Department of Surgery, Feinberg School of Medicine of Northwestern University, 303 East Superior Street, Lurie 4-111, Chicago, IL, 60611, USA.
Texas Tech University Health Sciences Center School of Medicine, Lubbock, TX, USA.
Ann Surg Oncol. 2022 Sep;29(9):5811-5820. doi: 10.1245/s10434-022-11900-x. Epub 2022 May 24.
Until 2001, the paradigm guiding the management of women with de novo metastatic breast cancer (dnMBC) stipulated that primary-site locoregional therapy (PSLT) did not alter the course of metastatic disease and was necessary only for palliation of symptoms. Since 2002, retrospective data have begun questioning this paradigm. However, selection biases driving an observed survival advantage associated with PSLT in dnMBC were quickly recognized and led to several randomized clinical trials (RCTs) addressing this question.
Four published RCTs have since tested the value of PSLT added to systemic therapy (ST) or not, with overall survival (OS) as the primary end point. The results of three published trials show no OS benefit for the addition of PSLT: Indian Tata Memorial, U.S./Canada E2108, and Austrian POSYTIVE (although POSYTIVE did not reach full accrual). The fourth RCT (Turkey, MF07-01) shows an OS benefit for PSLT at 5 years (42 % vs 24 % in the ST arm; hazard ratio [HR], 0.66; 95 % confidence interval [CI], 0.49-0.88). However, the 5-year survival in the PSLT arm of MF07-01 is similar to that in both arms of E2108, suggesting that the worse survival in the ST arm of MF07-01 is a result of biologically worse disease (from imbalanced randomization). Locoregional control was improved by PSLT in all trials, but without improvement in quality of life.
The current evidence fails to refute the 20th century paradigm guiding management of de novo metastatic breast cancer. Discussion continues regarding the survival value of PSLT for patients with bone-only disease or oligometastases, but unbiased evidence is lacking.
直到 2001 年，指导新诊断转移性乳腺癌（dnMBC）管理的范例规定，原发部位局部区域治疗（PSLT）不会改变转移性疾病的进程，仅用于缓解症状是必要的。自 2002 年以来，回顾性数据开始质疑这一范例。然而，与 PSLT 相关的观察到的生存优势背后的选择偏见很快被认识到，并导致了几项针对这一问题的随机临床试验（RCT）。
自那时以来，四项已发表的 RCT 已经测试了在系统治疗（ST）中添加或不添加 PSLT 的价值，以总生存期（OS）作为主要终点。三项已发表试验的结果表明，添加 PSLT 对 OS 没有益处：印度塔塔纪念医院、美国/加拿大 E2108 和奥地利 POSYTIVE（尽管 POSYTIVE 没有达到全额入组）。第四项 RCT（土耳其 MF07-01）显示 PSLT 在 5 年时的 OS 获益（PSLT 组为 42%，ST 组为 24%；风险比[HR]，0.66；95%置信区间[CI]，0.49-0.88）。然而，MF07-01 的 PSLT 组的 5 年生存率与 E2108 的两个组相似，这表明 MF07-01 的 ST 组的生存率更差是由于生物学上更差的疾病（由于不平衡的随机化）。所有试验中 PSLT 均改善了局部区域控制，但并未改善生活质量。
目前的证据未能反驳指导新诊断转移性乳腺癌管理的 20 世纪范例。关于 PSLT 对仅有骨转移或寡转移患者的生存价值的讨论仍在继续，但缺乏无偏见的证据。
