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    • Impact of Angiotensin-Converting Enzyme Inhibitors (acei) on Pathologic Complete Response with Neoadjuvant Chemotherapy (NAC) for Muscle-Invasive Bladder Cancer (MIBC).

    Journal of Clinical Oncology（2022）

    Dana-Farber Cancer Institute | University of Virginia Comprehensive Cancer Center | McGill University | H. Lee Moffitt Cancer Center and Research Institute | Brigham and Women's Hospital | McMaster University | Massachusetts General Hospital

    Cited 0|Views22
    Abstract
    485 Background: The renin-angiotensin system (RAS) has been demonstrated to modulate cell proliferation, desmoplasia, angiogenesis and immunosuppression. Angiotensin pathway inhibitors are postulated to favorably reprogram the stroma in part by inhibition of transforming growth factor-β, a major mechanism of resistance, and have been previously reported to be associated with improved outcomes in the setting of immune checkpoint inhibitors (ICIs) for metastatic urothelial carcinoma (Jain R, Clin Genitourin Cancer 2021). In this analysis, we examined the association of angiotensin inhibitors in the setting of NAC for MIBC preceding radical cystectomy (RC). Methods: Pts with MIBC who received NAC preceding radical cystectomy were assembled from 3 institutions: Dana-Farber Cancer Institute (DFCI), Moffitt Cancer Center (MCC) and McGill University Health Center (MUHC). Pts were retrospectively assessed for the association of concurrent ACEi/angiotensin receptor blockers (ARB) use at initiation of NAC on pathologic complete response (pCR), defined as pT0N0, and overall survival (OS). Pathologic features, performance status (PS), clinical stage, type/number of cycles of NAC, and toxicities were collected. The Kaplan-Meier method was used to estimate OS. Logistic and Cox regression were used to explore factors potentially prognostic for pCR and OS respectively. Results: 302 MIBC pts who received NAC preceding RC were available from 3 institutions: DFCI (n = 187), MCC (n = 50) and MUHC (n = 65). Overall, 141 pts (46.7%) received Cisplatin/Gemcitabine, 130 (43.1%) received dose dense MVAC and the remaining received other regimens. The overall pCR rate was 26.2%. The 5-year OS was 62%. 63 (20.9%) pts were receiving an ACEi and 41 (13.6%) were receiving an ARB. ACEi prior to NAC approached significance for association with pCR (odds ratio = 1.71 (95% CI = 0.94-3.11) p = 0.077). Pts with cT3/4N0-N1 disease receiving ACEi had higher pCR rates (30.8% (8/26) vs 17.7% (14/98), p = 0.056) than those not on ACEi; no difference was observed for pts with cT2N0 tumors (31.1% vs 31.3%, p = 0.99). pCR, ECOG-PS and clinical stage were significantly associated with improved OS. ARB intake was not associated with pCR or OS. Conclusions: ACEi intake appeared potentially associated with increased pCR in pts with MIBC receiving NAC, which was more pronounced in those with higher clinical stages cT3/4N0-1. Given the association of pCR with OS, our data suggest the potential relevance of angiotensin as a therapeutic target in aggressive MIBC. Future prospective validation is warranted to repurpose angiotensin inhibitors in this setting, given their excellent toxicity profile and low costs.
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    Muscle-invasive bladder cancer,angiotensin,drug synergism,neoadjuvant chemotherapy,treatment outcomes
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    【要点】：该论文探讨了血管紧张素抑制剂对肌层浸润性膀胱癌（MIBC）患者新辅助化疗（NAC）后病理完全反应（pCR）的影响。
    

    【方法】：研究者进行了一项回顾性队列研究，比较了接受NAC治疗的MIBC患者中，使用血管紧张素转换酶抑制剂（ACEi）与未使用ACEi的群体的pCR率。
    

    【实验】：研究结果显示，使用ACEi的患者pCR率更高，这表明ACEi可能改善NAC对MIBC的治疗效果。数据集未具体说明。