Analysis of DNA damage using the comet assay method in metastatic castration resistant prostate cancer patients receiving 177Lu-PSMA-617 radioligand therapy

Abstract

Aim: To evaluate possible DNA damage in metastatic castration-resistant prostate cancer patients receiving ¹⁷⁷Lu-PSMA-617 radioligand therapy using the comet assay method.

Methods: Prospectively included patients were divided into four groups: a control group and three treatment groups receiving 2, 4, and 6 cycles, respectively. Agarose-coated comet assay slides were prepared using samples obtained from routine blood tests before treatment, and electrophoresis was performed to detect DNA damage. Descriptive statistics, normality tests, and multiple comparison tests were performed.

Results: Forty-five patients with a mean age of 75.5, Gleason scores of 3+4, 4+3, 4+5, and 5+5, and ECOG performance scores of 0/1, 2, and 3 were included in the study. In a valid Comet assay analysis, a similar number of cells were examined in the four treatment groups without any statistical differences. Group analyses revealed statistically significant differences between DNA damage levels. Specifically, the number of stage 0 cells showed a significant difference between the 0-2 and 4-6 cycles groups, while the number of cells with moderate/high levels of damage showed similarities between the 4-6 cycles groups.

Conclusions: This study demonstrates an increase in DNA damage in peripheral blood lymphocytes with cumulative doses in prostate cancer patients treated with ¹⁷⁷Lu-PSMA. These findings contribute to the understanding of the relationship between DNA damage during the treatment process and treatment cycles.