Metabolic Blood Profiles May Predict Survival and Treatment Response in Advanced Prostate Cancer

A new analysis from the randomized phase II SAKK 08/14 trial suggests that metabolic markers circulating in the blood may help predict survival and treatment response in patients with metastatic castration-resistant prostate cancer (mCRPC). However, the analysis found no reliable metabolic signature identifying patients who benefit from adding metformin to enzalutamide.

The study investigated metabolomics, the comprehensive measurement of small molecules involved in metabolism, including amino acids, fatty acid derivatives and lipids. Researchers analyzed fasting blood samples from 166 patients enrolled in SAKK 08/14, which compared enzalutamide alone with enzalutamide plus metformin.

Using baseline metabolic profiles, investigators evaluated whether specific groups of metabolites could predict overall survival, disease control at 15 months, and a PSA reduction of at least 90%.

In the calibration dataset of 135 patients, metabolic profiles showed predictive value across all three outcomes. For overall survival, the most informative metabolite classes included acylcarnitines, amine oxides, amino acids, vitamins and cofactors, achieving a cross-validated area under the curve (AUC) of 0.73.

Metabolic signatures associated with disease control at 15 months achieved an AUC of 0.72, while those predicting a PSA90 response reached 0.82, suggesting potentially useful discrimination between patients with different treatment outcomes.

The findings are particularly interesting because several identified metabolites are involved in cellular energy production, lipid metabolism and mitochondrial function, biological processes increasingly investigated in prostate cancer progression and treatment resistance.

However, no metabolic signature reliably predicted additional benefit from metformin after correction for multiple statistical comparisons.

This observation is consistent with the main SAKK 08/14 trial results, which found that adding metformin to enzalutamide did not significantly improve disease control or overall survival in the overall study population.

Importantly, this was an exploratory biomarker analysis rather than a prospective validation of a clinical prediction test.

Moreover, the relatively small sample size, the large number of metabolites investigated and the absence of external validation limit the immediate clinical applicability of these findings.

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