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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 2014:
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 if 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]
(Refer to the Palliative Interventions section of the PDQ summary on Pain for more information.)
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 since 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.
AJCC Stage Groupings and TNM Definitions
The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification.
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 Web site.
Treatment Options for Stages I and II Pancreatic Cancer
Treatment options for stages I and 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.
Evidence (postoperative chemotherapy):
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
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I pancreatic cancer and stage II pancreatic cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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 8 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.
Taken together, the FFCD and GERCOR studies provide support for gemcitabine-based chemotherapy for at least 3 months, followed by chemoradiation in the absence of metastatic disease. This approach has yet to be validated in a prospective phase III trial.
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
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III pancreatic cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
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:
The low objective response rate and lack of survival benefit with current chemotherapy indicates that clinical trials are appropriate treatment of all newly diagnosed patients. Occasionally, patients have palliation of symptoms when treated with chemotherapy with well-tested older drugs, such as 5-FU. Gemcitabine has demonstrated activity in patients with pancreatic cancer and is a useful palliative agent.[1,15,16]
Treatment Options Under Clinical Evaluation for Stage IV Pancreatic Cancer
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV pancreatic cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
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
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent pancreatic cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
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.
General Information About Pancreatic Cancer
Updated statistics with estimated new cases and deaths for 2014 (cited American Cancer Society as reference 1).
Stage I and Stage II Pancreatic Cancer Treatment
Revised text to state that median disease-free survival was 13.4 months in the gemcitabine arm and 6.7 months in the observation arm. Also added that in the initial publication of results, there was no significant difference in overall survival (OS) between the gemcitabine arm and the control arm.
Added text to state that with a median follow-up of 136 months, long-term follow-up of the CONKO-001 study demonstrates a significant improvement in OS that favors gemcitabine. Also added that gemcitabine compared with observation alone yielded improved survival rates at 5 years of 20.7% for the gemcitabine arm versus 10.4% for the observation-alone arm and survival rates at 10 years were 12.2% for the gemcitabine arm versus 7.7% for the observation-alone arm (cited Oettle et al. as reference 21 and level of evidence 1iiA).
Stage III Pancreatic Cancer Treatment
Revised text in the chemotherapy treatment option to add gemcitabine and nab-paclitaxel.
Added text to include a multicenter, international phase III trial of gemcitabine and nab-paclitaxel versus gemcitabine alone as evidence that nab-paclitaxel plus gemcitabine is a standard treatment option for patients with advanced pancreatic cancer. Also added that the trial included 861 patients with metastatic pancreatic adenocarcinoma who had not previously received chemotherapy for metastatic disease (cited Von Hoff et al. as reference18 and level of evidence 1iiA). Added that the median OS and the median progression-free survival (PFS) favored the nab-paclitaxel/gemcitabine group; however, nab-paclitaxel/gemcitabine was more toxic than gemcitabine. Quality-of-life data have not yet been published.
Stage IV Pancreatic Cancer Treatment
Added text to include a multicenter, international phase III trial of gemcitabine and nab-paclitaxel versus gemcitabine alone as evidence that nab-paclitaxel plus gemcitabine is a standard treatment option for patients with advanced pancreatic cancer. Also added that the trial included 861 patients with metastatic pancreatic adenocarcinoma who had not previously received chemotherapy for metastatic disease (cited Von Hoff et al. as reference 20 and level of evidence 1iiA). Added that the median OS and the median PFS favored the nab-paclitaxel/gemcitabine group; however, nab-paclitaxel/gemcitabine was more toxic than gemcitabine. Quality-of-life data have not yet been published.
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 Web site's Contact Form. 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.
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The preferred citation for this PDQ summary is:
National Cancer Institute: PDQ® Pancreatic Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/pancreatic/HealthProfessional. Accessed <MM/DD/YYYY>.
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Last Revised: 2014-02-21
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