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Introduction: New knowledge showed a negative relationship between metabolic syndrome and its components and low-stage incident prostate cancer in contrast with other cancer manifestations including high-stage prostate cancer (1).
Objective: To explore the implications for PSA screening procedures.
Results: We formulated the hypothesis that these anomalous observations in prostate cancer research are explained by the fact that the diagnostic procedure in the 1990s was driven by symptoms; therefore, more men with high-stage prostate cancer were diagnosed. By contrast, the diagnostic approach in the 2000s was PSA-driven with an increased proportion of low-stage prostate cancer. The test of our hypothesis showed that the link between metabolic syndrome components and incident prostate cancer was negative in reports dominated by low-stage prostate cancer and positive in reports dominated by high-stage prostate cancer. Our findings support the hypothesis that the inverse link between metabolic syndrome and its components and low-stage incident prostate cancer in the 2000s is related to a bias mechanism rather than to prostate cancer biology. Inherent in this interpretation is that men with metabolic syndrome and its components have lower testosterone levels than men without these conditions. The testosterone level controls prostate-specific antigen (PSA) production Thus, men with metabolic syndrome and its components have lower PSA levels than men without these disorders. Consequently, fewer men with metabolic syndrome and its components than men without these conditions have a prostate cancer diagnosis, as more men will end up under the PSA cut off level (PSA >3.0 ng/ml) for prostate biopsy. Thus, the findings suggest that the negative link between metabolic syndrome and its components and incident prostate cancer in low-stage prostate cancer is related to a metabolic syndrome associated bias mechanism rather than related to prostate cancer biology.
Conclusion: It is concluded that when a PSA screening approach is used for prostate cancer detection, the PSA-level should be evaluated considering the metabolic profile of the man. This evaluation should be performed before the decision of a prostate gland biopsy is made for the pupose of reducing an under-diagnosis and under-treatment of metabolically unhealthy men and over-diagnosis and over-treatment of metabolically healthy men.
1. Hammarsten et al. Nature Reviews Urology 2018 5:321-33
