Explorative analysis of a predictive score for patients with metastatic, castration resistant prostate cancer undergoing radioligand therapy with [177Lu]Lu-labeled prostate-specific membrane antigen

Abstract Background: Up to 60% of patients with metastatic, castration-resistant prostate cancer (mCRPC) treated with [177Lu]Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) achieve partial biochemical response with a decrease of >50% in prostate-specific antigen (PSA) levels. The remaining fraction of patients, however, do not respond to RLT. The aim of this explorative analysis was to identify pretherapeutic factors for the prediction of response. Methods: 46 patients (age = 68 years [53-87]) with mCRPC who consecutively underwent RLT with [177Lu]Lu-PSMA (median applied activity = 6 GBq [2.9-6.2]) were included and analysed retrospectively. Association of different clinical and laboratory factors and parameters from pretherapeutic 68Gallium-PSMA positron emission tomography (PET) with the outcome of RLT was tested (Fisher’s test). Outcome was defined as PSA changes 8 weeks after the second RLT (partial response [PR], PSA decrease >50%; progressive disease [PD], PSA increase ≥25%; stable disease [SD], others). Significant risk factors were combined in a predictive score. Results: Median pretherapeutic PSA was 79 ng/ml. Thirty percent of the patients showed a post-treatment PR (median: 73% PSA decrease), 35% SD (median: 17% PSA decrease) and 35% PD (median: 42% PSA increase). Significant predictors for PD were alkaline phosphatase (ALP) >135 U/l (p=0.030), PSA >200 ng/ml (p=0.036), and maximum standardized uptake value (SUVmax) of the “hottest lesion” in pretherapeutic PET <45 (p=0.005). The predictive score including PSA, ALP, and SUVmax could separate 2 distinct groups of patients: ≤2 risk factors (81% PR or SD, 19% PD) and 3 risk factors (10% PR or SD, 90% PD). Conclusion: The presented predictive score allowed a pretherapeutic estimate of the expected response to RLT. This is hypothesis generating. Prospective trials are needed to test these predictive risk factors