CA19-9 going up and back pain at night - recurrence?

@mmatunis , Disclaimer -- I have no medical training!

I don't see the attachment, but 7 -> 28 -> 76 is a trend... I don't know anything about cholangiocarcinoma, so is CA19-9 considered a biomarker for it to the same degree it is with pancreatic cancers?

Regardless, I would begin by asking for more frequent CA19-9 testing (2-4 week intervals max). This will help you evaluate the urgency level while waiting for your next scans.

I would also recommend seeking out second opinions from well-respected specialists. It can take a long time to get the appointments, so if you start lining them up now, you'll be able to see the specialist as soon as you have new data.

If the CA19-9 goes up again, I would request re-imaging sooner than your 3-month schedule, like immediately, and maybe an MRI instead of CT?

Also, if the CA19-9 goes up again and you don't have a better treatment option or specialist 2nd opinion, I would _consider_ asking them to restart you on Folfirinox. If it controlled your cancer and brought CA19-9 down before the Whipple, it might be a good way to control it now. If it shows the same effect (dropping your CA19-9), then it's possibly attributable to an anti-cancer effect (implying a cancer is hiding in there somewhere).

In my case, with PDAC, I had clean margins and 0/22 lymph nodes positive after Whipple. CA19-9 went from 12 -> 33 -> 77 in 3.5 months, with 3 ctDNA tests and an EUS biopsy all negative, despite MRI (4.5 months post-op) showing tumor regrowth at the original site. By the time ctDNA (Signatera) finally went positive (very low level) 6 weeks later, CA19-9 had gone to 277, the recurrent tumor was larger, and a met was discovered elsewhere in my abdomen. Another 6-week delay seeking second opinions before starting treatment allowed more mets to develop.

I was also receiving no treatment after surgery. We went with the Total Neoadjuvant Therapy (12 biweekly Folfirinox before Whipple) and no adjuvant therapy because there was no evidence of disease at that point. Slowly rising CA19-9 was the first real clue, and I wish we had reacted to it much quicker.

So, whatever you do, DON'T just sit back and wait.

Wishing you the best, quickly!!!

--mm

Thank you for your response. I am not sure why the attachment did not appear, but it shows a steady decline from 160 U/ml to 7 over the six months of treatment. I am being cared for by well-respected specialists at Johns Hopkins who are very responsive to my concerns. At some level there is a standard of care they can follow, but at another level the right course of action is not so obvious. You suggest what I was alreading thinking. I do not have formal medical training either, but I am a cancer research scientist who appreciates the value of more data points. I will therefore ask for more frequent CA19-9 tests. Did you go back on FOLFIRINOX, or another drug regimen? In anycase, I hope you are doing well!

You're very welcome, and thank you for the good wishes. (FWIW, I forgot to mention I was stage II at initial diagnosis.)

I don't have the graph on my current computer, but my CA19-9 graph was pasted as an attachment on the third page of this thread: https://connect.mayoclinic.org/discussion/abort-chemo-rx-go-straight-to-surgery-while-i-am-still-stage-1/?pg=3#chv4-comment-stream-header

It shows the pre-Whipple Folfirinox didn't do much for me. Post-op pathology graded it as a "partial response" (2 on a scale of 1-3).

After recurrence, CA19-9 hit 677 before I began chemo. We went with Gemcitabine + Abraxane since the Folfirinox didn't do much, and added Cisplatin since I have the ATM mutation. The right-hand tail of the graph suggests that was a good choice, since CA19-9 is now bouncing between mid-30's to low 40's. Too bad that wasn't my neoadjuvant regimen, but my hindsight is that I wish I had gone straight to surgery instead of doing any neoadjuvant treatment. (And total pancreatectomy instead of Whipple, but that's water under the bridge now.)

Anyway, despite the CA19-9 numbers and all bi-monthly Signatera ctDNA tests remaining negative (except for the Dec 2022 test, score = 0.14), I'm still stage-4 radiographically, but feeling rather good. Really no ill effects I can discern from the cancer, but having the usual post-Whipple digestive issues, and the fatigue/neuropathy that go with chemo. My muscle mass and cardio fitness are down, but that's from spending more time seeking out clinical trials and less time at the gym. I will learn soon if I qualify for a tissue-engineered Natural Killer cell trial as a maintenance therapy option or alternative if my Gem/Abrax/Cis cocktail runs out of gas or runs me and my nerve endings into the ground.

Weight remains stable, as my wife is an amazing cook! 🙂

BTW, if you have time, it's worth reading prior posts by @stageivsurvivor -- he is (was) also a cancer researcher. His posts on this forum are pure gold.

omus,

As mm noted, above, I too would note that restarting chemo is essential at this point. I'm not a medical professional, but every thread I've read indicates continued, maintenance chemo is essential - for as long as you can tolerate it - in whichever of the two varieties works. Pancan cells must be killed and any gap in chemo allows them to grow and spread.

In the liver and pancreas center I am associated with, post whipple chemo has become de rigeur.
If this disease is in your blood system it has the ability to hide and reappear! Being termed NED almost seems momentary.
We have to beat it down until we can find the right immunotherapies for our specific situation.

Please forgive me I'm repeating myself once too often here, but for readers who may not have seen the older threads:

1) The promise of ctDNA tests for presence/recurrence seems to be less than advertised for pancreatic cancer (PDAC in particular). My PA told me if Signatera is positive I almost definitely have cancer. If Signatera is negative, I might still have cancer. Two negative Signateras and one negative Grail/Galleri shortly before my recurrence was identified on MRI (and hinted at by my rising CA19-9) demonstrate there is something sneaky about PDAC cells that evades these tests. Likewise, the post-recurrence spread obvious on imaging while Signatera continues to report "0.00" ... (Fine print on the report indicates cancer may be present below detectable threshold. One cell is all it takes... 🙁 )

2) CA19-9 is not the holy grail, but one indicator that can be combined with others to add confidence to a conclusion. It's cheap and easy and should be done frequently pre-op and post-op so you know your own normal and have a "low noise" data set to help detect trends.

3) https://pubmed.ncbi.nlm.nih.gov/34751822/
It's only one paper, but recent, and says:

"During the last twenty years, it has been well established
that all surgical approaches to pancreatic cancer need to be
supplemented by adjuvant therapy."

and

"it remains clear that resectable pan-
creatic cancer patients should not be treated with a neoadju-
vant therapy outside clinical studies"

The paper does also have some blanket statements I disagree with, and I acknowledge that I don't have the medical training to judge the paper's accuracy. The authors do cite references for most of these statements, but I think some come across as more broadly applicable than they're meant to. I also acknowledge that I can't remove confirmation bias from my interpretation of scientific papers, given my own experience and outcome.

< rant deleted about the mythical median patient>

Summary: Err on the side of caution. Your life depends on it!!!

Thank you again for your response. I am waiting to hear back from my oncologist about scheduling more frequent CA19-9 tests. Here are two reports that make a good case for paying attention to ~2.5 fold increase in levels (my surgeon is a co-author on one of them!):
https://pubmed.ncbi.nlm.nih.gov/37389896/
https://pubmed.ncbi.nlm.nih.gov/31992753/

With CA19-9 not a specific marker solely to PDAC cancer but also occurs in benign conditions as well, oncologists won’t jump the gun and prescribe chemo unless other methods are done to confirm recurrence. The elevation you mention is well within a range that could be attributed to an inflammatory situation. Oncologists I have association with as a patient advocate with several national cancer organizations in the GI space generally start raising an eyebrow when a level of 250 is reached. I know of one post-Whipple patient whose CA19-9 at 5 years out is and has been 600 for a number of years and has remained steady with no disease detected. It is his new normal.

ctDNA is continually improving and is now very accurate for colon cancers. I just got off a Zoom call with a committee of GI oncologists and asked that question on accuracy improvements. I’ve been familiar with ctDNA for minimal residual disease having had a career in cancer and immunology research as well as a long-term survivor of stage IV pancreatic cancer. ctDNA has been used for long-term surveillance of my case since 2014. I have a BRCA mutation where the accuracy in ctDNA measurements is the highest. It is done quarterly and I have a low dose CT for chest and an MRI for abdomen every 6 months. The test results have always been in concordance.

Improving the accuracy of ctDNA in pancreas cancers is ongoing. The highest accuracy achieved in in those with BRCA mutations at 89.%. That means in 11% that have recurrence, it won’t be detected any earlier than by conventional imaging methods. In the 89% group, ctDNA is capable of detecting dna fragments of metastasis related to the primary tumor about 8 weeks earlier. Oncologists are still on the fence about beginning treatment before a confirmatory test. This was the case in treating colon cancers but as ctDNA improved in that area, oncologists became more comfortable with starting treatment earlier as they were more assured it was recurrence and not due to some inflammatory response.

Oncologists follow treatment protocols from the National Comprehensive Cancer Network based on recommendations from a working group oncology experts. These protocols are periodically reviewed and modified in conjunction with new findings from clinical studies. No oncologist I am aware of would use chemotherapy on the assumption of disease. There are side effects with chemo and adverse events of more serious nature that can cause permanent damage to tissues and organs-hence the cautious approach when a patient says start me back on chemo without confirmatory evidence of disease. When something is not visualized by CT or MRI, then it is worth inquiring about doing a PET scan which looks for increased metabolic activity in the body using a radioactive tracer attached to a sugar molecule that a cell with higher metabolic activity will utilize at a faster rate than surrounding normal cells.

Going back to ctDNA in cancers of the pancreas where the best accuracy achieve to date has been in BRCA mutations at 89%, in is lower in the other mutation types and drops to a low of 64%. There are many companies with ctDNA testing and all are actively working on improving the accuracy in pancreatic cancer as they did in colon and other solid tumor cancers. It is a matter of time and iterations in improving the methodology that higher accuracy will be achieved.

A short list on some benign conditions that can lead to an elevation of CA19-9:
Non-cancerous conditions that can cause high CA 19-9 levels include:
* Gallstones
* Biliary infection (cholangitis)
* Blockage of the bile duct (jaundice)
* Pancreatitis (swelling of the pancreas)
* Cystic fibrosis
* Liver disease

@stageivsurvivor ,

Thanks very much for the update on where ctDNA testing stands, but I have a question regarding your comment:

"No oncologist I am aware of would use chemotherapy on the assumption of disease. "

Isn't that assumption the basis for all adjuvant post-op chemo after R0 resection?

Similarly, isn't the neoadjuvant philosophy of treating "resectable" disease when imaging (PET/CT/MRI) only shows a primary tumor based on the assumption that disease also lies elsewhere?

Also the comment:

"There are side effects with chemo and adverse events of more serious nature that can cause permanent damage to tissues and organs-hence the cautious approach when a patient says start me back on chemo without confirmatory evidence of disease."

I think there is a boundary where an oncologist can make the judgment call about an otherwise healthy patient who responded well to Folfirinox (for pre-op disease control) and also tolerated it well going back on it and being able to recognize if new side effects were becoming problematic.

In the video that I frequently cite, https://youtu.be/nd1l5-GrdVQ?si=eN53OyMbTZPHPWPb&t=192 at the 3:13 mark, Dr, Katz discusses pre-op (at diagnosis) CA19-9 levels and overall survival outcomes. It appears/implies he is using CA19-9 level as a proxy for the degree/probability of metastasis in patients considered anatomically resectable. The outcomes are notably worse for patients starting above 500 and significantly worse if above 1000. It only took about 6 weeks for my CA19-9 to go from 277 to 677, and my disease was indeed metastatic already at the 277 reading. My big concern for anyone in this situation is being able to make a quick enough response to avoid a similar fate.

Later in the video (6:52), Dr. Katz points out that of patients who had neoadjuvant therapy, approximately 80% have a recurrence after surgery, and approximately 80% of them recur within two years. It would seem assumption of disease is the winning bet more often than not.

FWIW, I have not even been able to bribe an oncologist into doing another PET scan since the one that followed my initial diagnosis/EUS. My surgeon has told me his MRIs detect smaller tumors than PET and are able to show characteristics that basically distinguish live tumor tissue from necrotic tissue, so he didn't expect sugar uptake on PET to yield any new info on me at this point, and that chest CT + Abd/Pelvic MRI would catch the first locations any new mets were likely to deposit themselves.

Thanks again,

--mm

I can't speak to any of this surgery/recurrence stuff, since I don't qualify for surgery. However, I noted your comment re trying to get a PET scan. I had an oncologist appointment today, and as part of that I asked whether it was worth getting a PET scan to determine the extent of abdominal mets. My thinking was that if we could determine that the chemo had killed the abdominal mets, maybe radiation on the main tumor would now be appropriate. He said that a PET scan can't pick up anything smaller than 1.5cm diameter, and by the time a met was that large, it would have shown up on the CT scan I had Wednesday, and it would likely make my CA 19-9 increase. That would seem to jibe with what your surgeon said.