Circulating tumor DNA (ctDNA) as a way to predict survival in Stage III melanoma patients

If you have Stage III melanoma, trying to determine whether or not to embark on adjuvant treatment (treatment taken after all obvious melanoma has been removed) via either immunotherapy or targeted therapy is - at best - difficult!!!  Will such treatment really help?  Well, the data strongly supports - YES!!!  Here are a zillion such articles!  But, we also know that some folks can remain Stage III for years and years with no advancement of their disease.  Is the very real possibility of significant life changing side effects worth it?  Wouldn't it be great if you could do a simple blood test to see if you fall among the folks who are Stage III AND at increased risk for progression if you do not attain treatment?

Well!  Before we get to that, remember all my rants about simple blood tests that can tell us soooooooo much about our melanoma status?  Here are a few zillion of those - looking at circulating tumor DNA (little bits of tumor, floating around in our blood) in particular:  The many ways measuring circulating tumor DNA can help melanoma patients  Basically, that link takes you to tons and tons of data, with some of my explanations, about what measuring circulating bits of tumor via a simple blood draw can do to impact melanoma patients and their treatment choices.  I note: "There are many blood markers, all much easier to collect that actual tumor samples, that can be used to diagnosis melanoma, determine tumor type, prognosis and response to therapy." 

Here's the latest:

Pre-operative ctDNA predicts survival in high-risk stage III cutaneous melanoma patients.  Lee, Saw, Thompson, et al. Ann Oncol. 2019 Mar 12. 

The outcomes of patients with stage III cutaneous melanoma who undergo complete surgical resection can be highly variable, and estimation of individual risk of disease relapse and mortality remains imprecise. With recent demonstrations of effective adjuvant targeted and immune checkpoint inhibitor therapy, more precise stratification of patients for costly and potentially toxic adjuvant therapy is needed. We report the utility of pre-operative circulating tumour DNA (ctDNA) in patients with high-risk stage III melanoma.

ctDNA was analysed in blood specimens that were collected pre-operatively from 174 patients with stage III melanoma undergoing complete lymph node dissection. Cox regression analyses were used to evaluate the prognostic significance of ctDNA for distant metastasis recurrence free survival (DM-RFS) and melanoma specific survival (MSS).

The detection of ctDNA in the discovery and validation cohort was 34% and 33% respectively, and was associated with larger nodal melanoma deposit, higher number of melanoma involved LNs, more advanced stage and high lactose dehydrogenase (LDH) levels. Detectable ctDNA was significantly associated with worse MSS in the discovery and validation cohort and remained significant in a multivariable analysis. ctDNA further sub-stratified patients with AJCC stage III substage, with increasing significance observed in more advanced stage melanoma.

Pre-operative ctDNA predicts MSS in high-risk stage III melanoma patients undergoing complete LN dissection, independent of stage III subclass. This biomarker may have an important role in prognosis and stratifying patients for adjuvant treatment.

So ~ in this study researchers looked at one group of Stage III melanoma patients to see how many of them would have circulating tumor DNA present in their blood sample.  Then they took another group to determine the presence of ctDNA and its correlation to other risk factors and melanoma outcomes.  They determined that the presence of circulating bits of tumor in the blood was consistent across both groups at about 34%.  They found that ctDNA in the Stage III melanoma patient's blood was associated with those who had larger amounts of tumor in melanoma positive lymph nodes, a greater number of lymph nodes affected, advanced stage, and increased LDH levels.  In the end, when they looked at all the variables, ctDNA was significantly associated with melanoma specific survival.

Is the presence of ctDNA the end all, be all?  Of course not!  BUT!!!  If you knew where you stood in regard to bits of tumor floating in your blood - or NOT!! - then that could be critical in making a decision about whether or not to proceed with adjuvant treatment.  Further, if I were a Stage IIIb patient today, as I was back in 2003, and found I did NOT have measurable ctDNA, I might be comfortable in postponing adjuvant treatment.  HOWEVER, I would request serial blood draws to determine if that status changed over time, with the understanding that should ctDNA show up in my blood I would begin adjuvant therapy ASAP!  I believe (given all the data I've reviewed) that evaluating patients for ctDNA is a much more sensitive and sensible way to follow Stage III peeps for progression than repeated radiographic scans and (hopefully!!!) will be the wave of the future. 

So...what are we waiting for???????????  Lives are at stake!  Let's make measuring ctDNA a routine, accepted method of evaluating melanoma patients - TODAY!!!! ~  c