Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ann Surg Oncol. 2020 Aug;27(8):2915-2926. doi: 10.1245/s10434-019-08174-1. Epub 2020 Jan 2.
Immune checkpoint blockade (ICB) has transformed melanoma treatment, but optimal sequencing of ICB and surgery for clinically evident nodal metastasis remains undefined. We evaluated adjuvant-only (AT) and neoadjuvant/adjuvant (NAT) ICB with respect to survival outcomes in this patient population.
Patients who underwent lymphadenectomy (1 January 2011 to 31 July 2018) and received perioperative ICB at an academic center were identified. AT was defined as postoperative ICB, and NAT was defined as one to two cycles of ICB prior to resection with continuation of therapy following surgery. Three-year disease-free survival (DFS), locoregional recurrence-free survival (LRFS), distant disease-free survival (DDFS), and melanoma-specific survival (MSS) were estimated.
Of 59 patients, 18 (31%) received AT and 41 (69%) received NAT. The AT and NAT groups did not differ in age (median 53 vs. 62 years, p = 0.16) or stage (IIIB 33% vs. 29%, IIIC 56% vs. 68%, IIID 11% vs. 2%, p = 0.34). Although 3-year DFS did not differ significantly by treatment sequencing (NAT vs. AT, hazard ratio [HR] 0.56, p = 0.17), NAT was associated with improved 3-year DDFS (HR 0.38, p = 0.028). Of 39 NAT patients with evaluable pathologic response, 23 (59%) and 5 (13%) had a pathologic partial response (pPR) and pathologic complete response (pCR), respectively. Patients with pPR/pCR experienced improved 3-year DFS (HR 0.16, p = 0.001), LRFS (HR 0.17, p = 0.003), and DDFS (HR 0.26, p = 0.029) compared with those with no response. Three-year MSS did not differ significantly by response (p = 0.062).
NAT may be associated with improved 3-year DDFS compared with AT sequencing, and allows for early assessment of pathologic response. Further prospective evaluation of treatment sequencing is warranted.
免疫检查点阻断（ICB）改变了黑色素瘤的治疗方式，但对于有临床明显淋巴结转移的患者，ICB 与手术的最佳序贯治疗仍未确定。我们评估了辅助治疗（AT）和新辅助/辅助（NAT）ICB 对这部分患者的生存结果的影响。
本研究纳入了在学术中心接受淋巴结切除术（2011 年 1 月 1 日至 2018 年 7 月 31 日）并接受围手术期 ICB 治疗的患者。AT 定义为术后 ICB，NAT 定义为在切除前接受一至两个周期的 ICB，并在手术后继续治疗。估计了患者的 3 年无病生存（DFS）、局部区域无复发生存（LRFS）、远处无病生存（DDFS）和黑色素瘤特异性生存（MSS）。
59 例患者中，18 例（31%）接受 AT，41 例（69%）接受 NAT。AT 组和 NAT 组在年龄（中位年龄 53 岁比 62 岁，p=0.16）或分期（IIIB 33%比 29%，IIIC 56%比 68%，IID 11%比 2%，p=0.34）方面无显著差异。尽管治疗序贯治疗（NAT 比 AT）并未显著影响 3 年 DFS（风险比[HR]0.56，p=0.17），但 NAT 与 3 年 DDFS 的改善相关（HR 0.38，p=0.028）。在 39 例可评估病理反应的 NAT 患者中，分别有 23 例（59%）和 5 例（13%）患者有病理部分缓解（pPR）和病理完全缓解（pCR）。有 pPR/pCR 的患者 3 年 DFS（HR 0.16，p=0.001）、LRFS（HR 0.17，p=0.003）和 DDFS（HR 0.26，p=0.029）均显著优于无反应者。无反应患者与有反应患者的 3 年 MSS 无显著差异（p=0.062）。
与 AT 序贯治疗相比，NAT 可能与改善 3 年 DDFS 相关，并且允许早期评估病理反应。需要进一步前瞻性评估治疗序贯治疗。
