A large clinical phase 3 study shows that immediate
removal of all regional lymph nodes from patients with melanoma and
metastases in the sentinel node does not improve their melanoma
specific survival. The Netherlands Cancer Institute participated in
this study and has stopped carrying out this surgical procedure.
The results were published in the New England Journal of
Medicine (NEJM) on June 8th.
Many melanoma patients undergo dissection of the sentinel node,
the lymph node closest to the tumor. In case a metastasis is found
in this node, it used to be common practice to also remove the
other lymph nodes in the same regional basin. Earlier clinical
studies suggested this would be beneficial for patients. However,
this surgical procedure comes with potentially severe side effects
and conclusive evidence of the efficacy was lacking. But not
anymore. A total of 63 treatment centers all over the world
included roughly 2000 patients in a study showing no effect of
extensive lymph node dissection on melanoma specific survival
compared to observation with ultrasound.
This second Multicenter Selective Lymphadenectomy Trial
(MSLT-II) randomly assigned 1943 melanoma patients with metastasis
in their sentinel node to either regular observation with
ultrasound or immediate removal of the regional lymph nodes. 39 of
them were included in the Netherlands Cancer Institute. In total,
1755 patients completed the assigned treatment and could be
evaluated. Three years after treatment the melanoma specific
survival was the same for both groups. The patients that had
additional nodes removed, however, suffered from the potentially
severe side effect lymphedema more often (24%) than the control
group (6%). NEJM published an informative video about the study results.
One could argue that removing the regional lymph nodes could
still be useful for staging the disease and obtaining prognostic
information. However, once the results of the MSLT-II study came
in, surgeon Alexander van Akkooi and his colleagues at the
Netherlands Cancer Institute started a soon to be published study
in their own patient database. They found that the tumor staging of
only 4.7% percent of the patients who have their regional lymph
nodes removed actually changed because of the extra information
retrieved from the removed nodes. Van Akkooi: "The potential
benefit for this very small group doesn't outweigh the side effects
many more patients will experience."
The surgeons of the Netherlands Cancer Institute decided to
adjust their treatment strategy last December. Van Akkooi: "The
results of this study are very clear and help us prevent
unnecessary surgical procedures. We decided to stop doing the
regional node dissection in patients with sentinel node metastases.
Instead, our standard policy is now to monitor them with
ultrasound. In the near future I hope we can offer these patients
new forms of adjuvant immunotherapy or targeted therapy instead of
surgery. Several of those therapies are being investigated."
As chairman of the national melanoma workgroup of the Netherlands
comprehensive cancer organization IKNL Van Akkooi has also initiated the
adjustment of the Dutch melanoma treatment guideline. Van Akkooi:
"The new guideline will probably be released in 2018. Hopefully,
hospitals in The Netherlands and abroad will adapt their treatment
strategy well before that."