Scan Growth Without PSA Rise: Key Finding in Enzalutamide-Treated Prostate Cancer

In a detailed review of two large clinical trials called ARCHES and PROSPER, doctors found that some patients experienced cancer growth visible on scans(known as radiographic progression) without seeing the usual rise in PSA blood levels, a key marker doctors often track. This mismatch highlights why regular imaging tests might be just as crucial as PSA checks during treatment.

The studies involved over 2,500 patients: ARCHES focused on men whose cancer had already spread (metastatic hormone-sensitive prostate cancer, or mHSPC), while PROSPER looked at those with cancer that hadn’t spread yet but resisted castration levels of hormones (non-metastatic castration-resistant prostate cancer, or nmCRPC). Led by Dr. Andrew J. Armstrong from Duke Cancer Institute, the team analyzed data sponsored by Pfizer and Astellas, the makers of enzalutamide. They discovered that in the ARCHES trial, about 3.5% of men on enzalutamide plus ADT had scan-detected progression without a PSA increase, and 8.5% without full PSA progression. In PROSPER, those numbers were 4.4% and 10.3%, respectively.

What stood out was how often this happened specifically on enzalutamide compared to ADT alone. For instance, in ARCHES, a quarter of those with scan progression on the combo therapy had no PSA rise, versus only 7.4% on ADT by itself. Similarly, in PROSPER, over 20% on enzalutamide lacked a PSA rise with progression, far higher than the placebo group. Patients showing this scan progression, with or without PSA changes, tended to have worse overall survival, emphasizing the need to catch it early. Liver metastases were also notably more common, over five times higher, in those on enzalutamide who progressed on scans.

This doesn’t mean PSA tests are useless; they’re still valuable. But the findings suggest enzalutamide might sometimes suppress PSA while the cancer keeps growing underneath, a phenomenon called discordance. As a result, experts now recommend routine imaging surveillance, like CT or MRI scans, alongside blood tests to get the full picture and adjust treatments sooner if needed.

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