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对于临床检查肿瘤较小、腋窝淋巴结阴性而前哨淋巴结活检阳性的早期乳腺癌患者，传统的腋窝淋巴结清扫后复发率较低、淋巴水肿等并发症较多，腋窝放疗后并发症较少，那么腋窝放疗能否取代腋窝淋巴结清扫？2001年，欧洲癌症研究与治疗组织（EORTC）发起大规模临床试验AMAROS研究对肿瘤大小≤5厘米、临床未见腋窝淋巴结肿大而前哨淋巴结活检阳性乳腺癌患者的腋窝淋巴结清扫与腋窝放疗进行了比较，2014年《柳叶刀》肿瘤学分册发表该研究中位随访6.1年初步报告，腋窝淋巴结清扫与腋窝放疗相比，5年腋窝复发率为0.43%比1.19%，5年总体生存率和无病生存率相似，1年、3年和5年淋巴水肿发生率较高。由于当时腋窝复发数量太少，分别为4例与7例，计划的非劣效检验效力不足。临床试验通常包括不同时间成熟的多个终点，初步报告通常根据主要终点，可能在关键计划共同主要终点或次要终点分析尚不可用时发布。对于已经报告主要终点的研究，临床试验更新可提供传播研究更多结果的机会。 AMAROS / EORTC-10981-22023 (NCT00014612): After Mapping Of The Axilla: Radiotherapy Or Surgery (Comparison of Complete Axillary Lymph Node Dissection With Axillary Radiation Therapy in Treating Women With Invasive Breast Cancer) 2022年11月16日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表比利时布鲁塞尔EORTC总部、荷兰癌症研究院、莱顿大学医学中心、哈格兰登医疗中心、莱茵州立医院、格勒医院、新斯梅林赫医院、凯瑟琳医院、阿姆斯特兰医院、执事医院、斯帕恩医院、海牙医院、奈梅亨大学医学中心、阿姆斯特丹大学医学中心、英国卡迪夫大学、曼彻斯特大学、意大利佛罗伦萨大学卡雷吉医院、斯洛文尼亚肿瘤研究院、法国奥斯卡·兰布雷特癌症中心、法国巴黎第十二大学、瑞士日内瓦大学医院的AMAROS研究10年结果，报告了预先计划的10年腋窝复发率、总体生存和无病生存分析以及5年并发症和生活质量分析更新。 该国际多中心大样本非盲随机对照三期非劣效试验于2001年2月19日～2010年4月29日从9个欧洲国家34个中心入组临床T1-2期原发乳腺癌且无明显淋巴结肿大患者4806例接受前哨淋巴结活检，其中1425例淋巴结阳性，按1∶1的比例随机分配接受腋窝淋巴结清扫（744例）或腋窝放疗（681例）。 
结果，中位随访10.0年，根据意向治疗分析，腋窝淋巴结清扫与腋窝放疗相比： 10年腋窝复发数：7例比11例 10年腋窝复发率：0.93%比1.82%（95%置信区间：0.18～1.68、0.74～2.94；风险比：1.71，95%置信区间：0.67～4.39） 10年总体生存率：84.6%比81.4%（95%置信区间：81.5～87.1、77.9～84.4；风险比：1.17，95%置信区间：0.89～1.52，P=0.26） 10年无病生存率：75.0%比70.1%（95%置信区间：71.5～78.2、66.2～73.6；风险比：1.19，95%置信区间：0.97～1.46，P=0.11） 5年手臂淋巴水肿发生率：24.5%比11.9%（P<0.001） 5年生活质量问卷评分：相似
根据探索性分析，腋窝淋巴结清扫与腋窝放疗相比： 因此，该研究10年随访结果分析证实，对于早期乳腺癌前哨淋巴结阳性患者，腋窝放疗与腋窝淋巴结清扫相比，腋窝复发率都较低，总体生存率、无病生存率和局部控制率都相似。考虑到手臂并发症发生率较低，对于cT1-2期乳腺癌前哨淋巴结阳性患者，腋窝放疗优于腋窝淋巴结清扫。如果认为有必要进行腋窝治疗，腋窝放疗是不错的选择，腋窝淋巴结清扫应仅限于淋巴结转移严重的患者。不过，现在真正的问题是：对于淋巴结转移有限的患者，是否还有必要对腋窝进行任何治疗？ J Clin Oncol. 2022 Nov 16. IF: 50.717Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast Cancer: 10-Year Results of the Randomized Controlled EORTC 10981-22023 AMAROS Trial.Bartels SAL, Donker M, Poncet C, Sauvé N, Straver ME, van de Velde CJH, Mansel RE, Blanken C, Orzalesi L, Klinkenbijl JHG, van der Mijle HCJ, Nieuwenhuijzen GAP, Veltkamp SC, van Dalen T, Marinelli A, Rijna H, Snoj M, Bundred NJ, Merkus JWS, Belkacemi Y, Petignat P, Schinagl DAX, Coens C, van Tienhoven G, van Duijnhoven F, Rutgers EJT.European Organisation for Research and Treatment of Cancer Headquarters, Brussels, Belgium; Netherlands Cancer Institute, Amsterdam, Netherlands; Leiden University Medical Center, Leiden, Netherlands; Haaglanden Medical Center, Den Haag, Netherlands; Rijnstate Hospital, Arnhem, Netherlands; Gelre Hospital, Apeldoorn, Netherlands; Nij Smellinghe Hospital, Drachten, Netherlands; Catharina Hospital, Eindhoven, Netherlands; Amstelland Hospital, Amstelveen, Netherlands; Diakonessenhuis, Utrecht, Netherlands; Spaarne Gasthuis, Haarlem, Netherlands; Haga Hospital, Den Haag, Netherlands; Radboud University Medical Center, Nijmegen, Netherlands; Amsterdam UMC, Amsterdam, Netherlands; Cardiff University, Cardiff, United Kingdom; University of Manchester and Manchester University Foundation Trust, Manchester, United Kingdom; Careggi University Hospital, Florence, Italy; Institute of Oncology, Ljubljana, Slovenia; Centre Oscar Lambret, Lille, France; University of Paris Est Creteil (UPEC), Créteil, France; Geneva University Hospital, Geneva, Switzerland.Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.PURPOSE: The European Organisation for Research and Treatment of Cancer 10981-22023 AMAROS trial evaluated axillary lymph node dissection (ALND) versus axillary radiotherapy (ART) in patients with cT1-2, node-negative breast cancer and a positive sentinel node (SN) biopsy. At 5 years, both modalities showed excellent and comparable axillary control, with significantly less morbidity after ART. We now report the preplanned 10-year analysis of the axillary recurrence rate (ARR), overall survival (OS), and disease-free survival (DFS), and an updated 5-year analysis of morbidity and quality of life.METHODS: In this open-label multicenter phase III noninferiority trial, 4,806 patients underwent SN biopsy; 1,425 were node-positive and randomly assigned to either ALND (n = 744) or ART (n = 681).RESULTS: Per intention-to-treat analysis, 10-year ARR cumulative incidence was 0.93% (95% CI, 0.18 to 1.68; seven events) after ALND and 1.82% (95% CI, 0.74 to 2.94; 11 events) after ART (hazard ratio [HR], 1.71; 95% CI, 0.67 to 4.39). There were no differences in OS (HR, 1.17; 95% CI, 0.89 to 1.52) or DFS (HR, 1.19; 95% CI, 0.97 to 1.46). ALND was associated with a higher lymphedema rate in updated 5-year analyses (24.5% v 11.9%; P < .001). Quality-of-life scales did not differ by treatment through 5 years. Exploratory analysis showed a 10-year cumulative incidence of second primary cancers of 12.1% (95% CI, 9.6 to 14.9) after ART and 8.3% (95% CI, 6.3 to 10.7) after ALND.CONCLUSION: This 10-year analysis confirms a low ARR after both ART and ALND with no difference in OS, DFS, and locoregional control. Considering less arm morbidity, ART is preferred over ALND for patients with SN-positive cT1-2 breast cancer.KEY OBJECTIVE: Can axillary radiotherapy (ART) replace axillary lymph node dissection in patients with sentinel node-positive early breast cancer?KNOWLEDGE GENERATED: After 10-year follow-up, both ART and axillary lymph node dissection showed excellent locoregional control and survival rates, with less morbidity after ART. If axillary treatment is deemed necessary, ART is a good option.RELEVANCE: With the long-term results of the AMAROS trial, axillary dissection should be limited to patients with gross nodal disease. For those with limited nodal disease, the real question is whether any axillary therapy is needed.DOI: 10.1200/JCO.22.01565
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