PSMA-Negative Lesion Progression Under 177Lu-PSMA Radioligand Therapy.

T his is the case of a 64-y-old man with metastatic castration-resistant prostate cancer treated with 5 cycles of 177 Lu-prostate-speci fi c membrane antigen (PSMA) radioligand therapy. After 2 cycles, prostate-speci fi c antigen levels declined from 26.1 to 15.2 ng/mL ( 2 42%) and interim PSMA PET/CT showed an overall favorable response with a decrease in whole-body PSMA tumor volume (1,430 cm 3 to 124 cm 3 , 2 91%) and no new lesions (Fig. 1A). Of note, a liver lesion with high baseline PSMA expression (SUV max , 28.0) showed a favorable response, with a decrease in size by CT (Fig. 1B), whereas PSMA-negative liver lesions (SUV max , 5.8) progressed, with signi fi cant increases in size (Fig. 1C). His prostate-speci fi c antigen level subsequently increased to 25 ng/mL after cycle 3, and he received 50 Gy delivered in 5 fractions of stereotactic body radiation therapy to the progressing liver lesions concomitantly with cycle 4, which led to a prostate-speci fi c antigen nadir of 10.9 ng/mL. Unfortunately, his prostate-speci fi c antigen level increased after cycle 5 (16.1 ng/mL) and the patient was switched to docetaxel and carbo-platin. His overall survival was 24 mo after baseline PET/CT. Low PSMA expression in prostate cancer cells can lead to low PSMA-targeted radiopharmaceutical uptake, insuf fi cient radiation dose delivery and subsequent growth of PSMA-negative