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This summary provides information about the treatment of exocrine pancreatic cancer. Other PDQ summaries containing information related to cancer in the pancreas include the following:
Incidence and Mortality
Estimated new cases and deaths from pancreatic cancer in the United States in 2018:
The incidence of carcinoma of the pancreas has markedly increased over the past several decades and ranks as the fourth leading cause of cancer death in the United States. Despite the high mortality rate associated with pancreatic cancer, its etiology is poorly understood.
Risk factors for development of pancreatic cancer include the following:[3,4]
Anatomy of the pancreas.
Cancers of the pancreas are commonly identified by the site of involvement within the pancreas. Surgical approaches differ for masses in the head, body, tail, or uncinate process of the pancreas.
Pancreatic cancer symptoms depend on the site of the tumor within the pancreas and the degree of tumor involvement.
In the early stages of pancreatic cancer there are not many noticeable symptoms. As the cancer grows, symptoms may include the following:
Diagnostic and Staging Evaluation
Pancreatic cancer is difficult to detect and diagnose for the following reasons:
To appropriately treat pancreatic cancer, it is crucial to evaluate whether the cancer can be resected.
The use of imaging technology may aid in the diagnosis of pancreatic cancer and in the identification of patients with disease that is not amenable to resection. Imaging tests that may be used include the following:
In a case series of 228 patients, positive peritoneal cytology had a positive predictive value of 94%, specificity of 98%, and sensitivity of 25% for determining unresectability.
No tumor-specific markers exist for pancreatic cancer; markers such as serum cancer antigen (CA) 19-9 have low specificity. Most patients with pancreatic cancer will have an elevated CA 19-9 at diagnosis. Following or during definitive therapy, the increase of CA 19-9 levels may identify patients with progressive tumor growth.[Level of evidence: 3iDiii] The presence of a normal CA 19-9, however, does not preclude recurrence.
Prognosis and Survival
The primary factors that influence prognosis are:
Exocrine pancreatic cancer is rarely curable and has an overall survival (OS) rate of less than 6%.
The highest cure rate occurs when the tumor is truly localized to the pancreas; however, this stage of disease accounts for less than 20% of cases. For patients with localized disease and small cancers (<2 cm) with no lymph node metastases and no extension beyond the capsule of the pancreas, complete surgical resection is associated with an actuarial 5-year survival rate of 18% to 24%.[Level of evidence: 3iA]
Surgical resection is the mainstay of curative treatment and provides a survival benefit in patients with small, localized pancreatic tumors. Patients with unresectable, metastatic, or recurrent disease are unlikely to benefit from surgical resection.
Pancreatic tumors are resistant to treatment with chemotherapy and radiation.
Patients with any stage of pancreatic cancer can appropriately be considered candidates for clinical trials because of the poor response to chemotherapy, radiation therapy, and surgery as conventionally used.
Palliation of symptoms may be achieved with conventional treatment.
Palliative measures that may improve quality of life while not affecting OS include the following:[12,13]
Pancreatic cancer includes the following carcinomas:
The staging system for pancreatic exocrine cancer continues to evolve. The importance of staging beyond establishing whether a tumor is resectable is uncertain because state-of-the-art treatment has demonstrated little impact on survival. However, knowledge of the extent of the disease is necessary to communicate a uniform definition of disease.
The American Joint Committee on Cancer (AJCC) has designated staging by TNM (tumor, node, and metastasis) classification.
AJCC Stage Groupings and TNM Definitions
Surgical resection remains the primary modality when feasible; on occasion, resection can lead to long-term survival and provides effective palliation.[1,2,3][Level of evidence: 3iA]
The role of postoperative therapy (chemotherapy with or without chemoradiation therapy) in the management of pancreatic cancer remains controversial because much of the randomized clinical trial data available are statistically underpowered and provide conflicting results.[4,5,6,7,8]
Complications of pancreatic cancer include the following:
The survival rate of patients with any stage of pancreatic exocrine cancer is poor. Clinical trials are appropriate alternatives for treatment of patients with any stage of disease and should be considered before palliative approaches are selected.
Information about ongoing clinical trials for pancreatic cancer is available from the NCI website.
Treatment Options for Stages I and II Pancreatic Cancer
Treatment options for stage I and stage II pancreatic cancer include the following:
Complete resection can yield 5-year survival rates of 18% to 24%, but ultimate control remains poor because of the high incidence of both local and distant tumor recurrence.[9,10,11][Level of evidence: 3iA]
Approximately 20% of patients present with pancreatic cancer amenable to local surgical resection, with operative mortality rates of approximately 1% to 16%.[12,13,14,15,16] Using information from the Medicare claims database, a national cohort study of more than 7,000 patients undergoing pancreaticoduodenectomy between 1992 and 1995 revealed higher in-hospital mortality rates at low-volume hospitals (<1 pancreaticoduodenectomy per year) versus high-volume hospitals (>5 per year) (16% vs. 4%, respectively; P < .01).
Postoperative chemoradiation therapy
The role of postoperative therapy (chemotherapy with or without chemoradiation therapy) in the management of this disease remains controversial because much of the randomized clinical trial data available are statistically underpowered and provide conflicting results.[3,4,5,6,7]
Evidence (postoperative chemoradiation therapy):
Several phase III trials examined the potential overall survival (OS) benefit of postoperative adjuvant 5-FU–based chemoradiation therapy:
The EORTC/U.S. Gastrointestinal Intergroup RTOG-0848 phase III adjuvant trial evaluating the impact of chemoradiation after completion of a full course of gemcitabine with or without erlotinib is currently enrolling patients.
Historically, multiple randomized trials have established that adjuvant gemcitabine monotherapy  or adjuvant 5-FU monotherapy  improve OS for 6 months after surgical resection compared with surgery alone. More recent studies have looked at newer combination regimens that might further improve outcomes after surgical resection.
Evidence (postoperative chemotherapy):
For patients with good performance status, adjuvant gemcitabine/capecitabine should be considered. However, for older patients or patients with marginal performance status, adjuvant gemcitabine or 5-FU monotherapy can be considered.
Additional trials are still warranted to determine more effective adjuvant therapy for this disease.
Treatment Options Under Clinical Evaluation for Stages I and II Pancreatic Cancer
Treatment options under clinical evaluation include the following:
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Treatment Options for Stage III Pancreatic Cancer
While stage III and stage IV pancreatic cancer are both incurable, the natural history of stage III (locally advanced) disease may be different than it is for stage IV disease. An autopsy series demonstrated that 30% of patients presenting with stage III disease died without evidence of distant metastases.[Level of evidence: 1iiA] Therefore, investigators have struggled with the question of whether chemoradiation for patients presenting with stage III disease is warranted.
Treatment options for stage III pancreatic cancer include the following:
A significant proportion (approximately one-third) of patients with pancreatic cancer will present with stage III or locally advanced disease. Patients with stage III pancreatic cancer have tumors that are technically unresectable because of local vessel impingement or invasion by tumor. These patients may benefit from palliation of biliary obstruction by endoscopic, surgical, or radiological means.
The role of chemoradiation in locally advanced pancreatic cancer remains controversial. Table 7 summarizes phase III randomized studies of chemoradiation for stage III pancreatic cancer.
Evidence (chemoradiation therapy):
Three trials attempted to look at combined modality therapy versus radiation therapy alone.[5,6,7] The trials had substantial deficiencies in design or analysis. Initially, the standard of practice was to give chemoradiation therapy based on data from the first two studies; however, with the publication of the third study, standard practice has changed to chemotherapy followed by chemoradiation in the absence of metastases.
The LAP07 study represents the most robust, prospective, randomized phase III data regarding the role of chemoradiation therapy in the setting of gemcitabine-based induction chemotherapy that demonstrates no OS benefit. However, this study was initiated before the advent of FOLFIRINOX (leucovorin calcium, 5-FU, irinotecan hydrochloride, and oxaliplatin) chemotherapy, which has been widely adopted into the locally advanced setting. The role of chemoradiation in the setting of more active chemotherapy regimens, including gemcitabine/paclitaxel and FOLFIRINOX, has yet to be evaluated.
Chemotherapy is the primary treatment modality for patients with locally advanced pancreatic cancers. Although gemcitabine has long been considered the standard regimen, newer chemotherapy regimens have recently emerged.
Treatment Options Under Clinical Evaluation for Stage III Pancreatic Cancer
Treatment Options for Stage IV Pancreatic Cancer
Treatment options for stage IV pancreatic cancer include the following:
Palliative therapy for advanced pancreatic cancer includes the following:
Because of the low objective response rate and limited efficacy of palliative chemotherapy regimens, enrollment into clinical trials should be considered for all newly diagnosed patients. Multiagent chemotherapy combinations have recently been shown to prolong outcomes compared with single-agent gemcitabine.[5,6,7]
Evidence (single-agent chemotherapy):
Evidence (multiagent chemotherapy):
Evidence (second-line chemotherapy):
Treatment Options Under Clinical Evaluation for Stage IV Pancreatic Cancer
Treatment Options for Recurrent Pancreatic Cancer
Treatment options for recurrent pancreatic cancer include the following:
Palliative therapy for recurrent pancreatic cancer includes the following:
Chemotherapy occasionally produces objective antitumor response, but the low percentage of significant responses and lack of survival advantage warrant use of therapies under evaluation.
Treatment Options Under Clinical Evaluation for Recurrent Pancreatic Cancer
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Stage Information for Pancreatic Cancer
Updated staging information for 2017 (cited American Joint Committee on Cancer as reference 1).
Stage I and Stage II Pancreatic Cancer Treatment
Added text about multiple randomized trials using postoperative chemotherapy, which have historically established that adjuvant gemcitabine monotherapy (cited Oettle et al. as reference 21) or adjuvant 5-fluorouracil (5-FU) monotherapy improves overall survival (OS) for 6 months after surgical resection compared with surgery alone. Also added that more recent studies have looked at newer combination regimens that might further improve outcomes after surgical resection.
Added text about evidence-producing postoperative chemotherapy trials, including the European Study Group for Pancreatic Cancer (ESPAC-4) trial that randomly assigned 732 patients with resected pancreatic cancer to receive either six cycles of gemcitabine alone or oral capecitabine (cited Neoptolemos et al. as reference 22 and level of evidence 1iiA). Added statistical data from ESPAC-4 to verify that the adjuvant combination of gemcitabine and capeticabine should be the new standard of care after a resection for pancreatic cancer. Included data about gemcitabine/capecitabine yielding improvement in estimated 5-year OS, the lack of a significant difference in overall rates of grade 3/4 toxicities between treatment arms, and the lack of significant effects on quality of life in the treatment groups.
Added text about the Japan Adjuvant Study Group of Pancreatic Cancer (JASPAC-01) study, a phase III, multicenter, noninferiority trial in Japan that randomly assigned 385 patients to receive either gemcitabine for six cycles or S-1 (cited Uesaka et al. as reference 23 and level of evidence 1iiA). Added data from JASPAC-01 about an early interim analysis and results that were associated with a 5-year OS of 24.4% in the gemcitabine group and 44.1% in the S-1 group; the differences between the groups in grade 3/4 toxicities, and an explanation of the effect of S-1 on Eastern and Western populations. Stated that S-1 is an effective treatment in Japan but needs further study in non-Asian populations and approval by the U.S. Food and Drug Administration in the United States.
Added text to state that for patients with good performance status, adjuvant gemcitabine/capecitabine should be considered; however, for older patients or patients with marginal performance status, adjuvant gemcitabine or 5-FU monotherapy can be considered.
Stage IV Pancreatic Cancer Treatment
Revised text to state that because of the low objective response rate and limited efficacy of palliative chemotherapy regimens, enrollment into clinical trials should be considered for all newly diagnosed patients. Multiagent chemotherapy combinations have recently been shown to prolong outcomes compared with single-agent gemcitabine.
Added text about second-line chemotherapy evidence and included the NAPOLI-1 trial that evaluated the role of nanoliposomal irinotecan in patients with metastatic pancreatic cancer who were previously treated with gemcitabine-based therapies. Described nanoliposomal irinotecan as an encapsulated formulation of irinotecan designed to increase intratumoral levels of irinotecan and its active metabolite. Added statistical data from the study of 417 patients who were randomly assigned to either nonliposomal irinotecan monotherapy, 5-FU and folinic acid, or nanoliposomal irinotecan and folinic acid (cited Wang-Gillam et al. as reference 11 and level of evidence 1iiD) that included a comparison of the two groups regarding median OS, which on a multivariate analysis, concluded that nanoliposomal irinotecan plus 5-FU and folinic acid was associated with improved OS, grade 3/4 adverse events, and quality of life. Concluded by stating that there is a lack of clarity about the benefit of using nanoliposomal irinotecan rather than unencapsulated irinotecan because the regimen for the control arm of this study was 5-FU/folinic acid; additionally, the value of using nanolipisomal irinotecan after FOLFIRINOX (leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin) in the first-line setting is not clear.
Added text about folinic acid, fluorouracil, oxaliplatin (FOLFOX) versus 5-FU/leucovorin (LV) after gemcitabine chemotherapy by including statistical data about the PANCREOX study, a prospective, multicenter trial that randomly assigned 108 patients with advanced pancreatic cancer who had previously received first-line gemcitabine-based chemotherapy to receive 5-FU/LV either with or without oxaliplatin, which was administered as modified FOLFOX (mFOLFOX)-6 (cited Gill et al. as reference 12 and level of evidence 3iA). The statistical data about the two groups included the median progression-free survival rates, the lack of difference in response rate and quality of life, the overall incidence of grade 3/4 adverse events, the lack of benefit with the addition of oxaliplatin, administered in the mFOLFOX-6 regimen, versus infusional 5-FU/LV among patients with advanced pancreatic cancer after first-line gemcitabine-based chemotherapy, suggesting that oxaliplatin-based regimens for metastatic pancreatic cancer may yield the greatest benefit in the first-line setting.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pancreatic cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Pancreatic Cancer Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Pancreatic Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389394]
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Last Revised: 2018-05-24
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