Systemic Immune-Inflammation Index (SII) as Prognostic Indicator for BCG Therapy in Bladder Cancer: A Systematic Review and Meta-analysis

Abstract

Background Bacillus Calmette-Guérin (BCG) immunotherapy is standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) after tumor resection. However, not all patients respond to BCG therapy. Reliable prognostic markers are needed predict treatment outcomes. This study reviewed prognostic value of systemic immune-inflammation index (SII) and related markers in BCG response. Methods A systematic literature search was conducted in PubMed, Web of Science, and Scopus databases from inception to October 2023 for studies on SII, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in bladder cancer patients receiving BCG therapy. Four retrospective studies involving 1,124 patients met inclusion criteria and were included in qualitative synthesis. Three studies were included in meta-analysis of progression-free survival (PFS) and recurrence-free survival (RFS). Data on study characteristics and demographics, follow-up duration, cancer stage/grade, and pre-treatment marker levels were extracted. Hazard ratios were pooled using a random effects model. Results Elevated pre-treatment SII was associated with significantly worse PFS (HR 3.72, 95% CI: 1.74-7.98, p<0.001) and RFS (HR 3.72, 95% CI: 1.42-9.77, p=0.007). However, significant heterogeneity was found between trials for OS (I2= 83.49, P= 0.002) and RFS (I2=89.69%, p=0.002). In multivariable analysis, SII>672.75 was an independent predictor of BCG failure (OR 2.229, 95% CI: 1.172-4.238, p=0.015). NLR, PLR, and MLR also showed potential prognostic value with AUC values ranging from 0.592 to 0.663 for predicting non-response to BCG therapy. Specifically, NLR>3.0435, PLR>123.4398, and MLR>0.1995 were significantly associated with BCG non-response (p<0.001 for all). On univariable analysis, BCG non-response was associated with high pre-treatment levels of PLR, NLR, and MLR (p<0.001). Conclusion Pre-treatment SII and other inflammatory markers may predict poorer outcomes after BCG immunotherapy in bladder cancer patients. SII holds promise as accessible prognostic biomarker guide treatment decisions. Further large prospective studies are warranted validate these preliminary findings.