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目的:探讨肾上腺皮质癌(ACC)术后应用米托坦治疗的有效性。方法:对PubMed、EMBASE、Web of Science、Cochrane Library数据库行系统文献检索，检索时限自建库至2023年10月。检索词包括"mitotane""adrenocortical carcinoma或其同义词"。纳入标准：研究中比较了ACC术后是否应用米托坦的相应预后情况[(总生存期(OS)和/或无复发生存期(RFS)]；多因素Cox回归分析中报告调整后的风险比(HR)。排除标准：患者有远处转移、ACC的显微镜下残留(RI)切除、术前或术后辅助化疗。提取符合条件的研究数据，包括辅助米托坦的治疗浓度、治疗持续时间、肿瘤分期等。比较ACC术后是否应用米托坦对OS和RFS的影响，根据米托坦是否达到有效浓度或足够时间，以及肿瘤分期≤T 3期对RFS进行亚组分析。 结果:本研究最终纳入15篇研究，包括2 084例ACC患者，其中术后应用米托坦991例。肿瘤分期≤T 3期753例。术后应用米托坦组的OS( HR＝0.45，95% CI 0.34～0.58， I2＝0， P＝0.79)和RFS( HR＝0.65，95% CI 0.51～0.83， I2＝76%， P<0.01)明显优于未应用米托坦组。亚组分析结果显示，相比于术后应用米托坦未达到有效浓度或足够时间组，达到有效浓度或足够时间组[中位随访时间<45个月亚组( HR＝0.59，95% CI 0.44～0.79， I2＝0， P＝0.38)；中位随访时间≥45个月亚组( HR＝0.93，95% CI 0.90～0.96， I2＝0， P＝1.00)]的RFS更优。与T 4期相比，≤T 3期ACC患者( HR＝0.61，95% CI 0.47～0.79， I2＝0， P＝0.62)的RFS更优。 结论:ACC术后应用米托坦能延长患者的OS和RFS；尤其对于应用米托坦达到有效浓度或足够时间的患者，以及≤T 3期的患者，其延长RFS的效果更稳定。

Objective:Object To evaluate the therapeutic effectiveness of postoperative adjuvant mitotane therapy in the context of adrenocortical carcinoma (ACC) by using a meta-analysis methodology.Methods:A comprehensive literature review was conducted by systematically searching the PubMed, EMBASE, Web of Science, and Cochrane Library databases. The search spanned from the establishment of each database to October 2023. Search terms, "mitotane", "adrenocortical carcinoma" or synonyms. Inclusion criteria, Studies comparing outcomes (overall survival (OS) and/or recurrence-free survival (RFS)) in ACC patients with or without mitotane, reporting adjusted hazard ratios (HR) in multivariate Cox regression. Exclusion criteria, Patients with distant metastases, RI(Microscopic residual tumor) rection of ACC, or adjuvant chemotherapy. Data extracted on mitotane treatment concentration, duration, and tumor stage. A meta-analysis was conducted utilizing R4.2.2 software to assess the impact of ACC on OS or RFS through the calculation of HR and 95% confidence intervals (CI). Subgroup analysis of RFS was conducted based on the use of mitotane to reach effective levels or adequate duration, as well as tumor stage ≤T 3. Results:A meta-analysis was conducted, including a total of 15 studies and involving 2084 patients with ACC. Of these patients, 991 received post-surgical treatment with mitotane, while 753 had ACC classified as stages ≤T 3. The results showed that adjuvant mitotane therapy in the ACC group after surgery led to significantly improved OS ( HR=0.45, 95% CI 0.34-0.58, I2=0, P=0.79) and RFS ( HR=0.65, 95% CI 0.51-0.83, I2=76%, P<0.01) compared to non-adjuvant mitotane therapy. Subgroup analysis further revealed that patients with effective mitotane concentration or sufficient time after surgery[Subgroup a(Median follow-up duration < 45 months): HR=0.59, 95% CI 0.44-0.79, I2=0, P=0.38; Subgroup b(Median follow-up duration ≥ 45 months): HR=0.93, 95% CI 0.90-0.96, I2=0, P=1.00 ]and with ≤T 3 stage ACC ( HR=0.61, 95% CI 0.47-0.79, I2=0, P=0.62)had better RFS compared to those who did not achieve the requisite mitotane concentration or postoperative interval, as well as patients with stage T 4 ACC. Conclusions:The administration of adjuvant mitotane therapy following ACC resection has been shown to significantly extend patients' OS and RFS, particularly when the therapy achieves optimal concentration or is administered for an adequate duration. Furthermore, in patients with ACC classified as stage ≤T 3, the effect of adjuvant mitotane therapy on prolonging RFS appears to be more consistent and reliable.