Final analysis of our experience with Lu-177-PSMA radioligand treatment at Emory University

Introduction: After the success of VISION trial, FDA approved the use of PSMA radioligand therapy on March 23, 2023. The first successful PSMA treatment cycle at Emory University Midtown Hospital, Atlanta GA took place on July 20, 2022. We report our experience with the first 66 patients eligible for 177Lu-PSMA therapy in our institution. Biochemical and radiological responses to treatment were assessed.

Methods: This is a retrospective analysis of men with metastatic castration resistant prostate cancer undergoing 177Lu-PSMA radioligand treatment (RLT) in our institution. PSA post each cycle from 1-3 were compared with baseline PSA and categorized into 1) increasing/stable PSA, 2) any PSA decrease and 3) >50% PSA decrease. Twelve of the 66 patients had both baseline and post-therapy follow-up 18F-PSMA/68Ga-PSMA PET-CT. Change in tumor burden was calculated using MIM Lesion ID, offered within MIM Encore(https://www.mimsoftware.com/nuclear-medicine/mim-encore). With MIM Lesion ID segmentation settings, potential ROI were created using PERCIST liver method. This method creates a 3 cm spherical cutout using the following equation (2 x reference mean) + (2 x reference standard deviation) using liver as the reference. Unwanted regions can be prevented by being contoured by defining lower and upper volume limits. We in our case used a lower volume limit of 10 ml and higher volume limit of 100 ml. ROI incorporating physiological areas of biodistribution were manually deleted by a resident physician and other contours were also manually corrected, if needed. Subsequently, with the software redefining settings, existing lesions were redefined by 41% of its maximum SUV values. Post this segmentation settings, the software displays tumor burden statistics. We focused on the pre and post treatment total lesion glycolysis as a measure for tumor burden.

Results: Median age of the patients was 71 years (range 47-91 years). 9 patients were deceased at the time of analysis. The median number of radioligand treatments received was 2.7 cycles (range 1-6). Median baseline PSA was 354.2 ng/mL (range 4.6- 1300 mL). For calculation purposes, lab reporting PSA > 1300 was considered to be 1300 ng/mL, and >1000ng/mL to be 1000ng/mL as per labs using whichever to be the higher cutoff limit.

After cycle 1 of treatment, 48 out of 66 had follow up PSA of which: 27 showed increasing/stable PSA and 21 showed any PSA decrease (Of which 6 showed >50% decrease, a subset of any PSA decrease). After cycle 2 of treatment, 30 out of 66 had follow up PSA of which:11 showed increasing/stable PSA and 19 showed any PSA decrease (Of which 10 showed >50% decrease). After cycle 3 of treatment, 21 out of 66 had follow up PSA of which: 10 showed increasing/stable PSA and 11 showed any PSA decrease (Of which 4 showed >50% decrease). On semiautomated radiological comparison; 3 out of 12 patients showed decrease while 9 showed increase in total lesion glycolysis(TLG). Average median increase in total lesion glycolysis (TLG) was 33.2%.

Conclusions: Our findings primarily indicate a favorable trend towards PSA reduction mainly after the second cycle of radioligand treatment. Additionally, in several patients whose PSA remained elevated after first cycle showed significant fall after the second cycle. Our study showed median increase in tumor burden, after the radioligand treatment. This could be because the follow up PET was mainly ordered for suspected treatment refractory cases. Small sample size also limits this interpretation.