Tumor-Infiltrating Lymphocytes (TILs) has been shown to be essential to predict disease outcome in several types of cancers. Moreover, the distribution of cytotoxic T lymphocytes (CD8+) and T cells in general (CD3+) have been used to establish an Immunoscore, as a new cancer prognosticator for survival in colon and lung cancer. In bladder cancer, immune activation has been shown to be associated with genomic subtypes of muscle invasive bladder cancer (MIBC). We sought to evaluate the prognostic impact of these immune cell types in MIBC patients treated with radical cystectomy. For this purpose, cystectomy sections (n = 67) with identifiable invasive margin were selected and stained for CD8+ and CD3+ tumour infiltrating lymphocytes (TILs); both tumor core (CT) and invasive margin (IM) were assessed. Immunoscore was calculated based on previously defined criteria and used to illustrate differences in survival. High density of CD8IM TILs was associated with better disease-free (DFS) (P = 0.01) and overall survival (OS) (P = 0.02) whereas CD3IM TILs were associated with better OS (P = 0.05). Immunoscore was associated with improved DFS (P = 0.02) and OS (P = 0.05). The expression of cytotoxic T cells (CD8+ T cells) in TCGA bladder cancer was also investigated from RNA-Seq profiles of 344 cases. T cell cytotoxicity associated genes (n = 113) were derived from MSig GSEA database. Luminal (n = 121) and basal (n = 68) samples were used to evaluate expression differences. Differential expression (P<0.05) of cytotoxic T cell genes was noted across different molecular subsets of bladder cancer within TCGA analysis. Our data suggests host immune system appears to play a valuable prognostic role in MIBC.
Objectives
To develop and validate the Preoperative Risk Evaluation for Partial Nephrectomy (PREP) score to predict the probability of major postoperative complications after partial nephrectomy (PN) based on patient comorbidities.
Patients and Methods
The Premier Healthcare Database was used to identify patients who had undergone elective PN. Through review of International Classification of Diseases ninth revision codes, we identified patient comorbidities and major surgical complications (Clavien–Dindo Grade III–V). Multivariable logistic regression was used to identify predictors of major complications. We used half of the set as the training cohort to develop our risk score and the other half as a validation cohort.
Results
From 2003 to 2015, 25 451 PNs were performed. The overall rate of major complications was 4.9%. The final risk score consisted of 10 predictors: age, sex, congestive heart failure, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, diabetes, hypertension, obesity, and smoking. In the training cohort, the area under the receiver operating characteristic curve (AUC) was 0.75 (95% confidence interval [CI] 0.73–0.78), while the AUC for the validation cohort was 0.73 (95% CI 0.70–0.75). The predicted probabilities of major complication in the low‐ (≤10 points), intermediate‐ (11–20 points), high‐ (21–30 points), and very high‐risk (>30 points) categories were 3% (95% CI 2.6–3.2), 8% (95% CI 7.2–9.2), 24% (95% CI 20.5–27.8), and 41% (95% CI 34.5–47.8), respectively.
Conclusions
We developed and validated the PREP score to predict the risk of complications after PN based on patient characteristics. Calculation of the PREP score can help providers select treatment options for patients with a cT1a renal mass and enhance the informed consent process for patients planning to undergo PN.
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