•LYSA provides pragmatic, evidence-based guidelines for LBCL management.
•Optimized PET/CT use for diagnosis, staging, and treatment decision-making.
•Integration of novel immunotherapies and CAR T-cell strategies in all lines.
•Tailored approaches based on age, comorbidities, and disease presentation.
•Clear algorithms for frontline, relapsed, and special LBCL clinical settings.
