PSA response following the 'steroid switch' in patients with castration-resistant prostate cancer treated with...

A 69-year-old man presented initially with back pain and incomplete bilateral lower limb paralysis. The level of prostate-specific antigen (PSA) in the patient was elevated to 167.0 ng/ml, and multiple bone metastases were detected. Thoracic laminectomy was performed in an emergency due to spinal decompression. Subsequently, the patient was diagnosed with prostate cancer from an examination of resected bone specimens. Combined androgen blockade with degarelix and bicalutamide was initiated in October 2013. Consequently, the serum PSA level decreased to <1.0 ng/ml, but thereafter gradually increased. Subsequent bicalutamide withdrawal response was not observed, and switch of anti-androgen therapy to flutamide also resulted in a poor response. Then, abiraterone (1,000 mg daily) in combination with prednisolone (10 mg daily) was initiated when the level of PSA increased to 35.9 ng/ml in June 2015. The level of PSA decreased to the lowest point of 4 ng/ml; however, PSA level increased again to 21.7 ng/ml in April 2016. Consequently, a 'steroid switch' was attempted. Abiraterone therapy was continued, but concomitant corticosteroid was switched from prednisone to dexamethasone (1.0 mg per day). Fortunately, serum PSA level decreased promptly to the lowest point of 0.6 ng/ml. In the present case report, a review of recent literature was presented and potential explanations of the mechanism underlying the 'steroid switch' were described. Pharmacokinetic differences between dexamethasone and prednisolone may partially explain why the 'steroid switch' occurs. Other mechanisms may include the activation of the glucocorticoid receptor, mineralocorticoid receptor and/or mutant androgen receptor. Corticosteroids accelerate a number of transcription factors, cellular growth factors and cytokines, which may also be potential mechanisms. The 'steroid switch' at PSA progression might be a feasible option for therapy, which may delay the development of the disease. Although the underlying mechanisms require further study, clinicians should pay attention to this phenomenon.