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Modern Chemotherapy Mitigates Adverse Prognostic Effect of Regional Nodal Metastases in Stage IV Colorectal Cancer

  • 2013 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Background

In colorectal cancer, the involvement of regional lymph nodes with metastasis is an established prognostic factor. The impact of the number of positive nodes on patient outcome with stage IV disease is not well defined.

Methods

A retrospective review was performed of 1,421 patients at two tertiary referral centers with stage IV colorectal cancer who underwent primary tumor resection. Associations between regional nodes, lymph node ratio (LNR), and overall survival (OS) from date of diagnosis were analyzed.

Results

The number of positive regional nodes and LNR correlated with multiple sites of metastases (p < 0.001). Survival was significantly associated with the number of positive nodes and LNR, with a median OS of 43 months with negative nodes, compared to 20 months with ≥7 positive nodes (p < 0.001). The number of regional nodal metastases correlated with OS among 400 patients undergoing resection of liver metastases (p = 0.005) but lost prognostic significance in the subset of 223 patients who underwent hepatectomy with perioperative oxaliplatin- or irinotecan-based chemotherapy (p = 0.48).

Conclusions

In stage IV colorectal cancer, an increasing number of positive regional nodes and LNR correlate with multiple sites of metastases and poorer survival. The number of metastatic regional lymph nodes loses prognostic significance with modern chemotherapy in patients undergoing resection of liver metastases.

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Conflict of Interest

The authors do not have any relevant relationships to disclose.

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA

    Alan A. Thomay, Elin R. Sigurdson & Yun Shin Chun

  2. Division of Gastroenterologic and General Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    David M. Nagorney & Mark J. Truty

  3. Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA

    Steven J. Cohen, Barbara Burtness & Michael J. Hall

Authors
  1. Alan A. Thomay
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  2. David M. Nagorney
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  3. Steven J. Cohen
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  4. Elin R. Sigurdson
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  5. Mark J. Truty
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  6. Barbara Burtness
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  7. Michael J. Hall
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  8. Yun Shin Chun
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Corresponding author

Correspondence to Yun Shin Chun.

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Discussant

Dr. J. Nicolas Vauthey (Houston, TX, USA): The authors should be congratulated for presenting another paper indicating the absence of prognostic value of the status of primary lymph nodes in patients undergoing resection of colorectal liver metastases after receiving preoperative modern oxaliplatin- or irinotecan-based chemotherapy. This paper may explain why studies have increasingly shown limited value in this new era of preoperative chemotherapy of the scores developed in the 1990s to predict the survival of patients undergoing resection of colorectal liver metastases.

The authors of this paper have presented two very different cohorts of patients with metastatic colorectal cancer: those who did not and those who did undergo resection of their metastases. The patients who did not undergo resection are an unselected group, while the patients who did undergo resection are a doubly selected group—i.e., patients who were selected on the basis of good response to chemotherapy and who then were selected for resection on the basis of multiple factors. Therefore, it is likely that not only “modern chemotherapy” but also additional selection tools such as high-quality imaging, a longer duration of preoperative chemotherapy, and improved intraoperative ultrasonography and surgical techniques all contributed to the observed similar survivals irrespective of primary nodal status. I have two sets of questions for the authors:

1. What are the authors’ current recommendation regarding perioperative adjuvant chemotherapy in patients with colorectal liver metastases? Should all patients receive preoperative chemotherapy as a selection tool prior to resection? Should some patients be considered for up-front surgery without preoperative chemotherapy?

2. Recent studies have indicated a lack of predictive value of colorectal risk scores or other prognostic models in the new era of preoperative chemotherapy for colorectal liver metastases. Considering the wide range of biologic responses often seen with preoperative chemotherapy, which prognostic tools should be used now or evaluated in the future to predict the prognosis of patients undergoing resection of colorectal liver metastases?

Closing Discussant

Dr. Alan Thomay: We greatly appreciate Dr. Vauthey's thoughtful review of the manuscript and insightful questions. Our bias at Fox Chase Cancer Center is to administer preoperative oxaliplatin- or irinotecan-based chemotherapy to most patients with colorectal liver metastases, based on the results of the EORTC 40983 trial. We limit the amount of preoperative chemotherapy to 4–6 cycles because of potential chemotherapy-associated hepatotoxicity. We favor up-front surgery for patients with small, solitary metastases that may disappear radiographically with preoperative chemotherapy. In addition, we avoid preoperative chemotherapy in patients with residual neuropathy from prior oxaliplatin or who have a contraindication to treatment with irinotecan, particularly steatohepatitis.

Regarding prognostic tools, rather than traditional criteria such as size and number of hepatic metastases, we use radiologic and pathologic responses to preoperative chemotherapy, which are independent predictors of survival, as shown by Dr. Vauthey and colleagues at M. D. Anderson. In addition, the M. D. Anderson group has demonstrated that patients treated with adjuvant FOLFOX after resection of colorectal cancer who then develop metachronous liver metastases are more likely to harbor KRAS mutations in their liver metastases (Andreou A et al. Annals of Surgery 2012). These patients have inferior survival after hepatic resection compared to those treated with 5-FU only after primary tumor resection. Other molecular markers will likely emerge as important prognostic factors in our new era of preoperative chemotherapy.

This paper was presented as a 2013 SSAT Plenary Presentation Manuscript, May 2013, Orlando, FL, USA.

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Thomay, A.A., Nagorney, D.M., Cohen, S.J. et al. Modern Chemotherapy Mitigates Adverse Prognostic Effect of Regional Nodal Metastases in Stage IV Colorectal Cancer. J Gastrointest Surg 18, 69–74 (2014). https://doi.org/10.1007/s11605-013-2329-8

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  • DOI: https://doi.org/10.1007/s11605-013-2329-8

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