Skip to main content

Advertisement

SpringerLink
Log in

Lymph-Node Ratio in Patients with Cutaneous Melanoma: A Multi-Institution Prognostic Study

  • Melanomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Lymph node ratio (LNR)—the number of metastatic lymph nodes (LNs) over the number of excised LNs after lymphadenectomy—is a prognostic factor for many solid tumors, but controversies still exist for skin melanoma. We investigated the prognostic relevance of LNR in melanoma patients and formulated a proposal for considering the LNR in the current American Joint Committee on Cancer (AJCC) N staging system.

Methods

Retrospective data of 2,526 melanoma patients with LN metastasis from nine Italian institutions were collected in a multicenter database. The prognostic value of the LNR (categorized as A, ≤0.1; B, 0.11–0.25; and C, >0.25) was assessed by multivariable survival analysis.

Results

LNR was a significant independent prognostic factor for melanoma-specific survival (LNR B vs. A: hazard ratio [HR] 1.47, 95 % CI 1.16–1.87, p = 0.002; LNR C vs. A: HR 1.84, 95 % CI 1.29–2.61, p = 0.001). The LNR had prognostic value in patients with AJCC N1a (one positive LN after sentinel LN biopsy [SLNB], HR 2.33, 95 % CI 1.49–3.63, p < 0.001) and N2a (two to three positive LNs after SLNB, HR 1.62, 95 % CI 1.09–2.40, p = 0.016) substages, but not in those with N1b (one clinically positive LN, p = 0.765), N2b (two to three clinically positive LNs, p = 0.165), and N3 (≥ four positive LNs, p = 0.084) substages.

Conclusion

The LNR is a prognostic factor in melanoma patients with one (AJCC N1a) and two to three (AJCC N2a) positive LNs after SLNB. This easy-to-obtain parameter should be considered for the staging of melanoma patients with LN metastasis, along with the number of positive LNs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27:6199–6206.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Balch CM, Gershenwald JE, Soong SJ, et al. Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol. 2010;28:2452–2459.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Soong SJ, Ding S, Coit D, et al. Predicting survival outcome of localized melanoma: an electronic prediction tool based on the AJCC Melanoma Database. Ann Surg Oncol. 2010;17:2006–2014.

    Article  PubMed  Google Scholar 

  4. Bauer J, Buttner P, Murali R, et al. BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor, and the degree of solar elastosis at the primary tumor site. Pigment Cell Melanoma Res. 2011;24:345–351.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Broekaert SM, Roy R, Okamoto I, et al. Genetic and morphologic features for melanoma classification. Pigment Cell Melanoma Res. 2010;23:763–770.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Long GV, Menzies AM, Nagrial AM, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011;29:1239–1246.

    Article  PubMed  Google Scholar 

  7. Mann GJ, Pupo GM, Campain AE, et al. BRAF mutation, NRAS mutation, and the absence of an immune-related expressed gene profile predict poor outcome in patients with stage III melanoma. J Invest Dermatol. 2012;133:509–517.

    Article  PubMed  Google Scholar 

  8. Schramm SJ, Campain AE, Scolyer RA, Yang YH, Mann GJ. Review and cross-validation of gene expression signatures and melanoma prognosis. J Invest Dermatol. 2012;132:274–283.

    Article  CAS  PubMed  Google Scholar 

  9. Hoek KS. DNA microarray analyses of melanoma gene expression: a decade in the mines. Pigment Cell Res. 2007;20:466–484.

    Article  CAS  PubMed  Google Scholar 

  10. Pasquali S, van der Ploeg AP, Mocellin S, Stretch JR, Thompson JF, Scolyer RA. Lymphatic biomarkers in primary melanomas as predictors of regional lymph node metastasis and patient outcomes. Pigment Cell Melanoma Res. 2013;26:326–37.

    Article  CAS  PubMed  Google Scholar 

  11. Rossi CR, Mozzillo N, Maurichi A, et al. The number of excised lymph nodes is associated with survival of melanoma patients with lymph node metastasis Ann Oncol. 2014;25:240–246.

    CAS  Google Scholar 

  12. Galliot-Repkat C, Cailliod R, Trost O, et al. The prognostic impact of the extent of lymph node dissection in patients with stage III melanoma. Eur J Surg Oncol. 2006;32:790–794.

    Article  CAS  PubMed  Google Scholar 

  13. Chan AD, Essner R, Wanek LA, Morton DL. Judging the therapeutic value of lymph node dissections for melanoma. J Am Coll Surg. 2000;191:16–22; discussion 22–13.

    Article  CAS  PubMed  Google Scholar 

  14. Mocellin S, Pasquali S, Rossi CR, Nitti D. Validation of the prognostic value of lymph node ratio in patients with cutaneous melanoma: a population-based study of 8,177 cases. Surgery. 2011;150:83–90.

    Article  PubMed  Google Scholar 

  15. Rossi CR, Mocellin S, Pasquali S, Pilati P, Nitti D. N-ratio: a novel independent prognostic factor for patients with stage-III cutaneous melanoma. Ann Surg Oncol. 2008;15:310–315.

    Article  PubMed  Google Scholar 

  16. Spillane AJ, Cheung BL, Winstanley J, Thompson JF. Lymph node ratio provides prognostic information in addition to American Joint Committee on Cancer N stage in patients with melanoma, even if quality of surgery is standardized. Ann Surg. 2011;253:109–115.

    Article  PubMed  Google Scholar 

  17. van der Ploeg AP, van Akkooi AC, Schmitz PI, et al. Therapeutic surgical management of palpable melanoma groin metastases: superficial or combined superficial and deep groin lymph node dissection. Ann Surg Oncol. 2011;18:3300–3308.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Xing Y, Badgwell BD, Ross MI, et al. Lymph node ratio predicts disease-specific survival in melanoma patients. Cancer. 2009;115:2505–2513.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Wevers KP, Bastiaannet E, Poos HP, van Ginkel RJ, Plukker JT, Hoekstra HJ. Therapeutic lymph node dissection in melanoma: different prognosis for different macrometastasis sites? Ann Surg Oncol. 2012;19:3913–3918.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Berger AC, Fierro M, Kairys JC, et al. Lymph node ratio is an important and independent prognostic factor for patients with stage III melanoma. J Surg Oncol. 2012;105:15–20.

    Article  PubMed  Google Scholar 

  21. Grotz TE, Huebner M, Pockaj BA, Perkins S, Jakub JW. Limitations of lymph node ratio, evidence-based benchmarks, and the importance of a thorough lymph node dissection in melanoma. Ann Surg Oncol. 2013;20:4370–4377.

    Article  PubMed  Google Scholar 

  22. Egger ME, Scoggins CR, Martin RC 2nd, et al. The lymph node ratio has limited prognostic significance in melanoma. J Surg Res. 2013;179:10–7.

    Article  PubMed  Google Scholar 

  23. Brown RE, Ross MI, Edwards MJ, et al. The prognostic significance of nonsentinel lymph node metastasis in melanoma. Ann Surg Oncol. 2010;17:3330–3335.

    Article  PubMed  Google Scholar 

  24. Janssen KJ, Donders AR, Harrell FE Jr, et al. Missing covariate data in medical research: to impute is better than to ignore. J Clin Epidemiol. 2010;63:721–727.

    Article  PubMed  Google Scholar 

  25. Mackinnon A. The use and reporting of multiple imputation in medical research: a review. J Intern Med. 2010;268:586–593.

    Article  CAS  PubMed  Google Scholar 

  26. Spillane AJ, Winstanley J, Thompson JF. Lymph node ratio in melanoma: a marker of variation in surgical quality? Cancer. 2009;115:2384–2387.

    Article  PubMed  Google Scholar 

  27. Pasquali S, Spillane AJ, de Wilt JH, et al. Surgeons’ opinions on lymphadenectomy in melanoma patients with positive sentinel nodes: a worldwide web-based survey. Ann Surg Oncol. 2012;19:4322–4329.

    Article  PubMed  Google Scholar 

  28. Spillane AJ, Cheung BL, Stretch JR, et al. Proposed quality standards for regional lymph node dissections in patients with melanoma. Ann Surg. 2009;249:473–480.

    Article  PubMed  Google Scholar 

  29. Lens MB, Dawes M, Goodacre T, Newton-Bishop JA. Elective lymph node dissection in patients with melanoma: systematic review and meta-analysis of randomized controlled trials. Arch Surg. 2002;137:458–461.

    PubMed  Google Scholar 

  30. Morton DL, Thompson JF, Cochran AJ, et al. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med. 2006;355:1307–1317.

    Article  CAS  PubMed  Google Scholar 

  31. Pasquali S, Mocellin S, Campana LG, et al. Early (sentinel lymph node biopsy-guided) versus delayed lymphadenectomy in melanoma patients with lymph node metastases: personal experience and literature meta-analysis. Cancer. 2010;116:1201–1209.

    Article  PubMed  Google Scholar 

  32. Morton DL, Thompson JF, Cochran AJ, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370:599–609.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Morton DL. Overview and update of the phase III Multicenter Selective Lymphadenectomy Trials (MSLT-I and MSLT-II) in melanoma. Clin Exp Metastasis 2012;29:699–706.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Pasquali S, Spillane A. Contemporary controversies and perspectives in the staging and treatment of patients with lymph node metastasis from melanoma, especially with regards positive sentinel lymph node biopsy. Cancer Treat Rev. 2014;40:893–899.

    Article  PubMed  Google Scholar 

  35. Spillane AJ, Pasquali S, Haydu LE, Thompson JF. Patterns of recurrence and survival after lymphadenectomy in melanoma patients: clarifying the effects of timing of surgery and lymph node tumor burden. Ann Surg Oncol. 2014;21:292–299.

    Article  PubMed  Google Scholar 

  36. van der Ploeg AP, van Akkooi AC, Verhoef C, Eggermont AM. Completion lymph node dissection after a positive sentinel node: no longer a must? Curr Opin Oncol. 2013;25:152–159.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

The authors thank Marta Rotella for her project managing support, Mrs Marilyn Ward for editing the manuscript, and the colleagues of the following institutions that are participating this study: National Cancer Institute, Milan (N = 904); National Cancer Institute Pascale, Naples (N = 550); Veneto Institute of Oncology and Department of Surgery, Oncology and Gastroenterology of the University of Padova (N = 317); Dermatologic Clinic, Department of Medical Sciences, University of Turin (N = 229); S. M. Annunziata Hospital, Tuscan Tumor Institute, Florence (N = 222); National Cancer Research Institute of Genoa, Genoa (N = 91); Riuniti Hospitals, Bergamo (N = 82); S. Pio X Hospital, Milan (N = 71), University of Bari, Bari (N = 60).

Disclosures

The authors have no disclosures.

Author information

Authors and Affiliations

  1. Surgery Branch, Department of Surgery Oncology and Gastroenterology, University of Padova, Padua, Italy

    Pasquali Sandro MD, Mocellin Simone MD, PhD & Rossi Carlo Riccardo MD

  2. Melanoma and Sarcoma Unit, Fondazione Istituto Nazionale Tumori, Milan, Italy

    Maurichi Andrea MD, Patuzzo Roberto MD, Marone Ugo MD & Santinami Mario MD

  3. Department of Surgery “Melanoma, Soft Tissues, Head and Neck”, National Cancer Institute “Pascale”, Naples, Italy

    Mozzillo Nicola MD & Caracò Corrado MD

  4. Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy

    Macripò Giuseppe MD & Ribero Simone MD

  5. Plastic Surgery Unit, Regional Melanoma Referral Center, S.M. Annunziata Hospital, Tuscan Tumor Institute, Florence, Italy

    Borgognoni Lorenzo MD

  6. Division of Surgical Oncology, IRCCS San Martino Hospital – National Cancer Institute of Genoa, Genoa, Italy

    Solari Nicola MD

  7. Unit of Surgery, Riuniti Hospital, Bergamo, Italy

    Piazzalunga Dario MD

  8. Unit of General Surgery, San Pio X Hospital, Milan, Italy

    Mascheroni Luigi MD

  9. Department of Plastic and Reconstructive Surgery, University of Bari, Bari, Italy

    Giudice Giuseppe MD

  10. Melanoma and Sarcomas Unit, Veneto Institute of Oncology, Padua, Italy

    Rossi Carlo Riccardo MD

Authors
  1. Pasquali Sandro MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maurichi Andrea MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mozzillo Nicola MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mocellin Simone MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Macripò Giuseppe MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Borgognoni Lorenzo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Solari Nicola MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Piazzalunga Dario MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mascheroni Luigi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Giudice Giuseppe MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Patuzzo Roberto MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Caracò Corrado MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ribero Simone MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Marone Ugo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Santinami Mario MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Rossi Carlo Riccardo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mocellin Simone MD, PhD.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 16 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sandro, P., Andrea, M., Nicola, M. et al. Lymph-Node Ratio in Patients with Cutaneous Melanoma: A Multi-Institution Prognostic Study. Ann Surg Oncol 22, 2127–2134 (2015). https://doi.org/10.1245/s10434-014-4132-5

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-014-4132-5

Keywords

Search

Navigation