Circulating tumor cell detection and prognostic relevance in patients with metastatic genitourinary cancers.

826 Background: Circulating tumor cells (CTCs) are detectable and quantifiable in the peripheral blood of patients (pts) with certain malignancies and can be assessed by liquid biopsy. The presence and change in quantity of CTCs may correspond to tumor burden and therapeutic response. This study aims to explore the utility of CTC quantification and serial measurement in pts with metastatic GU cancers. Methods: This study is a retrospective pooled analysis of CTCs in metastatic GU cancer pts enrolled on several clinical trials from 7/2016 to 3/2023. Plasma for CTCs was drawn on Cycle (C)1 Day (D)1, C2D1 and C3D1 of treatment and quantified using the EPIC Sciences CTC platform. CTCs >4/mL was considered the threshold for positive detection. The association of CTC values and trends from baseline C1 and on treatment (C2 or C3) with PFS and OS was assessed using Cox-proportional Hazards Ratios. CTC trend with best response (partial or complete response vs stable disease or progressive disease) was assessed using logistic regression. Results: There were 76 pts with 158 samples (52 with at least 2 paired samples) included in this retrospective study. The median age was 63 years (IQR 55 – 71) and most pts were male (71.6%). Most common histology was urothelial carcinoma (UC) (n = 66). All were metastatic at enrollment, 75% had lymph node involvement, 69.5% had visceral mets, 35.3% had liver mets and 33.8% had osseous mets. Most pts received VEGF TKI with checkpoint inhibition (n = 56), other regimens included IO-cytokine combination (n = 9), chemotherapy (n = 5) and PARP inhibitor (n = 5). CTCs were present in 20 of 71 pts (28.2%) at C1D1, 16 of 47 (34.0%) at C2D1, and 10 of 41 (24.4%) at C3D1. OS and PFS did not differ by CTC presence at C1D1 or on treatment. The absolute value (log2-transformed) of CTCs at C1D1 was associated with OS in all pts (Hazard Ratio (HR) 1.19, 95% CI 1.03 – 1.37, p = 0.017) and in UC pts (HR 1.21, 95% CI 1.05 – 1.40, p = 0.008), but not at C2D1 or C3D1 for either. A decrease in CTCs versus an increase from C1-C2 (up to C2D15) was significantly associated with improved PFS in all pts (HR 0.48, 95% CI 0.24 – 0.98, p = 0.043), and in UC pts (HR 0.42, 95% CI 0.19 – 0.91, p = 0.029) but not OS for all patients (HR = 0.70, 95% CI 0.35 – 1.40, p = 0.308) or UC pts (HR 0.62, 95% CI 0.29 – 1.33, p = 0.220). CTC trend was not significantly associated with achieving objective response in all pts (Odds Ratio (OR) 3.0, 95% CI 0.63-14.37, p = 0.169) and in UC pts (OR 2.8, 95% CI 0.56 – 14.0, p = 0.209). Conclusions: Absolute CTC values prior to treatment were associated with OS while CTC trend after initial treatment was associated with PFS in all patients and in pts with UC. These findings signal the potential utility of CTCs in providing minimally invasive prognostic information. Further work is needed to identify thresholds for CTC quantification and refine on-treatment response monitoring.