PSA monitoring alone proves inadequate for detecting prostate cancer progression

Abstract

Prostate-specific antigen (PSA) monitoring should not be used alone to monitor patients with metastatic hormone-sensitive prostate cancer (HSPC) or nonmetastatic castration-resistant prostate cancer (CRPC) who are being treated with androgen receptor inhibitors according to the results of a recent analysis.¹

Researchers led by Andrew J. Armstrong, MD, FACP, a professor of medicine at the Duke Cancer Institute Center for Prostate and Urologic Cancers in Durham, North Carolina, conducted a post hoc analysis using data from two phase 3 clinical trials—ARCHES and PROSPER—to evaluate the development of radiographic progression occurring without PSA levels rising or progressing.^{2, 3}

ARCHES included patients with metastatic HSPC treated with enzalutamide plus androgen deprivation therapy (ADT); PROSPER included patients with nonmetastatic CRPC treated with enzalutamide plus ADT.

The results revealed a discordance between imaging-based progression and PSA changes during enzalutamide treatment.

“We clearly found that patients were often developing radiographic progression without meeting PSA progression or without even having a rise in PSA,” Dr Armstrong says. “At radiographic progression, about a quarter of all patients had no rise in PSA at all.”

In ARCHES, 23.2% of patients developed radiographic progression. Among patients treated with enzalutamide plus ADT, 3.5% had no PSA rise, and 8.5% did not meet the parameters of PSA progression at radiographic progression. Among patients with radiographic progression who received enzalutamide plus ADT, 25.3% showed no rise in PSA, and 62.0% did not experience PSA progression; in contrast, the corresponding values were 7.4% and 38.3% for those treated with ADT alone. In PROSPER, 29.3% of patients developed radiographic progression. Among those treated with enzalutamide plus ADT, 4.4% experienced no PSA rise, and 10.3% showed no PSA progression, at the time of radiographic progression. Among patients with radiographic progression, 21.9% had no PSA rise, and 51.3% did not experience PSA progression; in contrast, the corresponding values were 3.6% and 18.8% for patients assigned to the ADT-alone group.

Commenting on the results, Rana R. McKay, MD, a medical oncologist and professor of medicine and urology at the University of California, San Diego, says, “These data highlight that PSA alone is not going to provide the full story for how someone is doing clinically and should serve as one data point out of other data points. The results reinforce a need for periodic surveillance imaging, even in the metastatic hormone-sensitive and nonmetastatic castration resistant setting.”

Dr Armstrong agrees. “We are not saying that clinicians have to do imaging as rigorously as we did in the ARCHES study, which was every 3 months. I would do it every 6 months for the first 2 to 3 years; then over time, if the patient is doing well, I might continue with imaging every 6 to 12 months.”

Dr Armstrong emphasizes that the discordant progression events in their analysis were not associated with the presence of symptoms.

“We can’t rely on a patient telling us when to do imaging; these were not prompted by pain or any change in symptoms,” Dr Armstrong says. “This has to be part of their routine medical care.”