scholarly journals Prognostic impact of tumor infiltrating lymphocytes on patients with metastatic urothelial carcinoma receiving platinum based chemotherapy

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Hui-Shan Huang ◽  
Harvey Yu-Li Su ◽  
Pei-Hsu Li ◽  
Po-Hui Chiang ◽  
Cheng-Hua Huang ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Impact ◽  
Platinum Based Chemotherapy ◽  
Metastatic Urothelial Carcinoma ◽  
Infiltrating Lymphocytes

scholarly journals Prognostic Impact of APOBEC3B Expression in Metastatic Urothelial Carcinoma and Its Association with Tumor-Infiltrating Cytotoxic T Cells

2021 ◽  
Vol 28 (3) ◽  
pp. 1652-1662
Author(s):  
Hyunho Kim ◽  
Okran Kim ◽  
Myung Ah Lee ◽  
Ji Youl Lee ◽  
Sung-Hoo Hong ◽  
...  
Keyword(s):  
T Cells ◽  
Confidence Interval ◽  
Urothelial Carcinoma ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Impact ◽  
Cox Regression Analysis ◽  
Platinum Based Chemotherapy ◽  
Metastatic Urothelial Carcinoma ◽  
Infiltrating Lymphocytes

APOBEC3B enzymes are endogenous carcinogenic mutagens. Metastatic urothelial carcinomas often harbor APOBEC3B-mediated mutations in which tCw to T or G substitution occurs. Here, we evaluated patient survival and CD8+ T-cell density according to APOBEC3B expression in patients with metastatic urothelial carcinoma who underwent cytotoxic chemotherapy. We performed a retrospective study on 94 patients with urothelial carcinoma who were treated with first line palliative chemotherapy. APOBEC3B expression and CD8+/CD3+ ratio of tumor-infiltrating lymphocytes were evaluated using immunohistochemistry. Kaplan–Meier survival curves were generated and the log-rank test was employed. The association between APOBEC3B expression and tumor-infiltrating lymphocytes was analyzed using Pearson’s chi-squared test. High APOBEC3B expression was detected in 71 of the 94 patients (75.5%). The median overall survival was longer in patients with high APOBEC3B expression (15 months) than in those with low expression (p = 0.045). The hazard ratio obtained based on the Cox regression analysis was 0.292 (95% confidence interval 0.118–0.723, p = 0.008). APOBEC3B expression was associated with the CD8+/CD3+ ratio (2.914, 95% confidence interval 1.030–8.249, p = 0.039). Collectively, APOBEC3B expression was an independent prognostic factor in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy. Tumor-infiltrating cytotoxic T cells were associated with APOBEC3B expression.

Prognostic Impact of APOBEC3B Expression for Tumor-infiltrating Cytotoxic T cells in Metastatic Urothelial Carcinoma

2020 ◽  
Author(s):  
Hyunho Kim ◽  
Okran Kim ◽  
Myung Ah Lee ◽  
Ji Youl Lee ◽  
Sung-Hoo Hong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Confidence Interval ◽  
Urothelial Carcinoma ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Rank Test ◽  
Log Rank Test ◽  
Metastatic Urothelial Carcinoma ◽  
Infiltrating Lymphocytes

Abstract Background: The APOBEC3B enzymes are endogenous carcinogenic mutagens. Metastatic urothelial carcinomas often harbor APOBEC3B-mediated mutations in which tCw to T or G substitution occurs. A high mutation burden in urothelial carcinoma can increase T-cell immunity against cancer cells, affecting prognosis. In this study, we aimed to evaluate patient survival and CD8+ T-cell density according to APOBEC3B expression in patients with metastatic urothelial carcinoma who underwent cytotoxic chemotherapy.Methods: We performed a retrospective study in 94 patients with urothelial carcinoma who were treated with the first line palliative chemotherapy. Immunohistochemistry staining was performed to evaluate APOBEC3B expression and CD8+/CD3 ratio of tumor-infiltrating lymphocytes. Survival curves according to APOBEC3B expression were generated using the Kaplan–Meier method and compared using the log-rank test. The correlation between APOBEC3B expression and tumor-infiltrating lymphocytes was analyzed using Pearson’s chi-squared test. Results: A high APOBEC3B expression was detected in 71 of the 94 patients (75.5%). The median overall survival of patients with high APOBEC3B expression (15 months) was longer than that of patients with low APOBEC3B expression (p = 0.045 by log-rank test). The hazard ratio based on the Cox regression analysis was 0.252 (95% confidence interval 0.082–0.781, p = 0.017). APOBEC3B expression was associated with the CD8+/CD3+ ratio of tumor-infiltrating lymphocytes (odds ratio 2.914, 95% confidence interval 1.030–8.249, p = 0.039).Conclusions: APOBEC3B expression was an independent prognostic factor in patients with metastatic urothelial carcinoma treated with platinum-based chemotherapy. Tumor-infiltrating cytotoxic T cells correlated with APOBEC3B expression.

The prognostic role of tumor-infiltrating lymphocytes in urothelial carcinoma of bladder: A systematic review and meta-analysis

2020 ◽  
Author(s):  
Zhiqiang Yang ◽  
Yujin Bai ◽  
Xu Hu ◽  
Ping Han
Keyword(s):  
Systematic Review ◽  
Urothelial Carcinoma ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Cochrane Library ◽  
Prognostic Impact ◽  
Infiltrating Lymphocytes ◽  
Urothelial Carcinoma Of Bladder

Abstract Background: Tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment are associated with different prognosis in various malignancies. However, their prognostic impact remains controversial in urothelial carcinoma of bladder (UCB). In this systematic review and meta-analysis, we aimed to investigate the prognostic value of TILs in UCB patients.Methods: A systematic review and meta-analysis was performed using Pubmed, Embase and Cochrane Library. Studies were eligible if they investigated the prognostic value of CD3+, CD4+, CD8+, Foxp3+ lymphocytes or TILs in UCB patients, by time-to-event survival analysis. All studies were appraised for risk of bias using the Quality and Prognosis Studies (QUIPS) criteria. Hazard rations (HRs) with their 95% confidence interval (CIs) from each study were used to generate pooled HRs. Results: A total of 14 studies assessing the impact of TILs on prognostic outcomes in UCB patients were included in final analysis. The pooled analysis indicated a favorable role of CD3+ TILs (HR 0.74 (95% CI 0.62-0.88) for overall survival) and CD8+ TILs (HR 0.46 (95% CI 0.28-0.74) for OS) in the clinical outcomes of UCB, while Foxp3+ TILs were associated with worse survival (HR 2.21 (95% CI 1.47-3.32) for recurrence-free survival). Conclusions: This systematic review and meta-analysis confirmed the favorable prognostic impact of CD3+ and CD8+ tumor-infiltrating T cells in UCB patients and found the association between Foxp3+ TILs and worse survival. Future studies using large cohorts and standardized methodology with regard to tumor subsites, stages and treatment modalities are needed to incorporate TILs with clinical practice.

Early Bone Metastases are Associated with Worse Outcomes in Metastatic Urothelial Carcinoma

2021 ◽  
pp. 1-10
Author(s):  
Ariel A. Nelson ◽  
Robert J. Cronk ◽  
Emily A. Lemke ◽  
Aniko Szabo ◽  
Ali R. Khaki ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Urothelial Carcinoma ◽  
Clinical Outcomes ◽  
De Novo ◽  
Opioid Analgesic ◽  
Multivariable Analysis ◽  
Unmet Need ◽  
Risk Of Death ◽  
Platinum Based Chemotherapy ◽  
Metastatic Urothelial Carcinoma

BACKGROUND: Outcomes of patients with metastatic urothelial carcinoma (mUC) with early bone metastases (eBM) vs no early bone metastases (nBM) have not thoroughly been described in the age of immuno-oncology. OBJECTIVE: To compare survival and other clinical outcomes in patients with eBM and nBM. METHODS: We used a multi-institutional database of patients with mUC treated with systemic therapy. Demographic, metastatic site, treatment patterns, and clinical outcomes were recorded. Wilcoxon rank-sum, chi-square tests were performed. Survival was estimated by Kaplan-Meier method; multivariable Cox analysis was performed. RESULTS: We identified 270 pts, 67%men, mean age 69±11 years. At metastatic diagnosis, 27%had≥1 eBM and were more likely to have de novo vs. recurrent metastases (42%vs 19%, p <  0.001). Patients with eBM had shorter overall survival (OS) vs. those with nBM, (6.1 vs 13.7 months, p <  0.0001). On multivariable analysis, eBM independently associated with higher risk of death, HR = 2.52 (95%CI: 1.75–3.63, p <  0.0001). OS was shorter for patients with eBM who received initial immune checkpoint inhibitor vs platinum-based chemotherapy, (1.6 vs 9.1 months, p = 0.02). Patients with eBM received higher opioid analgesic doses compared to patients with nBM and received quantitatively more palliative radiation. CONCLUSIONS: Patients with mUC and eBM have poorer outcomes, may benefit less from anti-PD-1/PD-L1 therapy and represent an unmet need for novel therapeutic interventions. Dedicated clinical trials, biomarker validation to assist in patient selection, as well as consensus on reporting of non-measurable disease are required.

The prognostic impact of bone metastasis in urothelial carcinoma treated with first-line platinum-based chemotherapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 415-415
Author(s):  
Husam Alqaisi ◽  
Zachary William Neil Veitch ◽  
Carlos Stecca ◽  
Jeenan Kaiser ◽  
Scott A. North ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Performance Status ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Prognostic Impact ◽  
First Line ◽  
Ecog Performance Status ◽  
Cancer Centre ◽  
Platinum Based Chemotherapy ◽  
Line Setting

415 Background: Metastatic urothelial carcinoma (mUC) is an aggressive disease with a median overall survival (OS) of ≈ 15 months. In the first-line setting, key prognostic factors include ECOG performance status, white blood cell count, and response to treatment per the Galsky nomogram. Bone metastases (BM) in mUC are associated with morbidity and mortality but are grouped with visceral disease; hence, their impact on prognosis is not well established. We aimed to assess the survival impact of BM in mUC patients treated with first-line platinum-based chemotherapy (PBC). Methods: A retrospective collection of patient and tumor characteristics, with clinical response to treatment (complete response [CR], partial response [PR]; stable disease [SD] or progressive disease [PD]) for patients treated at Princess Margaret Cancer Centre, Tom Baker Cancer Centre, and Cross Cancer Institute from 2005-2018 was performed. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method. Univariate (UVA) followed by multivariate analysis (MVA) of patient variables [Cox] using PFS and OS was performed. Results: Overall 376 mUC patients were included; 222 (59%) had soft-tissue metastases (STM) only, 70 (19%) had bone-only metastases, and 84 (22%) had both STM and BM. Overall, 35% had PR or CR, 19% had SD, and 39% had PD (7%: unknown response). The median PFS and OS for the whole cohort were 5.6 months (95%CI: 4.8-6.4) and 9.7 months (95% CI: 8.8-10.8) respectively. Select UVA by metastatic site showed inferior PFS for bone-only (p=0.03) and combination STM and BM (p=0.017). Only combination STM and BM were significant on UVA for OS (p=0.002). MVA showed that bone-only metastases (p=0.03) and ECOG 3-4 (p<0.0001) were associated with worse PFS (Table). Predictors of worse OS were the combination of STM and BM (p=0.02), ECOG 3-4 (p=0.001), and WBCs ≥ULN (p=0.02), (Table). Conclusions: BM are a significant predictor of worse outcomes for mUC patients treated with first-line PBC. Consideration as a treatment stratification factor for future studies is suggested. Strategies for the treatment of mUC patients with BM (ie: bone targeted agents) in the first-line setting should be addressed in future trials. [Table: see text]

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