR) diet ( < 130 grams/day) to decrease the bioavailability of glucose in patients with DM and BC, a “Warburg-like” tumor, has potential therapeutic benefit. We designed a study to assess the feasibility of a CR diet in patients with (pre)diabetes and non-muscle invasive bladder cancer receiving BCG therapy. Methods: This is a pilot study of 5 (pre)diabetic patients (defined as HgbA1c > 5.7) with NMIBC receiving BCG and maintenance. A CR diet ( < 130 g/day) was supplied for the first 12 weeks through a meal delivery service. Patients received weekly coaching with a nutritionist for 6 weeks during induction BCG and at the 3 month surveillance cystoscopy with dietary and activity goals implemented. Patients had laboratory evaluation at baseline and at 3 month intervals. Patients tracked their diet. Two (1 weekday, 1 weekend day) unannounced 24 hour diet recalls were obtained to monitor compliance. Dietary compliance was defined as < 130 grams/day of carbohydrate intake. Results: Between 09/2016 and 05/2017, 5 patients were enrolled. Mean age was 66.2 years (Range 59-74). Three patients had diabetes and two patients had pre-diabetes. Two patients had CIS, 1 patient had high-grade Ta, and 2 patients had high-grade T1 disease. Mean baseline hemoglobin A1c was 7.6% (Range 5.9-11.8). Mean bodyweight and BMI were 92 kg (Range 66-105) and 28.2 (Range 23.1- 31.3) respectively. Regarding compliance, 4/5 (80%) patients completed dietary logs and weekly labs. Three patients (60%) achieved their goal of < 130 grams carbohydrates/day on 24-hour dietary recall. Average 3-month HbA1c improved from 7.6% to 6.6% (Range 5.6-7.9). Conclusions: Eighty percent of patients completed dietary logs for the first three months of the trial; 60% achieved compliance with the CR diet. These data demonstrate the feasibility of a dietary intervention utilizing CR in patients with high-grade NMIBC undergoing BCG. Clinical trial information: NCT02716623.

703 Flow cytometry based immunoassay to monitor the BCG-therapy of the non muscle invasive bladder cancer

2013 ◽  
Vol 12 (1) ◽  
pp. e703
Author(s):  
J. Elsaesser ◽  
M. Janssen ◽  
F. Becker ◽  
H. Suttmann ◽  
C-H. Ohlmann ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Bladder Cancer ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bcg Therapy ◽  
Muscle Invasive
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