Five-year survival of patients with non-small cell lung cancer treated with alkalization therapy

Acidic tumor microenvironments promote malignant progression, immune evasion, and drug resistance. This single-center retrospective cohort study evaluated whether, among patients with stage IV non-small cell lung cancer (NSCLC) who participated in a pragmatic "alkalization therapy"-defined as a low potential renal acid load diet plus oral sodium bicarbonate and/or potassium/sodium citrate-urinary pH was associated with long-term survival, and whether these associations differed by EGFR/ALK mutation status. Urinary pH was used as a surrogate marker of systemic alkalization. All consecutive patients with stage IV NSCLC who first attended Karasuma Wada Clinic between January 2014, and December 2019 were included (n = 203; EGFR/ALK mutation-negative, n = 100; EGFR/ALK mutation-positive, n = 103). All outpatients received standardized instruction in alkalization therapy. For each patient, a mean urine pH value (excluding the first visit) was calculated. Survival was analyzed using Kaplan-Meier methods with log-rank and Gehan-Breslow-Wilcoxon tests, and Cox proportional hazards regression models incorporating recurrence status and urine pH. Overall, the 5-year survival rate was 49·0 % and was similar by mutation status (EGFR/ALK mutation-positive, 49·9 %; EGFR/ALK mutation-negative, 48·6 %). Among EGFR/ALK mutation-negative patients, postoperative recurrence was associated with a more favorable outcome than de novo stage IV disease at initial diagnosis (5-year survival 65·5 % vs 42·0 %; log-rank p = 0·02). In this subgroup, a mean urine pH ≥7·5 was associated with superior 5-year survival (70·0 % vs 39·3 %; log-rank p = 0·04). Given potential confounding, this shows association-not a causal benefit. Urinary pH may serve as a pragmatic marker of acid-base status, particularly in EGFR/ALK-mutation-negative disease.