精准预测初诊晚期乳腺癌患者结局

　　绝大多数乳腺癌患者初次就诊时为早期，经过手术等积极治疗可能治愈，也可能复发转移为晚期，即IV期，此时通常已经失去积极治疗机会。可是，大约5.9%的美国乳腺癌患者初次就诊时已经转移为晚期，这既可能代表乳腺癌发生发展比较迅速、无法手术、患者结局较差，也可能代表乳腺癌发生发展比较隐匿、可以手术、患者结局较好。精准预测初诊晚期乳腺癌患者结局，有助于避免预后较好患者失去积极治疗机会。不过，既往预测初诊晚期乳腺癌患者结局的研究极少，而且样本量较小，对于此类患者的治疗仍然存在争议，临床大多根据医师经验和主观判断或者专家投票表决结果，按照复发转移的晚期乳腺癌患者进行处理。

　　2023年3月21日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表杜克大学、密歇根大学、德克萨斯大学MD安德森癌症中心、斯坦福大学、格兰德维尤癌症中心、威斯康星大学、西达赛奈医疗中心、洛杉矶加利福尼亚大学、堪萨斯大学、布法罗大学、罗斯威尔帕克综合癌症中心、比利时癌症登记处的大样本研究报告，开发出新的预后分期系统，用于预测初诊晚期乳腺癌患者的生存结局。

　　该研究从美国癌症学会和美国外科医师学会共同建立的全国癌症数据库（NCDB）筛选出2010～2016年初诊晚期乳腺癌患者4万2467例，采用递归分区分析，根据临床肿瘤分期、分级、雌激素受体、孕激素受体、HER2、组织学、器官系统转移部位（仅骨、仅脑、内脏）以及器官系统转移数量等指标，将3年总生存率相似的患者分为4个分期组：

• IV期A组：>70%
• IV期B组：50%～70%
• IV期C组：25%～50%
• IV期D组：<25%

　　随后通过自助抽样1000次，并根据最常出现的分配进行最终分期分配，对未校正总生存进行比较分析。

　　最后利用国家癌症研究所监测流行病学最终结果（SEER）数据库和NCDB进行验证分析。

　　结果，中位随访52.9个月，原始队列4万2467例患者中位总生存35.4个月（95%置信区间：34.8～35.9）。

　　通过递归分区分析将患者分为53组，3年总生存率为73.5%～5.7%；将这些组合并为4个分期组，3年总生存率分别为IV期A组73.2%、IV期B组61.9%、IV期C组40.1%、IV期D组17%（对数秩P<0.001）。

　　随后，自助抽样1000次，4个分期组的生存结局仍然存在显著差异（对数秩P<0.001）。

　　最后，利用SEER数据（2万0469例）和NCDB独立队列（7645例）对该分期系统进行验证，4个分期组的生存结局都存在显著差异（对数秩P<0.001）。

　　因此，该大样本初诊晚期乳腺癌患者结局差异回顾研究结果表明，新的预后分期系统可以指导未来修订现有美国癌症联合委员会针对新诊断IV期乳腺癌患者的分期指南，可以促进医患共同决策，而非仅仅医师经验和主观判断或者专家投票表决结果，故有必要对该研究结果进行独立前瞻验证。

J Clin Oncol. 2023 Mar 21. IF: 50.717

Novel Prognostic Staging System for Patients With De Novo Metastatic Breast Cancer.

Plichta JK, Thomas SM, Hayes DF, Chavez-MacGregor M, Allison K, de Los Santos J, Fowler AM, Giuliano AE, Sharma P, Smith BD, van Eycken E, Edge SB, Hortobagyi GN.

Duke University Medical Center, Durham, NC; Duke Cancer Institute, Durham, NC; Duke University, Department of Biostatistics & Bioinformatics, Durham, NC; University of Michigan Rogel Cancer Center, Ann Arbor, MI; University of Michigan, Ann Arbor, MI; The University of Texas MD Anderson Cancer Center, Houston, TX; Stanford University School of Medicine, Stanford, CA; Grandview Cancer Center, Department of Radiation Oncology, Birmingham, AL; University of Wisconsin School of Medicine and Public Health, Madison, WI; University of Wisconsin Carbone Cancer Center, Madison, WI; Cedars-Sinai Medical Center, University of California-Los Angeles, Los Angeles, CA; University of Kansas Medical Center, Westwood, KS; University at Buffalo, Buffalo, NY; Roswell Park Comprehensive Cancer Center, Buffalo, NY; Belgian Cancer Registry, Brussels, Belgium.

PURPOSE: Given the heterogeneity and improvement in outcomes for metastatic breast cancer (MBC), we developed a staging system that refines prognostic estimates for patients with metastatic cancer at the time of initial diagnosis, de novo MBC (dnMBC), on the basis of survival outcomes and disease-related variables.

METHODS: Patients with dnMBC (2010-2016) were selected from the National Cancer Database (NCDB). Recursive partitioning analysis (RPA) was used to group patients with similar overall survival (OS) on the basis of clinical T category, grade, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2, histology, organ system site of metastases (bone-only, brain-only, visceral), and number of organ systems involved. Three-year OS rates were used to assign a final stage: IVA: >70%, IVB: 50%-70%, IVC: 25 to <50%, and IVD: <25%. Bootstrapping was applied with 1,000 iterations, and final stage assignments were made based on the most commonly occurring assignment. Unadjusted OS was estimated. Validation analyses were conducted using SEER and NCDB.

RESULTS: At a median follow-up of 52.9 months, the median OS of the original cohort (N = 42,467) was 35.4 months (95% CI, 34.8 to 35.9). RPA stratified patients into 53 groups with 3-year OS rates ranging from 73.5% to 5.7%; these groups were amalgamated into four stage groups: 3-year OS, A = 73.2%, B = 61.9%, C = 40.1%, and D = 17% (log-rank P < .001). After bootstrapping, the survival outcomes for the four stages remained significantly different (log-rank P < .001). This staging system was then validated using SEER data (N = 20,469) and a separate cohort from the NCDB (N = 7,645) (both log-rank P < .001).

CONCLUSION: Our findings regarding the heterogeneity in outcomes for patients with dnMBC could guide future revisions of the current American Joint Committee on Cancer staging guidelines for patients with newly diagnosed stage IV disease. Our findings should be independently confirmed.

KEY OBJECTIVE: To develop a staging system on the basis of survival outcomes and disease-related variables for patients with de novo metastatic breast cancer (dnMBC) that refines prognostic estimates.

KNOWLEDGE GENERATED: Patients with dnMBC have highly variable survival outcomes, which are associated with select disease-related variables. These associations can be used to stratify patients into four distinct subgroups, and our findings could be used to revise the current staging guidelines for patients with dnMBC.

RELEVANCE: Patients with de novo metastatic disease are often considered together with those whose disease has recurred after initial therapy. This analysis defines the unique and varied prognosis of patients with de novo metastatic disease, facilitating shared decision making.

PMID: 36944149

DOI: 10.1200/JCO.22.02222