Tumor sink effect in patients with Metastatic Castration-Resistant Prostate Cancer undergoing [225Ac]Ac-PSMA Targeted Alpha Therapy: treatment efficacy evaluation

Ziel/Aim: The change in organs at risk (OAR) uptake level due to total tumor volume (TTV) reduction after therapy, known as the tumor sink effect, could be used as a parameter for assessing treatment efficacy and outcomes after Targeted Alpha Therapy (TAT). The study aims to determine the treatment efficacy and outcomes of [²²⁵Ac]Ac-PSMA TAT in patients who had refractory to radioligand therapy (RLT) and assessment of the treatment efficacy impact on the tumor sink effect.

Methodik/Method: The clinical data including blood test results and pre and post-treatment [⁶⁸Ga]Ga-PSMA-11 PET images obtained following [²²⁵Ac]Ac-PSMA-617 TAT, were retrospectively evaluated. The quantitative parameters including SUV_max and SUV_mean were extracted for salivary and parotid glands as OARs, and TTV through segmentation. The treatment outcome was evaluated using biochemical response, survival analysis including overall survival (OS) and progression-free survival (PFS), molecular tumor response, and disease control rate (DCR) metrics.

Ergebnisse/Results: 12 patients totally 59 [⁶⁸Ga]Ga-PSMA-11 PET/CT images included in our study. The biochemical response results showed that 7/12 experienced a>50% PSA decline. Moreover, 4/12 patients experienced an increase in PSA level, with 3 patients with disease progression. The molecular response results showed 7/12 patients (58%) experienced a partial response, 3/12 had stable disease, and 2/12 had disease progression. The OS, PFS, and DCR were 53, 27 weeks, and 86%, respectively. An interesting result was correlation between TTV reduction and decline in PSA levels, were observed in 7/12 patients. Median SUV_mean differences for OAR were -63.7% and -45.5%, respectively. While they were -39.9% and -22.6% after [¹⁷⁷Lu]Lu-PSMA RLT. Correlation between blood biomarkers and OS showed that higher PSA, Creatinine, and lower Hemoglobin and platelet count, were associated with reduced OS.

Schlussfolgerungen/Conclusion: The results showed that TAT had a promising DCR for patients who had refractory to RLT with a strong correlation between OS and blood biomarker levels. An excellent correlation between TTV and PSA levels in patients was observed. The results indicate patients experience tumor sink effect, increased uptake in OAR during TAT, which could be observed in the median decline of uptake values in post-treatment PET images.

 

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Artikel online veröffentlicht:
12. März 2025