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Home > Health Library > Pancreatic Cancer Treatment (Adult) (PDQ®): Treatment - Health Professional Information [NCI]
This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
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 2020:
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%. As pancreatic cancer is associated with significant morbidity and mortality, and treatment decisions are complex, management with a comprehensive multidisciplinary team should be considered.
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, but should be considered only alongside systemic therapy. Patients with unresectable, metastatic, or recurrent disease are unlikely to benefit from surgical resection.
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 (systematic chemotherapy).
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. Clinical staging is guided by resectability, which is strongly influenced by surgical judgment. Consensus guidelines for surgical resectability (e.g., National Comprehensive Cancer Network, MD Anderson Cancer Center, American Hepato-Pancreato-Biliary Association, and International Hepato-Pancreato-Biliary Association) continue to be refined, but are traditionally stratified by the following:
The American Joint Committee on Cancer (AJCC) has designated staging by TNM (tumor, node, 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] Treatment is often guided by resectability, but this may vary depending on surgical judgment and experience. Referral to a high-volume center should be considered.
The addition of postoperative chemotherapy improves overall survival, but the role of chemoradiation remains controversial.
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.
Palliative therapies can be considered in patients with any stage of disease. Refer to the Palliative Therapy section of this summary for more information.
Treatment Options for Resectable or Borderline Resectable Pancreatic Cancer
Treatment options for resectable or borderline resectable pancreatic cancer include the following:
Neoadjuvant therapy is chemotherapy with or without chemoradiation therapy given before surgery. The role of neoadjuvant therapy has been evaluated in retrospective studies (Surveillance, Epidemiology, and End Results [SEER] database and National Cancer Database) and is recommended by multiple consensus guidelines for the management of patients with borderline resectable pancreatic cancer. It is being evaluated in resectable pancreatic cancer, however, large randomized clinical trials have not yet been completed.[9,10,11]
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. Thus, systemic therapy is also recommended for treatment.[12,13,14][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%.[15,16,17,18,19] 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).
Historically, multiple randomized trials have established that adjuvant gemcitabine monotherapy  or adjuvant 5-FU monotherapy  improve overall survival (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.
For patients with good performance status, adjuvant FOLFIRINOX (oxaliplatin, leucovorin, irinotecan, and 5-FU) chemotherapy or the combination of gemcitabine and capecitabine should be considered. However, for older patients or patients with marginal performance status, adjuvant gemcitabine or 5-FU monotherapy can be considered. In Asia, S-1 (tegafur, gimeracil, and oteracil potassium) is an appropriate alternative to gemcitabine-based therapies.
Evidence (postoperative chemotherapy):
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.[4,5,6,7,8]
Evidence (postoperative chemoradiation therapy):
Several phase III trials examined the potential 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 therapy after completion of a full course of gemcitabine with or without erlotinib has closed and results are pending.
Additional trials are still warranted to determine more effective systemic therapy for this disease.
Treatment Options Under Clinical Evaluation for Resectable or Borderline Resectable 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 Locally Advanced Pancreatic Cancer
While locally advanced and metastatic pancreatic cancer are both incurable, the natural history of locally advanced disease may be different than it is for metastatic disease. An autopsy series demonstrated that 30% of patients presenting with locally advanced disease died without evidence of distant metastases.[Level of evidence: 1iiA] Therefore, investigators have struggled with the question of whether chemoradiation therapy for patients presenting with locally advanced disease is warranted.
Treatment options for locally advanced pancreatic cancer include the following:
Chemotherapy with or without targeted therapy
Chemotherapy is the primary treatment modality for patients with locally advanced pancreatic cancers and uses the same regimens as those used to treat patients with metastatic disease.
The role of chemoradiation in locally advanced pancreatic cancer remains controversial. Table 7 summarizes phase III randomized studies of chemoradiation for locally advanced pancreatic cancer.
Evidence (chemoradiation therapy):
Three trials attempted to look at combined modality therapy versus radiation therapy alone.[14,15,16] 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 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.
Patients with locally advanced pancreatic cancer have tumors that are technically unresectable because of local vessel impingement or invasion by tumor. However, with the combination of chemotherapy and chemoradiation therapy, some patients may become candidates for radical pancreatic resection.
A significant proportion (approximately one-third) of patients with pancreatic cancer will present with locally advanced disease. Patients may benefit from palliation of biliary obstruction by endoscopic, surgical, or radiological means.
Treatment Options Under Clinical Evaluation for Locally Advanced Pancreatic Cancer
Treatment Options for Metastatic or Recurrent Pancreatic Cancer
Treatment options for metastatic or recurrent pancreatic cancer include 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 been shown to prolong outcomes compared with single-agent gemcitabine.[1,2,3]
Evidence (single-agent chemotherapy):
Evidence (multiagent chemotherapy):
Evidence (second-line chemotherapy):
Special considerations for patients with germlineBRCA1/BRCA2mutations
In patients with pancreatic adenocarcinoma, 4% to 8% have germline mutations in BRCA1 or BRCA2.[9,10]BRCA1/BRCA2 encode for proteins in the homologous repair pathway and DNA double-stranded break repair, and thus may be more sensitive to further DNA damage. Pancreatic tumors with BRCA1/BRCA2 mutations demonstrate improved responses to platinum-based therapies. Poly (ADP-ribose) polymerase (PARP) inhibition has been posited to act synergistically with BRCA1/BRCA2 mutations by inhibiting single-stranded break repair. Several PARP inhibitors have been approved for treatment of patients with BRCA1/BRCA2 mutated advanced ovarian and breast cancers, and are actively being studied for the management of patients with BRCA1/BRCA2 mutated pancreatic adenocarcinoma.
Olaparib (a PARP inhibitor) maintenance therapy can be considered for patients with germline BRCA1/BRCA2 mutations and metastatic pancreatic adenocarcinoma who have responded to first-line platinum-based therapy for more than 4 months.
Treatment Options Under Clinical Evaluation for Metastatic or Recurrent Pancreatic Cancer
Palliative therapy options for patients with pancreatic cancer include the following:
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.
Editorial changes were made to this summary.
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 adult 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 reviewer for Pancreatic Cancer Treatment (Adult) is:
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 (Adult). 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: 2020-05-15
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