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Do Lymph Node Metastases Matter in Appendiceal Cancer with Peritoneal Carcinomatosis? A US HIPEC Collaborative Study

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Journal of Gastrointestinal Surgery

Abstract

Background

Whether formal regional lymph node (LN) evaluation is necessary for patients with appendiceal adenocarcinoma (AA) who have peritoneal metastases is unclear. The aim of this study was to evaluate the prognostic value of LN metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

Methods

A retrospective analysis of the US HIPEC collaborative, a multi-institutional consortium comprising 12 high-volume centers, was performed to identify patients with AA who underwent CRS-HIPEC with adequate LN sampling (≥ 12 LNs).

Results

Two hundred-fifty patients with AA who underwent CRS-HIPEC were included. Outcomes were compared between LN − and LN + disease. Baseline patient characteristics between groups were similar, with most patients undergoing complete cytoreduction (0/1: 86.0% vs. 76.8%, p = 0.08), respectively. More adverse tumor factors were found in patients with LN + disease, including poor differentiation, signet ring cells, and lymphovascular invasion. Multivariate analysis of overall survival (OS) found LN + disease was independently associated with worse OS (HR: 2.82 95%CI: 1.25–6.34, p = 0.01), even after correction for receipt of systemic therapy. On Kaplan–Meier analysis, median OS was lower in patients with LN + disease (25.9 months vs. 91.4 months, p < 0.01). LN + disease remained associated with poor OS following propensity score matching (HR: 4.98 95%CI: 1.72–14.40, p < 0.01) and in patients with PCI ≥ 20 (HR: 3.68 95%CI: 1.54–8.80, p < 0.01).

Conclusions

In this large multi-institutional study of patients with AA undergoing CRS-HIPEC, LN status remained associated with worse OS even in the setting of advanced peritoneal carcinomatosis. Formal LN evaluation should be performed for most patients with AA undergoing CRS-HIPEC.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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Authors and Affiliations

  1. Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Kevin M. Turner, Mackenzie C. Morris, Aaron M. Delman & Dennis Hanseman

  2. Department of Surgery, Johns Hopkins University, Baltimore, MD, USA

    Fabian M. Johnston & Jonathan Greer

  3. Department of Surgery, Division of Surgical Oncology, University of Wisconsin, Madison, WI, USA

    Kara Vande Walle & Daniel E. Abbott

  4. Department of Surgery, Division of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, USA

    Mustafa Raoof

  5. Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA

    Travis E. Grotz

  6. Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Keith Fournier

  7. Department of Gastrointestinal Oncology, Moffitt Cancer Center, Morsani College of Medicine, Tampa, FL, USA

    Sean Dineen

  8. Department of Surgery, Division of Surgical Oncology, University of California, San Diego, San Diego, CA, USA

    Jula Veerapong

  9. Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA

    Ugwuji Maduekwe & Anai Kothari

  10. Division of Surgical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Charles A. Staley & Shishir K. Maithel

  11. Peritoneal Surface Malignancy Program Section of Surgical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Laura A. Lambert

  12. Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Alex C. Kim & Jordan M. Cloyd

  13. Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, Medical Science Building, 231 Albert Sabin Way, Cincinnati, OH, 45267-0558, USA

    Gregory C. Wilson, Jeffrey J. Sussman, Syed A. Ahmad & Sameer H. Patel

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Contributions

Authors who made substantial contributions to conception and design:

K.M.T.; M.C.M.; A.M.D.; G.C.W.; J.J.S.; S.A.A.; S.H.P.

Authors who made substantial contribution to acquisition of data:

All authors: K.M.T.; M.C.M.; A.M.D.; D.H.; F.M.J.; J.G.; K.V.W.; D.E.A.; M.R.; T.E.G.; K.F.; S.D.; J.V.; U.M.; A.K.; C.A.S.; S.K.M.; L.A.L.; A.C.K.; J.M.C.; G.C.W.; J.J.S.; S.A.A.; S.H.P.

Authors who made substantial contribution to data analysis and interpretation of data:

K.M.T.; M.C.M.; A.M.D.; D.H.; S.H.P.

Authors who participated in drafting the manuscript.

K.M.T.; M.C.M.; A.M.D.; G.C.W.; J.J.S.; S.A.A.; S.H.P.

Authors who participated in revising the manuscript:

All authors: K.M.T.; M.C.M.; A.M.D.; D.H.; F.M.J.; J.G.; K.V.W.; D.E.A.; M.R.; T.E.G.; K.F.; S.D.; J.V.; U.M.; A.K.; C.A.S.; S.K.M.; L.A.L.; A.C.K.; J.M.C.; G.C.W.; J.J.S.; S.A.A.; S.H.P.

Authors give final approval of the version to be published:

All authors: K.M.T.; M.C.M.; A.M.D.; D.H.; F.M.J.; J.G.; K.V.W.; D.E.A.; M.R.; T.E.G.; K.F.; S.D.; J.V.; U.M.; A.K.; C.A.S.; S.K.M.; L.A.L.; A.C.K.; J.M.C.; G.C.W.; J.J.S.; S.A.A.; S.H.P.

Corresponding author

Correspondence to Sameer H. Patel.

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Oral Presentation at the 2022 Advanced Cancer Therapies Meeting 2022.

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Turner, K.M., Morris, M.C., Delman, A.M. et al. Do Lymph Node Metastases Matter in Appendiceal Cancer with Peritoneal Carcinomatosis? A US HIPEC Collaborative Study. J Gastrointest Surg 26, 2569–2578 (2022). https://doi.org/10.1007/s11605-022-05489-5

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