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15 september 2021: Bron:  Author manuscript; available in PMC 2014 Aug 13 Met dank aan arts-bioloog drs. Valstar die mij op deze studie wees

Uit een grote fase III studie uitgevoerd in Nieuw-Zeeland en Australië blijkt dat op gegevens van een biopsie gebaseerde stadiumvaststelling van middelgrote of dikke primaire melanomen belangrijke voorspellende informatie geeft. Deze aanpak wijst patiënten aan met lymfklieruitzaaiingen die baat kunnen hebben bij onmiddellijke volledige lymfadenectomie = verwijdering van lymfklieren door operatie.

Op door een biopsie verkregen gegevens gebaseerde behandelingen verlengt de ziektevrije overleving voor alle patiënten met een melanoom, ongeacht de dikte en verlengt de ziektevrije overleving van patiënten met uitzaaiingen op afstand en de melanoomspecifieke overleving voor patiënten met lymfklieruitzaaiingen van melanomen van gemiddelde dikte. Echter was er geen verschil in overall overleving tussen patiënten waarbij standaard de lymfklieren werden weggehaald en de patiënten waarbij er alleen een biopt werd gedaan.  

Deze resultaten komen uit een fase III studie bij 2001 patiënten. De onderzoekers evalueerden de resultaten bij 2001 patiënten met primaire cutane melanomen die gerandomiseerd werden ingedeeld in drie groepen:

  • 1. een groep die een brede operatie plus lymfklierobservatie kreeg.
  • 2. een groep patiénten kreeg een lymfadenectomie = verwijdering van lymfklieren door operatie voordat zich lymfklieruitzaaiingen hadden voorgedaan (observatiegroep).
  • 3. een groep patiënten kreeg een brede operatie en standaard een schildwachtklierbiopsie, met direct een lymfadenectomie voor lymfklieren met uitzaaiingen vastgesteld door een biopsie (biopsie groep). 
Onder alle patiënten uit alle drie de groepen werd geen behandelingsgericht verschil gezien in 10-jaars overleving. Dus standaard schildwachtklier weghalen maakte geen verschil met alleen een biopt nemen. Wel werd een verschil gezien tussen patiënten met en zonder lymfklieruitzaaiingen bij de start van de studie, (20,8% met en 79,2% zonder lymfklieruitzaaiingen) in de 10-jaars melanoomspecifieke overlevingskans.

  • Gemiddelde (±SE) 10-jaars ziektevrije overlevingspercentages waren statistisch significant verbeterd in de biopsiegroep, vergeleken met de observatiegroep, bij patiënten met melanomen van gemiddelde dikte, gedefinieerd als 1,20 tot 3,50 mm (71,3 ± 1,8% vs. 64,7 procent). ± 2,3%; hazard ratio voor recidief of metastase, 0,76; P = 0,01), en die met dikke melanomen, gedefinieerd als > 3,50 mm (50,7 ± 4,0% vs. 40,5 ± 4,7%; hazard ratio 0,70; P = 0,03) .
  • Bij patiënten met melanomen van gemiddelde dikte was het 10-jaars melanoomspecifieke overlevingspercentage 62,1 ± 4,8% bij degenen met uitzaaiingen versus 85,1 ± 1,5% voor degenen zonder uitzaaiingen (hazardratio voor overlijden door melanoom, 3,09; P<0,001);
  • Bij patiënten met dikke melanomen waren de respectievelijke percentages 48,0 ± 7,0% en 64,6 ± 4,9% (hazard ratio, 1,75; P = 0,03).
  • Op biopsie gebaseerde behandeling verbeterde het 10-jaarspercentage van ziektevrije overleving op afstand (hazardratio voor metastasen op afstand, 0,62; P = 0,02) en het 10-jaarspercentage van melanoomspecifieke overleving (hazardratio voor overlijden door melanoom, 0,56; P = 0,006) voor patiënten met melanomen van gemiddelde dikte en knoopmetastasen.

Het volledige studierapport is gratis in te zien of te downloaden met nog veel meer gedetailleerde gegevens. Klik op de titel van het abstract:

 Author manuscript; available in PMC 2014 Aug 13.
Published in final edited form as:
PMCID: PMC4058881
PMID: 24521106

Final Trial Report of Sentinel-Node Biopsy versus Nodal Observation in Melanoma

Associated Data

Supplementary Materials



Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase 3 trial.


We evaluated outcomes in 2001 patients with primary cutaneous melanomas randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (observation group), or wide excision and sentinel-node biopsy, with immediate lymphadenectomy for nodal metastases detected on biopsy (biopsy group).


No significant treatment-related difference in the 10-year melanoma-specific survival rate was seen in the overall study population (20.8% with and 79.2% without nodal metastases). Mean (±SE) 10-year disease-free survival rates were significantly improved in the biopsy group, as compared with the observation group, among patients with intermediate-thickness melanomas, defined as 1.20 to 3.50 mm (71.3±1.8% vs. 64.7±2.3%; hazard ratio for recurrence or metastasis, 0.76; P = 0.01), and those with thick melanomas, defined as >3.50 mm (50.7±4.0% vs. 40.5±4.7%; hazard ratio, 0.70; P = 0.03). Among patients with intermediate-thickness melanomas, the 10-year melanoma-specific survival rate was 62.1±4.8% among those with metastasis versus 85.1±1.5% for those without metastasis (hazard ratio for death from melanoma, 3.09; P<0.001); among patients with thick melanomas, the respective rates were 48.0±7.0% and 64.6±4.9% (hazard ratio, 1.75; P = 0.03). Biopsy-based management improved the 10-year rate of distant disease–free survival (hazard ratio for distant metastasis, 0.62; P = 0.02) and the 10-year rate of melanoma-specific survival (hazard ratio for death from melanoma, 0.56; P = 0.006) for patients with intermediate-thickness melanomas and nodal metastases. Accelerated-failure-time latent-subgroup analysis was performed to account for the fact that nodal status was initially known only in the biopsy group, and a significant treatment benefit persisted.


Biopsy-based staging of intermediate-thickness or thick primary melanomas provides important prognostic information and identifies patients with nodal metastases who may benefit from immediate complete lymphadenectomy. Biopsy-based management prolongs disease-free survival for all patients and prolongs distant disease–free survival and melanoma-specific survival for patients with nodal metastases from intermediate-thickness melanomas. (Funded by the National Cancer Institute, National Institutes of Health, and the Australia and New Zealand Melanoma Trials Group; ClinicalTrials.gov number, NCT00275496.)

Regional node management in melanoma has remained controversial since Snow recommended elective complete lymphadenectomy for all patients with melanoma, regardless of whether there was clinical evidence of regional nodal metastases. However, routine elective lymphadenectomy exposes all patients to procedure-related complications and cannot benefit the majority, who have no regional nodal metastases. Multiple randomized trials have suggested a benefit of routine lymphadenectomy in at least some groups of patients with melanoma.

Because of dissatisfaction with both elective lymphadenectomy and nodal observation, lymphatic mapping and sentinel-node biopsy were introduced for individualized management of regional lymph nodes. Sentinel-node biopsy is a minimally invasive, low-morbidity staging procedure performed with the use of blue dye and radiolabeled colloids. It identifies the first (i.e., sentinel) node or nodes in the regional basin that receive lymph from the primary melanoma site. Because the sentinel node is the initial site of regional metastasis, its tumor status accurately predicts the tumor status of other nodes in the lymphatic basin. If focused pathological scrutiny of the sentinel node identifies no metastases, other regional nodes will probably also be negative.

The Multicenter Selective Lymphadenectomy Trial (MSLT-I) commenced in 1994 to determine whether sentinel-node biopsy could be used to identify patients with clinically occult nodal metastases and whether immediate-completion lymphadenectomy yielded better outcomes than complete lymphadenectomy performed only when nodal recurrence was revealed during observation. Enrollment closed in 2002, after 2001 patients had been registered. The 5-year results of the third interim analysis, published in 2006, highlighted patients in the primary study group who had primary melanomas of intermediate thickness (defined as 1.20 to 3.50 mm). We now report 10-year follow-up data for that group as well as for patients with thick primary melanomas (defined as >3.50 mm thick). We also report the results of a new accelerated-failure-time latent-subgroup analysis of the treatment effect of sentinel-node biopsy.


The content of this report is solely the responsibility of the authors and does not necessarily represent the official view of the National Cancer Institute or the National Institutes of Health.

Supported by a grant from the National Cancer Institute (CA 29605, to Dr. Morton), with additional support at Australian centers provided by the Australian and New Zealand Melanoma Trials Group.

Dr. Thompson reports receiving fees for service on advisory boards from GlaxoSmithKline and Roche and honoraria and travel support from GlaxoSmithKline and Provectus; and Dr. Kashani-Sabet, receiving fees for service on advisory boards from Merck and Myriad Genetics, honoraria and grant support from Merck, holding stock in Melanoma Diagnostics, and holding a patent on the molecular classification of melanoma (patent no. 8492102), which has been licensed to Myriad Genetics.


The authors’ full names and academic degrees are as follows: Donald L. Morton, M.D., John F. Thompson, M.D., Alistair J. Cochran, M.D., Nicola Mozzillo, M.D., Omgo E. Nieweg, M.D., Ph.D., Daniel F. Roses, M.D., Harald J. Hoekstra, M.D., Ph.D., Constantine P. Karakousis, M.D., Ph.D., Christopher A. Puleo, P.A.-C., Brendon J. Coventry, B.M., B.S., Ph.D., Mohammed Kashani-Sabet, M.D., B. Mark Smithers, M.B., B.S., Eberhard Paul, M.D., William G. Kraybill, M.D., J. Gregory McKinnon, M.D., He-Jing Wang, M.D., Robert Elashoff, Ph.D., and Mark B. Faries, M.D.

The authors’ affiliations are as follows: the Departments of Surgical Oncology (D.L.M., M.B.F.) and Biostatistics (H.-J.W., R.E.), John Wayne Cancer Institute at Saint John’s Health Center, Santa Monica, CA; Melanoma Institute Australia and the University of Sydney, Sydney (J.F.T.), the Department of Surgery, Royal Adelaide Hospital, Adelaide (B.J.C.), and Princess Alexandra Hospital, Brisbane (B.M.S.) — all in Australia; the Departments of Pathology, Laboratory Medicine, and Surgery (A.J.C.) and Biostatistics (R.E., H.-J.W.) and the Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles; the Department of Surgical Oncology, National Cancer Institute, Naples, Italy (N.M.); the Department of Surgery, Netherlands Cancer Institute, Amsterdam (O.E.N.); the Department of Surgery, New York University School of Medicine, New York (D.F.R.); the Department of Surgical Oncology, University Medical Center Groningen and Groningen University, Groningen, the Netherlands (H.J.H.); the Department of Surgery, Millard Fillmore Hospital (C.P.K.), and Roswell Park Cancer Institute (W.G.K.) — both in Buffalo, NY; H. Lee Moffitt Cancer Center, Tampa, FL (C.A.P.); Center for Melanoma Research and Treatment, California Pacific Medical Center Research Institute, San Francisco (M.K.-S.); the Klinikum Nord, Nuremberg, Germany (E.P.); and Tom Baker Cancer Centre, Calgary, AB, Canada (J.G.M.).


No other potential conflict of interest relevant to this article was reported.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article is dedicated to the memory of Donald L. Morton, M.D., an exceptional leader and cancer researcher, who died very shortly before its publication.


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