Rapid Development of Spinal Epidural Lipomatosis after Treatment of Metastatic Castration-Resistant Prostate Cancer with Second-Generation Androgen Receptor Antagonists

BACKGROUND: Previous studies have described the association of spinal epidural lipomatosis with several conditions including chronic steroid therapy, Cushing's syndrome, obesity, Paget disease, and hypothyroidism. We present a report of rapid development of spinal epidural lipomatosis after treatment with second-generation anti-androgen therapy, a new strategy for treatment of metastatic castration-resistant prostate cancer that has been increasingly employed in the past few years. A comprehensive discussion of the underlying molecular networks involving androgen receptor blockage and adipocyte differentiation, as well as the clinical implications of such a phenomenon, are provided. CASE DESCRIPTION: We describe the clinical and radiological evolution of a 58-year-old male patient with metastatic prostate cancer, who developed new onset of rapidly progressing lumbosacral epidural lipomatosis with significant compression of the nerve roots of the cauda equina a few months after initiation of treatment with second-generation androgen receptor antagonists. CONCLUSIONS: The underlying pathophysiology of adipose tissue growth following the administration of anti-androgen therapy is discussed, with emphasis on both the canonical Wnt/beta-catenin pathway as well as in the Wnt-independent pathway involving direct activation of downstream transcription factors from the T-cell factor family by the androgen receptor. As second-generation androgen receptor antagonists have been increasingly used for treatment of castration-resistant stage metastatic prostate cancer, new onset of symptomatic epidural lipomatosis should be considered as a possible differential diagnosis, especially because the urinary symptoms of cauda equina compression may be improperly attributed to the primary prostate neoplasm.