Baseline Imaging Derived Predictive Factors of Response Following [¹⁷⁷Lu]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 [¹⁷⁷Lu]Lu-PSMA-617 in metastatic castration resistant prostate cancer patients (mCRPC). The current study investigated whether imaging-derived factors on baseline [⁶⁸Ga]Ga-PSMA-11 PET/CT can potentially predict the response after two cycles of [¹⁷⁷Lu]Lu-PSMA-617 treatment, in a lesion- and patient-based analysis in men with mCRPC. Included patients had histologically proven mCRPC and a [⁶⁸Ga]Ga-PSMA-11 PET/CT before and after two cycles of [¹⁷⁷Lu]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 [⁶⁸Ga]Ga-PSMA-11 PET/CT (most avid lesion SUV_peak/max ≥ 30% reduction) (<i>p</i> < 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) (<i>p</i> = 0.019 and <i>p</i> = 0.015). In pre-treatment with [⁶⁸Ga]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 [¹⁷⁷Lu]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.