Intense.

Top Line: Does the intensity of PSMA uptake predict a better response to Lu177-PSMA?

The Study: With the proliferation of PET imaging for prostate cancer, it can be challenging to change the way we think about the information provided by different types of PET scans. With FDG-PET, we’ve been trained to think in terms of hypermetabolic activity. In contrast, PSMA-PET images PSMA expression–not necessarily the metabolic activity or proliferation of cancer cells. TheraP was a phase 2 trial that randomized patients with metastatic, castration resistant prostate cancer (mCRPC) progressing after an androgen receptor pathway inhibitor and docetaxel to either Lu177-PSMA or cabazitaxel. It originally showed that progression free survival (PFS) was longer with Lu177-PSMA. Enrolled patients had both a PSMA-PET and an FDG-PET. This study compared outcomes from TheraP based on the intensity of PSMA and FDG activity. SUVmax and SUVmean were calculated for all scans, and metabolic tumor volume was calculated for FDG scans. They defined “high” PSMA uptake as an SUV ≥10 in all lesions and a high FDG uptake as an MTV ≥200 cc. Conveniently, 30% of patients in each arm had high uptake for both PSMA and FDG. While PSA response was higher with Lu177-PSMA than cabazitaxel, the difference in response was much greater among those with high PSMA uptake (91% v 47%) than with low PSMA uptake (52% v 32%). Conversely, those with a higher FDG MTV had a lower PSA response rate (38% v 56%) regardless of treatment arm. Another recent study that generated nomograms to predict outcomes to PSMA therapy also utilized PSMA-PET SUVmean.

TBL: PSMA-PET SUVmean ≥10 in all lesions is a predictive biomarker for a positive response to Lu177-PSMA while a high volume of FDG-avid disease predicts a worse response to any treatment among those with mCRPC. | Buteau, Lancet Oncol 2022