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 a 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 to predict treatment outcomes. Objectives: This study reviewed the 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 index, 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 1124 patients met the inclusion criteria and were included in qualitative synthesis. Three studies were included in the 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 (HRs) 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, P672.75 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 area under the curve (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 non-response to BCG (P<0.001 for all). In univariate 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 poor outcomes after BCG immunotherapy in bladder cancer patients. SII holds promise as an accessible prognostic biomarker that can guide treatment decisions. Further large prospective studies are warranted to validate these preliminary findings.

Keywords

• bladder cancer
• bacillus calmette-guérin
• systemic inflammatory response index
• neutrophil-to-lymphocyte ratio
• platelet-to-lymphocyte ratio
• monocyte-to-lymphocyte ratio