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

ABSTRACT: Tumor 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.

SUBMITTER: Eckstein M

PROVIDER: S-EPMC8429693 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:(1) Purpose: Although assessment of tumor-infiltrating lymphocytes (TILs) has been acknowledged to have important predictive prognostic value in muscle-invasive bladder cancer (MIBC), it is limited by inter- and intra-observer variability, hampering widespread clinical application. We aimed to evaluate the prognostic value of quantitative TILs score based on a machine learning (ML) algorithm to identify MIBC patients who might benefit from immunotherapy or the de-escalation of therapy. (2) Methods: We constructed an artificial neural network classifier for tumor cells, lymphocytes, stromal cells, and "ignore" cells from hematoxylin-and-eosin-stained slide images using the QuPath open source software. We defined four unique TILs variables based on ML to analyze TILs measurements. Pathological slide images from 133 MIBC patients were retrospectively collected as the discovery set to determine the optimal association of ML-read TILs variables with patient survival outcomes. For validation, we evaluated an independent external validation set consisting of 247 MIBC patients. (3) Results: We found that all four TILs variables had significant prognostic associations with survival outcomes in MIBC patients (p < 0.001 for all comparisons), with higher TILs score being associated with better prognosis. Univariate and multivariate Cox regression analyses demonstrated that electronic TILs (eTILs) variables were independently associated with overall survival after adjustment for clinicopathological factors including age, sex, and pathological stage (p < 0.001 for all analyses). Results analyzed in different subgroups showed that the eTILs variable was a strong prognostic factor that was not redundant with pre-existing clinicopathological features (p < 0.05 for all analyses). (4) Conclusion: ML-driven cell classifier-defined TILs variables were robust and independent prognostic factors in two independent cohorts of MIBC patients. eTILs have the potential to identify a subset of high-risk stage II or stage III-IV MIBC patients who might benefit from adjuvant immunotherapy.

Project description:BackgroundThe expression alterations of B4GALT1 have been noted in some types of cancer and they are related to cancer cell proliferation, invasiveness, metastasis, and drug resistance. We aimed to establish the expression of B4GALT1 in bladder cancer and its connection to patient outcomes, as well as forecasting the advantages of adjuvant chemotherapy (ACT) in patients with muscle-invasive bladder cancer (MIBC).MethodsThere were 142 and 112 MIBC patients who were consecutively recruited and treated via radical cystectomy from 2008 to 2012 in Shanghai Zhongshan Hospital and Fudan University Shanghai Cancer Center (FUSCC), respectively. Tissue microarrays (TMAs) were constructed in triplicate from specimens that had been fixed in formalin and embedded in paraffin samples. Immunohistochemistry was conducted to evaluate B4GALT1 expression in tumor cores, the connection between B4GALT1 expression and patients' clinical characteristics, and clinical results.ResultsB4GALT1 expression was not connected to clinical prognosis markers, but it was linked to overall survival (OS) (P = 0.013 and P = 0.010, respectively) in the two groups. Moreover, the high levels of B4GALT1 expression were independent indicators of poor OS (P = 0.026 and P = 0.046, respectively). Inclusion of B4GALT1 in the prognostic model revealed a greater predictive accuracy than the primary models. In addition, no differences were observed between B4GALT1 expression (low vs. high) and CD8+ T cell infiltration density (number/cm2) within tumor cores, but there was a positive Pearson correlation between B4GALT1 expression and expression of inhibitory receptor ligands, such as PD-L1 and CTLA4. Most significantly, the advantage of ACT noted in pT3/4 or N+ bladder cancer patients with low B4GALT1 expression was greater than in patients with a high B4GALT1 expression.ConclusionsOur evaluation indicated that B4GALT1 may be a possible prognosticator of MIBC, and it may be a predictive marker for the choice of ACT in pT3/4 or N+ patients.

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

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