Should Upfront Therapy With Androgen Receptor Signaling Inhibitors Be Used in All Japanese Patients With Metastatic Castration-sensitive Prostate Cancer?

[BACKGROUND/AIM] Treatment strategies for metastatic castration-sensitive prostate cancer (mCSPC) have become complex. This study aimed to investigate the role of androgen receptor signaling inhibitors (ARSI) as upfront therapy for Japanese patients with mCSPC.

[PATIENTS AND METHODS] This retrospective study was conducted using the MAHOROBA database. A total of 418 patients who received ARSI as first-line treatment (group A, n=143) or vintage hormonal therapy as first-line and ARSI as second-line treatment (group B, n=275) were extracted. Propensity score matching (PSM) was conducted to minimize differences between the groups. In group B, secondary progression was defined as progression with ARSI as the second-line treatment after progression to castration-resistant prostate cancer (CRPC). We compared adverse events, first progression-free survival (PFS) rate, second PFS rate, and overall survival (OS) rates.

[RESULTS] Grade 2 or higher adverse events after first-line treatment were observed in 22.4% of patients in Group A and 7.6% of patients in Group B. A total of 234 patients (117 in each group) were identified after PSM. The median follow-up periods for groups A and B were 23 and 47 months, respectively. There was no significant difference in OS between the two groups (=0.46). The first PFS rate was significantly higher in group A than in group B (<0.001). However, when comparing the first PFS rate in group A group with the second PFS in group B, there was no significant difference (=0.35).

[CONCLUSION] Upfront ARSI therapy for Japanese patients with mCSPC significantly extended the time to CRPC but did not demonstrate a benefit in OS compared to vintage hormonal therapy.