Postlewait Lauren M, Ethun Cecilia G, Tran Thuy B, Prescott Jason D, Pawlik Timothy M, Wang Tracy S, Glenn Jason, Hatzaras Ioannis, Shenoy Rivfka, Phay John E, Keplinger Kara, Fields Ryan C, Jin Linda X, Weber Sharon M, Salem Ahmed, Sicklick Jason K, Gad Shady, Yopp Adam C, Mansour John C, Duh Quan-Yang, Seiser Natalie, Solorzano Carmen C, Kiernan Colleen M, Votanopoulos Konstantinos I, Levine Edward A, Staley Charles A, Poultsides George A, Maithel Shishir K
Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA.
Department of Surgery, Stanford University School of Medicine, Stanford, CA.
J Am Coll Surg. 2016 Apr;222(4):480-90. doi: 10.1016/j.jamcollsurg.2015.12.013. Epub 2015 Dec 21.
Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines.
Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS).
Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p < 0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS.
When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.
当前治疗指南推荐，对于具有高危特征（如肿瘤破裂、切缘阳性、淋巴结阳性、高级别、有丝分裂指数升高及晚期）的肾上腺皮质癌患者，术后使用米托坦辅助治疗。关于这些实践指南相关结局的数据有限。
纳入1993年至2014年在美国肾上腺皮质癌协作组的13家学术机构接受肾上腺皮质癌切除术的患者。确定与米托坦使用相关的因素。主要终点为无复发生存期（RFS）和总生存期（OS）。
207例患者中，88例（43%）接受了米托坦辅助治疗。接受米托坦治疗与激素分泌（58%对32%；p = 0.001）、晚期TNM分期（IV期：42%对23%；p = 0.021）、辅助化疗（37%对5%；p < 0.001）及辅助放疗（17%对5%；p = 0.01）相关，但与肿瘤破裂、切缘状态或N分期无关。中位随访时间为44个月。米托坦辅助治疗与RFS降低（10.0个月对27.9个月；p = 0.007）及OS降低（31.7个月对58.9个月；p = 0.006）相关。多变量分析显示，米托坦与RFS或OS无独立相关性，切缘状态、晚期TNM分期及化疗的接受情况与生存相关。排除所有接受化疗的患者后，米托坦辅助治疗仍与RFS降低及相似的OS相关；多变量分析再次显示与复发或生存无关。两个队列的分期特异性分析均显示，米托坦辅助治疗与改善RFS或OS无关。
在考虑分期及不良肿瘤和治疗相关因素时，肾上腺皮质癌切除术后使用米托坦辅助治疗与改善RFS或OS无关。应重新审视当前指南并开展前瞻性试验。
