Staging

Hi Eli,

I emailed Dr. Olivier Farges, the lead author for the paper checking the staging in the 7th edition, about the inconsistencies between the paper and the 7th edition. His answer is as follows:

Mr Baird,

Thank you for your interest in our paper and your comment.

This comment is perfectly correct and the explanation is the following.

Our primary aim was to validate the findings of Nathan et al (“A Proposed Staging System for Intrahepatic Cholangiocarcinoma” published in Ann Surg Oncol 2008) from which the 7th edition was derived.

In this paper the authors indicate that their proposal for a new staging is the following: “A corresponding ICC stage grouping system was also developed: I – sT1N0M0, II – sT2N0M0, III – sT3N0M0 or N1M0 (any sT), and IV – M1 (any sT, any N).”

As there were a (confusing) number of staging systems at that time, we have chosen to stick to the proposed stagings.

We understand that the 7th staging of the AJCC is slightly at variance with Nathan’s proposal but this does not change the message for the following reasons:

– Stage III in Nathan’s (and our study) includes essentially N1 tumors and very few T3N0 tumors (53 and 4 patients respectively)

– in our study, survival (in particular the median survival) of patients with T3N0 tumors and Stage III tumors was essentially the same.

– therefore, Stage III in Nathan’s (and our study) correspond in practice to the stage IVA of the 7th edition.

We acknowledge that we should have clarified this. However, I also wish to underline that in its current form, there are two weaknesses in the AJCC staging:

– stage III (T3, N0, M0) is going to be underrepresented as this situation is very rare

– T4 tumors (Tumor with periductal invasion) is ill-defined, in particular for mass-forming cholangiocarcinoma with an associated periductal-infiltrating growth pattern (which is a frequent situation).

Do not hesitate to get back to me if your require further information,

Kind regards,

Olivier Farges

Dear Dr. Farges,

I am a member of the of the Cholangiocarcinoma Foundation ( http://www.cholangiocarcinoma.org/)A comment about a paper, for which you were listed as lead author, was posted on one of our discussion boards. The paper is “AJCC 7th Edition of TNM Staging Accurately Discriminates Outcomes of Patients with Resectable Intrahepatic Cholangiocarcinoma” (http://onlinelibrary.wiley.com/doi/10.1002/cncr.25712/full).

The comment was that the results presented in the paper, specifically in figures 4 and 2, did not reflect the actual AJCC 7th Edition staging for intrahepatic cholangiocarcinoma. For example, in figure 4, N1M0 is identified as stage III and M1 is identified as stage IV, whereas the AJCC 7th edition identifies N1M0 as stage IVA and M1 as stage IVB.

Is there a reason for the inconsistencies?

Thank you,

Bruce Baird

Thanks Eli for the info that the foundation’s link on staging is out of date. I found that I could download all of the previous AJCC Cancer Staging Manuals from the AJCC website for free. I downloaded the 6th version (2003-2009) and found that it matches the foundation’s info on staging for ICC (pp131-138 of the manual.) I also finally looked at the NCCN Guidelines for ICC (7th ed., 2010) which you mentioned and found the staging that Percy previously stated. It’s interesting that they dropped the MX classification (which the Ochsner pathologist used) so I assume, since they didn’t find any distant metastasis, M0 must apply. If that’s the case, my wife’s stage is Stage IVA.

At least that’s what it looks like until after I digest Percy’s comments. Percy, I just learned today, after reading the 6th edition of the cancer staging manual that there is both clinical staging and pathologic staging. The surgeon never told us the clinical stage. He did say that it was intrahepatic cholangiocarcinoma but because the cancerous lymph node, which was pressing against the common bile duct and causing it to bleed on the inside, I thing he said he was going to perform the surgery more like he would do extrahepatic cholangiocarcinoma surgery. We had conflicting opinions on whether the lymph node had fused to the common bile duct. I believe the surgeon thought it had and the doctor who inserted the stent thought they were separable. The surgeon intially said that he would have to remove all of the right lobe and some of the left lobe, a total of 72%, but after the surgery, he said he didn’t have to remove as much as he initially thought. A couple of weeks after the surgery we met in his office and he gave me a copy of the pathology report and he went throught it with us, emphasizing that it was the best he could have ever expected, specifically addressing the 1 positive node out of 7, and the 2 cm margins. Later the oncologist went through the report with us and the one thing she was concerned with was the “poorly differentiated” histologic grade.

The pathologist report shows the following:

SPECIMEN:
1) Falciform ligament – fibrofatty and vascular tissue. Negative for malignancy
2) Hepatic Artery Lymph Node – One (1) benign lymph node
3) Biliary Stent: Gross Diagnosis only
4) Proximal Bile Duct Margin: Negative for Malignancy
5) Liver Segments 4B, 5, 7, and 8; Partial Hepatectory: See Synoptic Report:

Specimen: Liver
Procedure: partial hepatectomy, major hepatectomy
Tumor size: 6.4 cm
Tumor focality: Solitary
Histologic type: Cholangiocarcinoma
Histologic grade: Poorly differentiated G3 out of 4
Tumor growth pattern: Mass forming
Microscopic tumor extension: Confined to the hepatic parenchyma
Hepatic parenchymal margin: uninvolved, 2 cm from tumor
Bile duct margin uninvolved
No lymphovascular or perineural invasion identified
pT1 N1 MX
One (1) hilar lymph node positive for metastatic carcinoma out of 6
Additionally, hepatic artery lymph node is benign
Background liver is unremarkable

Immunostains performed with appropriate positive and negative controls. Tumor cells are positive for keratin 7 and negative for keratin 20, hepatocyte antigen, and estrogen receptor. Findings are consistent with intrahepatic cholangiocarcinoma. Tumor surrounds and invades a medium sized branch of the biliary tree. There is marked acute inflammation and necrosis in the tumor.

I think I included both info from the surgeon and the pathology report in my previous messages on the discussion boards.

When I said “spread to the liver” I envisioned the cancer starting in a small bile duct contained within the liver and spreading from there to the liver which is in direct contact.

Thanks for the advice on the PET scan. The surgeon said that their policy is a CT scan every 6 months. Maybe this is a Medicare thing. I’ll ask the oncologist about the PET scan.

Right now my wife is scheduled to get GemCis for 4 months on a 21 day cycle, the amounts being the same as used in the Phase III study, and radiation with 5FU for 5 weeks, 5 days a week. So, as you suggest, what I’m trying to do is research what we can do to extend the recurrence time. I’ve read a lot of the published studies and I can’t find the answer there, so I’m trying to research the members of this foundation to document their experience. So, far I’ve got about 50 on the spreadsheet, but unfortunately, only 1 of the 50 comes close to my wife’s condition. I thought you might be a candidate because of the Stage IIB you reported. The report I had said Stage IIB for bile duct cancer indicated the cancer had spread to nearby lymph nodes in addition to other factors.

Percy, thank you for your kind remarks about my contribution to the board. Eli and I are both engineers, and I think it is in our nature to be detailed oriented. I’m 76, retired when I was 57, and most of my career as an electrical engineer was supporting NASA on the Saturn/Apollo “moon” program, the Space Shuttle, and the International Space Station. After the moon landing in 1969, people said, “If we can put men on the moon, then we should be able to _____ (fill in the blank).” Perhaps this should also apply to finding a cure for this horrible disease.

Bruce