Baseline Imaging Derived Predictive Factors of Response Following [ 177 Lu]Lu-PSMA-617 Therapy in Salvage Metastatic Castration-Resistant Prostate Cancer: A Lesion- and Patient-Based Analysis.

Earlier studies have mostly identified pre-therapeutic clinical and laboratory parameters for the prediction of treatment response to [ 177 Lu]Lu-PSMA-617 in metastatic castration resistant prostate cancer patients (mCRPC). The current study investigated whether imaging-derived factors on baseline [ 68 Ga]Ga-PSMA-11 PET/CT can potentially predict the response after two cycles of [ 177 Lu]Lu-PSMA-617 treatment, in a lesion- and patient-based analysis in men with mCRPC. Included patients had histologically proven mCRPC and a [ 68 Ga]Ga-PSMA-11 PET/CT before and after two cycles of [ 177 Lu]Lu-PSMA-617 treatment. The imaging-based response was evaluated on lesion-level (standardized uptake value (SUV) reduction) and patient-level (total lesion PSMA (TL-PSMA) reduction). In the lesion-level analysis, a clear relationship was found between SUV peak/max and the imaging-based response to [ 68 Ga]Ga-PSMA-11 PET/CT (most avid lesion SUV peak/max ≥ 30% reduction) ( p < 0.001), with no significant difference in cut-off values between different sites of metastases (i.e., lymph node, bone or visceral metastasis). In patient-level analysis, baseline PSA and SUV peak values of most avid metastasis were significantly associated with imaging-based response (TL-PSMA ≥ 30% reduction) ( p = 0.019 and p = 0.015). In pre-treatment with [ 68 Ga]Ga-PSMA-11 PET/CT, a clear accumulation-response relationship in lesion-level was found for SUV peak/max in men with mCRPC receiving two cycles of [ 177 Lu]Lu-PSMA-617 treatment. The SUV peak of the most avid lesion was the only image-derived factor predictive of the imaging-based response at the patient-level.