Time to Castration Resistance is Associated With Overall Survival Even After the Achievement of Castration Resistance in Metastatic Prostate Cancer

ABSTRACT Background Recent clinical trials have shown that patients with metastatic castration‐sensitive prostate cancer in real‐world settings have different overall survival (OS) rates after stratifying for tumor burden or visceral metastasis. However, some patients with a low tumor burden and without visceral metastasis still have a poor survival. Androgen receptor signaling is still a main therapeutic target of prostate cancer treatment even after the achievement of castration resistance. In this regard, we hypothesized that time to castration resistance can be a prognostic factor of metastatic castration‐sensitive prostate cancer even after achieving castration resistance. The current study aimed to assess the novel prognostic factors, particularly time to castration resistance, of prostate cancer in patients at a real‐world single institution. Methods The data of 261 patients who were newly diagnosed with metastatic castration‐sensitive prostate cancer from January 2007 to December 2023 were retrospectively analyzed. Results The median OS was 60.7 months, and the median time to castration resistance was 13.1 months. Among 261 patients, 158 developed castration‐resistant prostate cancer. A shorter time to castration resistance, the presence of distant lymph node metastasis, ISUP grade group 5, and older age were associated with a shorter OS in patients who developed castration‐resistant prostate cancer. A shorter time to castration resistance was significantly associated with a shorter OS regardless of the tumor burden. Further, it was associated with a shorter OS even after the achievement of castration resistance. Conclusions The study results support the presence of persistent androgen receptor signaling even after achieving castration resistance in prostate cancer, and time to castration resistance can be a biomarker for the activation of androgen receptor signaling regardless of tumor burden.