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Trends in Survival after Surgery for Cholangiocarcinoma: A 30-Year Population-Based SEER Database Analysis

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

The prognosis of patients with cholangiocarcinoma historically has been poor, even after surgical resection. Although data from some single-institution series indicate improvement over historical results, survival after surgical therapy for cholangiocarcinoma has not been investigated in a population-based study. We used the Surveillance, Epidemiology, and End Results database to identify patients who underwent surgery for cholangiocarcinoma from 1973 through 2002. Multivariate modeling of survival after surgery for intrahepatic cholangiocarcinoma showed an improvement in survival only within the last decade studied, resulting in a cumulative 34.4% improvement in survival from 1992 through 2002. In contrast, multivariate modeling of survival after surgery for extrahepatic cholangiocarcinoma revealed a 23.3% increase in adjusted survival per each decade studied, resulting in a cumulative 53.7% improvement from 1973 through 2002. We conclude that survival after surgery for extrahepatic cholangiocarcinoma has dramatically improved since 1973. Patients with intrahepatic cholangiocarcinoma, however, have achieved an improvement in survival largely confined to more recent years. We suggest that these trends are largely caused by developments in imaging technology, improvements in patient selection, and advances in surgical techniques.

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Acknowledgements

Dr. Nathan is supported by the Johns Hopkins-NIH Clinical Research Scholars Program (NIH K12RR017627). We are indebted to Richard E. Thompson, Ph.D., and Dorry L. Segev, M.D., for their advice on statistical analysis.

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Authors and Affiliations

  1. Department of Surgery, The Johns Hopkins University School of Medicine, Room 442, Cancer Research Building, 1650 Orleans Street, Baltimore, MD, 21231-1000, USA

    Hari Nathan, Timothy M. Pawlik, Christopher L. Wolfgang, Michael A. Choti, John L. Cameron & Richard D. Schulick

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  1. Hari Nathan
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  2. Timothy M. Pawlik
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Correspondence to Richard D. Schulick.

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DISCUSSION

Bryan M. Clary, M.D. (Durham, NC): This is another very nice paper. I must admit when I read reports of this nature, I am not always sure what to do with them. Number one, I would like to commend you on your manuscript. This type of a study is all about the statistics, and in your manuscript’s methods section you very eloquently state the methods that you use, and you also include a number of very relevant references to help guide individuals such as myself as to what the statistics mean.

Again, the problem is what you gain from this. You in general get a look at how we are doing in certain eras, and trying to come up with the explanations as to why that is, is really pure speculation. One of the main concerns I have with the intrahepatic cholangio population is just the definition as to what is an intrahepatic cholangiocarcinoma during different eras. In eras past, including the ’70s and ’80s, this was essentially adenocarcinoma of unknown primary in the liver, and really it was a diagnosis of exclusion for cytokeratin staining was not as sophisticated as it is now. And so I would venture to guess that one of the problems that you have in this series is that a large proportion of your intrahepatic cholangiocarcinomas were adenocarcinomas metastatic from other sites such as occult pancreatic cancers which were very common with poor imaging back then, and possibly even gastric cancers and lung cancers, et cetera. I wonder if you might make some comment to that specific issue.

The thing that clearly isn’t brought out in this, which you already mentioned, is that of chemotherapy and the issue about rural populations not doing as well. Again, that explanation may not be a surgical issue but it instead that in their follow-up they don’t have medical oncologists who were offering chemotherapy, et cetera. But again, those types of things are pure speculation.

Hari Nathan, M.D. (Baltimore, MD): Dr. Clary, thank you very much for your review of our manuscript and your insightful questions. Your first question was whether the intrahepatic cholangiocarcinomas are truly cholangiocarcinomas. We specifically designed our selection criteria with that issue in mind. The SEER data allow the identification of tumors based on two codes: one is a topography code indicating the location of the tumor and the other is a histology code indicating the pathological diagnosis. For tumors that were located in the liver, the intrahepatic cholangiocarcinomas, we specifically excluded adenocarcinomas that were not otherwise specified and other lesions that we could not specifically identify as being cholangiocarcinomas. We were less stringent, for example, in the extrahepatic biliary tree, where we might accept a histological diagnosis of adenocarcinoma, not otherwise specified. But in the liver or at the ampulla we were much more strict about requiring a specific histological diagnosis of cholangiocarcinoma. So we feel very comfortable that we have excluded metastatic malignancies and other adenocarcinomas not arising from the bile ducts.

With regard to chemotherapy and rural patients, you are correct in pointing out that one of the weaknesses of the study is that we just don’t have the depth of data in this database that would be required to specifically identify what the reasons for the improvements are. But I think this study provides two important pieces of information.

One, it gives us a sense as to the generalizability of the results that we see reported from single institutions. In terms of prognostication for patients and to get a general sense of how we are doing in the country as a whole, it is important to have that reality check of not exclusively relying on reports from specialized centers to guide our impression of how we are doing across the entire country.

And the other contribution is that it points to a direction for future research. There are other data that are available that may help us to identify why exactly, for example, rural patients with ECC have worse survival. The SEER-Medicare data, for example, which we are currently trying to acquire, do include information on chemotherapy receipt. So as we investigate further why these disparities do exist in patient outcomes, not just with cholangiocarcinoma but with a variety of malignancies, I think that this study and others like it give us a starting point. In future work, we hope to move from describing the differences to identifying the reasons for these disparities and actually trying to do something about them.

Thanks again for your comments and questions.

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Nathan, H., Pawlik, T.M., Wolfgang, C.L. et al. Trends in Survival after Surgery for Cholangiocarcinoma: A 30-Year Population-Based SEER Database Analysis. J Gastrointest Surg 11, 1488–1497 (2007). https://doi.org/10.1007/s11605-007-0282-0

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