Abstract 1936: Circulating epithelial tumor cells as a biomarker to predict treatment failure of radiotherapy in breast and prostate cancer

Abstract Background: In primary breast and prostate cancer, radiotherapy is an integral part of the treatment toolbox. However, despite the significant reduction in local relapses in both breast and prostate cancer, distant relapses still occur in a considerable number of patients. Therefore, biomarkers are urgently needed to identify patients at increased risk of developing metastatic disease. Distant metastases arise from cells released from the primary tumor that are capable of forming metastatic tumors in distant organs, ultimately leading to fatal outcomes. Methods: We have therefore used the maintrac® approach to monitor and characterize circulating epithelial tumor cells (CETC/CTC) numbers during radiotherapy and to correlate them with treatment outcomes. Results: In breast cancer, an increase in CETC/CTC numbers during the course of radiotherapy was highly predictive of relapse, particularly in the neoadjuvant setting, with a hazard ratio of 4.886 (p<0.01). This finding suggests that an increase in CETC/CTC during radiotherapy in breast cancer patients previously treated with neoadjuvant chemotherapy indicates the need for additional treatment following radiotherapy.In prostate cancer, where radiotherapy is increasingly used without surgery due to the advanced age and frailty of patients and the considerable side effects of prostatectomy, adjuvant radiotherapy was administered to 12 patients. Among these, two patients showed an increase in CETC/CTC numbers from mid-treatment to the end of radiotherapy, and both experienced relapse.In patients receiving definitive radiotherapy without surgery, cell counts were available for 27 individuals. Of these, 8 showed an increase in CETC/CTC numbers. Three of the 8 patients experienced relapse, while 5 have remained in complete remission for up to 8 years despite increasing cell numbers. Additionally, 1 out of 19 patients with decreasing cell numbers experienced a local relapse.Although patients with increasing CETC/CTC counts from mid-treatment to the end of radiotherapy had a significantly higher risk of relapse, not all of them experienced relapse. Other cell characteristics, such as PD-L1 expression, might also play a crucial role. In fact, the fraction of PD-L1-positive cells increased from before to after radiotherapy in patients who experienced relapse during adjuvant radiotherapy but decreased in patients who remained in complete remission. This pattern was similarly observed in patients undergoing definitive radiotherapy. Conclusion: These results highlight the potential of monitoring both CETC/CTC numbers and their characteristics as a prognostic tool. This approach could help identify patients who require more intensive adjuvant treatment, which may contribute to improved treatment outcomes in the future. Citation Format: Dorothea Schott, Matthias Maurer, Monika Pizon, Katharina Pachmann. Circulating epithelial tumor cells as a biomarker to predict treatment failure of radiotherapy in breast and prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1936.