Rising CEA while on palliative therapy for oligometastatic colorectal cancer

[skb]

Hi,
My signature shows the course I have been on. Since multiple sub-centimeter metastatic lung nodules were discovered in Oct 2023, I have been on palliative chemotherapy (Capecitabine pills) for the last 10 months. This has been effective in curbing the growth of nodules . However the latest scan from this week shows that although there is no new nodules, the size of the existing nodules has increased in three months. The largest nodule that was 5x4 mm is now 7x7 mm. The CEA has increased to 5.6. It was 2.6 in May 2024

Looks like capecitabine pills is no longer effectively suppressing cancer.

Has anyone been in this situation before? I am meeting with my oncologist in few days. What can I expect?

Any input helps.

Thanks,
skb

[Green Tea]

... I am meeting with my oncologist in few days. What can I expect?

Any input helps.

Thanks, skb

I'm not sure exactly what you can expect, but one possibility is that the oncologist might suggest that you switch to a different regimen. If that's the case, then you could prepare for the meeting by reviewing the different regimens that apply for second-line, third-line, and last-resort (palliative) treatment.

To do that, though, you would need to know your tumor's primary genomic profile, namely:

• MSI status: MSS or MSI-H
• KRAS mutation status: KRAS-mutant or KRAS-wildtype

There are therefore 4 different possible types:

Type #1: (MSS) & KRAS(wildtype)
Type #2: (MSS) & KRAS(mutant)
Type #3: (MSI-H) & KRAS(wildtype)
Type #4: (MSI-H) & KRAS(mutant)

You would need to look at the pathology report from the tumor to get this information.

Once you have this information and know your tumor's primary genomic profile then you can look at the list of approved drugs for colorectal cancer and see which ones are appropriate for your situation.

The list of drugs currently approved for treating colorectal cancer is shown in the quote below:

Here is information on the range of FDA approved drugs for colorectal cancer as of 2024, and restrictions on their use. You can ask your oncologist if there are any drugs on this list that could halt the currrent progression.

For reference, here are the main chemo drugs and chemo drug-combinations in use right now, along with their dates of original FDA approval :

Drugs used in colorectal cancer
1962 5-FU (fluorouracil Injection) - no restrictions
1998 Xeloda (capecitabine) - no restrictions
2000 Camptosar (irinotecan hydrochloride) - no restrictions
2004 Avastin (bevacizumab) - mCRC 1st line+
2004 Eloxatin (oxaliplatin) - no restrictions
2004 Erbitux (cetuximab) - mCRC 1st line+, KRAS wild type only
2006 Vectibix (panitumumab) - mCRC 1st line+, KRAS wild type only
2012 Keytruda (Pembrolizumab) - mCRC 1st line, MSI-H only
2012 Zaltrap (ziv-Aflibercept) - mCRC 2nd line,
2012 Stivarga (regorafenib) - no restrictions
2014 Cyramza (ramucirumab) - mCRC 2nd line
2015 Lonsurf (trifluridine and tipiracil hydrochloride) - no restrictions
2017 Opdivo (nivolumab) - mCRC 1st line+, MSI-H only
2018 Yervoy (ipilimumab) - mCRC 1st line+, MSI-H only
2019 Zirabev (bevacizumab.alt) - mCRC 1st line+
2020 Braftovi (encorafenib) - mCRC, BRAF V600E only
2023 Tukysa (tucatinib) - mCRC 2nd line, RAS wild-type HER2-positive
2023 Fruzaqla (fruquintinib) - mCRC 2nd line

Drug Combinations Used in Rectal Cancer
FOLFIRI
FOLFOXIRI
FOLFOXIRI+AVASTIN
FOLFIRI+AVASTIN
FOLFIRI+ERBITUX
FOLFIRI+VECTIBIX
FOLFOX
FOLFOX+AVASTIN
5FU+LV
XELIRI
XELOX(CAPEOX)
==================================
FDA-APPROVED COLORECTAL CANCER TREATMENTS, May 2024
https://www.empr.com/wp-content/uploads/sites/7/2024/05/FDA-Approved-Colorectal-Cancer-Treatments-r0524.pdf

[Jacques]

... The largest nodule that was 5x4 mm is now 7x7 mm. The CEA has increased to 5.6. It was 2.6 in May 2024

Looks like capecitabine pills is no longer effectively suppressing cancer.

Has anyone been in this situation before?

Yes, acquired resistance is a well-documented phenomenon. You can review the highly technical details in the "Capecitabine" section of the article cited below:

Pharmacologic resistance in colorectal cancer: a review (2015)
https://journals.sagepub.com/doi/10.1177/1758834015614530

[Green Tea]

... I am meeting with my oncologist in few days..

skb -
I hope you don't mind, but have a few more questions before your upcoming meeting with the oncologist.

1. When will this meeting with your oncologist take place?
2. Is this the same oncologist who originally put you on the W&W protocol, i.e., the same oncologist who put you on FOLFOX in August 2017?
3. Is this the same oncologist who advised you on possible post-surgery chemo after your August 2019 VATS surgery?
4. Is this the same oncologist who put you on FOLFIRI in October 2021?
5. Is this the same oncologist who then put you on palliative XELODA in October 2023?
6. Where was your 2019 VATS surgery done, and was the surgeon a board-certified surgeon?
7. Where was your 2021 abdominal surgery done, and was the surgeon a board-certifed surgeon?
8. Do you have the pathology reports from your last two surgeries, and do they have information on the MSI-status and KRAS mutation status of the resected mets?

I'm trying to understand what happened over the course of your tumultuous 7-year Habr-Gama W&W journey.

Here are your (re-formatted) updates since 2017 as I see them:

March 23, 2017: DX: Stage 2 Distal Rectal tumor, T3N0M0

April 18, 2017: Starting Chemo/Radiation with XELODA/IMRT

In line for permanent colostomy, which I'm trying to avoid.

June 28, 2017 (5 weeks after completion of chemoradiation with oral XELODA and daily radiation for about a month):
MRI Scan: Approximately 10% of the mass demonstrated tumour signal intensity, with the remainder appearing to represent fibrosis. This corresponds to a tumour response grade of 2. No suspicious lymphadenopathy.

June 30, 2017: Flexible Sigmoidoscopy with biopsy:
A nodule/bump was all that remained in the place where the tumor used to be. A biopsy of deep tissue from where the tumor used to be revealed no evidence of adenocarcinoma.

August 7, 2017: (10 weeks after completion of chemoradiation): MRI Scan:
Approximately less than 5% of the mass demonstrated tumour signal intensity, with the remainder appearing to represent fibrosis. This corresponds to a tumour response grade of mrTRG-2.

August 9, 2017: (10 weeks after completion of chemoradiation): MRI Scan and PET scans as part of a study at Mayo clinic:
MRI report: No evidence of primary tumor. No evidence of distal metastasis

August 11, 2017: Oncologist at University of Minnesota Masonic Cancer Center calls the above reports an excellent response and places me in Wait and Watch Program if I am interested. I choose the Wait and Watch program after understanding risks and after signing up for an intensive follow up program.

August 17, 2017: Mop-up Chemotherapy to start. IV infusion of FOLFOX with Oxaliplatin. Every two weeks for approximately 5 months.

August 2017 to December 2017: FOLFOX

August 2019 - VATS - 1cm lung nodule, no followup chemo.

July 2021 - Clean CT, CEA 15.6 !

August 2021- PET, biopsy finds met in abdomen

October 2021- Surgery , 12 rounds of FOLFIRI -ended April 2022

April 2022 to January 2023- Clean scan, normal CEA

October 2023- four sub-centimeter lung nodules, on palliative XELODA

September 2024: CEA 5.6, largest nodule 7x7mm

Summary: Your chemo regimens so far have all been based on 5FU. If your four mets have now developed resistance to XELODA (a 5FU pro-drug) this suggests that the next chemo regimen should probably not be based on any 5FU related regimens. That's just my opinion. You can discuss your current options with your oncologist.

You can also ask about clinical trials:

https://clinicaltrial.cancer.umn.edu/sip/#

Good luck!

[skb]

@Green Tea,
Thank you very much for your detailed response.
Here are the responses.

1. The oncologist appt. was on Friday Sep 6th. (Dr. Lou at Uni of Minnesota ). He felt that I was overly anxious and said that I could benefit listening to another voice. So I am trying to get a new oncologist appointment at Univ of Minn with Dr. Prakash

2. 3,4,5: Yes, same oncologist from 2017

6. 2019 VATS at Univ of Minnesota, Dr Andrade performed the surgery. Dont know if he is board certified. But certainly seemed like a very experienced surgeon.

7. The abdominal surgery in 2021: the surgeon was Dr. Genevieve Melton-Meaux. She is a professor at the University of Minnesota and I guess is board certified. She had offered the Habr Gama protocol in 2017.

8. MS stable, no KRAS mutation.

Looks like I am a failed case of Habr Gama W&W

[roadrunner]

I have seen studies that conclude that CRC pulmonary metastases are seeded many years before they are detectable. Further, from your signature, you do not appear to have had a local recurrence. While those two points are certainly not decisive (there may be complicating factors with both), they suggest that a W&W decision might not have been the culprit in your case.

[Green Tea]

The oncologist appt. was on Friday Sep 6th. (Dr. Lou at Uni of Minnesota ). He felt that I was overly anxious and said that I could benefit listening to another voice. So I am trying to get a new oncologist appointment at Univ of Minn with Dr. Prakash

skb-

In the links below you can find information on board certification for the two oncologists that you mentioned.

https://providers.mhealthfairview.org/p ... ou/2239195

https://providers.mhealthfairview.org/p ... sh/2239481

I hope that you manage to get an appointment soon with Dr. Prakash. I think he should be able to tell you if you might qualify for a different type of chemo regimen -- for example, Erbitux (cetuximab), or Vectibix (panitumumab) -- since your tumors were KRAS(non-mutant). It's worth a try, in my opinion.

[skb]

I have seen studies that conclude that CRC pulmonary metastases are seeded many years before they are detectable. Further, from your signature, you do not appear to have had a local recurrence. While those two points are certainly not decisive (there may be complicating factors with both), they suggest that a W&W decision might not have been the culprit in your case.

Thank you, that makes sense.

[Green Tea]

I have seen studies that conclude that CRC pulmonary metastases are seeded many years before they are detectable. Further, from your signature, you do not appear to have had a local recurrence. While those two points are certainly not decisive (there may be complicating factors with both), they suggest that a W&W decision might not have been the culprit in your case.

Thank you, that makes sense.

Here is one of the articles on the "seed and soil" hypothesis.

Seed and Soil: Tracing the Journey of Spreading Cancer Cells
https://www.mskcc.org/news/seed-and-soil-tracing-journey-spreading-cancer-cells

Also, here is a preclinical study on the effect of exposure to smoke on CRC pulmonary metastasis:

The Impact of Smoking on Pulmonary Metastasis in Colorectal Cancer (2020)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533240/



.

[utahgal7]

Hi,

I agree with the other posts here. In addition, have you considered ablation of the lung nodules? What course of action is your oncologist recommending?

Good luck to you and keep us posted,

Paige

[skb]

The current oncologist is just asking me to continue with capicetabine. I felt like he was giving up on me. Asked me to see other oncologists.

I do not know if ablation is offered at Univ of Minnesota. Do you know where it is offered? I can travel

[utahgal7]

skb,

I would think that ablation would be available at any of NCI designated cancer centers. I would definitely consider getting a 2nd medical opinion. I am a little surprised that you weren't given the option to retry FOLFIRI or FOLFOX and/or try another medication such as Lonsurf or regorafenib.


Paige

[Green Tea]

The current oncologist is just asking me to continue with capecitabine. I felt like he was giving up on me. Asked me to see other oncologists.

I do not know if ablation is offered at Univ of Minnesota. Do you know where it is offered? I can travel

skb -

I think that ablation is probably offered at Univ of Minnesota. It is probably done in the Radiation Oncology Department there, and it might be called Stereotactic Body Radiotherapy (SBRT) there.

Univ. Minnesota has several doctors who are qualified as Radiation Oncologists.

Here is what the Maplewood branch of the hospital says about the SBRT program there.

Stereotactic Body Radiotherapy (SBRT)

SBRT is a new and rapidly evolving technique used to treat lung, spine, liver, prostate and other cancers. SBRT does for the rest of the body what Gamma Knife technology does for the brain. It delivers precise, high-dose radiation to tumors or other abnormalities in the body using 3-D treatment planning, a body-immobilizing frame and a CT scan-based IGRT. SBRT is typically delivered in fewer treatments than traditional radiation.

Also:

The Latest on Lung Ablation
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9433157/

For nonsurgical candidates, minimally invasive percutaneous thermal ablation therapies have become recognized as safe and effective treatment alternatives, including radiofrequency ablation, microwave ablation, and cryoablation. Lung ablation is also an acceptable treatment for limited oligometastatic and oligorecurrent diseases.

[skb]

Thank you Green Tea.

My current oncologist has said that trying to get rid of multiple lung nodules is like medical malpractice and systemic therapy is what is more meaningful.

He gave me a referral to a radiologist, Elizabeth Ester who is part of the network. When I met her in May, she said that SBRT was not warranted at that time and the nodules are small.(sub centimeter)

The technology is there but I understand that it is not being offered to someone in my situation.

[beach sunrise]

Do not take advice from an onc about surgery and do not take advice from surgeon about oncology.

I would find the best Board Certified' surgeon. There are out there and I would do it asap! And definitely search for a new onc that is board certified also in crc
JMO