The FGF signaling network plays a key role in tumorigenesis and is recognized as a potential therapeutic target. FGF23 is predominately expressed in bone osteocytes and can act as an autocrine, paracrine and/or endocrine growth factor in cancer. In this study, we aimed to assess the role of circulating FGF23 levels in the prognosis of cancer patients with bone metastases.
This study included a cohort of 112 patients with cancer (63% breast;16% prostate) and metastatic bone disease treated with bone targeting agents (BTA), in which serum baseline FGF23 was quantified by ELISA and further dichotomized in two groups (FGF23high and FGF23low). Cut-off was defined by mean + one standard deviation. The association of FGF23 with overall survival (OS) and with time to skeletal related events (TTSRE) was investigated. Time to event outcomes was calculated using the Kaplan-Meier method and tested using univariate/multivariate Cox regression models controlling for established prognostic factors across patients with solid tumors and bone metastases: extra-bone involvement, urinary N-terminal telopeptide (uNTX), presence of bone fractures, and calcemia.
Mean FGF23 was 38.16 ± 26.15 pg/mL (interquartile range [IQR] 19.77-50.72). 16.8% of patients were classified as FGF23high (n = 19). Baseline characteristics were balanced between groups, except for the median uNTX level, which was higher in the FGF23high group (824.30 vs 118.02 nmol BCE/mmol creatinine, p = 0.040). Median time from beginning of BTA was similar between groups (1.28 vs 1.10 months, p = 0.161). After a median follow-up of 26.0 months (IQR 13.0-47.0), median OS was 34.4 months in the FGF23low group and 12.2 months in the FGF23high group (multivariate HR 0.18, 95% CI 0.07 – 0.44, p = 0.001; univariate p = 0.001). As a continuous variable, FGF23 at baseline kept its prognostic association (p = 0.001). Patients with FGF23low status at baseline had a longer TTSRE (13.0 vs 2.0 months, p = 0.04).
In this exploratory cohort, patients in the FGF23low group had a longer OS and TTSRE. Further studies are warranted to define its role as a prognostic biomarker and as a potential predictor of response to drugs targeting the FGF axis.
Clinical trial identification
Legal entity responsible for the study
Instituto de Medicina Molecular.
Has not received any funding.
Joana Cavaco Silva - Medical Writer (Medical Oncology Department - Hospital de Santa Maria - Centro Hospitalar Lisboa Norte).
All authors have declared no conflicts of interest.