A large analysis of two major clinical trials has found that the spread of prostate cancer can be detected on imaging scans even when biomarkers remain stable in patients treated with androgen receptor inhibitors, according to the study published in the Journal of Clinical Oncology.
The findings, drawn from more than 2,500 patients, raise questions about how physicians monitor prostate cancer treatment response and suggest that relying solely on prostate-specific antigen (PSA) levels — the most commonly used blood biomarker for the disease — may leave some disease progression undetected.
“This is a retrospective analysis looking at the potential association of PSA progression with imaging progression,” said study co‑author Maha Hussain, MD, the Genevieve E. Teuton Professor of Medicine in the Division of Hematology and Oncology, a prostate cancer expert who served as a principal investigator on one of the trials. “PSA is a biomarker. It’s a test that we do across the spectrum of prostate cancer.”
PSA has long been a mainstay of prostate cancer management, helping clinicians track how well therapies are working and when prostate cancer is progressing. But investigators behind the new study found that in a meaningful subset of patients receiving the drug enzalutamide, radiographic progression — worsening disease detectable on imaging — occurred without a corresponding rise in PSA.
The analysis examined data from two large trials: one that enrolled patients with metastatic hormone-sensitive prostate cancer and another that studied patients with nonmetastatic castration-resistant prostate cancer.
In both trials, radiographic progression without PSA progression was substantially more common among patients treated with enzalutamide plus androgen-deprivation therapy than among patients receiving control treatments.
“What was interesting is that in both of these trials, there were patients who actually progressed, but their PSA never went up,” said Hussain, who is also deputy director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
This data indicates that radiographic progression represents a worsening of disease, not merely an incidental finding, Hussain said.
“This is something we’re beginning to see more in the era of the more powerful androgen receptor inhibitors,” she said, compared with decades past.
Together, the findings challenge the long-standing assumption that PSA trends alone are sufficient to monitor prostate cancer disease status including response or progression, particularly in patients receiving potent androgen receptor inhibitors like enzalutamide.
While PSA levels remain a valuable biomarker, the results underscore the need for a more nuanced approach to prostate cancer monitoring, Hussain said.
“I think the big picture is this: clearly we need to balance management of the patients and making sure that we are evaluating the cancer and not just go by blood tests,” Hussain said. “Periodic imaging is needed.”
When it comes to tracking prostate cancer progression, what clinicians can’t see in the blood may still show up on the scan, Hussain said.
“Anytime we see scans looking worse, if it doesn’t make sense — meaning this does not seem like fitting within what the prostate cancer is doing — it’s critical to biopsy, especially if people develop new metastases in the liver or in the lung,” she said.
The study was supported by Pfizer Inc. and Astellas Pharma Inc.
