Abstract 5101: Urine based dynamically monitoring reflect pathologic response in MIBC patients with neoadjuvant immunotherapy

Abstract

Abstract Background: The recommended standard of care treatment for nonmetastatic muscle-invasive bladder cancer (MIBC) is radical cystectomy (RC). Even with urinary diversion, radical cystectomy has a major impact on patients' quality of life. Although high rates of overall and disease-specific survival were observed in patients managed with bladder preservation, who achieved a clinically complete response to neoadjuvant therapy. Frequent evaluation of tumor response based cystoscopy implementing personalized bladder-sparing treatment paradigms. Case Presentation: Here, we report on a case of urine-based dynamically monitoring during neoadjuvant immunotherapy in a MIBC patient treated with RC. A 57-year-old male presented macrohematuria and was diagnosed with bladder urothelial carcinoma by transurethral resection of bladder tumor (TURBT) with clinical stage IIIA (high-grade, multiple, cT2N0M0). He received 3 cycles of Tislelizumab monotherapy and sequential radical cystectomy. The RC specimen showed a complete pathological response (pCR). Four urine samples were collected prior to TURBT, on a day after TURBT, at beginning of neoadjuvant immunotherapy, and on the day of CR. Mutations status in 17 genes and methylation level of ONECUT2 were analyzed by a high-throughput sequencing-based urine test panel (genetron-uro-V1). In urine sediment DNA, which was collected before TURBT, the TERT promoter mutations C228T, TP53 D281H, and ERBB2 D277Y were detected in urine sediment DNA at variant allele frequencies (VAF) of 31.8%, 10.5%, and 0.5%, respectively. After removing in most parts of tumor, the VAF of TERT C228T decreased to 19.6% and mutation in TP53 and ERBB2 could not be detected. Without neoadjuvant immunotherapy, the VAF of TERT C228T still stayed above 12%. After 3 cycles of Tislelizumab monotherapy on the day of CR, all mutation was below the detection limit in urine sediment DNA, which was consistent with pCR in the pathological report of RC specimen. Conclusions: This case suggested that urine-based dynamically monitoring reflected pathologic response, which could support personalized care and help select patients for bladder-sparing treatment. Citation Format: Xiao Yang, Lingkai Cai, Qiang Cao, Min Shi, Yiming Liang, Yurong Qu, Qiang Lu. Urine based dynamically monitoring reflect pathologic response in MIBC patients with neoadjuvant immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5101.