Explorative analysis of a score predicting the therapy response of patients with metastatic, castration resistant prostate cancer undergoing radioligand therapy with ¹⁷⁷Lu-labeled prostate-specific membrane antigen

Objective

Up to 60% of patients with metastatic, castration-resistant prostate cancer (mCRPC) treated with ¹⁷⁷Lu prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) achieves a partial biochemical response with a decrease of > 50% in prostate-specific antigen (PSA) levels. The remaining fractions, however, do not respond to RLT. The aim of this explorative analysis was to identify pre-therapeutic factors for the prediction of response.

Methods

46 patients [age = 68 years (50-87)] with mCRPC who consecutively underwent RLT with ¹⁷⁷Lu PSMA [median applied activity = 6 GBq (2.9-6.2)] were included and analysed retrospectively. The association of different clinical and laboratory factors and parameters from pre-therapeutic ⁶⁸Ga PSMA positron emission tomography (PET) with the outcome of RLT was tested (Fisher's test). Outcome was defined as PSA changes 8 weeks after second RLT [partial response (PR), PSA decrease > 50%; progressive disease (PD), PSA increase ≥ 25%; stable disease (SD), others]. Significant predictive factors were combined in a predictive score.

Results

30% 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 = 0.002), PSA > 200 ng/ml (p = 0.036), and maximum standardized uptake value (SUVmax) of the "hottest lesion" in pre-therapeutic PET < 45 (p = 0.005). The predictive score including PSA, ALP and SUVmax could separate 2 distinct groups of patients: ≤ 2 predictive factors (19% PD) and 3 predictive factors (90% PD).

Conclusion

The presented predictive score allowed a pre-therapeutic estimate of the expected response to 2 cycles of RLT. As our study was retrospective, prospective trials are needed for validation.