The Efficacy of Enzalutamide for PSA Decline Prior to Lu-177 PSMA Therapy

The androgen signaling pathway plays an important role in the development of prostate cancer, as androgen receptor signaling is a main driver for the growth of prostate cancer cells. Several drugs, including abiraterone and enzalutamide, interfere with the androgen signaling pathway and are used for the treatment of prostate cancer by upregulating prostate-specific membrane antigen (PSMA) expression in prostate cancer cells.

Enzalutamide and other antiandrogens are often used before lutetium-177 PSMA (Lu-PSMA) radioligand therapy (RLT) with promising results, but there is a lack of data on whether or not the upregulation of PSMA expression increases the effect of Lu-PSMA when it is used before RLT.

A research team from Mount Sinai Hospital in New York recently carried out a study to compare the outcomes of patients with prostate cancer who received enzalutamide as an androgen receptor signaling inhibitor with patients who did not receive enzalutamide prior to Lu-PSMA.

A total of 37 patients diagnosed with prostate cancer were included in the study. Each patient had previously undergone Lu-PSMA RLT at a tertiary referral center. Of the 37 patients, 21 who had received prior enzalutamide therapy were placed in the EZ+ group and 16 who had not received enzalutamide therapy were placed in the EZ− group.

Most patients in the EZ+ group were treated with prostatectomy and radiotherapy (10 patients, 47.6%) and received docetaxel (11 patients, 52.3%). In the EZ- group, 6 patients (37.5%) had received prostatectomy and 11 patients (68.7%) had received docetaxel. All P values were greater than .05.

Upon pretreatment 18 F-DCFPyL scan, the EZ+ group had a higher mean standardized uptake value (SUV; 78 vs 27; P=.03) compared with the EZ− group. Little difference was noted in the highest SUV_max values (76 vs 67, EZ+ and EZ−; P=.71). In both groups, most patients had extensive osseous metastatic disease, including 13 (61.9%) patients in the EZ+ group and 10 (62.5%) in the EZ− group. The mean prostate-specific antigen (PSA) level prior to Lu-PSMA was higher in the EZ+ group (368 vs 146; P=.17).

Overall, patients who were treated with enzalutamide prior to Lu-PSMA therapy had higher mean SUV values before treatment with 18 F-DCFPyL scans. Patients who did not receive enzalutamide prior to Lu-PSMA had a higher decline in PSA level after all cycles and did not reach statistical significance. Further studies on progression-free survival and overall survival are needed to determine the impact of enzalutamide on the upregulation of PSMA receptors.