Pretreatment NPLH as a Potential Predictor of Pathologic Complete Response to Accelerated MVAC Neoadjuvant...

Background. Accurate prediction of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in muscle-invasive urothelial bladder cancer (MIBC) remains an unmet clinical need. The neutrophil-to-platelet/hemoglobin-to-lymphocyte (NPLH) ratio, a composite hematologic index that reflects both systemic inflammation and nutritional oxygen-carrying capacity, has not been previously evaluated as a predictor of NAC response in this setting. Methods. We retrospectively analyzed 114 consecutive patients with MIBC (cT2-T4, N0-N3) who received accelerated MVAC (aMVAC) NAC followed by radical cystectomy at a single academic center. Pretreatment NPLH (calculated as [neutrophils × platelets]/[hemoglobin × lymphocytes]) was assessed as a predictor of pCR (ypT0N0) and tumor regression grade (TRG). Receiver operating characteristic (ROC) curve analysis, Mann-Whitney U test, and logistic regression were used. NPLH performance was compared to NLR and PLR. Results. pCR was achieved in 35 patients (30.7%). Median NPLH was significantly lower in pCR vs. non-pCR patients (33.9 [IQR 23.1-42.4] vs. 47.6 [IQR 30.7-90.4]; p = 0.0007). NPLH yielded an AUC of 0.700 (bootstrap 95% CI 0.596-0.794) for pCR prediction, numerically superior to NLR (AUC 0.645 [0.542-0.741]) and PLR (AUC 0.643 [0.533-0.747]); DeLong test: NPLH vs. NLR p = 0.079, NPLH vs. PLR p = 0.090. At the optimal cut-off of 44.5, NPLH demonstrated 80.0% sensitivity and 57.0% specificity. pCR rates declined progressively across NPLH quartiles: 48.3% (Q1) to 10.3% (Q4). On multivariate logistic regression, log-transformed NPLH was the only independent predictor of pCR (parsimonious model, OR 0.292, 95% CI 0.131-0.652; p = 0.003; EPV = 17.5). A positive correlation was observed between NPLH and TRG score (Spearman r = 0.284; p = 0.0022), with significant differences between TRG 1 and TRG 3 subgroups (p = 0.0036). Conclusions. Pretreatment NPLH is an independent predictor of pCR to aMVAC in MIBC and is numerically superior to NLR and PLR (DeLong p = 0.079). Consisting exclusively of standard complete blood count parameters, NPLH is readily available and inexpensive. This single-center exploratory study is hypothesis-generating and requires prospective external validation before clinical implementation.