Neoadjuvant for melanoma stage 3c

Aside from living in Florida, I don't know much about melanoma, and have zero medical training. I'm a pancreatic cancer patient who wound up in this thread by a random link. 🙂

With that said, in pancreatic cancer, the standard surgery (Whipple procedure) is very invasive and debilitating for several weeks/months; the average patient requires that much time for recovery before any adjuvant chemo or immunotherapy can start. They sometimes use neoadjuvant chemo to reduce tumor incursion into major arteries before surgery, and sometimes use it just to provide systemic therapy to prevent/kill potential metastases before surgery.

With melanoma on the arm, surgical removal doesn't seem like it should delay the immediate startup of immunotherapy. My inclination would be to undertake both immediately to prevent the spread and start the (potential) cure.

With pancreatic cancer (and many others; not sure about melanoma), the resected malignant tissue can be sequenced in various ways to identify mutations and also to create a tumor-specific ctDNA test like Signatera.

Signatera is a repeat blood test that counts the number of ctDNA cells matching your original tumor per mL of blood. It can be used as a metric to determine a treatment's effectiveness (e.g., it gives a quantitative result that you hope will go downward from non-zero to zero over the course of treatment).

It takes a couple weeks from tissue acquisition to create the Signatera test; the sooner they acquire and submit tissue the sooner they can start using it. It sounds like they already have tissue they could submit based on what they removed last year.

You would miss a few blood test opportunities if you started immunotherapy before the initial Signatera test is ready. The sooner you get it created, the sooner you can start using it. Again, I'm not sure if this is applicable for melanoma.

But the sooner you get surgery and immunotherapy, the sooner you start attacking the cancer from both sides. I would ask if there is any benefit to delaying the surgery vs. having surgery AND starting immunotherapy immediately.

Wishing you the best. Hope you can share your oncologist's responses regarding the above.

Thank you. The previous tumor that was removed showed positive TPS 6-10% and a TMB that is considered high at 52.6. Supposedly these qualities of the tumor make it a good candidate for the keytruda or immunotherapy. Yes the NEO in front of immuno means they start the drug before they take the tumor out. The believe is if the tumor is there, then the drug has something to work against and if it shrinks they know it is working. If they cut it out first, then they would still do the immunotherapy, but would do the full year, but not really know immediately if it was working or not. I guess my fear is it spreads while waiting after 6 weeks or so to see if it’s working. I have a very fast growing nodular melanoma. It came up between visits to the dermatologist, and by the time they got to it, it already spread to my lymph node. My doctor says there is a 50 percent chance it will grow while doing the treatment but still feels it’s the best thing to do.

Understood. So I would ask:

1) If they can use the Signatera test or something similar to determine if the immunotherapy is working, instead of just leaving the time-bomb in there and hoping to see it shrink

2) What benefit is there to YOU of leaving the tumor in place, other than a "potentially" shorter course of immunotherapy?

3) Even if they watch the main tumor shrink down to nothing, how will they know it didn't spread anywhere else?

Well, my research on "Their" research says with stage 3 melanoma cancer there is a 37% recurrence rate the cancer will come back after getting the Neoadjuvant therapy, compared to 67% chance coming back if you just do the adjuvant. Furthermore, one study states 3 year survival rate for neoadjuvant to be 80% compared to just having adjuvant therapy at 60%. Another study states event free survival at 2 years with neo at 72% compared with just adjuvant at 49%. Thats a big difference. Therefore, it has been hypothesized that neoadjuvant therapy may be able to activate more antitumor T cells and improve clinical outcomes than administration of the same amount of drug delivered postoperatively. I'll have to ask about that signatera test. To answer your 3) question. I assume if the drug is indeed shrinking the tumor it would do the same to all the cancer cells in the body.

@williamfh, I noticed that you wished to post a link to an article with your posts. You will be able to add URLs to your posts in a few days. There is a brief period where new members can't post links. We do this to deter spammers and keep the community safe. Allow me to post it for you:
- Neoadjuvant–Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma https://www.nejm.org/doi/full/10.1056/NEJMoa2211437

In addition to @markymarkfl helpful posts, I'd also like to bring in fellow melanoma members like @jrc3vette @notdefinedbyyou @rblegend50 @yrarbil @grammato3 into the discussion and experiencing with immunotherapy.

Welcome @williamfh to the club no one wants to be in, however, I have to say I find the support to be tremendous and much needed. Hope we can provide the same to you, although it helps to keep in mind of course every case is individual and what works for some - or how some react - may not be the same for everyone.

As a retired medical professional myself, I also did quite a bit of online research. One thing I learned is advances in melanoma are taking place so rapidly that treatments and prognoses we find by google searches may be outdated. It helps to always check for more recent data and/or for participating in sessions offered by reliable organizations. For example, I've participated in zoom sessions conducted by the Melanoma Research Alliance and will be attending one at a nearby university in a few weeks. This is due to my own diagnosis of Stage 4 metastatic melanoma nearly 5 years status post WLE of a 1A amelatonic skin lesion. I am due for my third Keytruda infusion next week; to date, I've experienced no untoward side effects despite being informed and reading of several potential ones online prior to treatment. The infusion staff has been very reassuring about the low incidence they've observed with this form of immunotherapy.

I'm also a candidate for possible surgical removal of my identified lung nodule once I undergo a CT scan later this month. The rationale for this is based on a SWOG study my oncologist referenced and I found more readilyy explained in an NIH document Immunotherapy before Surgery Appears Effective for Some with Melanoma.

I hope these references provide you with some additional resources.

I’m starting keytruda neoadjuvaunt on Tuesday morning. I’ll keep you posted. I’m at the university of Utah