Advanced adrenocortical cancer (ACC) is a rare, highly aggressive malignancy, which typically has a poor prognosis. In advanced ACC, the overall trend is toward a short PFS interval following first-line systemic therapy, highlighting a clear need for improved second-/third-line treatment strategies. We conducted a review of the literature and relevant scientific guidelines related to systemic therapy for advanced ACC. Public indexes including PubMed/MEDLINE were searched. Treatment selection in the second-line setting is based on small phase 2 trials, case reports, and pre-clinical evidence. The best data available for initial second-line therapy selection supports the use of gemcitabine and capecitabine (G + C) or streptozotocin (S), both with or without mitotane. G + C is becoming increasingly recommended based on phase 2 clinical trial data in patients of good PS, due to the inferred superior PFS and OS from non-comparative trials. Alternatively, streptozotocin was better tolerated than EDP + M in the FIRM-ACT study and remains an option when warranted. Beyond this, further treatment approaches should be tailored to individual patient characteristics, utilizing a mixture of systemic therapies, local therapies, and enrolment in clinical trials where available. Additionally, the role of molecular stratification, predictive biomarkers, and immune checkpoint inhibitors in specific individuals, such as Lynch syndrome, is evolving and may become increasingly utilized in clinical practice. Advanced ACC necessitates a multidisciplinary approach and is best managed in a specialist center. Although there is no one definitive second-line treatment strategy, there are some favorable approaches, which require further validation in larger clinical trials.

中文翻译：

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晚期肾上腺皮质癌（ACC）：重点关注二线治疗的综述。

晚期肾上腺皮质癌（ACC）是一种罕见的、高度侵袭性的恶性肿瘤，通常预后不良。在晚期 ACC 中，总体趋势是一线系统治疗后 PFS 间隔较短，这突出表明明显需要改进二线/三线治疗策略。我们对与晚期 ACC 全身治疗相关的文献和相关科学指南进行了回顾。检索了包括 PubMed/MEDLINE 在内的公共索引。二线治疗的选择基于小型 2 期试验、病例报告和临床前证据。用于初始二线治疗选择的最佳数据支持使用吉西他滨和卡培他滨 (G + C) 或链脲佐菌素 (S)，联合或不联合米托坦。由于从非比较试验中推断出优越的 PFS 和 OS，基于 PS 良好的患者的 2 期临床试验数据，G + C 越来越受到推荐。另外，在 FIRM-ACT 研究中，链脲佐菌素比 EDP + M 具有更好的耐受性，并且在必要时仍然是一种选择。除此之外，进一步的治疗方法应根据患者的个体特征进行定制，综合利用全身治疗、局部治疗以及在可能的情况下参加临床试验。此外，分子分层、预测生物标志物和免疫检查点抑制剂在特定个体（例如林奇综合征）中的作用正在不断发展，并且可能在临床实践中得到越来越多的应用。高级 ACC 需要采用多学科方法，最好在专家中心进行管理。尽管没有一种明确的二线治疗策略，但有一些有利的方法，需要在更大规模的临床试验中进一步验证。