Nutraceuticals in Uro-Oncology: A Structured Expert Review and Precision-Oriented Framework

Abstract

Urologic malignancies (UMs), including prostate cancer (PCa), bladder cancer (BCa), renal cell carcinoma (RCC), and testicular germ cell tumors (TGCT), are governed by interconnected molecular pathways that regulate proliferation, angiogenesis, metabolism, invasion, immune escape, and treatment resistance. Key pathways include PI3K/AKT/mTOR, VEGF/VEGFR, EGFR, FGFR, c-MET, androgen receptor signaling, DNA damage response, inflammatory transcriptional programs, and regulation of the tumor microenvironment. This structured expert review evaluates mechanistic, translational, epidemiological, and clinical evidence on food- and botanical-derived nutraceuticals that may influence cancer-related signaling, redox balance, inflammation, metabolic adaptation, and host-tumor interactions. Nutraceuticals are considered investigational adjunctive exposures rather than anticancer treatments or alternatives to standard care. Relevant literature was identified through a structured, non-systematic search of PubMed/MEDLINE, Scopus, Web of Science Core Collection, and Embase from database inception to 17 June 2026, supplemented by backward and forward citation searches. Eligible evidence comprised preclinical, observational, interventional, pharmacokinetic, formulation, safety, and drug-nutraceutical interaction studies. Evidence was evaluated by cancer type, compound class, molecular context, formulation, exposure, translational maturity, and safety, and was classified into five stages: prevention signal, mechanistic plausibility, bioavailability and exposure feasibility, exposure-linked biomarker activity, and clinical benefit. An exposure-species-compartment framework was used to assess whether parent compounds and relevant metabolites reached systemic, urinary, or target-tissue concentrations compatible with the proposed effects. Findings based solely on supraphysiological concentrations of unconjugated parent compounds were considered hypothesis-generating unless supported by human exposure or tissue-distribution data. Curcumin, green tea catechins, isoflavones, carotenoids, flavonols, stilbenes, and triterpenoids affect several cancer-related pathways, primarily in experimental models. Translation to clinical practice is constrained by inconsistent formulations, limited bioavailability, inadequate target-tissue exposure data, few biomarker-linked studies, and possible interactions with anticancer therapies. PCa and BCa provide the most suitable settings for exposure-verified mechanistic studies. In RCC, safety and treatment interactions should be prioritized, whereas in TGCTs, non-interference with curative cisplatin-based therapy must be demonstrated. Future studies should use chemically defined formulations, verify clinically relevant exposure, incorporate mechanism-matched biological-response endpoints, and confirm compatibility with established treatment. Current evidence does not support nutraceuticals as treatments for urologic malignancies.