Pancreatic Cancer Guidelines 

Updated: Dec 23, 2016
  • Author: Lewis J Rose, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Pancreatic Cancer Screening

Guidelines on pancreatic cancer screening have been issued by the following organizations:

  • U.S. Preventive Services Task Force (USPSTF)
  • American Academy of Family Physicians (AAFP)
  • International Cancer of the Pancreas Screening (CAPS) Consortium

The USPSTF found no evidence that screening for pancreatic cancer is effective in reducing mortality and recommends against routine screening in asymptomatic adults using abdominal palpation, ultrasonography, or serologic markers. [1] The AAFP guidelines concur with the USPSTF recommendation. [2]

The USPSTF did not review the effectiveness of screening individuals at high risk for pancreatic cancer.

In 2012, the International CAPS Consortium, a panel of 49 multidisciplinary experts, released consensus guidelines for pancreatic cancer screening. While also recommending against routine screening in the general population, the members recommended screening with endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) for the following high-risk groups [3] :

  • Individuals with two or more blood relatives, and at least one first-degree relative, with pancreatic cancer
  • Carriers of p16, PALB2, or BRCA2 mutations with a first-degree relative with pancreatic cancer
  • All individuals with Peutz-Jeghers syndrome
  • Individuals with Lynch syndrome and a first-degree relative with pancreatic cancer

(In practice, however, many carriers of p16, PALB2, or BRCA2 mutations opt for screening even if they do not have a relative with the disease.)

The panel agreed that to be considered successful, screening should detect and lead to treatment of T1N0M0 margin-negative pancreatic cancer and high-grade dysplastic precursor lesions (pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm). However, the group did not reach consensus on the optimal management of detected lesions, the age to begin screening, or screening intervals.

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Use of Tumor Markers in Pancreatic Cancer

In its 2006 update, the American Society of Clinical Oncology (ASCO) expanded the scope of the guidelines for use of tumor markers in gastrointestinal cancer to include CA 19-9 as a marker for pancreatic cancer. The recommendations for evaluation of CA 19-9 levels are as follows [5] :

  • CA 19-9 is least sensitive for small, early-stage pancreatic carcinomas and thus is not effective for the early detection of pancreatic cancer or as a screening tool
  • Use of CA 19-9 levels alone is not recommended for use in determining operability
  • Rising levels of CA 19-9 postoperatively may predict recurrent disease, but confirmation with imaging studies and/or biopsy is required.
  • CA 19-9 can be measured at the start of treatment for locally advanced metastatic disease and every 1-3 months during active treatment; elevation of levels in serial determinations may be an indication of progressive disease, but confirmation with other studies is required
  • 5-10% of patients lack the enzyme necessary to produce CA 19-9; in these patients with low or absent titer of CA 19-9, monitoring disease with this tumor marker will not be possible

Both the European Society of Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN) guidelines for diagnosis and treatment of pancreatic cancer recommend the measurement of serum CA 19-9 levels after surgery and before adjuvant therapy to guide treatment and follow up. [6, 7]

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Diabetes Mellitus as Risk Factor for Pancreatic Cancer

The NCCN guideline for pancreatic adenocarcinoma acknowledges long-standing diabetes mellitus as a risk factor for pancreatic cancer. The guideline also notes an association between sudden onset of type 2 diabetes mellitus in an adult older than 50 years and a new diagnosis of pancreatic cancer. NCCN guidelines states that clinicians should consider pancreatic cancer in patients with diabetes who have unusual symptoms such as continuous weight loss and abdominal problems. [7]

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Diagnosis

The European Society of Medical Oncology (ESMO) recommendations for diagnosis of pancreatic cancer include the following [6] :

  • Abdominal ultrasound for the initial examination
  • Endoscopic ultrasound (EUS), contrast-enhanced multi-detector computed tomography (MD-CT) and MRI combined with magnetic resonance cholangiopancreatography (MRCP) for additional evaluation
  • Endoscopic retrograde cholangiopancreatography (ERCP) only to relieve bile duct obstruction
  • ERCP and biliary stenting should be performed only if surgery is not possible
  • Positron emission tomography (PET) is not recommended for diagnosis
  • Biopsy is recommended only when imaging results of a pancreatic lesion are ambiguous; EUS-guided biopsy is preferred and percutaneous sampling should be avoided
  • Metastatic lesions can be biopsied percutaneously under ultrasound or CT guidance or during EUS

The NCCN guidelines recommend that diagnostic management involve multidisciplinary consultation and be done at a high-volume center with appropriate high-quality imaging that includes specialized pancreatic CT or MRI. Additional recommendations include the following [7] :

  • Patients should undergo triphasic multidetector CT with thin-slice, cross-sectional imaging; the difference in contrast enhancement is highest during the second phase, so a triphasic approach enables a clear distinction between a hypodense lesion and the rest of the pancreas
  • Contrast MRI is acceptable when CT is not possible, but MRI has not been shown to be more effective or accurate in diagnosing and staging pancreatic cancer; however, MRI can be a useful adjunct in diagnosing high-risk patients
  • PET/CT is not a substitute for high-quality contrast-enhanced CT, but may be considered after CT to detect small metastatic deposits
  • EUS is complementary to CT, particularly if a CT scan shows no lesions or there is possible involvement of blood vessels or lymph nodes
  • EUS-guided fine-needle aspiration (FNA) offers better safety and lower risk of peritoneal seeding than CT-guided FNA

The NCCN recommends staging laparoscopy in patients who meet any of the following criteria [7] :

  • CA 19-9 level > 150 U/mL
  • Low-volume ascites
  • Tumor in the body of the pancreas
  • Borderline resectable tumor
  • Tumor size > 3 cm
  • Common bile duct lymphadenopathy

The NCCN guidelines aside, staging laparoscopy may not be absolutely necessary in a patient with a borderline resectable tumor, if the treatment team plans to use neoadjuvant chemotherapy to shrink the tumor before resection.

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Localized Disease Management

Defining Resectability Status

The National Comprehensive Cancer Network (NCCN) has adopted criteria for defining resectability status, which the European Society of Medical Oncology (ESMO) also recommends. For tumors to be considered localized and clearly resectable, they must demonstrate the following [7] :

  • No distant metastases
  • No evidence of superior mesenteric vein (SMV) or portal vein (PV) distortion
  • Clear fat planes around the celiac axis, hepatic artery and superior mesenteric artery (SMA)

Borderline resectable tumors include the following:

  • No distant metastases Involvement of the SMV or PV with distortion or narrowing or occlusion of the vein with vessel proximal and distal, allowing for resection and replacement
  • Gastroduodenal artery encasement up to the hepatic artery, without extension to the celiac axis.
  • Tumor abutment to the SMA <180° of the circumference of the vessel wall.

The American Society of Clinical Oncology (ASCO) recommends primary surgical resection of the primary tumor and regional lymph nodes for all patients meeting the following criteria [8] :

  • No clinical evidence for metastatic disease
  • Performance status and comorbidity profile that can withstand major abdominal surgery
  • No radiographic interface between primary tumor and mesenteric vasculature
  • CA 19-9 level suggestive of localized disease

Treatment

In 2016, the American Society of Clinical Oncology released guidelines for the treatment of potentially curable pancreatic cancer which included the following key recommendations [8] :

  • After histopathologic confirmation of the diagnosis, a multiphase CT scan of the abdomen and pelvis using a pancreatic protocol or MRI  should be performed to gauge the anatomic relations of the tumor to other internal structures and to evaluate patients for the presence of intra-abdominal metastases.
  • Supplemental studies may include endoscopic ultrasound, diagnostic laparoscopy, or both.
  • Performance status, symptom burden, and comorbidity profile should be carefully evaluated at baseline, and the goals of care should be shaped by patient preferences before arriving at a multidisciplinary treatment plan.
  • Patients should be informed about any relevant clinical trials for experimental or palliative care.

Preoperative therapy is recommended for patients who meet any of the following criteria [8] :

  • Radiographic findings are suspicious but not diagnostic for extrapancreatic disease
  • Poor performance status or comorbidities not conducive to major abdominal surgery if it is thought that their status might be reversed after treatment
  • A radiographic interface between the primary tumor and mesenteric vasculaturea radiographic interface that does not meet appropriate criteria for primary resection
  • CA 19-9 level (in absence of jaundice) suggestive of disseminated disease

After preoperative treatment, patients should be restaged before making plans for surgery.

Post-operative recommendations include the following [8] :

  • In the absence of medical or surgical contraindications, patients who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy with either gemcitabine or fluorouracil plus folinic acid initiated within 8 weeks of surgical resection.
  • Patients who have not received preoperative therapy and who have microscopically positive margins or node-positive disease after 4 to 6 months of adjuvant chemotherapy should be offered adjuvant chemoradiation.
  • For patients who underwent peroperative therapy, although evidence supporting the duration of post-operative therapy is weak, the panel recommends that patients receive a total of 6 months of adjuvant therapy, including time spent on the preoperative regimen.
  • Adjuvant combination chemotherapy regimens are not recommended outside of a clinical trial. 
  • Patients  should receive ongoing supportive care for symptom burden that may result from the operation and (preoperative and/or adjuvant) chemotherapy
  • Patients who have completed treatment and have no evidence of disease should be monitored for recovery of treatment-related toxicities and recurrence. Visits may be offered at 3- to 6-month intervals but the role of serial cross-sectional imaging, the extent to which surveillance intervals should be prolonged over time, and the duration of recommended surveillance are all undefined 

The European Society of Medical Oncology (ESMO) recommendations for treatment of pancreatic cancer include the following [6] :

  • Radical surgery is the only curative treatment and is mainly suitable for patients with stage I and some patients with stage II
  • In elderly patients (>75 years old), comorbidity can be a reason to abstain from resection; the risk of perioperative mortality in patients undergoing pancreatic resection can be estimated using a  surgical outcomes analysis and research (SOAR) pancreatectomy score

ESMO recommendations for treatment of resectable disease are as follows [6] :

  • Pancreatoduodenectomy (Whipple procedure) is the treatment of choice for tumors of the pancreatic head
  • For tumors in the body or tail of the pancreas, distal pancreatectomy, including the resection of the body and the tail of the pancreas and the spleen, is usually performed
  • No evidence exists that extended lymphadenectomy is beneficial; standard lymphadenectomy should involve the removal of ≥15 lymph nodes to allow adequate pathologic staging
  • Postoperative gemcitabine or 5-fluorouracil (5-FU) chemotherapy is recommended
  • No chemoradiation should be given to patients after surgery except in clinical trials

For patients with borderline resectable lesions, ESMO recommends participation in clinical trials wherever possible. Otherwise, preoperativechemotherapy (gemcitabine or FOLFIRINOX) followed by chemoradiation and then surgery appears to be the best option.

NCCN treatment guidelines concur that resection is the only potentially curative treatment for pancreatic cancer, but note that 80% of patients present with uncurablly advanced disease. Key recommendations for treatment of localized disease include [7] :

  • Decisions about treatment and resectability should involve input from a multidisciplinary group of specialists
  • Selection of patients for surgery should be based on the probability of cure, as determined by resection margins; other factors include comorbidities, overall performance status, and age
  • Post-operative adjuvant therapy improves outcomes but no definite standard has been set. Options for patients that did no receive preoperative neoadjuvant therapy include clinical trials (preferred), chemotherapy or chemoradiation. When chemotherapy alone is chosen, gemcitabine is preferred over 5-FU/leucovorin; capecitabine should only be considered when other options are contraindicated.
  • For patients who received neoadjuvant therapy, post-operative therapy options are dependant on response to neoadjuvant therapy and other clinical considerations. 

Like ESMO, NCCN recommends considering preoperative neoadjuvant thereapy for patients with borderline resectable tumors.However, no form of neoadjuvant therapy in pancreatic carcinoma should be regarded as standard; this remains an area for clinical trial study. [7]

 

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Locally Advanced Disease

The 2016 ASCO guidelines include the following recommendations for treatment of locally advanced, unresectable disease [9] :

  • Multiphase  CT scans to assess disease extent in the chest, abdomen, and pelvis. Other staging studies should be performed only as dictated by symptoms 
  • Patients should also be assessed for baseline performance status, symptom burden, and comorbidities, and clinicians again need to discuss the goals of treatment in collaboration with a multidisciplinary team shaped by patient preferences.
  • Patients should  be informed about any relevant clinical trials for which they might be eligible.
  • Initial treatment should include some form of combination regimen for individuals who have a performance status of 0 or 1, who have a favorable comorbidity profile, and who want to and are able to undergo an aggressive medical regimen.
  • There is no clear evidence to support one regimen over another and therapy may be offered on the basis of extrapolation from data derived from studies in the metastatic setting.
  • Chemoradiotherapy (CRT) or stereotactic body radiotherapy (SBRT) may be offered to patients with local progression but no metastases, provided they have a performance status of 2 or less and a favorable comorbidity profile.
  • CRT or SBRT may be offered to patients who have responded to an initial 6 months of chemotherapy or have stable disease, have developed unacceptable chemotherapy-related toxicities, or have a decline in performance status as a consequences of chemotherapy toxicity
  • If patients respond or their disease has at least stabilized after 6 months of induction chemotherapy, CRT or SBRT may be offered as an alternative to continuing chemotherapy alone
  • SBRT may be offered even though evidence supporting SBRT is not robust.

On completion of treatment, patients whose disease has stabilized or who have no disease progression should have a follow-up visit every 2 to 3 months in which they undergo liver and renal function tests. They should also be tested for CA 19-9 levels and undergo CT scans at least every 3 months in the first 2 years after completion of treatment, and every 6 months if disease remains stable. [9]

Patients who do not benefit from first-line treatment recommendations and who progress despite clinicians' best efforts should be treated according to the ASCO guidelines for the treatment of metastatic pancreatic cancer. [9]

In patients with locally advanced (unresectable) tumors, ESMO recommendations are as follows [6] :

  • The standard of care is 6 months of gemcitabine
  • Chemoradiation may have a minor role, but no regimen other than the combination of capecitabine and radiotherapy can be recommended

NCCN treatment guidelines include the following recommendations [7] :

  • FOLFIRINOX or gemcitabine plus nab-paclitaxel is a first-line treatment for patients who have good performance status
  • Gemcitabine monotherapy, or palliative therapy and best supportive care, is recommended for locally advanced unresectable disease in symptomatic patients with poor performance status
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Metastatic Disease

The 2016 ASCO guidelines include the following recommendations for treatment of metastatic disease [9] :

  • First-line treatment for metastatic pancreatic cancer is the FOLFIRINOX regimen consisting of leucovorin, fluorouracil, irinotecan, and oxaliplatin.
  • The FOLFIRINOX regimen can be offered to anyone with a performance status of 0 or 1 and a favorable comorbidity profile who wants to and is able to withstand an aggressive medical regimen. Alternatively, patients can be treated with gemcitabine plus nanoparticle albumin-bound (NAB)-paclitaxel.
  • For those with more advanced disease (performance status, 2) or who cannot tolerate a more aggressive regimen but who still wish to received cancer-directed therapy, gemcitabine can be given alone or together with either capecitabine or erlotinib.
  • For patients with a performance status 3 or more with poorly controlled comorbid conditions despite ongoing active medical care, r emphasis should be on optimizing supportive care measures 
  • For patients who experience either disease progression on first-line therapy or intolerable toxicity, gemcitabine plus NAB-paclitaxel may be used as second-line therapy,
  • If patients received gemcitabine plus NAB-paclitaxel as first-line treatment, fluorouracil plus oxaliplatin, irinotecan, or nanoliposomal irinotecan can be given as second-line therapy, provided patients want and can tolerate aggressive medical treatment
  • For those who cannot tolerate aggressive therapy, clinicians can offer either gemcitabine or fluorouracil as a second-line option.
  • If patients are on cancer-directed therapy, they should undergo CT scan to assess first response to treatment 2 to 3 months after treatment initiation.
  • Patients should be offered aggressive treatment to control pain and other symptoms related to the cancer or the treatment

ASCO found no data to establish how long cancer-directed therapy should continue or whether a third-line treatment should be used. 

For patients with advanced/metastatic disease, ESMO recommendations are as follows:

  • For biliary stenting, the endoscopic method is safer than percutaneous insertion and is as successful as surgical hepatojejunostomy
  • Pain control is mandatory and frequently requires consultation with a pain specialist
  • In patients with Eastern Cooperative Oncology Group (ECOG) performance status 3/4, with significant morbidities and a very short life expectancy, only symptomatic treatment can be considered
  • In very selected patients with performance status 2 due to heavy tumor load, gemcitabine and nab-paclitaxel can be considered for best chance of response
  • In patients with performance status 2 and/or bilirubin level higher than 1.5 times the upper limit of normal, monotherapy with gemcitabine should be considered
  • In patients with performance status 0 or 1 and bilirubin level less than 1.5 times the upper limit of normal, combination chemotherapy with either FOLFIRINOX or the combination of gemcitabine and nab-paclitaxel should be considered
  • The efficacy of treatment has to be evaluated every 2 months with a comparative CT scan

NCCN treatment guidelines include the following recommendations [7] :

  • Decisions about treatment and resectability should involve input from a multidisciplinary group of specialists
  • Selection of patients for surgery should be based on the probability of cure, as determined by resection margins; other factors include comorbidities, overall performance status, and age
  • FOLFIRINOX or gemcitabine plus nab-paclitaxel is recommended as a first-line treatment for patients with metastatic or locally advanced unresectable disease who have good performance status
  • Gemcitabine monotherapy, or palliative therapy and best supportive care, is recommended for metastatic or locally advanced unresectable disease in symptomatic patients with poor performance status

No form of neoadjuvant therapy in pancreatic carcinoma should be regarded as standard; this remains an area for clinical trial study

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Palliative Care

The National Comprehensive Cancer Network (NCCN) guidelines for palliative care include the following [7] :

  • Endoscopic biliary metal stent is preferred for biliary obstruction
  • Enteral stent for gastric outlet obstruction
  • Consider radiation therapy with or without chemotherapy to palliate pain
  • Pancreatic enzyme replacement for pancreatic insufficiency
  • Low-molecular-weight heparin is preferred over warfarin for management of thromboembolic disease

The European Society of Medical Oncology (ESMO) guidelines for palliative care recommend morphine as the drug of choice for pain management. Parenteral or transdermal administration may be considered for patients with swallowing impairment or gastrointestinal obstructions. For patients with poor tolerance for opioids, percutaneous celiacoplexus blockade is suggested. [6]

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Nutrition and Physical Activity

The American Cancer Society (ACS) has issued guidelines for cancer prevention that focus on recommendations for individual choices regarding diet and physical activity patterns. Because individual choices are impacted by community measures that can either facilitate or create barriers to healthy behaviors, recommendations for community action are also included.

The ACS guidelines include recommendations for maintaining a healthy weight, adopting a physically active lifestyle, consuming a healthy diet, and limiting alcohol consumption.

The guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion.

The ACS guidelines include the following specific dietary recommendations for patients with pancreatic cancer [4] :

  • Supplementation with omega-3 fatty acids
  • Pancreatic enzyme replacement therapy, along with diet modification, to manage disease symptoms and treatment side effects
  • Consultation and close follow-up with a registered dietitian for an individualized dietary prescription
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