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National Trends in the Management and Survival of Surgically Managed Gallbladder Adenocarcinoma Over 15 years: A Population-Based Analysis

  • 2010 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Introduction

National Comprehensive Cancer Network (NCCN) guidelines recommend hepatic resection and lymphadenectomy (LND) for gallbladder adenocarcinoma (GBA). We sought to evaluate compliance with these recommendations and to assess trends in the management and survival of patients with GBA.

Methods

Using Surveillance, Epidemiology and End Results (SEER)-Medicare-linked data, we identified 2,955 patients with GBA who underwent cancer-directed surgery from 1991 to 2005. We assessed clinicopathologic data, trends in surgical management, and survival.

Results

From 1991 to 2005, preoperative evaluation included CT (62%), MRI (6%), and PET (2%). Only 383 (13%) patients underwent radical resection/hepatectomy with a temporal increase over the study period (1991–1995, 12%; 1996–1999, 10%; 2000–2002, 12.0%; 2003–2005, 16%; P < 0.001). For patients undergoing radical resection/hepatectomy, LND ≥ 3 nodes was performed in 96 (3%) patients. Among patients who had LND, 47% had nodal metastasis. The overall 1-, 3-, and 5-year survival was 56%, 30%, and 21%. On multivariate analysis, radical resection/hepatectomy (hazard ratio (HR) = 0.71) and LND ≥ 3 nodes (HR = 0.56) were independently associated with increased survival. There was no significant improvement in survival over time (P = 0.60).

Conclusions

Compliance with NCCN guidelines for GBA remains poor. Survival of patients with surgically managed GBA has not improved over time.

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Author information

Authors and Affiliations

  1. Department of Surgery, The Johns Hopkins University School of Medicine, Harvey 611, 600 N. Wolfe Street, Baltimore, MD, 21287, USA

    Skye C. Mayo, Hari Nathan, Barish Edil, Christopher L. Wolfgang, Kenzo Hirose, Richard D. Schulick, Michael A. Choti & Timothy M. Pawlik

  2. Health Policy and Management, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Andrew D. Shore

  3. Radiation Oncology, The Johns Hopkins Hospital, Baltimore, MD, USA

    Joseph Herman

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  1. Skye C. Mayo
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Correspondence to Timothy M. Pawlik.

Additional information

Discussion

Discussant

Dr. Gerard V. Aranha (Maywood, IL): Dr. Mayo and his co authors from the Department of Surgery at Johns Hopkins University have reviewed SEER-Medicare linked data and concluded that the National Comprehensive Cancer Network guidelines for the surgical treatment of gallbladder cancer are not being followed by a majority of institutions in this country.

Unfortunately, this is not just true for gallbladder cancer but it is true for many other malignancies. Being a surgical oncologist, I’m pretty aware of that and in my opinion, it requires urgent attention and intervention.

I have the following questions.

In your paper, you state that those patients who had extended hepatectomy had a 20% mortality compared to those who had a regular hemihepatectomy, which was 5%. Were the extended hepatectomies done at a local community hospital, low- or high-volume center, and whom in gallbladder cancer do you think should have an extended hepatectomy?

How do we change the culture so that the NCCN guidelines will be followed in this country? Do you think that, at least in gallbladder cancer, that the patients who need surgical treatment should be referred to high-volume centers where maybe the guidelines are followed? Or do you believe that this should be done through the Commission on Cancer of the American College of Surgeons? I think this is a topic that you should address in your manuscript and needs attention.

I think you did a great job with your presentation, Dr. Mayo, and I commend it to the membership at large.

Closing Discussant

Dr. Skye C. Mayo: Thank you for your excellent questions and comments, Dr. Aranha. In our manuscript, we show that there was no difference in mortality between patients undergoing an extended hepatectomy versus a partial or hemihepatectomy. The number of patients who had a hepatectomy who suffered a peri-operative mortality was low. For instance, of the people that had an extended hepatectomy, one patient died post-operatively. Amongst the patients who had a partial hepatectomy or a hemihepatectomy, there were two peri-operative deaths. The numbers are very small and statistically fragile. I would be hesitant to draw conclusions from these data.

As for patients who should undergo a more extended procedure for clearance of their cancer, I believe the recent literature supports that an extended hepatectomy should not be performed on a routine basis for patients with gallbladder cancer, but instead should be performed only for certain patients to achieve clearance of their disease. An extended hepatectomy is associated with a higher morbidity, but it has not been shown to improve long-term survival. The recent literature has shown that it’s not the extent of resection that’s important, but rather the status of the surgical margin that influences patient outcome. I think the surgeon’s aim should be to achieve a microscopically complete resection with disease clearance and limit the resection at that.

As for the cultural change and the NCCN guidelines, I agree with you that it’s a very pressing issue and one that is very difficult to address. I think it has to start with standardization of documentation at a more national level and then be disseminated to the smaller hospitals and community centers. Checklists and guidelines should be developed that allow the surgeon and the hospital to collect these data prospectively to ensure that they are following the recommended guidelines appropriately.

In regards to patient referral to high-volume centers, I really wish that we could have looked at volume within the study, but within the SEER database there’s really no reliable measure of volume.

Discussant

Dr. Sharon Weber (Madison, WI): I am trying to put this in the context of what we see clinically. These are clearly unbelievably low numbers of patients that are getting referred on for definitive resection. But so often clinically what we see is the patient who had an incidental finding of gallbladder cancer after laparoscopic cholecystectomy, and we see them and obtain a re-staging MRI or CT scan and they are found to have metastatic disease, and therefore we never operate on them.

How would this dataset code that patient? Are those patients counted as having metastatic disease based on the imaging studies? Or is the pathologic staging based solely on the operation which they had, in that case, just a lap chole?

The second question I have for you is about predictors of patients that underwent radical resection. Did you do a multivariate logistical regression trying to sort this out a little more, to understand which patients actually were more likely to undergo radical resection for their gallbladder cancer?

Closing Discussant

Dr. Skye C. Mayo: Thank you for your questions, Dr. Weber. As for patients with metastatic disease being included in this database, one of our exclusion criteria was to use the SEER summary stages and the historical cancer stage to exclude patients with metastatic disease. Whether those patients are undergoing a laparoscopic cholecystectomy and later having metastatic disease added onto their record, I don’t believe that is the case. The SEER database collects tumor specific information at the time of diagnosis and treatment and records only if the patient had metastatic disease at the time of their diagnosis. I’m not certain how the database handles a patient that develops metastatic disease in the time period between their cholecystectomy and their referral for re-resection.

In regards to factors associated with patients who underwent a radical resection, we found that patients who were in the younger age quartile of our cohort, and patients who had a more recent operation were more likely to have had a radical resection.

Discussant

Dr. Henry Pitt (Indianapolis, IN): This analysis and presentation was very good. Your data suggest that an extended operation is warranted with T2 and T3 tumors. However, I didn’t see you comment on an extended operation for T1b tumors. I presume the data were not robust enough to answer this question. For your information, I just reviewed a meta-analysis of the literature that suggests that extended cholecystectomy is also warranted in T1b. Can you comment further from your analysis?

Closing Discussant

Dr. Skye C. Mayo: Thank you, Dr. Pitt for your question. In the data from recently published literature, in patients with T1b cancers, approximately 10% have residual disease in their gallbladder fossa that is found at their re-resection. Due to this percentage, many surgeons advocate radical cholecystectomy for those patients with a T1b cancer discovered after their initial cholecystectomy. In our data, not surprisingly, there was a survival benefit for patients who had a T1b cancer, but we chose to focus T2 and T3 for our discussion today. It’s more fully delineated in our paper.

Discussant

Dr. Fabrizio Michelassi (New York, NY): Nice presentation. My question relates to the survival curves according to extent of surgery in lymph node negative patients. I believe that you showed a graph with two distinct survival curves, one for patients who had undergone a radical resection, and the second one, for patients without a radical resection. Am I interpreting the data correctly?

Closing Discussant

Dr. Skye C. Mayo: Thank you, Dr. Michelassi. There were two different survival curves. The first one compared the survival impact of radical resection for patients with T2 versus T3 cancers. The second assessed the survival impact of lymphadenectomy on patients with T2 versus T3 cancers. It was irrespective of radical resection. We show an increase of 18 months median survival in patients with a T2 cancer who underwent a lymphadenectomy as indicated by their SEER-Medicare data.

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Mayo, S.C., Shore, A.D., Nathan, H. et al. National Trends in the Management and Survival of Surgically Managed Gallbladder Adenocarcinoma Over 15 years: A Population-Based Analysis. J Gastrointest Surg 14, 1578–1591 (2010). https://doi.org/10.1007/s11605-010-1335-3

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