Pathologic Response of Index Lymph Node and Concordance With Total Nodal Basin Pathologic Response in Stage III Melanoma

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In a retrospective analysis reported in JAMA Surgery, Reijers et al found that pathologic response in largest lymph node metastasis (index lymph node [ILN]) was highly concordant with response in the total lymph node bed in patients with stage III melanoma receiving neoadjuvant nivolumab/ipilimumab.

As stated by the investigators, “Neoadjuvant checkpoint inhibition in patients with high-risk stage III melanoma shows high pathologic response rates associated with a durable relapse-free survival. Whether a therapeutic lymph node dissection can be safely omitted when a major pathologic response in the … ILN is obtained is currently being investigated.”

The retrospective analysis included 82 patients from the Australian-Dutch OpACIN and OpACIN-neo trials who received 6 weeks of neoadjuvant nivolumab/ipilimumab followed by therapeutic lymph node dissection (TLND).  

Key Findings

Responses in the ILN were pathologic compete response (pCR) in 34 patients (41%), near-pCR in 15 (18%), pathologic partial response (pPR) in 11 (13%), and pathologic nonresponse (pNR) in 22 (27%). Responses in the entire TLND specimen were pCR in 34 (41%), near-pCR in 16 (20%), pPR in 10 (12%), and pNR in 22 (27%). Pathologic response in the ILN was concordant with the entire TLND specimen response in 81 (99%) of 82 patients and concordant with response in every individual lymph node in 79 (96%).

In the one patient with discordant response, the ILN response (20% viable tumor, pPR) underrepresented the entire TLND specimen response (5% viable tumor, near-pCR). In two other patients, one small non-index node contained 80% viable tumor (pNR), with all other nodes including the ILN showing pPR. As noted by the investigators, risk of regional relapse might have been increased in these two patients had TLND been omitted.

The investigators concluded, “The results of this study suggest that the pathologic response of the ILN may be considered a reliable indicator of the entire TLND specimen response and may support the ILN response-directed omission of TLND in a prospective trial.”

Christian U. Blank, MD, PhD, of the Department of Medical Oncology and Division of Molecular Oncology & Immunology, The Netherlands Cancer Institute, Amsterdam, is the corresponding author for the JAMA Surgery article.  

Disclosure: The study was supported by the National Health and Medical Research Council of Australia and others. For full disclosures of the study authors, visit

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