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Management of unresectable pancreatic ductal cancer
Consensus Statement
Management of Unresectable Pancreatic Ductal Cancer The SSAT, AGA, AASLD, ASGE, AHPBA ConsensusPanel*
General Summary
1. The median duration of survival for patients with unresectable pancreatic ductal cancer is 6 to 10 months. 2. Given this modest duration of survival, quality of life is an important clinical end point in the management of patients with unresectable pancreatic ductal cancer. Relief or palliation of biliary tract and gastroduodenal obstruction and pain are the major clinical issues affecting quality of life. 3. Multiple therapeutic approaches have been evaluated for the management ofbiliary tract and gastroduodenal obstruction. Choice of therapeutic approach is dictated by the temporal recognition of unresectability. Two broad groups of patients with unresectable pancreatic cancer are (1) the majority of patients with unresectable pancreatic ductal cancer recognized nonoperatively (by imaging) and (2) the minority of patients with unresectable pancreatic ductal cancer recognized intraoperatively. 4. The preponderance of controlled and uncontrolled studies strongly support the consensus that endoscopic biliary stenting provides optimal relief of jaundice in patients with unresectable pancreatic ductal cancer recognized nonoperatively. Percutaneous transhepatic stenting is reserved for patients in whom endoscopic stenting has failed or is precluded technically. When unresectable pancreatic ductal cancer is recognized intraoperatively, controlled and uncontrolled data support operative bilioenteric bypass, regardless of prior biliary stenting. 5. Accumulated data support open gastroenterostomy for palliation of gastroduodenal obstruction. Data are insufficient for consensus on prophylactic gastroenterostomy during operative bilioenteric bypass. 6. Pain adversely affects quality of life in a majority of patients with unresectable pancreatic ductal cancer; pain control improves quality of life. Both controlled and uncontrolled data support the consensus that both operative and percutaneous neurolytic celiac plexus block are more effective than oral analgesia for relief of pain. 7. Antineoplastic therapy--irradiation, chemotherapy, and immunotherapy--currently have limited impact on
overall duration of survival. Controlled data for combined irradiation and systemic chemotherapy and chemotherapy alone show overall survival is improved by a few months. Sparse data on immunotherapy do not support a survival benefit. There are insufficient controlled or uncontrolled data to support a consensus on a standard antineoplastic therapeutic regimen for patients with unresectable pancreatic ductal cancer. . Future studies of patients with unresectable pancreatic ductal cancer should address objective measures of quality of life and survival. Stage of disease and specific symptoms should be carefully defined for patients in studies. Palliation o f J a u n d i c e a n d G a s t r o d u o d e n a l Obstruction The panel agrees that biliary trace and gastroduodenal obstructions are major clinical problems facing patients with unresectable pancreatic ductal cancer. Quality of life improves substantially with relief of either or both obstructions.
Endoscopic Stenting for Palliation of Jaundice. If unresectable pancreatic ductal cancer is recognized preoperatively, endoscopic biliary stenting is preferred. Biliary stenting is technically feasible in 95% of patients. Current data support the use of either a plastic stent or an expandable metallic stent. Metallic stents, although not exchangeable, are preferred when life expectancy exceeds 3 months. Occlusion of either type of stent by ductal debris or tumor remains a problem. Further study of the composition and design of stents with regard to quality of life and cost efficiency are needed. Percutaneous TransbepaticStenting. Percutaneous transhepatic biliary stenting is reserved for those patients with unresectable pancreatic ductal cancer in whom endoscopic biliary stenting fails, or in the absence of endoscopic expertise. Technical feasibility ex-
Correspondence: DavidM. Nagorney,M.D., General Surgery-W6B,Mayo Clinic Rochester,200 First Street SW, Rochester,MN 55905. *The Society for Surgery of the Alimentary Tract, American Gastroenterological Association, American Association for the Study of Liver Diseases,American Societyfor Gastrointestinal Endoscopy,and American Hepato-Pancreato-BiliaryAssociation. 331
332
Journal of Gastrointestinal Surgery
ConsensusStatement
ceeds 95%. The durability of transhepatic biliary stenting is similar to that of endoscopic stenting. Operative Bilioenteric Bypass. When unresectable pancreatic ductal cancer is established intraoperatively, bilioenteric bypass for biliary obstruction is recommended even if prior nonoperative stenting has been employed successfully. Technical feasibility approaches 98% unless precluded by carcinomatosis or extensive local disease. Operative bypass of the hepatic or common duct is preferred over the gallbladder. Recurrence of jaundice is less common after operative than nonoperative methods. Laparoscopic bilioenteric bypass is yet unestablished. Gastric Outlet Obstruction. When gastroduodenal obstruction occurs in patients with unresectable pancreatic ductal cancer, operative gastrojejunostomy is indicated. In patients with unresectable pancreatic ductal cancer established intraoperatively without gastroduodental obstruction, no objective intraoperative criteria reliably predict subsequent gastric outlet obstruction. Although prophylactic gastrojejunostomy in these patients does not increase mortality, morbidity is increased. Current data are insufficient to recommend routine prophylactic gastrojejunostomy in such patients. Endoscopic or radiologic gastrointestinal stenting is yet unestablished.
Pain Management Pain is a significant clinical problem in most patients with unresectable pancreatic ductal cancer and warrants specific treatment. Most patients who have pain are candidates for management through a stepwise pharmacologic progression of oral or transdermal analgesia. However, side effects can significantly impair quality of life. Recent controlled data suggest that a percutaneous neurolytic splanchnic plexus block provides better initial pain relief and improved quality of life, compared with oral analgesia, in patients with unresectable pancreatic ductal cancer. Although duration of response is limited, repeat blocks can be successful. Transthoracic (thorascopic) splanchnicectomy and endoscopic ultrasonographic splanchnic plexus blocks are yet unestablished. Further studies comparing neurolytic blocks--either operative or nonoperative--to a pro-
gressive pharmacologic pain management ladder for efficacy of pain relief and quality of life are warranted. Current controlled data support intraoperative chemical neurolytic splanchnic block in patients found unresectable at operation. Benefit has been demonstrated in intensity and duration of pain relief, quality of life, and perhaps survival. Intraoperative chemical splanchnicectomy should be strongly considered in all patients who are found to be unresectable at operation. Antineoplastic T h e r a p y
Irradiation. Irradiation has been employed to control tumor growth in patients with locally unresectable pancreatic cancer with a good clinical performance status. External-beam radiation with 5-fluorouracil provides a median survival of 10 months and a 2-year survival of 12 %. External-beam irradiation plus intraoperative irradiation plus 5-florouracil provides a median survival of 12 months and a 2-year survival of 20%. External-beam irradiation with newer radiation sensitizers warrants further study. Current data do not suggest that there is a significant enough survival benefit for intraoperative irradiation to warrant that procedure in patients with unresectable pancreatic ductal cancer except in controlled trials. Chemotherapy. Currently the results of chemotherapy for patients with unresectable pancreatic ductal cancer remain disappointing with respect to survival. Alternative measures of tumor control and quality of life are under evaluation. Presently the two most active agents against pancreatic ductal cancer are 5-fluorouracil and gemcitabine. Median survival, however, remains approximately 6 months. To date, combination chemotherapy has not improved survival over single-agent chemotherapy in patients with nnresectable pancreatic ductal cancer. Immunotberapy. Regardless of type, immunotherapy remains unestablished for patients with unresectable pancreatic ductal cancer. Results of immunotherapy on survival, tumor regression, and quality of life are few. Further studies, however, are warranted in well-defined subgroups of patients with unresectable pancreatic ductal cancer.
M e m b e r s of the C o n s e n s u s Panel were:
James Becket, M.D., Division of Surgery, Boston Medical Center, Boston, Mass.; Gregory Bulkley, M.D., Johns Hopkins Medical Institutions, Baltimore, Md.; Doug Evans, M.D., The University of Texas M.D. Anderson Cancer Center, Houston, Tex.;Joseph E. G e e n e n , M.D., Gastroenterology Consultants, Milwaukee, Wis.;James H. Grendell, M.D., Division of Digestive Disease, Department of Medicine, New York Hospital-Cornell Medical Center, New York, N.Y.; Robin McLeod, M.D., Mount Sinai Hospital, Toronto, Ontario, Canada; David M. Nagorney, M.D., Mayo Clinic, Rochester, Minn.; Anthony Venbrux, M.D., Johns Hopkins Medical Institutions, Baltimore, Md.
Management of Unresectable Pancreatic Ductal Cancer The SSAT, AGA, AASLD, ASGE, AHPBA ConsensusPanel*
General Summary
1. The median duration of survival for patients with unresectable pancreatic ductal cancer is 6 to 10 months. 2. Given this modest duration of survival, quality of life is an important clinical end point in the management of patients with unresectable pancreatic ductal cancer. Relief or palliation of biliary tract and gastroduodenal obstruction and pain are the major clinical issues affecting quality of life. 3. Multiple therapeutic approaches have been evaluated for the management ofbiliary tract and gastroduodenal obstruction. Choice of therapeutic approach is dictated by the temporal recognition of unresectability. Two broad groups of patients with unresectable pancreatic cancer are (1) the majority of patients with unresectable pancreatic ductal cancer recognized nonoperatively (by imaging) and (2) the minority of patients with unresectable pancreatic ductal cancer recognized intraoperatively. 4. The preponderance of controlled and uncontrolled studies strongly support the consensus that endoscopic biliary stenting provides optimal relief of jaundice in patients with unresectable pancreatic ductal cancer recognized nonoperatively. Percutaneous transhepatic stenting is reserved for patients in whom endoscopic stenting has failed or is precluded technically. When unresectable pancreatic ductal cancer is recognized intraoperatively, controlled and uncontrolled data support operative bilioenteric bypass, regardless of prior biliary stenting. 5. Accumulated data support open gastroenterostomy for palliation of gastroduodenal obstruction. Data are insufficient for consensus on prophylactic gastroenterostomy during operative bilioenteric bypass. 6. Pain adversely affects quality of life in a majority of patients with unresectable pancreatic ductal cancer; pain control improves quality of life. Both controlled and uncontrolled data support the consensus that both operative and percutaneous neurolytic celiac plexus block are more effective than oral analgesia for relief of pain. 7. Antineoplastic therapy--irradiation, chemotherapy, and immunotherapy--currently have limited impact on
overall duration of survival. Controlled data for combined irradiation and systemic chemotherapy and chemotherapy alone show overall survival is improved by a few months. Sparse data on immunotherapy do not support a survival benefit. There are insufficient controlled or uncontrolled data to support a consensus on a standard antineoplastic therapeutic regimen for patients with unresectable pancreatic ductal cancer. . Future studies of patients with unresectable pancreatic ductal cancer should address objective measures of quality of life and survival. Stage of disease and specific symptoms should be carefully defined for patients in studies. Palliation o f J a u n d i c e a n d G a s t r o d u o d e n a l Obstruction The panel agrees that biliary trace and gastroduodenal obstructions are major clinical problems facing patients with unresectable pancreatic ductal cancer. Quality of life improves substantially with relief of either or both obstructions.
Endoscopic Stenting for Palliation of Jaundice. If unresectable pancreatic ductal cancer is recognized preoperatively, endoscopic biliary stenting is preferred. Biliary stenting is technically feasible in 95% of patients. Current data support the use of either a plastic stent or an expandable metallic stent. Metallic stents, although not exchangeable, are preferred when life expectancy exceeds 3 months. Occlusion of either type of stent by ductal debris or tumor remains a problem. Further study of the composition and design of stents with regard to quality of life and cost efficiency are needed. Percutaneous TransbepaticStenting. Percutaneous transhepatic biliary stenting is reserved for those patients with unresectable pancreatic ductal cancer in whom endoscopic biliary stenting fails, or in the absence of endoscopic expertise. Technical feasibility ex-
Correspondence: DavidM. Nagorney,M.D., General Surgery-W6B,Mayo Clinic Rochester,200 First Street SW, Rochester,MN 55905. *The Society for Surgery of the Alimentary Tract, American Gastroenterological Association, American Association for the Study of Liver Diseases,American Societyfor Gastrointestinal Endoscopy,and American Hepato-Pancreato-BiliaryAssociation. 331
332
Journal of Gastrointestinal Surgery
ConsensusStatement
ceeds 95%. The durability of transhepatic biliary stenting is similar to that of endoscopic stenting. Operative Bilioenteric Bypass. When unresectable pancreatic ductal cancer is established intraoperatively, bilioenteric bypass for biliary obstruction is recommended even if prior nonoperative stenting has been employed successfully. Technical feasibility approaches 98% unless precluded by carcinomatosis or extensive local disease. Operative bypass of the hepatic or common duct is preferred over the gallbladder. Recurrence of jaundice is less common after operative than nonoperative methods. Laparoscopic bilioenteric bypass is yet unestablished. Gastric Outlet Obstruction. When gastroduodenal obstruction occurs in patients with unresectable pancreatic ductal cancer, operative gastrojejunostomy is indicated. In patients with unresectable pancreatic ductal cancer established intraoperatively without gastroduodental obstruction, no objective intraoperative criteria reliably predict subsequent gastric outlet obstruction. Although prophylactic gastrojejunostomy in these patients does not increase mortality, morbidity is increased. Current data are insufficient to recommend routine prophylactic gastrojejunostomy in such patients. Endoscopic or radiologic gastrointestinal stenting is yet unestablished.
Pain Management Pain is a significant clinical problem in most patients with unresectable pancreatic ductal cancer and warrants specific treatment. Most patients who have pain are candidates for management through a stepwise pharmacologic progression of oral or transdermal analgesia. However, side effects can significantly impair quality of life. Recent controlled data suggest that a percutaneous neurolytic splanchnic plexus block provides better initial pain relief and improved quality of life, compared with oral analgesia, in patients with unresectable pancreatic ductal cancer. Although duration of response is limited, repeat blocks can be successful. Transthoracic (thorascopic) splanchnicectomy and endoscopic ultrasonographic splanchnic plexus blocks are yet unestablished. Further studies comparing neurolytic blocks--either operative or nonoperative--to a pro-
gressive pharmacologic pain management ladder for efficacy of pain relief and quality of life are warranted. Current controlled data support intraoperative chemical neurolytic splanchnic block in patients found unresectable at operation. Benefit has been demonstrated in intensity and duration of pain relief, quality of life, and perhaps survival. Intraoperative chemical splanchnicectomy should be strongly considered in all patients who are found to be unresectable at operation. Antineoplastic T h e r a p y
Irradiation. Irradiation has been employed to control tumor growth in patients with locally unresectable pancreatic cancer with a good clinical performance status. External-beam radiation with 5-fluorouracil provides a median survival of 10 months and a 2-year survival of 12 %. External-beam irradiation plus intraoperative irradiation plus 5-florouracil provides a median survival of 12 months and a 2-year survival of 20%. External-beam irradiation with newer radiation sensitizers warrants further study. Current data do not suggest that there is a significant enough survival benefit for intraoperative irradiation to warrant that procedure in patients with unresectable pancreatic ductal cancer except in controlled trials. Chemotherapy. Currently the results of chemotherapy for patients with unresectable pancreatic ductal cancer remain disappointing with respect to survival. Alternative measures of tumor control and quality of life are under evaluation. Presently the two most active agents against pancreatic ductal cancer are 5-fluorouracil and gemcitabine. Median survival, however, remains approximately 6 months. To date, combination chemotherapy has not improved survival over single-agent chemotherapy in patients with nnresectable pancreatic ductal cancer. Immunotberapy. Regardless of type, immunotherapy remains unestablished for patients with unresectable pancreatic ductal cancer. Results of immunotherapy on survival, tumor regression, and quality of life are few. Further studies, however, are warranted in well-defined subgroups of patients with unresectable pancreatic ductal cancer.
M e m b e r s of the C o n s e n s u s Panel were:
James Becket, M.D., Division of Surgery, Boston Medical Center, Boston, Mass.; Gregory Bulkley, M.D., Johns Hopkins Medical Institutions, Baltimore, Md.; Doug Evans, M.D., The University of Texas M.D. Anderson Cancer Center, Houston, Tex.;Joseph E. G e e n e n , M.D., Gastroenterology Consultants, Milwaukee, Wis.;James H. Grendell, M.D., Division of Digestive Disease, Department of Medicine, New York Hospital-Cornell Medical Center, New York, N.Y.; Robin McLeod, M.D., Mount Sinai Hospital, Toronto, Ontario, Canada; David M. Nagorney, M.D., Mayo Clinic, Rochester, Minn.; Anthony Venbrux, M.D., Johns Hopkins Medical Institutions, Baltimore, Md.