PSA Decreases or Fluctuations During PSMA-Targeted Therapy Linked to Prolonged Survival in mCRPC

By Cecilia Brown - July 26, 2022

Decreases or fluctuations in prostate-specific antigen (PSA) levels were linked to significantly longer survival than PSA increases during prostate-specific membrane antigen (PSMA)-targeted radioligand therapy in men with metastatic castration-resistant prostate cancer (mCRPC). Data from the retrospective analysis led by Philipp Hartrampf, MD, of the University Hospital Wüerzburg, and Ralph Bundschuh, MD, of the University Hospital Bonn, were published in the European Journal of Nuclear Medicine and Molecular Imaging.

The study included 176 men with mCRPC who were treated with PSMA-targeted radioligand therapy at the University Hospital Würzburg (177Lutetium [Lu]-PSMA I&T; n = 89) and the University Hospital Bonn (177Lu-PSMA-617; n = 87). The median patient age was 71 years at the first radioligand cycle. PSA levels were assessed before the first radioligand therapy cycle and on admission days for subsequent radioligand therapy cycles. The median baseline PSA level was 179 ng/mL.

Sustained changes in PSA levels were reported in 147 patients (83.5%), with 86 patients (48.8%) showing a sustained decrease in PSA levels and 61 (34.7%) showing a sustained increase in PSA levels. PSA fluctuations were reported in 29 patients (16.5%), with an initial PSA decrease followed by a PSA increase in 22 of those patients. An initial PSA increase followed by a decrease was reported in 7 of the 29 patients who had PSA fluctuations.

The median overall survival (OS) was significantly longer in patients who had a sustained decrease in PSA levels (19 months) than in patients who had a sustained increase in PSA levels (8 months; hazard ratio [HR], 0.35; 95% CI, 0.22-0.56; P<.001).

There was no significant difference in median OS between patients who had PSA fluctuations (18 months) and patients who had a sustained PSA decrease (19 months; HR, 1.4; 95% CI, 0.78-2.49; P=.20). Patients with PSA fluctuations had a significantly longer median OS (18 months) than patients with a sustained PSA increase (8 months; HR, 0.49; 95% CI, 0.30-0.80; P<.01).

In patients with PSA fluctuations, there was no significant difference in median OS between patients who had an initial decrease (16 months) or increase (18 months) in PSA levels (HR, 1.2; 95% CI, 0.38-4.05; P=.68).

The “comparable survival benefit” between patients with sustained PSA decreases and patients with PSA fluctuations may help guide treatment decisions, according to the study’s investigators.

“Thus, such frequent tumor marker oscillations should not lead to an early discontinuation of PSMA- [targeted radioligand therapy],” the authors concluded. “This may apply in particular to scenarios that could be mistaken as progressive disease, such as in patients experiencing initial decline early in the treatment course followed by rise of PSA levels during follow-up, especially in the absence of radiological progression.”


Hartrampf PE, Bundschuh RA, Weinzierl FX, et al. mCRPC patients with PSA fluctuations under radioligand therapy have comparable survival benefits relative to patients with sustained PSA decrease. Eur J Nucl Med Mol Imaging. 2022. doi:10.1007/s00259-022-05910-w