New, overwhelmed: What's microsatellite stable?

Welcome @mommacandy. I know this is overwhelming. It sounds like your friend is in good hands with you helping to navigate these confusing new terms and appointments.

In layman's terms, a pathology report may mention the tumor's microsatellite stability or instability to see what type of treatments would be recommended. You're right that it is related to DNA.
This article explains:
- What is microsatellite instability? https://www.mdanderson.org/cancerwise/what-is-microsatellite-instability-MSI.h00-159617067.html

At this point in the diagnosis phase, it is too early to declare this as good or bad, and your friend's team is still gathering information about the tumor. What it indicates to me is that the team is being thorough. The more information they have, the more tailored the treatment plan will be for the type of tumor.

As you know being a thyroid cancer survivor yourself, this is a good time to start writing your list of questions for the upcoming meetings with the surgeon and medical oncologist. You can scroll to the very bottom of this page on the Mayo Clinic pancreatic cancer webpage for a starter list of questions to ask https://www.mayoclinic.org/diseases-conditions/pancreatic-cancer/diagnosis-treatment/drc-20355427

How is your friend doing with this news?

Hi! I'm so sorry to hear about your friend's diagnosis. You are already a great advocate! In my experience with my father, molecular profiling to determine microsatellite stability is important in the context of immunotherapy options. If a patient is determined to have microsatellite instability (MSI- high), it can be considered an actionable target in pancreatic cancer. There seems to be clinical benefit with immune checkpoint inhibitors in the MSI-high population. If your friend doesn't have this instability (which it sounds like not), then immunotherapies may not be considered in the treatment plan, but definitely check with the oncologist on this and any other targets based on the molecular profiling results. You have found an amazing support group here. Wishing for the best outcome for your friend.

he's up and down...he's an amputee vet (7 tours each of Iraq and Afghanistan and multiple other places) but because he's not an American vet he's not covered by our VA...which MIGHT be a good thing in this case from what i know from my other vet friends lol...
he has said repeatedly he's not afraid of death, he faced that every day on the front lines.. he just always thought it would be one of the 3 B's that got him...a bomb, bullet or blade, NOT a C ie cancer...he is in tremendous amts of pain (they have him on morphine 2x a day which in his words barely takes the edge off) and is struggling...mentally he's going up and down...sometimes he's talking about the next part of something he wants to get for his reenactment hobby then couple hours later he's looking at gravestones...so its really hard to say..
he'd said for MONTHS something was wrong but docs kept blowing him off.. ended up with acute pancreatitis which is how they found the "lesion" as that hospital called it when it measured 2 cm x 2.3 cm...ended up going through 2 more different hospitals before someone said HEY wait a min, this needs checked ASAP by a BIG teaching hospital...that doc told me to skip the local gastro person he had an appt with and she sent the referral straight to oncology at UVA...
one thing i've found VERY interesting is he started having seizures bout year and half ago after a fall, which is why he ended up in the 3rd hospital in July for an extended EEG and they decided they were "psychogenic" and ever since the diagnosis there's not been a SINGLE seizure...so i'm seriously convinced it was his mind trying to get medical to realize SOMETHING was wrong... anyways, i just wanted to reach out and HOPE someone could explain more before i have to go face doctors and not have a clue what to ask etc so thank you and any and all advice is greatly welcomed...compared to his, mine was nothing...

In case you weren't already familiar with the "T2" meaning, it's a scale called the "TNM" scale, different than the "Stage 1,2,3,4" that we hear most often.

In its complete form, the staging value is T#N#M# where the T stands for tumor size, N stands for node involvement, and M stands for distant metastasis. The # after each letter represents how large or how much.

There's a good description of it with examples here: https://www.cancer.gov/about-cancer/diagnosis-staging/staging

If your friend's was only described as "T2," it might imply N0 (no node involvement) or Nx (can't be measured), and might imply M0 (no metastasis) or Mx (can't be measured).

If there is no node involvement and no metastasis, then it _might_ be described as Stage-II on the familiar scale, or "resectable" on the surgical scale. Resectable is what you truly want, as surgery (complete removal) is the most dependable cure.

Make sure to ask if it is resectable. If the answer is no, ask why. It could mean there is vascular involvement or something else that really complicates the surgery. Sometimes it means they suspect metastasis but just haven't found it, and sometimes is just means the overall health of the patient could not withstand surgery.

If there is vascular involvement or some other anatomical complication, they might recommend chemo and/or radiation to try and shrink it before surgery. If that is the case, you might also begin by getting a second surgical opinion from someone who is reputable and experienced doing more complicated/aggressive surgeries others turn down. (Dr. Christopher Wolfgang at NY Langone might be a good one.)

If there's no evidence of metastasis, I lean toward surgery right away, based on the 6 months of "neoadjuvant" (before surgery) chemo being so ineffective in my case.

If you can't avoid chemo first, ask which regimen and why -- in particular if one or another is better suited to his genetics (hereditary and tumor-specific). They tend to go with a "Standard of Care" regimen first, which is probably Folfirinox if he's in good physical condition, or something starting with Gemzar (gemcitabine) if he's not. In my case (younger, athletic, Stage-II, resectable), I got the Folfirinox first. When my cancer came back after surgery, I got Gemcitabine + Abraxane + Cisplatin, and I've had a much better response to that. Not sure if it's because of my genetics (ATM mutation) or something else, but I wish they had tried that first.

Based on the lack of MSI, it seems they're doing the genetic tests they need to do, but be sure to ask if there will be any more; if so, which ones and how often.

One aspect of the tumor biology is its ability to repair itself and continue replicating. If it suffers some kind of DNA damage, it might have trouble replicating, and different drugs can target different aspects of DNA Damage Repair. To my knowledge, the tumor could be prone to single-strand breaks or double-strand breaks. The DNA testing they did may or may not reveal that, but it's another question to ask. I don't have the biology background to process all this; I just make sure it gets asked and addressed. 🙂

If radiation is recommended, ask what type. I don't know much about it, other than Proton Beam machines being more precise than traditional machines. Other forum members here can chime in with more details and options.

If you can't get someone to do surgery first, at least ask 1) If there are ANY clinical trial options that might be better than the Standard of Care (probably not for a first diagnosis and no prior failures of other treatment, but based on his status there might be, so do ask); ask 2) what is their roadmap for this treatment (how long before they decide whether to switch gears) and what they would do next if necessary. That will help you plan for the future and start the long process of getting future appointments with other specialists.

When it comes to the actual surgery, I think the procedure for the tail of the pancreas is called "distal pancreatectomy." (If you hear/read about the Whipple procedure, skip that -- it's for cancer in the head of the pancreas.) With distal pancreatectomy, I understand they usually remove the spleen as well, but ask for details.

Depending on how much pancreas needs to be removed, he may lose some ability to produce enzymes and/or insulin, and thus need supplementation after the surgery. Ask about that as well. And the surgery could be open, laparoscopic, or robot-assisted laparoscopic. One more question for the session...

Finally, another important detail is the overall surgeon and center -- their volume and experience. You can get those details elsewhere (e.g., PanCan, NPF, etc), but you want to get surgery (and ideally all treatment) at a center of excellence.

I hope it all works out; sounds like it can. And please thank him for his service to our country!!!

thank you SOOO much for this information...we're getting his care at University of Virginia which is a Cancer Center of Excellence...the surgeon we have an appt with on paper has excellent ratings and people i've talked to around the hospital seem to love him. we'll see 🙂 but i have hope...its almost a 5 hour drive for us but i'd MUCH rather trust them than these local folks...sorry don't have much confidence in our local docs..
i will certainly thank him for you.. he's a British vet (permanent green card holder)who moved to the US 16 yrs ago and worked as a private military contractor for the US after coming here. So he doesn't qualify for a lot of assistance (ie our vet care, disability etc)..he has no family left in England and no family here...he's the last one so my hubby and I and other friends are all he has in the way of "family".
From my understanding, we are meeting with the surgeon first to discuss surgery options, if its an option, whats involved, will it be done first etc and the following week we are meeting with an oncologist to discuss the rest of it... yes its two separate long drives but to wait on a day when we could do both was going to be at least a month out and tbh knowing how aggressive pancreatic cancer can be (my stepmom passed from it less than 3 months after she was diagnosed, it had already spread all over) i'd rather "get the ball rolling than sit around and wait on someone else to do it" so to speak and if it means two long drives so be it.
i DO already know that UVA has something like 11 clinical trials going atm for various pancreatic cancer treatments atm so who knows, he may fall into one of those.. we'll see
thank you so much for taking the time to give me all this info.. its exactly the kind of stuff i need..

You're very welcome, and I hope it helps lead to a positive outcome.

One thing I meant to elaborate on a little more was the neoadjuvant treatment. There was a study (can't find it & don't remember name) showing patients who got chemo before surgery had better outcomes (don't remember the exact outcome criteria either) than those who got surgery first.

Part of it is based on the likelihood that even without evidence of spread, there is often an undetectable "micro-level" spread already to places that surgery would miss, and that surgery with a tough recovery period would delay the start of "adjuvant" chemo to address it, which lets it spread anyway. Their thought process is that surgery in that case just puts the patient through unnecessary agony on the way to the inevitable. With neoadjuvant chemo, they figure a) it gives drugs a chance to target malignant cells that have spread elsewhere; and b) if they do see a spread while the patient was on chemo, then they conclude it was not controllable before surgery and thus would not have been controllable with basic chemo after the surgery. Sort of a patient-screening process to see who really benefits from surgery.

Another level of screening occurs when they do the actual surgery. While the actual procedure may be done "open" or laparoscopically, they typically do a "diagnostic laparoscopy" at the beginning of the procedure. It just means they make the minimal laparoscopic openings, insert some cameras, and look around. If they see evidence of tumors elsewhere, in too many places or a couple bad places, they close up and abort the bigger surgery.

"TNT" (TOTAL NEOadjuvant Therapy) is the approach of doing all chemo before surgery, and none after, on the presumption that if you got a full dose and could tolerate it, that's the best they could do. It was part of the failure in my case (faster spread after recurrence), which is one reason I'm not a fan.

I've attached a paper, with a quote from page 2, "During the last twenty years, it has been well established that all surgical approaches to pancreatic cancer need to be supplemented by adjuvant therapy."

But there are two 10-minute sides of that debate worth watching here:
https://youtu.be/naQ-HlZbEoI (Dr. Jordan Berlin, Vanderbilt, for TNT)
https://youtu.be/nd1l5-GrdVQ (Dr. Matthew Katz, MD Anderson, for surgery first)

thank you sooo much...atm i'll be honest, i'm starting to feel overwhelmed BUT i think a lot of that has to do with my frustrations of dealing with him...its like he's expecting the world to revolve around him at the moment...is that normal???

It's hard to say, but I spent the last year caring for my 85-year old dad during his battle with cancer (RIP last month). He was a US Navy veteran in the late 1950's, all peacetime. My father-in-law was a US Marine (also late 1950's) who just had a cancerous kidney removed but is recovering well. Both live(d) an hour away (opposite directions), so providing appropriate care was nearly impossible w/o outside professional help.

My impression is that veterans are tough as nails and want to be as self-reliant as they can be for as long as they possibly can. Not whiners at all, and when they reach the point of opening up about needing help, they really need it.

Inasmuch as you've looked to this group for expertise/experience on pancreatic cancer, he probably looks to you as a cancer survivor the same way.

I don't know what boundaries you can set (re: world revolving around him), or what other sources of help you can arrange for him, but the hardest part is not over yet. He may spend a week in the hospital after surgery, and then need assistance at home for a few weeks, at least cooking for himself and dealing with the fatigue while also on pain meds, and getting back for his first follow-up visit if required in person.

His questions and angst might settle down a little bit after the surgery consult, once some of the unknowns are resolved. If he's computer-savvy or computer-comfy, maybe you could set him up with an account here and let him post some of the questions himself.

Caregivers can suffer from the demands of caregiving. Hope you will find ways to take good care of yourself too.

Sigh...atm its feeling like the world is revolving around him...i've basically "took care of him" if you will since his amputation in 2019...i'm the one who recognizes the symptoms of when he's starting "down the rabbit hole" as he calls it...can get him to respond when he's "in iraq", have made sure he gets to doctors, grocery store, etc even making sure he has a roof over his head..he lives in a VERY rural area off grid with his 8 cats and chickens ...except for the past 6 weeks if he's not in a hospital, he's at my house for the most part...he lives about hour and half north of me..(long story on how he ended up there but basically that or on the streets) and so about every 3-4 days i'm traveling to feed his cats, change litter boxes, refill water and pet them for a bit...occasionally i'll stay overnight there just so they'll have some company for a while...they REALLY miss him... anyways thats another story for another time as well...but tbh i'd rather he didn't come to this board,,,i know that sounds selfish of me but its how i feel atm.. I'm just REALLY grateful i have a super understanding husband 😀