Management of Early-Stage Common Bile Duct Cancer
Illustrative Case Series
Management of Early-Stage Common Bile Duct Cancer
By Samir Kanani, MD, Associate Clinical Professor of Neurosurgery and Radiation Oncology, George Washington University, Radiation Oncology, Inova Fairfax Hospital, Falls Church, VA. Dr. Kanani reports no financial relationships relevant to this field of study.
A 52-year-old female presented with right flank pain, elevated bilirubin, and mild jaundice to her primary care physician. Endoscopic retrograde cholangiopancreatography demonstrated a common bile duct stricture just above the pancreatic head with a suggestion of neoplasia. A pancreaticoduodenectomy (Whipple) was performed and pathology revealed invasive, well-differentiated adenocarcinoma involving the full-thickness of the bile duct wall immediately adjacent to but not invading the pancreatic parenchyma. Final margins of excision were negative as were three adjacent lymph nodes (LNs) within the resected specimen. The pancreas itself demonstrated some focal pancreatic intraepithelial neoplasia, but without malignancy, and eight additional benign LNs were also noted. Appendix was removed and this was negative. A celiac LN also was removed and negative. Cholecystectomy was performed demonstrating acute cholecystitis and steatosis, but no additional evidence of malignancy. This was staged as a pathologic T2A N0 distal common bile duct adenocarcinoma. Imaging included a CT scan of the abdomen and pelvis, demonstrating no evidence of distant metastatic disease. Chest x-ray revealed no suspicious lesions. Postoperative recovery was unremarkable and she now presents for discussion of adjuvant therapy.
Discussion
Cholangiocarcinomas are relatively rare tumors in the United States. The incidence is approximately 3000 cases per year. Although most cases are sporadic, a history of primary sclerosing cholangitis does increase the risk significantly. Most cholangiocarcinomas are perihilar in location, and 20-25% are found in the distal bile duct. The pathology is consistent with adenocarcinoma in more than 90% of cases. CA19-9 and CA-50 are often elevated. MIB-1 > 29% predicts for worse outcomes.1
Surgery has been shown to be the only curative treatment for cholangiocarcinomas. The case illustrated above is uncommon in that < 30% of cases are actually resected with negative margins. Distal bile duct tumors are more likely to be resectable and have a better survival when compared to hilar tumors.2 Median survival is approximately 16 months for distal bile duct tumors and 11 months for proximal bile duct tumors. Long-term survival has been reported as high as 60% in distal bile duct carcinomas that are resected with negative margins.3 LNs are positive in ~50% of patients at presentation, and signify worse prognosis. It appears that patients with 5+ LNs have significantly worse survival than patients with 1-4 LNs.4
The role of adjuvant radiotherapy and chemotherapy for cholangiocarcinoma is unclear. There are no prospective trials that include this patient population. A number of retrospective studies do show a benefit in adjuvant therapy, particularly in patients with an R1 resection. The largest retrospective series to date has included more than 300 patients in China. This study demonstrated a survival advantage in those patients who received adjuvant chemotherapy and radiotherapy.5 There are, however, a number of other studies that do not show a clear advantage to postoperative radiotherapy in this setting, including studies from Johns Hopkins University and Thomas Jefferson University. These studies are fraught with the biases of retrospective studies. In my opinion, when a retrospective study demonstrates that the addition of adjuvant therapy either improves control or survival or demonstrates equivalence, then it is likely a benefit would be shown in a randomized trial. There must be a reason that a particular institution recommended adjuvant therapy in some patients and not other patients. That reason probably relates to adverse features in the patients who received adjuvant therapy. If you compare a worse cohort to a better cohort and the cohort that was supposed to do worse actually did as well as the cohort that was supposed to do well as a result of adjuvant intervention, then the intervention is likely beneficial. The potential benefits of adjuvant radiotherapy in decreasing local failures must be weighed against the risks of gastric/duodenal ulceration and obstruction. Most of the studies to date quote outdated radiation techniques. The use of modern IMRT techniques can decrease this risk if appropriately applied. Studies that document patterns of failure point to a 20% risk of liver failures, justifying a discussion about chemotherapy.
In conclusion, the above case presents an interesting challenge. I believe her 5-year overall survival is likely to be greater than 50%. She does have a risk of local recurrence and distal failure that could potentially be decreased with the use of adjuvant therapy including chemotherapy and radiotherapy. I would recommend a discussion about the potential complications of therapy, and based on the patient’s performance status and the details of her pathology report (margin status), I would offer adjuvant combined modality 5FU and radiotherapy similar to pancreatic cancer, with possible combination chemotherapy before or after combined chemoradiotherapy. One could make an argument to observe the patient based on a single-institution retrospective series that demonstrates distal bile duct tumors have a better prognosis. Although 5-year survivals of 50-60% are encouraging with surgery alone, there certainly is room for improvement.
References
1. Suto T, et al. Assessment of the expression of p53, MIB-1 (Ki-67 antigen), and argyrophilic nucleolar organizer regions in carcinoma of the extrahepatic bile duct. Cancer 1998;82:86-95.
2. Chao TC, Greager JA. Carcinoma of the extrahepatic bile ducts. J Surg Oncol 1991;46:145-150.
3. Todoroki T, et al. Treatment strategy for patients with middle and lower third bile duct cancer. Br J Surg 2001;88:364-370.
4. Hong SM, et al. The number of metastatic lymph nodes in extrahepatic bile duct carcinoma as a prognostic factor. Am J Surg Pathol 2005;29:1177-1183. Erratum in: Am J Surg Pathol 2005;29:1548.
5. Jan YY, et al. Prognostic analysis of surgical treatment of peripheral cholangiocarcinoma: Two decades of experience at Chang Gung Memorial Hospital. World J Gastroenterol 2005;11:1779-1184.
A 52-year-old female presented with right flank pain, elevated bilirubin, and mild jaundice to her primary care physician. Endoscopic retrograde cholangiopancreatography demonstrated a common bile duct stricture just above the pancreatic head with a suggestion of neoplasia.Subscribe Now for Access
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