Skip to main content

Advertisement

SpringerLink
Log in

Sentinel Node Status is the Most Important Prognostic Information for Clinical Stage IIB and IIC Melanoma Patients

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

Abstract

Background

Sentinel node biopsy (SNB) for melanoma patients has been questioned. We aimed to study high-risk stage II melanoma patients who underwent SNB to determine what the prognostic factors regarding recurrence and mortality were, and evaluate how relevant SNB status is in this scenario.

Methods

This was a retrospective analysis of clinical stage IIB/IIC melanoma patients who underwent SNB from 2000 to 2015 in a single institution. Prognostic factors related to distant recurrence-free survival (DRFS) and melanoma-specific survival (MSS) were assessed from multiple Cox regression. Relevant variables were used to create risk predictor nomograms for DRFS and MSS.

Results

From 1213 SNB, 259 were performed for clinical stage IIB/IIC melanoma patients. SNB status was the most important variable for both endpoints. Patients with positive SNB presented median DRFS of 35.73 months (95% CI 21.38–50.08, SE 7.32) and median MSS of 66.4 months (95% CI 29.76–103.03, SE 18.69), meanwhile both median DRFS and MSS were not achieved for those with negative SNB (logrank < 0.0001). Both nomograms have been internally validated and presented adequate calibration (C-index was 0.734 for DRFS and 0.718 for MSS).

Conclusions

SNB status was the most important risk factor in our cohort of clinical stage IIB and IIC patients and, in conjunction with well-established primary tumor characteristics, should not be abandoned. Their use in prognosis for these patients remains extremely useful for daily practice.

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
Fig. 2

Similar content being viewed by others

References

  1. Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127(4):392–9.

    Article  CAS  PubMed  Google Scholar 

  2. Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Nieweg OE, Roses DF, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370(7):599–609.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wong SL, Faries MB, Kennedy EB, Agarwala SS, Akhurst TJ, Ariyan C, et al. Sentinel lymph node biopsy and management of regional lymph nodes in melanoma: american society of clinical oncology and society of surgical oncology clinical practice guideline update. Ann Surg Oncol. 2018;25(2):356–77.

    Article  PubMed  Google Scholar 

  4. Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long G V., Ross MI, et al. Melanoma staging: evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA A Cancer J Clin. 2017;67(6):472–92.

  5. Madu MF, Wouters MWJM, van Akkooi ACJ. Sentinel node biopsy in melanoma: Current controversies addressed. Eur J Surg Oncol. 2017;43(3):517–33.

    Article  CAS  PubMed  Google Scholar 

  6. Zagarella S. Sentinel lymph node biopsy still provides no benefits for patients with melanoma. Am J Dermatopathol. 2020;00(00):1.

    Google Scholar 

  7. García-Doval I, Espinosa-Pereiro C, Zulaica Gárate A. Biopsia selectiva del ganglio centinela en melanoma: ni utilidad terapéutica, ni es buena para seleccionar los pacientes que podrían beneficiarse de la inmunoterapia adyuvante. Actas Dermosifiliogr. 2020.

  8. Bigby M, Zagarella S, Sladden M, Popescu CM. Time to reconsider the role of sentinel lymph node biopsy in melanoma. J Am Acad Dermatol. 2019;80(4):1168–71.

    Article  PubMed  Google Scholar 

  9. Sladden M, Zagarella S, Popescu C, Bigby M. No survival benefit for patients with melanoma undergoing sentinel lymph node biopsy: critical appraisal of the Multicenter Selective Lymphadenectomy Trial-I final report. Br J Dermatol. 2015;172(3):566–71.

    Article  CAS  PubMed  Google Scholar 

  10. Verver D, van Klaveren D, van Akkooi ACJ, Rutkowski P, Powell BWEM, Robert C, et al. Risk stratification of sentinel node–positive melanoma patients defines surgical management and adjuvant therapy treatment considerations. Eur J Cancer. 2018;96:25–33.

    Article  PubMed  Google Scholar 

  11. Bertolli E, Franke V, Calsavara VF, de Macedo MP, Pinto CAL, van Houdt WJ, et al. Validation of a nomogram for non-sentinel node positivity in melanoma patients, and its clinical implications: a Brazilian–Dutch study. Ann Surg Oncol. 2019;26(2):395–405. https://doi.org/10.1245/s10434-018-7038-9.

    Article  PubMed  Google Scholar 

  12. Ipenburg NA, Nieweg OE, Uren RF, Thompson JF. Outcome of melanoma patients who did not proceed to sentinel node biopsy after preoperative lymphoscintigraphy. Ann Surg Oncol. 2017;24(1):117–26.

    Article  PubMed  Google Scholar 

  13. Bellomo D, Arias-Mejias SM, Ramana C, Heim JB, Quattrocchi E, Sominidi-Damodaran S, et al. Model combining tumor molecular and clinicopathologic risk factors predicts sentinel lymph node metastasis in primary cutaneous melanoma. JCO Precis Oncol. 2020;47(4):319–34.

    Article  Google Scholar 

  14. Bertolli E, de Macedo MP, Calsavara VF, Pinto CAL, Duprat Neto JP. A nomogram to identify high-risk melanoma patients with a negative sentinel lymph node biopsy. J Am Acad Dermatol. 2019;80(3):722–6.

    Article  PubMed  Google Scholar 

  15. Luke JJ, Ascierto PA, Carlino MS, Gershenwald JE, Grob J-J, Hauschild A, et al. KEYNOTE-716: Phase III study of adjuvant pembrolizumab versus placebo in resected high-risk stage II melanoma. Future Oncol. 2020;16(3):4429–38.

    Article  CAS  Google Scholar 

  16. Eggermont AMM, Blank CU, Mandala M, Long G V., Atkinson V, Dalle S, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med. 2018;378(19):1789–801.

    Article  CAS  PubMed  Google Scholar 

  17. Gibson EJ, Begum N, Koblbauer I, Dranitsaris G, Liew D, McEwan P, et al. Economic evaluation of single versus combination immuno-oncology therapies: application of a novel modelling approach in metastatic melanoma. Clin Outcomes Res. 2020;12:241–52.

    Article  Google Scholar 

  18. Meng Y, Hertel N, Ellis J, Morais E, Johnson H, Philips Z, et al. The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Eur J Heal Econ. 2018;19(8):1163–72.

    Article  Google Scholar 

  19. Seiger K, Schmults CD, Silk AW, Ruiz ES. Cost and utilization of immunotherapy and targeted therapy for melanoma: cross-sectional analysis in the Medicare population, 2013 and 2015. J Am Acad Dermatol. 2020;82(3):761–4.

    Article  PubMed  Google Scholar 

  20. Duprat JP, Silva DCP, Coimbra FJF, Lima IAM, Lima ENP, Almeida OM, et al. Sentinel lymph node biopsy in cutaneous melanoma: analysis of 240 consecutive cases. Plast Reconstr Surg 2005;115(7):1944–51. discussion 1952–1953. A.

    Article  CAS  PubMed  Google Scholar 

  21. Bertolli E, De Macedo MP, Pinto CAL, Damascena AS, Molina AS, Ueno PS, et al. Evaluation of melanoma features and their relationship with nodal disease: the importance of the pathological report. Tumori. 2015;101(5):501–5.

    Article  CAS  PubMed  Google Scholar 

  22. Lausen B, Schumacher M. Maximally selected rank statistics. Biometrics. 1992;48(1):73.

    Article  Google Scholar 

  23. Cox DR. Regression models and life-tables. J R Stat Soc Ser B. 1972;34(2):187–220.

    Google Scholar 

  24. Steyerberg EW, Harrell FE. Prediction models need appropriate internal, internal-external, and external validation. J Clin Epidemiol. 2016; 69:245–7.

    Article  PubMed  Google Scholar 

  25. D. Schoenfeld. Partial residuals for the proportionnal hazards regression model. Biometrika. 1982;69(1):239–41.

    Article  Google Scholar 

  26. Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika. 1994;81(3):515–26.

    Article  Google Scholar 

  27. Faries MB, Thompson JF, Cochran AJ, Andtbacka RH, Mozzillo N, Zager JS, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med. 2017;376(23):2211–22.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Leiter U, Stadler R, Mauch C, Hohenberger W, Brockmeyer N, Berking C, et al. Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial. Lancet Oncol. 2016;17(6):757–67.

    Article  PubMed  Google Scholar 

  29. Leiter U, Stadler R, Mauch C, Hohenberger W, Brockmeyer NH, Berking C, et al. Final analysis of DeCOG-SLT trial: no survival benefit for complete lymph node dissection in patients with melanoma with positive sentinel node. J Clin Oncol. 2019;37(32):3000–8.

    Article  CAS  PubMed  Google Scholar 

  30. Guidelines N. Cutaneous melanoma. NCCN Clin Pract Guidel Oncol (NCCN Guidel. 2020;v3.2020.

  31. Long G V., Hauschild A, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377(19):1813–23.

    Article  CAS  PubMed  Google Scholar 

  32. Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, et al. adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377(19):1824–35.

    Article  CAS  PubMed  Google Scholar 

  33. de Melo AC, Wainstein AJA, Buzaid AC, Thuler LCS. Melanoma signature in Brazil. Melanoma Res. 2018;28(6):629–36.

    Article  PubMed  Google Scholar 

  34. Kandolf Sekulovic L, Guo J, Agarwala S, Hauschild A, McArthur G, Cinat G, et al. Access to innovative medicines for metastatic melanoma worldwide: Melanoma World Society and European Association of Dermato-oncology survey in 34 countries. Eur J Cancer. 2018;104:201–9.

    Article  CAS  PubMed  Google Scholar 

  35. Eggermont AMM, Chiarion-Sileni V, Grob J-J, Dummer R, Wolchok JD, Schmidt H, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016;375(19):1845–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bello DM, Han G, Jackson L, Bulloch K, Ariyan S, Narayan D, et al. The prognostic significance of sentinel lymph node status for patients with thick melanoma. Ann Surg Oncol. 2016;23(S5):938–45.

    Article  PubMed  Google Scholar 

  37. Morera-Sendra N, Tejera-Vaquerizo A, Traves V, Requena C, Bolumar I, Pla A, et al. Value of sentinel lymph node biopsy and adjuvant interferon treatment in thick (> 4 mm) cutaneous melanoma: an observational study. Eur J Dermatol. 2016;26(1):34–48.

    Article  CAS  PubMed  Google Scholar 

  38. Gyorki DE, Sanelli A, Herschtal A, Lazarakis S, McArthur GA, Speakman D, et al. Sentinel lymph node biopsy in T4 melanoma: an important risk-stratification tool. Ann Surg Oncol. 2016;23(2):579–84.

    Article  PubMed  Google Scholar 

  39. Ribero S, Osella-Abate S, Sanlorenzo M, Balagna E, Senetta R, Fierro MT, et al. Sentinel lymph node biopsy in thick-melanoma patients (N = 350): what is its prognostic role? Ann Surg Oncol. 2015;22(6):1967–73.

    Article  CAS  PubMed  Google Scholar 

  40. Balachandran VP, Gonen M, Smith JJ, DeMatteo RP. Nomograms in oncology: more than meets the eye. Lancet Oncol. 2015;16(4):e173–80.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Iasonos A, Schrag D, Raj G V., Panageas KS. How to build and interpret a nomogram for cancer prognosis. J Clin Oncol. 2008;26(8):1364–70.

    Article  PubMed  Google Scholar 

  42. Wong SL, Kattan MW, McMasters KM, Coit DG. A nomogram that predicts the presence of sentinel node metastasis in melanoma with better discrimination than the American joint committee on cancer staging system. Ann Surg Oncol. 2005; 12:282–8.

    Article  PubMed  Google Scholar 

  43. MacDonald S, Siever J, Baliski C. Performance of models predicting residual lymph node disease in melanoma patients following sentinel lymph node biopsy. Am J Surg. 2020;219(5):750–5.

    Article  PubMed  Google Scholar 

  44. Oliveira KCS, Ramos IB, Silva JMC, Barra WF, Riggins GJ, Palande V, et al. Current perspectives on circulating tumor DNA, precision medicine, and personalized clinical management of cancer. Mol Cancer Res. 2020;18(4):517–28.

    Article  PubMed  Google Scholar 

  45. Podlipnik S, Carrera C, Boada A, Richarz NA, López‐Estebaranz JL, Pinedo‐Moraleda F, et al. Early outcome of a 31‐gene expression profile test in 86 AJCC stage IB—II melanoma patients. A prospective multicentre cohort study. J Eur Acad Dermatol Venereol. 2019;33(5):857–62.

  46. Blank CU, Haanen JB, Ribas A, Schumacher TN. The “cancer immunogram.” Science. 2016;352(6286):658–60.

    Article  CAS  PubMed  Google Scholar 

  47. Naffouuje SA, Naffouje R, Chen J, Salti GI. Validation and enhancement of the clinicopathological melanoma nomogram via incorporation of a molecular marker in the primary tumor. Anticancer Res. 2016;36(12):6603–10.

    Article  Google Scholar 

Download references

Acknowledgment

There was neither grant support nor funding for this study.

Author information

Author notes

  1. Marcus Vitor Nunes Lindote, Marcus Rodrigo Monteiro and Eduardo Doria Filho have contributed equally to this work.

Authors and Affiliations

  1. Surgical Oncology Residence Program, A. C. Camargo Cancer Center, São Paulo, SP, Brazil

    Isabela Bartelli Fonseca MD, Marcus Vitor Nunes Lindote MD & Marcus Rodrigo Monteiro MD

  2. Department of Surgical Oncology, Clínica AMO, Salvador, BA, Brazil

    Eduardo Doria Filho MD

  3. Department of Pathology, A. C. Camargo Cancer Center, São Paulo, SP, Brazil

    Clovis Antonio Lopes Pinto MD, PhD

  4. Skin Cancer Department, A. C. Camargo Cancer Center, São Paulo, SP, Brazil

    Andrea Schiavinato Jafelicci MD, Matheus de Melo Lôbo MD, Eduardo Bertolli MD, PhD & João Pedreira Duprat Neto MD, PhD

  5. Department of Epidemiology and Statistics, A. C. Camargo Cancer Center, São Paulo, SP, Brazil

    Vinicius Fernando Calsavara PhD

Authors
  1. Isabela Bartelli Fonseca MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marcus Vitor Nunes Lindote MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marcus Rodrigo Monteiro MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eduardo Doria Filho MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Clovis Antonio Lopes Pinto MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrea Schiavinato Jafelicci MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Matheus de Melo Lôbo MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vinicius Fernando Calsavara PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eduardo Bertolli MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. João Pedreira Duprat Neto MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors participated in the conception, writing, and final revision of this manuscript. They all agree with the results and conclusions that have been presented.

Corresponding author

Correspondence to Eduardo Bertolli MD, PhD.

Ethics declarations

Disclosure

The authors have nothing to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fonseca, I.B., Lindote, M.V.N., Monteiro, M.R. et al. Sentinel Node Status is the Most Important Prognostic Information for Clinical Stage IIB and IIC Melanoma Patients. Ann Surg Oncol 27, 4133–4140 (2020). https://doi.org/10.1245/s10434-020-08959-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-020-08959-9

Search

Navigation