Combined assessment of peritumoral Th1/Th2 polarization and peripheral immunity as a new biomarker in the prediction of BCG response in patients with high-risk NMIBC.

Intravesical Bacille Calmette-Guérin (BCG) remains the most effective treatment for high-risk non-muscle-invasive bladder cancer (NMIBC), unfortunately there is no validated biomarker to predict clinical outcome. Here we tried to explore the possibility that a combination of the density of peritumoral infiltrating cells (Th1, Th2 and PD-L1) and the composition of peripheral immune cells (neutrophil and lymphocyte counts) could generate a more reliable prognostic biomarker. Twenty-two patients with high-risk NMIBC treated with BCG (10 BCG nonresponders and 12 BCG responders) were selected. BCG responders had significantly lower level of peritumoral T-bet+ cells with an associated higher GATA-3+/T-bet+ ratio (p = 0.04, p = 0.02, respectively). Furthermore, the immune polarization in tissue (GATA-3+/T-bet+ ratio) adjusted for the systemic inflammation (neutrophil-to-lymphocyte ratio) showed a significantly higher association with the BCG response (p = 0.004). A survival analysis demonstrated prolonged recurrence-free survival (RFS) in patients with a lower T-bet+/Lymphocyte ratio and higher GTR/NLR (p = 0.01). No association was observed between peritumoral PD-L1+ expression and the BCG response. In conclusion, alterations in overall immune function, both local and systemic, may influence the therapeutic response to BCG, therefore a combined analysis of tumoral (Th2/Th1 ratio) and peripheral (NLR) immune composition prior to treatment may be a promising approach to predict the BCG response in high-risk NMIBC patients.

Bladder cancer: Present and future. / Tumor vesical: presente y futuro.

Bladder cancer has a high incidence and involves high associated morbidity and mortality. Since its initial clinical suspicion, early diagnostic confirmation and multimodal treatment involve different medical specialties. For this reason, we consider it important to spread the current consensus for its management. Recent advances in immunology and Chemotherapy make it necessary to expose and reflect on future perspectives.

Role of Inflammation in the Perioperative Management of Urothelial Bladder Cancer With Squamous-Cell Features: Impact of Neutrophil-to-Lymphocyte Ratio on Outcomes and Response to Neoadjuvant Chemotherapy.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) might reflect an increased neutrophilic inflammatory response, and urothelial tumors with squamous-cell features (SqD) have been linked to inflammation. We hypothesized that NLR could be prognostic in these patients. PATIENTS AND METHODS: In patients with SqD muscle-invasive bladder cancer treated with curative intent, NLR and relationships with outcomes were analyzed by Cox regression, log-rank, and Kaplan-Meier analysis. RESULTS: Fifty patients presented SqD (median follow-up, 29 months). The ideal NLR cutoff (by receiver operating characteristic curves) was 5. Thirty-seven patients had NLR < 5 and 13 had NLR ≥ 5. The 5-year progression-free survival, cancer-specific survival (CSS), and overall survival were 46.8%, 48.4%, and 45% for NLR < 5 cases, and 10.3%, 10.3%, and 11.7% for NLR ≥ 5 cases (all P < .05). On multivariate analysis, NLR was prognostic (hazard ratio = 4.26, 6.21, and 4.08 for progression-free survival, CSS, and overall survival). Neoadjuvant chemotherapy (NAC) was of significant benefit in NLR < 5 patients, with a CSS of 91.2 months (n = 3) versus 38.1 months (n = 24) for those treated with up-front radical cystectomy (P = .009); Kaplan-Meier curves were also significantly different. These differences did not reach statistical significance for patients with NLR ≥ 5. For the 19 patients treated with NAC, NLR was also predictive of response to NAC. CONCLUSION: Inflammation, measured by NLR, is potentially prognostic in the perioperative management of SqD. NLR identifies 2 risk groups. Patients displaying low NLR had a 4-fold survival improvement and were highly responsive to NAC. NLR might be a good prognostic tool. Its role as a predictor of response to NAC deserves future study, along with its role as a selection criterion for therapies other than chemotherapy.

Low Pretreatment Neutrophil-to-Lymphocyte Ratio Predicts for Good Outcomes in Patients Receiving Neoadjuvant Chemotherapy Before Radical Cystectomy for Muscle Invasive Bladder Cancer.

PURPOSE: The pretreatment neutrophil-to-lymphocyte ratio (NLR) has been associated with cancer prognosis, influencing progression and chemosensitivity. We aimed to define the role of the NLR in predicting the outcomes to neoadjuvant chemotherapy (NAC) in patients with muscle invasive bladder cancer (MIBC). PATIENTS AND METHODS: The data from patients treated with NAC and radical cystectomy for MIBC from 2007 to 2015 at a tertiary care center were reviewed. The clinicopathologic pretreatment, including the NLR, and post-treatment predictors were documented. The NLR was evaluated as a continuous variable on uni- and multivariate analysis and dichotomized in Kaplan-Meier curves. The relationships with outcomes (progression-free survival [PFS], cancer-specific survival [CSS], and overall survival [OS]) were analyzed using Cox regression analysis and log-rank tests. The pathologic response (PR) included any downstaging from the baseline clinical stage to the final pathologic stage. RESULTS: Of 205 patients with MIBC, 75 underwent NAC (median follow-up, 31 months) with a 5-year PFS, CSS, and OS rate of 56%, 60%, and 52%, respectively, and a PR of 38.6%. On multivariate analysis, the PR, PFS, CSS, and OS were predicted by the NLR (hazard ratio > 0.8, 1.25, 1.27, and 1.12, respectively; P < .05 for all). The NLR with age and clinical stage predicted the PR. A NLR threshold of 2.26 better predicted CSS (P < .05) and OS (P = .055). The limitations included the retrospective design and modest number of cases. CONCLUSION: We have provided initial evidence that a low NLR helps understand the value of the underlying immune system in predicting a good outcome to NAC. The NLR is a simple and accessible biomarker that is easy to implement in clinical practice. In addition to established prognosticators and newer genomic predictors, the NLR could improve therapeutic algorithms and help in decision-making regarding the need for NAC, which is currently underused, in MIBC patients.