Clinical Pearls & Morning Reports
The management of regional lymph nodes has long been controversial in the treatment of many solid tumors, particularly melanoma. In the second Multicenter Selective Lymphadenectomy Trial (MSLT-II), conducted by Faries et al., the authors evaluated the usefulness of completion lymph-node dissection in patients with melanoma and sentinel lymph-node metastases as compared with observation with frequent nodal ultrasonography and dissection only in patients in whom clinically detected nodal recurrence had developed.
Q. What were the findings of the first Multicenter Selective Lymphadenectomy Trial (MSLT-I)?
A. The first Multicenter Selective Lymphadenectomy Trial (MSLT-I) confirmed the staging value of sentinel-node biopsy and showed a therapeutic advantage of early treatment of nodal metastases among patients with intermediate-thickness melanoma. Among patients with intermediate-thickness melanomas (defined as 1.2 to 3.5 mm in diameter) and nodal metastases, early surgical treatment, guided by sentinel-node biopsy, was associated with increased melanoma-specific survival (survival until death from melanoma). The findings of that trial provided support for the use of sentinel-node biopsy, which is now recommended in the guidelines of most national and professional organizations for the treatment of melanoma.
Q. Is immediate completion lymph-node dissection usually recommended for melanoma patients who have sentinel-node metastases?
A. Currently, immediate completion lymph-node dissection (removal of the remaining regional lymph nodes after sentinel-node excision) is usually recommended for patients with sentinel-node metastases. However, in patients with sentinel-node metastases, the value of completion lymph-node dissection remains controversial. Since most such patients have all nodal metastases removed by means of the sentinel-node biopsy procedure, they cannot derive additional therapeutic value from completion lymph-node dissection. Even microscopic nonsentinel-node metastases portend a markedly worse prognosis, similar to that of patients with bulky, clinically diagnosed metastases, than the prognosis in patients with metastases that are limited to the sentinel lymph nodes. Patients with nonsentinel-node metastasis may be unlikely to benefit from early dissection. Finally, completion lymph-node dissection is associated with higher morbidity than sentinel-node biopsy alone, so an appraisal of the value of the procedure is important. Previous data regarding this clinical question have been inconclusive.
A: At the third interim analysis of data from MSLT II, the data and safety monitoring board determined that detection of a significant survival difference between the trial groups was unlikely and recommended that the current primary end-point data be released. Intention-to-treat and per-protocol analyses of the outcome variables showed similar results. MSLT-II, in which 1939 patients underwent randomization with a median follow-up of 43 months, provided sufficient data to resolve the central question: no significant survival benefit was imparted by immediate completion lymph-node dissection among patients with sentinel-node metastases. The lack of a survival benefit with completion lymph-node dissection in patients in MSLT-II suggests that any increase in survival with early surgery occurred among patients with disease that was limited to the sentinel node. Patients with nonsentinel-node metastases may still undergo salvage treatment with completion lymph-node dissection, but the timing of that intervention does not appear to be critical.
A: Immediate completion lymph-node dissection reduced the rate of regional nodal recurrence by nearly 70%, leading to a small but significant decrease in the overall risk of recurrence. Since no significant difference between the groups was noted in the primary end point, differences with respect to the secondary end points must be interpreted with caution. A nonsignificant difference in distant metastasis–free survival was noted at late time points, but as of this writing, events at those time points have been few, and additional follow-up is necessary.