SLN biopsy. Delay of 40 days = WHAT???? (Plus some general guidelines)

While there is controversy around whether or not to do a complete lymph node dissection - with newer research indicating little to no increase in overall survival with the procedure - sentinel lymph node biopsy remains an essential part of diagnosis and thereby treatment!!!  How would you know you were Stage III (or not) if no sentinel node(s) evaluation was done after a cutaneous lesion is removed?????  How would you know what treatment and course of observation you would need to pursue????  Furthermore, insurance companies balk at covering anything!  When you don't have the argument of proof of metastasis to a node very few, if any, will cover important follow-up scans.
Here's a post covering a great deal of recent research on both SNL biopsy and CLND:

CLND - Complete lymph node dissection in melanoma - the whole shmegegge!!!!!!!!!!!

Now...there's this:

The intriguing effect of delay time to sentinel lymph node biopsy on survival: a propensity score matching study on a cohort of melanoma patients. Tejera-Vaquerizo, Descalzo-Gallego, Traves, et al. Eur J Dermatol. 2017 Sep 23. 

Time between primary melanoma excision and sentinel lymph node biopsy (SLNB) has not been sufficiently studied as an independent predictor of survival in cutaneous melanoma.

We used propensity score matching to evaluate whether early SLNB (performed  less than/= to 40 days from excisional biopsy) is associated with higher mortality in patients with cutaneous melanoma.

A retrospective cohort study at a tertiary melanoma referral centre. We included 787 consecutive patients from the melanoma database of the Instituto Valenciano de Oncología who underwent a SLNB between 1^st January 2000 and 31^st December 2015, of whom 350 were matched into pairs using propensity score matching. The variable of interest was the time between primary melanoma excision and SLNB (less than/= to 40 days vs greater than 40 days). The study outcomes were disease-free survival (DFS), melanoma-specific survival (MSS), and overall survival (OS).  

A delay time of 40 days or less was associated with worse DFS, and OS. Other variables associated with shorter MSS were age, tumour location and thickness, mitotic rate, and SLN status.  Early SLNB was associated with worse survival in patients with cutaneous melanoma after adjusting for classic prognostic factors. A delay time of over 40 days was not associated with higher mortality.

While this sounds a bit counter intuitive....in that leaving the positive node in place for 40 plus days...garners BETTER responses than removing the same node in 40 or fewer days in regard to disease free survival and overall survival.  However, the rational for this phenomenon is the idea that those positive lymph nodes are needed for the body to process the antigens in the melanoma cells that are present in the node(s) in order to facilitate the body's immune response.  If the immune response is never launched, the chance of persistent disease is greater.

Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update. Wong, Fariers, Kennedy, Agarawala, et al. Ann Surg Oncol, 2017 Dec 13.

To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma.  An ASCO-SSO panel was formed, and a systematic review of the literature was conducted regarding SLN biopsy and completion lymph node dissection (CLND) after a positive sentinel node in patients with melanoma.

Nine new observational studies, two systematic reviews and an updated randomized controlled trial (RCT) of SLN biopsy, as well as two randomized controlled trials of CLND after positive SLN biopsy, were included.

Routine SLN biopsy is not recommended for patients with thin melanomas that are T1a (non-ulcerated lesions less than 0.8 mm in Breslow thickness). SLN biopsy may be considered for thin melanomas that are T1b (0.8 to 1.0 mm Breslow thickness or less than 0.8 mm Breslow thickness with ulceration) after a thorough discussion with the patient of the potential benefits and risk of harms associated with the procedure. SLN biopsy is recommended for patients with intermediate-thickness melanomas (T2 or T3; Breslow thickness of greater than1.0 to 4.0 mm). SLN biopsy may be recommended for patients with thick melanomas (T4; greater than 4.0 mm in Breslow thickness), after a discussion of the potential benefits and risks of harm. In the case of a positive SLN biopsy, CLND or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathological factors. For higher risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND. Important qualifying statements outlining relevant clinicopathological factors, and details of the reference patient populations are included within the guideline.

So...not really much new here...but might be edifying for folks looking at making this decision.

Hang in there, peeps.  Melanoma-land is a crazy place.  - c

LATE ADDENDUM!
Sometimes I get tired, or lazy, or weary of beating the same old drum over and over.  But, sometimes...important topics NEED repeating, re-visiting, and re-evaluating.  Plus....2 heads are certainly better than one!  That being said, for those of you who don't follow the forum on MPIP, I am adding a discussion of this post that developed there thanks to my dear Edster. I think his points are worth bringing here, as are my thoughts about the "new" guidelines for SNLB which, though I have railed about them on this blog before, are perhaps even more pertinent at this time given the possibility of effective adjuvant care with minimal side effects.  That said, here you go:

Hi Celeste, does that journal article come in English or is it published in spainish? I have a thought about the time frame of the data, starting in 2000 and running to 2015. My thought is if they are looking at overall survival and progression free survival, you would think that the effect of adjuvant therapies and stage 4 therapies that would be available to the group in that time frame(2000-2013) were not very good and would make it hard to transfer finding to what is such a drastic land scape change, even in the last year and a half. Now, if they had data from say, MD Anderson from 2014-2016, with the better stage 4 drugs available to patients and Ipi approved in the adjuvant setting. If these observation held up then I could see the value of their study. I think that I am becoming to critical of research studies and wonder too much about alternative motives of researcher's. I had treatment on Friday #100 and there wasn't even a cake or candles or a marching band!!! I love the way that your blog makes me think and ask questions and how important it has been to so many of us,on our melanoma journey's!!! Hugs from a very cold Canadian!!!Ed

Hey Edster!

I think the questions you pose are good ones.  And as I noted in my comments...the data of better outcomes by delaying SLNB by 40+ days...is certainly counter intuitive.  Alternatively, there has been a good deal of data noting that a delay of 1-2 months before SLNB has not adversely affected outcomes.  I had BOTH my SLNB's within 2-3 weeks of my cutaneous biopsy results back in 2003 and 2007. (Maybe that's why I progressed to Stage IV!!  Ha!  Who knows?)   In theory, one would assume that researchers took the time frame of the patient's diagnosis and treatment changes into account.  However, I can't be sure about that.  One other factor to be considered is that adjuvant treatment for NED Stage III or IV patients is a relatively new thing...and many of these peeps would not have had treatment unless they had active disease.  But....it is still an important point to think about when we know the landscape of melanoma treatment has changed so radically just since 2011.  The complete article is in English if you have a mere $39.95!  Hee hee!  https://link.springer.com/article/10.1684/ejd.2017.3065  

I don't think that this article is enough to change current practice...though it is something researchers should think about.  Mostly, it should be very reassuring to those who find themselves...for whatever reason...going longer than they like before having their SNLB.  I know I wanted the suckers out of there!  I  have worked with many here on this forum and via my blog going nutters about any delay, so this should help provide a bit of prospective.

For another point relative to that post...I don't really agree with the new guidelines for SNLB.  For instance, I would still not technically qualify...as my first primary was only 0.61mm with no ulceration.  Yet, I had a positive node, developed a second primary 4 years later, and developed brain and lung mets 3 years after that.  NOT THAT EVERYONE DOES THIS!!!!!!!!!!!!!!!!   But, the more important point is that the positive node, took me from Stage 1b to Stage IIIa in one fell swoop.  Back then - it didn't matter very much.  There was no treatment.  TODAY, it makes a world of difference, because as you pointed out - ADJUVANT care!!!  Soooooo important and now thankfully exists and is FDA approved.

Additionally, the factors that make a difference for a thin melanoma are younger age (less than 40), mitotic rate (which folks don't really look at any more), higher Clark level, and sex.  Ultimately, guidelines are JUST guidelines.  A framework for a starting point...not the end all be all.  It remains very rare for thin melanomas to have lymph node involvement.  However, with a 5% chance of that positive node, now that we have various adjuvant treatment options...finding out if you are in that 5% makes a bigger difference.  

And as to the most important part of your comment - HAPPY 100th TREATMENT day, to you!!!!  I would totally have baked you a cake and had a Timmy with you!!  Salud!! You rock!!  Love you bunches...from a fairly cold Chatt town.  (Do I get to claim being cold if it's 34 degrees????) - c

Thanks, Edster.  This is important stuff and your attention to it makes the world a much better place for melanoma peeps!  love, c

To read more of this thread with really thought provoking comments from Janner, here's the link:  Discussion of SLNB post on MPIP