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

Andrew J Armstrong¹, Arun A Azad^2,3, Taro Iguchi⁴

¹Department of Medicine, Division of Medical Oncology, Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Durham, NC.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology

|March 27, 2026

Summary

This summary is machine-generated.

Radiographic progression without PSA rise is common in prostate cancer patients on enzalutamide. Imaging surveillance is crucial due to the poor prognosis associated with this discordance.

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Serum and Plasma Copy Number Detection Using Real-time PCR

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Published on: December 15, 2017

Area of Science:

Oncology
Prostate Cancer Research
Clinical Trials

Background:

Enzalutamide is a key treatment for metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC).
Prostate-specific antigen (PSA) rise is a common indicator of disease progression.
Radiographic progression (rPD) can occur independently of PSA changes.

Purpose of the Study:

To characterize radiographic progression (rPD) without prostate-specific antigen (PSA) rise in patients receiving enzalutamide.
To analyze the co-occurrence of rPD with or without PSA progression in mHSPC and nmCRPC.
To evaluate the prognostic significance of imaging-based progression versus PSA-based progression.

Main Methods:

Post hoc analysis of two phase III trials (ARCHES and PROSPER) involving 2,551 patients.
Evaluation of rPD co-occurrence with PSA progression criteria (Prostate Cancer Working Group 2/3).
Kaplan-Meier analysis for overall survival (OS) outcomes based on rPD and PSA status.

Main Results:

In mHSPC (ARCHES), 25.3% of enzalutamide-treated patients with rPD had no PSA rise, compared to 7.4% with ADT alone.
In nmCRPC (PROSPER), 21.9% of enzalutamide-treated patients with rPD had no PSA rise, compared to 3.6% with placebo/ADT.
Enzalutamide-treated patients with rPD, irrespective of PSA changes, exhibited worse overall survival compared to those without rPD.

Conclusions:

Frequent discordance between radiographic and PSA progression exists during enzalutamide treatment for mHSPC and nmCRPC.
Imaging-based progression without PSA changes indicates a poor prognosis.
Periodic imaging surveillance is recommended for patients on enzalutamide to detect rPD early.