Original Research|Articles in Press

Surgical outcomes of lymph node dissections for stage III melanoma after neoadjuvant systemic therapy are not inferior to upfront surgery

Published:March 07, 2023DOI:


      • Lymph node dissection (LND) is currently standard of care for stage IIIB-D melanoma.
      • Neoadjuvant systemic therapy (NAST) has shown high response rates in melanoma.
      • Surgical outcomes of LND after NAST are comparable to upfront surgery.



      Neoadjuvant systemic therapy has shown promising results in the treatment of high-risk stage III melanoma; however, the effects on surgery are currently unknown. This study aims to compare the surgical outcomes, in terms of postoperative complications, postoperative morbidity, duration of surgery and textbook outcomes, of patients with high-risk stage III melanoma who received neoadjuvant systemic therapy followed by lymph node dissection with patients who received an upfront lymph node dissection.


      In this retrospective cohort study, patients with high-risk stage III melanoma treated with neoadjuvant anti-PD1 and anti-CTLA4 in the OpACIN (NCT02437279) and OpACIN-neo (NCT02977052) trial between October 2014 and August 2018 were included and compared to patients who received upfront surgery in the same time period.


      A total of 120 patients were included in this study, of whom 44 received neoadjuvant systemic therapy and 76 underwent upfront surgery. There was no significant difference in the overall rate of postoperative complications between the neoadjuvant group and the upfront surgery group (31.8% versus 36.8%, p = 0.578) and neither in rate of postoperative morbidity (seroma 56.8% versus 57.9%, p = 0.908) (lymphedema 22.7% versus 13.2%, p = 0.175). There was a non-significant difference towards a slightly longer duration of surgery after neoadjuvant immunotherapy (105 versus 90 min, p = 0.077). There were no differences in textbook outcomes (50% versus 49%, p = 0.889).


      This study shows that the surgical outcomes for patients who underwent a lymph node dissection after neoadjuvant systemic immunotherapy or underwent upfront lymph node dissection for high-risk stage III melanoma are comparable.


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        • Rozeman E.A.
        • Hoefsmit E.P.
        • Reijers I.L.M.
        • et al.
        Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma.
        Nat Med. 2021; 27: 256-263
        • Blank C.U.
        • Reijers I.L.M.
        • Pennington T.
        • et al.
        First safety and efficacy results of PRADO: A phase II study of personalized response-driven surgery and adjuvant therapy after neoadjuvant ipilimumab (IPI) and nivolumab (NIVO) in resectable stage III melanoma.
        J Clin Oncol. 2020; 38 (10002-10002)
        • Amaria R.N.
        • Reddy S.M.
        • Tawbi H.A.
        • et al.
        Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma.
        Nat Med. 2018; 24: 1649-1654
        • Long G.V.
        • Saw R.P.M.
        • Lo S.
        • et al.
        Neoadjuvant dabrafenib combined with trametinib for resectable, stage IIIB–C, BRAFV600 mutation-positive melanoma (NeoCombi): a single-arm, open-label, single-centre, phase 2 trial.
        The Lancet Oncol. 2019; 20: 961-971
        • Patel S.
        • Othus M.
        • Prieto V.
        • et al.
        LBA6 Neoadjvuant versus adjuvant pembrolizumab for resected stage III-IV melanoma (SWOG S1801).
        Ann Oncol. 2022; 33: S808-S869
        • Gyorki D.E.
        • Yuan J.
        • Mu Z.
        • et al.
        Immunological insights from patients undergoing surgery on ipilimumab for metastatic melanoma.
        Ann Surg Oncol. 2013; 20: 3106-3111
        • Lorentzen T.
        • Heidemann L.N.
        • Moller S.
        • et al.
        Impact of neoadjuvant chemotherapy on surgical complications in breast cancer: A systematic review and meta-analysis.
        Eur J Surg Oncol. 2022; 48: 44-52
        • Hieken T.J.
        • Price D.L.
        • Piltin M.A.
        • et al.
        Surgeon assessment of the technical impact of neoadjuvant systemic therapy on operable stage III melanoma.
        Ann Surg Oncol. 2022; 29: 780-786
        • van Akkooi A.C.J.
        • Hieken T.J.
        • Burton E.M.
        • et al.
        Neoadjuvant Systemic Therapy (NAST) in patients with melanoma: surgical considerations by the International Neoadjuvant Melanoma Consortium (INMC).
        Ann Surg Oncol. 2022; 29: 3694-3708
        • Rozeman E.A.
        • Menzies A.M.
        • van Akkooi A.C.J.
        • et al.
        Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial.
        The Lancet Oncol. 2019; 20: 948-960
        • Blank C.U.
        • Rozeman E.A.
        • Fanchi L.F.
        • et al.
        Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma.
        Nat Med. 2018; 24: 1655-1661
        • Busweiler L.A.
        • Schouwenburg M.G.
        • van Berge Henegouwen M.I.
        • et al.
        Textbook outcome as a composite measure in oesophagogastric cancer surgery.
        Br J Surg. 2017; 104: 742-750
        • Kolfschoten N.E.
        • Kievit J.
        • Gooiker G.A.
        • et al.
        Focusing on desired outcomes of care after colon cancer resections; hospital variations in 'textbook outcome'.
        Eur J Surg Oncol. 2013; 39: 156-163
        • Karthaus E.G.
        • Lijftogt N.
        • Busweiler L.A.D.
        • et al.
        Textbook outcome: a composite measure for quality of elective aneurysm surgery.
        Ann Surg. 2017; 266: 898-904
        • Faut M.
        • Heidema R.M.
        • Hoekstra H.J.
        • et al.
        Morbidity after inguinal lymph node dissections: it is time for a change.
        Ann Surg Oncol. 2017; 24: 330-339
        • Stuiver M.M.
        • Westerduin E.
        • ter Meulen S.
        • et al.
        Surgical wound complications after groin dissection in melanoma patients - a historical cohort study and risk factor analysis.
        Eur J Surg Oncol. 2014; 40: 1284-1290
        • Chang S.B.
        • Askew R.L.
        • Xing Y.
        • et al.
        Prospective assessment of postoperative complications and associated costs following inguinal lymph node dissection (ILND) in melanoma patients.
        Ann Surg Oncol. 2010; 17: 2764-2772
        • Sun J.
        • Kirichenko D.A.
        • Chung J.L.
        • et al.
        Perioperative outcomes of melanoma patients undergoing surgery after receiving immunotherapy or targeted therapy.
        World J Surg. 2020; 44: 1283-1293
        • Blankenstein S.A.
        • Rohaan M.W.
        • Klop W.M.C.
        • et al.
        Neoadjuvant cytoreductive treatment with BRAF/MEK inhibition of prior unresectable regionally advanced melanoma to allow complete surgical resection, REDUCTOR: a prospective, single-arm, open-label phase II trial.
        Ann Surg. 2021; 274: 383-389