Changes in circulating tumor cells (CTCs) and HER2 expression in evaluating the efficacy of neoadjuvant disitamab vedotin plus toripalimab treatment in patients with muscle-invasive bladder cancer (MIBC).

837 Background: Disitamab vedotin (DV) combined with toripalimab has shown promising efficacy as neoadjuvant therapy for MIBC, with a pathological CR (pCR) rate of 62.1% in the previous report (2024 ASCO). In real-world practice, many patients who achieved clinical complete response (cCR) after neoadjuvant therapy, confirmed by re-TURBT, imaging, and urine cytology, opted for bladder-preserving treatment (BPT). However, biomarkers to confirm the absence of residual tumors in cCR pts are lacking. This study aims to evaluate the correlation between changes in CTCs and HER2+ CTCs during neoadjuvant therapy with clinical efficacy outcomes in MIBC. Methods: 18 pts were retrospectively included from July 2023 to July 2024. The primary endpoint was to assess the correlation between changes in CTCs and HER2+ CTCs before and after neoadjuvant therapy, and clinical efficacy (cCR or non-cCR). Eligible pts had previously untreated MIBC (cT2-T3N0-1M0) with HER2 expression of IHC ≥ 2+. Pts received DV (2 mg/kg) plus toripalimab (3 mg/kg) every two weeks for six cycles, followed by radical surgery or BPT for cCR pts (choice made after communication between the physician and the pts). cCR criteria included no residual tumor confirmed by re-TURBT, no evidence of tumor on imaging, and negative urine cytology. Peripheral blood samples were collected to measure CTC counts and HER2 phenotype by HER2-iFISH. Results: Among 18 pts, 15 (83.3%) achieved cCR, while 3 pts (16.7%) were in the non-cCR group, including 2 pts with cPR confirmed as pT2N0 postoperatively, and 1 pt with clinical progression (cPD). All 15 cCR pts underwent BPT. There were no significant differences in the total CTCs and HER2+ CTCs between the cCR and non-cCR groups before treatment (P = 0.426, P = 0.654, respectively). After neoadjuvant therapy, CTC and HER2+ CTC counts were significant lower in the cCR group compared to the non-cCR group (P = 0.039, P = 0.005, respectively). Only 1 (6.7%) cCR pt had detectable HER2+ CTCs post-treatment, while all 3 non-cCR pts had measurable HER2+ CTCs. Conclusions: Changes in CTCs and HER2+ CTCs correlated with clinical efficacy outcomes of DV plus toripalimab neoadjuvant therapy, particularly in HER2+ CTCs. CTCs and CTC HER2 expression may serve as potential biomarkers for evaluating clinical efficacy and guiding treatment strategies in MIBC. The clinicopathological characteristics of the 18 MIBC patients. Characteristic All patients (n=18) cCR (n=15) non-cCR (n=3) P value Clinical T stage, n (%) 1.00 cT2 10 (55.6) 8 (53.3) 2 (67) cT3 8 (44.4) 7 (46.7) 1 (33) Clinical N stage, n (%) 1.00 cN0 15 (83.3) 12 (80.0) 3 (100) cN1 3 (16.7) 3 (20.0) 0 (0) HER-2 expression, n (%) 0.44 2+ 15 (83.3) 13 (86.7) 2 (66.7) 3+ 3 (16.7) 2 (13.3) 1 (33.3)