Radiographic Progression With and Without Prostate-Specific Antigen Rise in Patients With Advanced Prostate Cancer Treated With Enzalutamide

Clinical Snapshot

Key Findings

• P Value: Not provided in abstract

• Effect Size: 3.4-fold higher rate of radiographic progression without PSA rise in enzalutamide-treated patients (ARCHES), 6.1-fold higher (PROSPER)

• Primary Outcome: Radiographic progression without PSA rise occurred in 25.3% vs 7.4% (ARCHES) and 21.9% vs 3.6% (PROSPER) of patients with enzalutamide vs control

• Nnt Or Sensitivity: Number needed to monitor: approximately 6 patients on enzalutamide to detect one case of radiographic progression without PSA rise

• Confidence Interval: Not provided in abstract

Clinical Application

Highly feasible - requires routine imaging surveillance already standard in Australian oncology practice Enzalutamide is PBS-subsidised for these indications. Results support RACGP and Cancer Council Australia guidelines recommending regular imaging in advanced prostate cancer management Australian patients with mHSPC or nmCRPC receiving enzalutamide through PBS

Abstract

PURPOSE: In patients who received enzalutamide, we characterized the development of radiographic progression (rPD) without prostate-specific antigen (PSA) rise or progression in metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). METHODS: We conducted a post hoc analysis in two phase III trials (N = 2,551; ARCHES [ClinicalTrials.gov identifier: NCT02677896]; PROSPER [ClinicalTrials.gov identifier: NCT02003924]) for co-occurrence of rPD ± Prostate Cancer Working Group 2/3-defined PSA progression, and rPD ± any PSA rise from baseline/nadir by treatment. Kaplan-Meier methods were used for overall survival (OS) outcomes. RESULTS: In ARCHES, 3.5% and 8.5% of 574 patients with mHSPC treated with enzalutamide plus androgen-deprivation therapy (ADT) had no PSA rise or PSA progression at rPD, respectively. Of 79 patients with rPD who received enzalutamide plus ADT, 25.3% had no PSA rise and 62.0% did not meet PSA progression criteria compared with 7.4% and 38.3% of 188 patients with rPD treated with ADT alone, respectively. In PROSPER, 4.4% and 10.3% of 933 patients with nmCRPC treated with enzalutamide plus ADT had no PSA rise or PSA progression, respectively, at rPD. However, of 187 patients with rPD who received enzalutamide plus ADT, 21.9% had no PSA rise and 51.3% did not meet PSA progression criteria compared with 3.6% and 18.8% of 224 patients treated with placebo/ADT, respectively. Liver metastases were >5-fold higher in enzalutamide-treated patients with rPD events versus control, although sample size was small. Compared with no rPD, enzalutamide-treated patients with rPD ± PSA rise or progression had worse OS. CONCLUSION: Given the frequent discordance and poor prognosis of imaging-based progression in the absence of PSA changes during enzalutamide treatment in mHSPC and nmCRPC, periodic surveillance using imaging is recommended.

References

1. 1.Armstrong, A. J., Azad, A. A., Iguchi, T., Stenzl, A., Mottet, N., Russell, D., Rosales, M., Haas, G. P., Saad, F., Hussain, M., & Sternberg, C. N. (2026). Radiographic progression with and without prostate-specific antigen rise in patients with advanced prostate cancer treated with enzalutamide. Journal of Clinical Oncology. https://doi.org/10.1200/JCO-24-02829