Study of predictive factors for response to 177LU-PSMA in patients with metastatic castration-resistant prostate cancer

Introduction Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive disease with a poor prognosis and few therapeutic options. In recent years, 177Lu-PSMA, a novel radioligand therapy, has shown promising results in patients who have failed conventional therapies. However, around 30% of patients do not respond adequately to this treatment. In this retrospective cohort study, we examined clinical, biological, and 68Ga-PSMA PET/CT-derived factors associated with poor treatment response. Materials and methods We conducted a retrospective cohort study including 63 patients treated at ICO Angers for progressive mCRPC following Novel Hormonal Agents and taxane-based chemotherapy. The primary endpoint was early treatment discontinuation, defined as stopping therapy at or before the 4th cycle. Secondary endpoints included PSA response and overall survival. Results A total of 63 patients were included in the study. Factors associated with early treatment discontinuation included a BMI < 25 kg/m2, PSA doubling time < 2 months, hemoglobin levels <10 g/dL, albumin levels <35 g/L, lactate dehydrogenase (LDH) levels >250 IU/L and alkaline phosphatase (ALP) levels >125 IU/L. On 68Ga-PSMA PET/CT imaging, low SULmax, high Total Tumor Volume, and a low PSG score were also linked to early treatment discontinuation. Conclusion This study identified several clinical, biological, and 68Ga-PSMA PET/CT-derived factors associated with early treatment discontinuation. Patients with poor overall health, aggressive or extensive disease, or low PSMA expression are at higher risk of treatment failure.