Is the Patient Actually Failing on Enzalutamide? A Case Report and Issues to Consider in Enzalutamide-Resistant Oligoprogressive Metastatic Castrate-Resistant Prostate Cancer

Background: Metastatic castrate-resistant prostate cancer (mCRPC) is a challenging disease, especially in heavily pretreated patients. Androgen pathway inhibitors have contributed to a notable improvement in the overall survival and quality of life in patients with mCRPC during the last decade. Still, a considerable percentage of patients are unable to draw benefits from this drug category and are deprived of a treatment that offers limited toxicity and preserves a good quality of life. The mechanisms leading to this pre-existing or acquired resistance, as well as the possible strategies to overcome this resistance have been put at the center of scientists’ attention. Case Presentation: With the present report we present the case of a 70-year-old patient with mCRPC, who was apparently an enzalutamide non-responder, but a multimodal approach with enzalutamide continuation and irradiation to his symptomatic oligoprogressive disease converted him to a responder with clinical, biochemical and imaging response; furthermore, we discuss the existing data providing evidence for the use of metastasis-directed therapy in combination with androgen pathway inhibitors in order to overcome drug resistance in patients with oligoprogressive disease. Conclusion: A considerable proportion of patients with oligometastatic or oligoprogressive prostate cancer who seem not to respond to androgen pathway inhibitors, such as enzalutamide, due to preexisting or acquired resistance, could benefit from MDT with a multimodal treatment approach. This strategy allows androgen pathway inhibitor continuation beyond biochemical progression and delays the switch to next-line systemic treatment.