THE PROGNOSTIC ROLE OF THE NEUTROPHIL-TO-LYMPHOCYTE RATIO (NLR) IN HIGH-RISK NON-MUSCLE-INVASIVE BLADDER CANCER PATIENTS TREATED WITH INTRAVESICAL GEMCITABINE AND DOCETAXEL

Mohamad Abou Chakra; Riitta Lassila; Sarah Mott; Nancy El Beayni; Michael O'Donnell

doi:10.1016/j.urolonc.2024.12.210

The management of non-muscle invasive bladder cancer (NMIBC) remains challenging, whereas accurate prediction of recurrence and progression is needed to understand long-term patient's prognosis. Inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), play a pivotal role in predicting response to Bacillus Calmette-Guerin (BCG) therapy used for NMIBC. Given the ongoing BCG shortages, intravesical sequential doublet chemotherapy that consists of Gemcitabine (Gem) and Docetaxel (Doce) has been used in multiple centers worldwide, both for BCG-naïve and BCG-unresponsive disease. Consequently, identifying reliable markers is imperative to ensure optimal patient care and protect them from ineffective intravesical therapy that could adversely impact their quality of life. Our study aims to investigate the role of pretreatment NLR and PLR in predicting the response to sequential intravesical Gem/Doce therapy in BCG-naive high-risk (HR) NMIBC patients. We conducted a retrospective analysis involving 115 patients who received intravesical Gem/Doce for BCG naïve HR-NMIBC between January 2011 and December 2021. Using Cox regression analysis, we assessed whether pretreatment NLR, PLR, and platelet counts were predictive of tumor recurrence and overall survival of patients. To evaluate the predictive performance of NLR and PLR, we utilized Uno's C-statistic. The median follow-up for the overall cohort was 23 months (IQR 13–36). The mean value of PLR was 142.2 (SD: 85.5); of NLR was 3.4 (SD: 2.3); and of platelet count was 225.2 (SD: 75.1) K/mm3. The NLR was able to predict recurrence-free survival (RFS) (C-index: 0.7, p<0.01) and high-grade (HG) RFS (C-statistic: 0.77, p<0.01) reasonably well. The NLR cutoff value of 3 provided a good trade off betweensensitivity and specificity (Figure 1). At this value, sensitivity and specificity were equal to 64.4% and 74.5%, respectively, for predicting RFS at 24 months. The PLR and platelet count did not significantly predict recurrence. In terms of overall survival, none of these inflammatory markers showed a statistically significant predictive value. In HR NMIBC patients undergoing intravesical Gem/Doce therapy, the NLR and other blood inflammatory markers merit prospective investigation as potential indicators of effectiveness of intravesical therapy. It's essential to recognize that individual immune responses to each therapy can vary and induce therapy resistance. Ongoing research should delve into how these therapies modulate the microenvironment of bladder cancer. Additionally, inflammatory markers may provide insights into the intricate molecular processes resulting from immune cell-cancer cell interactions, influencing therapy effectiveness.

THE PROGNOSTIC ROLE OF THE NEUTROPHIL-TO-LYMPHOCYTE RATIO (NLR) IN HIGH-RISK NON-MUSCLE-INVASIVE BLADDER CANCER PATIENTS TREATED WITH INTRAVESICAL GEMCITABINE AND DOCETAXEL

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