Cut it out!!! Prolonged overall survival following metastasectomy in Stage IV melanoma

When in doubt - cut it out!!!

Prolonged Overall Survival Following Metastasectomy in Stage IV Melanoma.  Elias, Behbahani, Maddukuri, et al.  J Eur Acad Dermatol Venereol. 2019 May 9.  Current literature supports mixed conclusions regarding the outcomes of metastatectomy in Stage IV melanoma. The objective of this national study was to determine the associations of non-primary site surgery with overall survival (OS) in Stage IV melanoma. The National Cancer Database (NCDB) was queried for all Stage IV melanoma cases diagnosed from 2004 to 2015. Cases missing treatment/staging data or undergoing palliative treatment were excluded (remaining n=14,034). Patients were separated into 'metastatectomy' (n=4,214, 30.0%) and 'non-metastatectomy' (n=9,820, 70.0%) cohorts. Survival outcomes were analyzed using Kaplan-Meier and Cox proportional hazards regressions. On univariate analysis, patients with Stage IV melanoma undergoing metastatectomy (median survival:15.67mo) had greater overall survival compared to those not receiving non-primary surgery (median survival: 7.13 mo) [5-year OS 13.2% vs. 5.6%]. Metastatectomy for Stage IV melanoma is independently associated with improved OS in metastatic cases involving the skin, lung, and visceral organs.

Here, researchers reviewed records of Stage IV melanoma peeps with tumors in their "skin, lung and visceral organs" recorded in the National Cancer Database from 2004-2015.  Leaving out those who had incomplete records and those on hospice, they found 14,034 cases to examine.  30% of those (4,214) had their tumors surgically removed, 70% (9,820) did not.  Median survival for those who had their melanoma cut out was almost 16 months while those who did not had a median survival of 7 months.  When looking at 5 year survival in these groups, it was 13.2% for those who had surgery vs 5.6% for those who did not.  

Now, to be fair, it is not clear which of these patients were able to attain effective systemic therapy vs those who did not as this time frame covers a period in which current immnotherapies and targeted therapies were and were NOT available.  Still, just like antibiotics and bacterial infections - we have learned that therapies work best with the lowest tumor burden.  Meaning - if you have a localized infection, antibiotics often take care of it easily.  However, if the bacterial growth becomes overwhelming, throwing all the antibiotics in the world at it will not prevent the patient from succumbing to sepsis.  Likewise, we know that when melanoma patients have their tumor removed completely or even debulked, immunotherapy works much better.  That is the entire premise of adjuvant care in melanoma.  But, because melanoma likes to be a completely freaky unpredictable be-atch, we are more recently noting, that "NEO-adjuvant" care, giving treatment before surgery, then having the tumor removed, while continuing the systemic therapy for a period of time after surgery, is showing promise.  We still have a lot to learn about that, with ratties currently leading the way, as researchers hypothesize that by utilizing this approach the immune system is primed (learns to recognize the tumor despite its upcoming removal), the systemic therapy not only shrinks the tumor making surgery less of a big deal, it then "sweeps the area" of microscopic or residual inoperable disease with its use after surgery as we have already proven with basic "adjuvant" care.  We have yet to see exactly how this will all play out in the long run, but I suspect surgery will still remain a very important life saving tool in melanoma care.

Here is a recent report (with additional links within) on neo-adjuvant treatment: BRAF/MEK before surgery as well as after is MUCH better, than just AFTER surgery for melanoma!! Plus trial still recruiting resectable stage III/IV melanoma peeps.

As well as this recent report on Clinical condition of melanoma peeps and associated outcomes when treated with anti-PD-1 vs anti-PD-1 and ipi, which notes:  [When looking at the use of anti-PD-1 alone] size of the largest tumor was independently associated with PFS, OS, and RR, whereas AJCC stage, lactate dehydrogenase, liver metastases, ECOG performance status, number of metastases, and prior therapies were not.In patients treated with anti-PD-1+ipilimumab, however, tumor bulk was not associated with outcomes, although number of metastases was associated with PFS  and RR but not OS.  Therefore, indicating that total tumor burden (most in patients treated with anti-PD-1 as a single agent and less with the ipi/nivo combo) continues to impact response to immunotherapy in melanoma patients.

Leave it to melanoma to make every decision as complicated as possible - but there is beauty...

...still. ~ c