Learning from failure: A multifactorial analysis of locoregionally advanced laryngeal cancer (LALC) recurrence and the impact of a standardized SOP in a resource-limited setting.

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Background: In low- and middle-income countries (LMICs), LALC prognosis is often compromised by treatment heterogeneity. This study aimed to stratify predictors of early versus late radiotherapy (RT) failure and evaluate the efficacy of a newly implemented Institutional Standard Operating Procedure (SOP) on survival outcomes. Methods: This two-phase study was conducted at a tertiary center. Phase I (Retrospective): A cohort of 1,000 patients (2016–2020) was reviewed. Failures were stratified by timing: Early (< 12 months) vs. Late (> 12 months). Univariate and multivariate Cox proportional hazards regression models were utilized to identify independent predictors of recurrence. Phase II (Prospective): Based on Phase I findings, a standardized SOP was implemented (2020–2021) for 100 Stage III/IV patients, prioritizing precise target delineation,stringent monitoring of set up error with adaptive replanning,implementation of radionomics with dose escalation and strict nutritional support. Primary endpoints were Recurrence-Free Survival (RFS) and 3-Year Overall Survival (3YOS), calculated using Kaplan-Meier analysis. Results: Phase I: Recurrence occurred in 20% (200/1,000) of the historical cohort. Failures were predominantly Early (n = 165; 82.5%), characterized by local failure (73%). Multivariate analysis identified geographical miss (HR > 1.5; p < 0.05), low RT dose, and poor nutrition as independent predictors of early failure. Late recurrences (n = 35; 17.5%) were driven by inadequate chemotherapy dose and aggressive tumor biology. Phase II: Following SOP implementation (n = 100), the total recurrence rate dropped to 12% at 4 years. Of the 12 failures, 8 occurred within 1 year and 4 between 12–18 months. The 4-year Recurrence-Free Survival (RFS) was 88%. Total mortality was 11% (7 cancer-related, 4 non-malignant), resulting in a 3-Year Overall Survival (3YOS) of approximately 89%. This represents a statistically significant improvement in disease control compared to historical controls. Conclusions: Historical analysis reveals distinct failure patterns: early recurrence is driven by technical and nutritional factors, while late recurrence is associated with systemic therapy inadequacy. Implementation of a targeted SOP addressing these specific vulnerabilities successfully improved RFS to 88% and OS to 89%, validating this protocol as a feasible standard of care for resource-limited settings.