Crookes Thomas R, Scolyer Richard A, Lo Serigne, Drummond Martin, Spillane Andrew J
Melanoma Institute Australia, 40 Rockland Roads, North Sydney, NSW, 2060, Australia.
School of Medicine Sydney, The University of Notre Dame, Sydney, Australia.
Ann Surg Oncol. 2017 May;24(5):1378-1385. doi: 10.1245/s10434-016-5723-0. Epub 2017 Jan 27.
Inconsistent data suggests extranodal spread (ENS) is an adverse prognostic factor in Stage III melanoma patients but it remains contentious. By rigorously matching cohorts, this study sought to clarify associations with recurrence and survival.
Melanoma patients with lymph node metastases (AJCC Stage III), with or without ENS, sub-classified on the basis of known (MKP) or unknown primary (MUP), were identified from a single institution prospective database. Of 725 ENS patients identified, 567 were able to be precisely matched 1:1 with a non-ENS cohort. Clinicopathologic factors were analyzed for associations with outcome.
There were 481 MKP and 86 MUP patients in each cohort. ENS, compared to non-ENS, was an independent predictor of worse melanoma specific survival (MSS) (HR = 1.71, 95% CI = 1.39-2.11, P < 0.0001) with median MSS 56.4 versus 175.2 months, P < 0.001; worse disease free survival (DFS) (HR = 1.16, 95%CI = 1.00-1.34, P = 0.044) with median DFS 15.6 versus 21.5 months, P = 0.009; and worse post-recurrence survival (PRS) (HR = 1.66, 95%CI = 1.37-2.02, P < 0.0001) with median PRS 20.1 versus 51.1 months, P < 0.001. ENS was also associated with reduced time to distant recurrence (Distant Disease Free Survival [DDFS]) (HR = 2.00, 95% CI = 1.24-3.24, P = 0.0047), however median time to distant recurrence not reached within the study time period.
ENS represents a significant independent predictor of worse MSS, DFS, PRS and DDFS in Stage III melanoma patients. ENS should be considered in the stratification of patients in adjuvant therapy trials.
数据不一致表明，结外扩散（ENS）是III期黑色素瘤患者的不良预后因素，但仍存在争议。通过严格匹配队列，本研究旨在阐明其与复发和生存的关联。
从一个单一机构的前瞻性数据库中识别出有或无ENS的黑色素瘤淋巴结转移患者（美国癌症联合委员会III期），并根据已知原发灶（MKP）或未知原发灶（MUP）进行亚分类。在725例ENS患者中，567例能够与非ENS队列进行精确的1:1匹配。分析临床病理因素与预后的关联。
每个队列中有481例MKP患者和86例MUP患者。与非ENS相比，ENS是黑色素瘤特异性生存（MSS）较差的独立预测因素（HR = 1.71，95%CI = 1.39 - 2.11，P < 0.0001），MSS中位数分别为56.4个月和175.2个月，P < 0.001；无病生存期（DFS）较差（HR = 1.16，95%CI = 1.00 - 1.34，P = 0.044），DFS中位数分别为15.6个月和21.5个月，P = 0.009；复发后生存期（PRS）较差（HR = 1.66，95%CI = 1.37 - 2.02，P < 0.0001），PRS中位数分别为20.1个月和51.1个月，P < 0.001。ENS还与远处复发时间缩短（远处无病生存期[DDFS]）相关（HR = 2.00，95%CI = 1.24 - 3.24，P = 0.0047），然而在研究时间段内未达到远处复发的中位时间。
ENS是III期黑色素瘤患者MSS、DFS、PRS和DDFS较差的重要独立预测因素。在辅助治疗试验的患者分层中应考虑ENS。
