同種エザルタミド再投与による転移性去勢抵抗性前立腺癌における化学療法なしでの深部かつ持続的なPSA奏効の症例報告

Contemporary guidelines recommend docetaxel as first-line chemotherapy for chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC) who progress on an androgen receptor signaling inhibitor (ARSI). Cabazitaxel is preferred after prior docetaxel and one ARSI. However, real-world constraints-such as patient preference, access, or comorbidity-often preclude chemotherapy, and cross-resistance among ARSIs is common, making robust responses to same-agent rechallenge uncommon. We report a 74-year-old man diagnosed in 2015 with de novo metastatic hormone-sensitive prostate cancer (Gleason 4 + 4; cT4N1M1b). Under continuous medical castration, he received sequential first- and next-generation ARSIs but consistently declined chemotherapy and radiotherapy. Following biochemical progression on enzalutamide in early 2025, which was accompanied by imaging findings suggestive of a new T12 lesion, and after a brief bicalutamide interval, enzalutamide was rechallenged under a time-limited, PCWG3-aligned protocol with predefined stop rules. Over five months, prostate-specific antigen (PSA) levels declined from 17.73 ng/mL to 2.62 ng/mL (~85% reduction); this PSA response was maintained for ≥5 months through the last follow-up while the patient remained on enzalutamide, without new adverse events or increased analgesic use. This case suggests that in a preference-constrained, chemotherapy-naïve patient, same-agent enzalutamide rechallenge can yield a clinically meaningful PSA response. The observation raises the hypothesis that ARSI resistance may be reversible in a subset of patients, warranting prospective evaluation of biomarker-guided rechallenge strategies to optimize patient selection and minimize opportunity cost.