Pancreatic cancer (PCA) is one of the most challenging malignancies faced by patients, their families, and their physicians. Symptoms related to metastatic disease (eg, malaise, fatigue, cachexia, and venous thromboembolism) may all contribute to poor quality of life. Moreover, the local component of PCA may also be associated with significant morbidity, including pain, biliary obstruction, gastrointestinal dysfunction or bleeding, and exocrine or endocrine pancreatic insufficiency. Fortunately, multidisciplinary engagement and multiple therapeutic modalities have gradually improved and been refined to optimize survival while preserving quality of life.
Currently, a convergence of several improved techniques and technologies, coupled with a better understanding of underlying tumor biology, now enables physicians to consider more aggressive therapies for select patients who present with limited metastatic disease.
First, improvements in cross-sectional imaging have facilitated the detection of very low-volume metastatic disease. Such metastatic foci, which can be limited to 1 or 2 lesions in a single organ, may have gone undetected in previous years. In addition, laparoscopy seems to be particularly effective in identifying occult metastatic disease that may otherwise be undetected by modern imaging modalities.1,2
Second, a broader array of radiation options that include image-guided (IGRT) and stereotactic body radiation therapy (SBRT) have demonstrated encouraging efficacy in the treatment of primary and metastatic tumors while minimizing toxicity. Importantly, these techniques can be delivered over relatively short time courses, thus limiting the delay of systemic therapies. However, longer follow-up is needed to determine the full extent of late toxicity.
Third, recent advances in combination chemotherapy yield higher response rates and survival. Although uncommon, some isolated case reports of complete or near-complete radiographic responses have been observed after combination chemotherapy regimens. With the widespread adoption of novel combination chemotherapy regimens, larger subsets of patients with metastatic disease may be considered for novel clinical trials to manage the metastatic compartment as a way to preserve or improve quality of life.
Fourth, image-guided percutaneous radiofrequency ablation (RFA) and laparoscopically assisted RFA may allow for management of limited metastatic disease and spare patients the toxicity associated with ongoing cytotoxic chemotherapy.
Lastly, the morbidity and mortality associated with metastatectomies or primary PCA resections continues to decline, particularly in high-volume centers. Whether these interventions lead to improved overall survival (OS) or disease-free survival (DFS) in the setting of limited metastases is not yet known.
The authors would like to thank Lauren M. Rosati, BS, for her technical assistance and contribution to the revision of this manuscript.
Satoi S, Yanagimoto H, Toyokawa H et al.. Selective use of staging laparoscopy based on carbohydrate antigen 19-9 level and tumor size in patients with radiographically defined potentially or borderline resectable pancreatic cancer. Pancreas 2011;40:426–432.
Burris HA 3rd, Moore MJ, Andersen J et al.. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997;15:2403–2413.
Royal RE, Wolff RA, Crane CH. Pancreas cancer. In: Devita VT, Hellman S, Rosenberg S, eds. Cancer: Principles and Practice of Oncology. 9th Edition. Philadelphia, PA: Lippincott, Williams and Wilkins; 2011:982–983.
Conroy T, Desseigne F, Ychou M et al.. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817–1825.
Von Hoff DD, Ervin T, Arena FP et al.. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013;36:1691–1703.
Fine RL, Fogelman DR, Schreibman SM et al.. The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic pancreatic cancer: a retrospective analysis. Cancer Chemother Pharmacol 2008;61:167–175.
Arnaoutakis GJ, Rangachari D, Laheru DA et al.. Pulmonary resection for isolated pancreatic adenocarcinoma metastasis: an analysis of outcomes and survival. J Gastrointest Surg 2011;15:1611–1617.
Shrikhande SV, Kleeff J, Reiser C et al.. Pancreatic resection for M1 pancreatic ductal adenocarcinoma. Ann Surg Oncol 2007;14:118–127.
McKenzie S, Mailey B, Artinyan A et al.. The incidence and outcomes of pancreatectomy in patients with metastatic pancreatic adenocarcinoma. JOP 2010;11:341–347.
Lillemoe KD, Cameron JL, Kaufman HS et al.. Chemical splanchnicectomy in patients with unresectable pancreatic cancer. A prospective randomized trial. Ann Surg 1993;217:447–455; discussion 456-457.
Yeo CJ, Cameron JL, Sohn TA et al.. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: pathology, complications, and outcomes. Ann Surg 1997;226:248–257; discussion 257-260.
Gleisner AL, Assumpcao L, Cameron JL et al.. Is resection of periampullary or pancreatic adenocarcinoma with synchronous hepatic metastasis justified? Cancer 2007;110:2484–2492.
Warshaw AL. Implications of peritoneal cytology for staging of early pancreatic cancer. Am J Surg 1991;161:26–29; discussion 29-30.
Ferrone CR, Haas B, Tang L et al.. The influence of positive peritoneal cytology on survival in patients with pancreatic adenocarcinoma. J Gastrointest Surg 2006;10:1347–1353.
Yachida S, Fukushima N, Sakamoto M et al.. Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer. Br J Surg 2002;89:573–578.
Yoshioka R, Saiura A, Koga R et al.. The implications of positive peritoneal lavage cytology in potentially resectable pancreatic cancer. World J Surg 2012;36:2187–2191.
Meszoely IM, Lee JS, Watson JC et al.. Peritoneal cytology in patients with potentially resectable adenocarcinoma of the pancreas. Am Surg 2004;70:208–213; discussion 213-214.
Pancreas (endocrine) cancer protocol. College of American Pathologists Web site. Available at: http://www.cap.org/apps/docs/cancer_protocols/2005/pancreasendo05_pw.pdf. Accessed January 6, 2014.
Cordera F, Arciero CA, Li T et al.. Significance of common hepatic artery lymph node metastases during pancreaticoduodenectomy for pancreatic head adenocarcinoma. Ann Surg Oncol 2007;14:2330–2336.
LaFemina J, Chou JF, Gonen M et al.. Hepatic arterial nodal metastases in pancreatic cancer: Is this the node of importance? J Gastrointest Surg 2013;17:1092–1097.
Shimada K, Sakamoto Y, Sano T, Kosuge T. The role of paraaortic lymph node involvement on early recurrence and survival after macroscopic curative resection with extended lymphadenectomy for pancreatic carcinoma. J Am Coll Surg 2006;203:345–352.
Masui T, Kubota T, Aoki K et al.. Long-term survival after resection of pancreatic ductal adenocarcinoma with para-aortic lymph node metastasis: case report. World J Surg Oncol 2013;11:195.
Seelig SK, Burkert B, Chromik AM et al.. Pancreatic resections for advanced M1-pancreatic carcinoma: the value of synchronous metastasectomy. HPB Surg 2010;2010:579672.
Takada T, Yasuda H, Amano H et al.. Simultaneous hepatic resection with pancreato-duodenectomy for metastatic pancreatic head carcinoma: does it improve survival? Hepatogastroenterology 1997;44:567–573.
Artifon EL, Sakai P, Cunha JE et al.. Surgery or endoscopy for palliation of biliary obstruction due to metastatic pancreatic cancer. Am J Gastroenterol 2006;101:2031–2037.
Lillemoe KD, Cameron JL, Hardacre JM et al.. Is prophylactic gastrojejunostomy indicated for unresectable periampullary cancer? A prospective randomized trial. Ann Surg 1999;230:322–328; discussion 328-330.
Tachezy M, Bockhorn M, Gebauer F et al.. Bypass surgery versus intentionally incomplete resection in palliation of pancreatic cancer: is resection the lesser evil? J Gastrointest Surg 2011;15:829–835.
Jeurnink SM, van Eijck CH, Steyerberg EW et al.. Stent versus gastrojejunostomy for the palliation of gastric outlet obstruction: a systematic review. BMC Gastroenterol 2007;7:18.
Poruk KE, Kim Y, Cameron JL et al.. What is the significance of indeterminate pulmonary nodules in patients undergoing resection for pancreatic adenocarcinoma? J Gastrointest Surg 2015;19:841–847.
Klempnauer J, Ridder GJ, Piso P, Pichlmayr R. Is liver resection in metastases of exocrine pancreatic carcinoma justified? Chirurg 1996;67:366–370.
Zhao Q, Rashid A, Gong Y et al.. Pathologic complete response to neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma is associated with a better prognosis. Ann Diagn Pathol 2012;16:29–37.
Iacobuzio-Donahue CA, Fu B, Yachida S et al.. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol 2009;27:1806–1813.
Winter JM, Tang LH, Klimstra DS et al.. Failure patterns in resected pancreas adenocarcinoma: lack of predicted benefit to SMAD4 expression. Ann Surg 2013;258:331–335.
Blackford A, Serrano OK, Wolfgang CL et al.. SMAD4 gene mutations are associated with poor prognosis in pancreatic cancer. Clin Cancer Res 2009;15:4674–4679.
Herman JM, Fan KY, Wild AT et al.. Correlation of Smad4 status with outcomes in patients receiving erlotinib combined with adjuvant chemoradiation and chemotherapy after resection for pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 2013;87:458–459.
Hoyer M, Roed H, Sengelov L et al.. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. Radiother Oncol 2005;76:48–53.
Schellenberg D, Goodman KA, Lee F et al.. Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2008;72:678–686.
Herman JM, Chang DT, Goodman KA et al.. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer 2015;121:1128–1137.
Chang DT, Swaminath A, Kozak M et al.. Stereotactic body radiotherapy for colorectal liver metastases: a pooled analysis. Cancer 2011;117:4060–4069.
Park JB, Kim YH, Kim J et al.. Radiofrequency ablation of liver metastasis in patients with locally controlled pancreatic ductal adenocarcinoma. J Vasc Interv Radiol 2012;23:635–641.
Birsen O, Aliyev S, Aksoy E et al.. A critical analysis of postoperative morbidity and mortality after laparoscopic radiofrequency ablation of liver tumors. Ann Surg Oncol 2014;21:1834–1840.
Ho AS, Picus J, Darcy MD et al.. Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors. AJR Am J Roentgenol 2007;188:1201–1207.
Stuart JE, Tan B, Myerson RJ et al.. Salvage radioembolization of liver-dominant metastases with a resin-based microsphere: initial outcomes. J Vasc Interv Radiol 2008;19:1427–1433.
Cao C, Yan TD, Morris DL, Bester L. Radioembolization with yttrium-90 microspheres for pancreatic cancer liver metastases: results from a pilot study. Tumori 2010;96:955–958.
De Jong MC, Farnell MB, Sclabas G et al.. Liver-directed therapy for hepatic metastases in patients undergoing pancreaticoduodenectomy: a dual-center analysis. Ann Surg 2010l;252:142–148.
Jazieh KA, Foote MB, Diaz LA Jr. The clinical utility of biomarkers in the management of pancreatic adenocarcinoma. Semin Radiat Oncol 2014;24:67–76.