Patient information sheet
Dr. Dixons letter to British Medical Journal about sentinel node biopsy
College Board has reviewed the current evidence and data on the usage of sentinel lymph node biopsy (SLNB) in management of melanoma.
Of note, we reviewed the MSLT1 trial on SLNB as published in the New England Journal of Medicine(NEJM) in September 2006 with further details published in Annals of Surgery in September 2005.
The Australasian College of Skin Cancer Medicine policy is as follows:
- Sentinel lymph node biopsy (SLNB) is not a standard of care in managing melanoma and should not be a routine component of managing melanoma, regardless of tumour Breslow thickness.
- SLNB and subsequent completion lymphadenectomy (CL) for node positive patients has been demonstrated to have no 5 year survival advantage for patients.
- SLNB has a concerning complication incidence. It is 10% in the MSLT1 trial.
- SLNB positive patients should not routinely progress to CL. It is unclear whether this affords them any benefit and trials are underway to address this question.
- Completion lymphadenectomy brings an alarming complication profile for the patient given the evidence of no survival advantage. MSLT1 trial demonstrated a 37% complication rate in patients who underwent CL.
- SLNB offers some added prognostic advice for patients and some may seek the surgery for this added information regarding their survival prospects.
- If a SLNB is contemplated, the surgeon should counsel the patient that: the intervention offers no survival advantage, has a significant complication incidence and that there is considerable uncertainty as to what could or should be done (if anything) in the event of a positive test.
The College encourages all members to abide this policy unless and until further evidence suggest an alternative approach.
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We also encourgae doctors to read the full text of the NEJM paper, not just the abstract:
Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, Nieweg OE, Roses DF, Hoekstra HJ, Karakousis CP, Reintgen DS, Coventry BJ, Glass EC, Wang HJ. Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 2006;355:1307-17.
The complications associated with the MSLT1 trial are not covered in the NEJM paper but are detailed in:
Morton DL, Cochran AJ, Thompson JF, Elashoff R, Essner R, Glass EC, Mozzillo N, Nieweg OE, Roses DF, Hoekstra HJ, Karakousis CP, Reintgen DS, Coventry BJ, Wang HJ. Sentinel node biopsy for early-stage melanoma: accuracy and morbidity in MSLT-I, an international multicenter trial. Ann Surg 2005;242:302-11; discussion 311-3.
The Journal "Nature Clinical Practice Oncology" published a short but succinct editoral on SLNB in January 2008.
It was written by Steven Rosenberg, Chief of Surgery, National Cancer Institute, Bethesda, Maryland, USA.
You can learn more on Dr. Rosenberg here
Why perform sentinel-lymph-node biopsy in patients with melanoma?
Steven A Rosenberg
Sentinel-lymph-node biopsy (SLNB) has become the standard of care for patients presenting with intermediate-thickness melanoma; however, there is no evidence that this procedure has a positive impact on survival. One study (Morton DL [2006] N Engl J Med 355: 1307–1317) was elegantly designed to determine the impact of SLNB on patient survival. In total, 1,269 patients with melanoma and no clinically palpable lymph nodes were prospectively randomized to receive either observation or SLNB, which if positive, was followed by lymph-node dissection. There was no suggestion of a difference in survival when the two groups were compared (P = 0.58).
Many subgroup analyses were performed on these data that had little bearing on this main point. The survival analysis comparing patients with positive sentinel-lymph nodes to patients who recurred with nodal disease is difficult to interpret since it assumes no false-positive analyses of the sentinel nodes and that all abnormal cells in the nodes would eventually form a tumor. This is not a valid assumption as discussed by Thomas in this issue of the journal (Thomas M [2008] Nat Clin Pract Oncol 5: 18–23). Whether one believes the assumption is correct or not, it does not alter the compelling data that there was no survival difference between the two groups. This finding is in accordance with several prospective, randomized trials, all of which showed that there was no survival benefit to prophylactic lymph-node dissection in patients with melanoma. (Veronesi U et al. [1977] N Engl J Med 297: 627–630; (Sim FH et al. [1978] Cancer 41: 948–956)
The small difference in progression-free survival that was observed in the Morton study was most likely attributable to the surgical removal of the nodes in one group, which removed the most common first site of recurrence in one group but not in the other.
The concluding sentence of the paper describing the randomized trial states that "...sentinel-lymph node biopsy should be preferred to observation". This conclusion is not justified by the data and should not be accepted. Although SLNB does provide prognostic information, patients should be clearly informed that SLNB, possibly followed by lymph-node dissection, is an expensive procedure with associated morbidity that confers no survival benefit. If the authors conclude that SLNB is "preferred" despite finding no survival benefit associated with this procedure, one wonders why the study was done at all.
MSLT2 Trial underway
The MSLT2 trial is currently underway and patients are being recruited into this trial in Queensland, South Australia, New South Wales and Victoria. This trial is designed to determine whether SLNB positive patients should progress to completion lymphadenectomy (CL). Patients who choose to have a SLNB and the test is positive can enroll in this trial. Patients are randomized into CL or not.
It is interesting that some surgeons who believe the MSLT1 invalid subanalysis are now involved in the MSLT2 trial. These doctors believe that there is a survival advantage afforded by early nodal surgery compared to late. They believe that SLNB done early and nodes found positive allows patients to have immediate block node excision leading to a better 5 year survival prospect. If such was truly the case, MSLT2 would be unethical and these doctors should not be involved in recruiting for MSLT2. In reality, MSLT2 trial is a valid and ethical trial because the subanalysis of MSLT1 is fundamentally flawed and invalid.
ACSCM supports the MSLT2 trial. To date no group of patients, on an intention to treat basis, has been demonstrated to have a survival advantage through the sentinel node intervention. If patients choose to have the SLNB test for prognostic advice, ACSCM strongly recommends node positive patients be enrolled in MSLT2 trial. This may mean that patients need to travel to multidisciplinary melanoma units for MSLT2 enrollment. We believe this is in the best interests of the patient as well as the best interests of furthering our knowledge of melanoma and its management.