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Cancer, Hypoxia, and Metabolism · Journal article
Cancer Nexus · August 10, 2026
Early or partial results. Treat as a signal, not a conclusion.
This retrospective single-center cohort of 1096 stage IV cancer patients receiving alkalizing therapy reports an association between higher urinary pH and improved overall survival, with each 1-unit increase in pH associated with a 25.3% lower hazard of death (HR 0.747, p=0.0004). The authors acknowledge the findings are associative and hypothesis-generating, explicitly cautioning against causal interpretation, and recommend prospective studies to establish causality.
Single-center retrospective cohort study. Stage IV cancer patients (>20 cancer types) at Karasuma Wada Clinic, January 2014 to April 2024; 1096 patients with ≥3 clinic visits included.. Intervention: Alkalizing therapy: low potential renal acid load (PRAL) diet plus oral sodium bicarbonate and/or potassium/sodium citrate. n = 1,096. Single center (Karasuma Wada Clinic), Japan.
5-year overall survival 39.8% and 10-year overall survival 28.8% across cohort pH ≤5.5 group (n=43) had 1-year survival rate 31.2%; pH >5.5 group (n=1053) had 1-year survival rate 73.2% Each 1-unit increase in urinary pH associated with HR 0.747 (95% CI 0.635–0.878; p=0.0004) for death
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Clinicians should recognize this as hypothesis-generating data only. The observed association between urinary pH and survival is substantial but uncontrolled and likely confounded; the study does not establish that alkalizing therapy itself improves survival, and no causal mechanism is demonstrated. Prospective randomized controlled trials are needed before any change in practice.
Single-center retrospective cohort with no concurrent control group, studying an association between urinary pH and survival in stage IV cancer patients; the authors explicitly state findings are associative and hypothesis-generating rather than causal, and call for prospective studies.
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Clinicians should recognize this as hypothesis-generating data only. The observed association between urinary pH and survival is substantial but uncontrolled and likely confounded; the study does not establish that alkalizing therapy itself improves survival, and no causal mechanism is demonstrated. Prospective randomized controlled trials are needed before any change in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
ABSTRACT Objective This single‐center retrospective cohort study evaluated whether, among patients with stage IV cancer 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. Methods All consecutive patients with stage IV cancer who first attended the Karasuma Wada Clinic between January 2014 and April 2024 were screened. Of 1414 patients with stage IV cancer, 1096 who had at least three clinic visits were included in the analytic cohort. All patients received alkalization therapy, consisting of low potential renal acid load (PRAL) dietary counseling, with oral sodium bicarbonate and/or potassium/sodium citrate added when the urinary pH target was not achieved with dietary intervention alone. Overall survival (OS) was estimated using the Kaplan–Meier method, and survival was compared between subgroups stratified by the 12.5% visit‐order‐trimmed mean urinary pH, defined as the mean after excluding the first and last 12.5% of measurements according to visit order. This study was conducted in accordance with the Declaration of Helsinki, approved by The University of Electro‐Communications (Approval number: H24052), and registered with the UMIN Clinical Trials Registry (UMIN000057017; date of registration: February 14, 2025). Results Across more than 20 cancer types, Kaplan–Meier analysis estimated a 5‐year overall survival of 39.8% and a 10‐year overall survival of 28.8%. When stratified by urinary pH (cutoff, 5.5), the pH ≤ 5.5 group ( n = 43) had a 1‐year survival rate of 31.2%. In contrast, the pH > 5.5 group ( n = 1053) had a 1‐year survival rate of 73.2%, with 5‐ and 10‐year survival rates of 38.5% and 29.2%, respectively. In the three‐group analysis, outcomes were most favorable in the pH ≥ 6.5 group (log‐rank p < 0.0001). In the Cox proportional hazards model stratified by primary tumor site and adjusted for age at the first clinic visit and sex, urinary pH was the only significant covariate; each 1‐unit increase in urinary pH was associated with a 25.3% lower hazard of death (HR, 0.747; 95% CI, 0.635–0.878; p = 0.0004). Conclusions In this retrospective stage IV cancer cohort, long‐term survival exhibited a long‐tail structure with an apparent late survival plateau in a subset of patients. Higher urinary pH may be an accessible measure influenced by renal acid excretion, diet, hydration, medication, and renal function. These findings should be interpreted as associative and hypothesis‐generating, rather than causal. Prospective studies with standardized treatment and longitudinal data capture are warranted to clarify the causality and clinical utility.
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