Pancreatic Cancer Guidelines

Updated: Oct 02, 2020
  • Author: Tomislav Dragovich, MD, PhD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Guidelines

Guidelines Summary

Guidelines Contributor:  Lewis J Rose, MD Clinical Associate Professor of Medical Oncology, Division of Regional Cancer Care, Kimmel Cancer Center, Thomas Jefferson University Hospital; Consulting Staff, LRCRZ Associates

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
  • American Gastroenterological Association (AGA)

USPSTF recommendations

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. [90]  The AAFP guidelines concur with the USPSTF recommendation. [91]

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

International CAPS Consortium recommendations

The International CAPS Consortium, a panel of 49 multidisciplinary experts, released consensus guidelines for pancreatic cancer screening in 2012 and updated them in 2020. [92, 93] The consortium recommends screening for stage I pancreatic cancer and pancreatic cancer precursor lesions with high-grade dysplasia in the following high-risk groups [93] :

  • All patients with Peutz-Jeghers syndrome (carriers of a germline LKB1/STK11 gene mutation)
  • All carriers of a germline CDKN2A mutation
  •  Carriers of a germline BRCA2, BRCA1, PALB2, ATM, MLH1, MSH2, or MSH6 gene mutation with at least one affected first-degree blood relative
  • Individuals who have at least one first-degree relative with pancreatic cancer who in turn also has a first-degree relative with pancreatic cancer (familial pancreatic cancer kindred)

The recommended age at which to start surveillance varied by gene mutation status and family history, as follows [93] :

  • Familial pancreatic cancer kindred (without a known germline mutation) -  Start at age 50 or 55, or 10 years younger than the youngest affected blood relative
  • CDKN2A or Peutz-Jegher syndrome - Start at age 40
  • BRCA2,ATM, PALB2 BRCA1, MLH1/MSH2 - Start at age 45 or 50, or 10 years younger than the youngest affected blood relative

Recommended screening techniques are as follows [93] :

  • At baseline - Magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) plus endoscopic ultrasound (EUS) plus fasting blood glucose and/or HbA1c
  • During followup - Alternate MRI/MRCP and EUS; routinely test fasting blood glucose and/or HbA1c
  • As indicated -  Serum CA 19–9, if concerning features on imaging; EUS-FNA only for solid lesions of ≥5 mm, cystic lesions with worrisome features, or asymptomatic main pancreatic duct (MPD) strictures (with or without mass); CT only for solid lesions, regardless of size, or asymptomatic MPD strictures of unknown etiology (without mass)

The consortium recommends a screening interval of every 12 months in patients with no abnormalities, or only non-concerning abnormalities (eg, pancreatic cysts without worrisome features), and every 3 or 6 months in patients with abnormalities that are not suspicious for malignancy but are concerning; immediate surgical resection is indicated for abnormalities suspicious for malignancy. [93]

American Gastroenterological Association recommendations

In 2020, the AGA published a clinical practice guideline update containing best practice advice for identifying and screening patients at high risk for pancreatic cancer. The goal of screening is to detect resectable stage 1 pancreatic ductal adenocarcinoma, and high-risk precursor neoplasms such as intraductal papillary mucinous neoplasms (IPMNs) with high-grade dysplasia and some enlarged pancreatic intraepithelial neoplasias. [94]

The guideline recommends against screening average-risk individuals for pancreas cancer. The guideline recommends considering screening in patients determined to be at high risk, including first-degree relatives of patients with pancreas cancer with at least two affected genetically related relatives, and in patients with genetic syndromes associated with an increased risk of pancreas cancer, including all patients with the following [94] :

  • Peutz-Jeghers syndrome
  • Hereditary pancreatitis
  • CDKN2A gene mutation
  • One or more first-degree relatives with pancreas cancer with Lynch syndrome
  • Mutations in BRCA1, BRCA2, PALB2, and ATM genes

Further recommendations are as follows [94] :

  • Consider genetic testing and counseling for familial pancreas cancer relatives who are eligible for surveillance. A positive germline mutation is associated with an increased risk of neoplastic progression and may also lead to screening for other relevant associated cancers.
  • When possible, high-risk patients undergoing pancreas cancer screening should participate in a registry or be referred to a pancreas center of excellence.
  • Begin pancreas cancer screening in high-risk individuals at age 50, or 10 years younger than the initial age of familial onset. Initiate screening at age 40 in CKDN2A and PRSS1 mutation carriers with hereditary pancreatitis and at age 35 in patients with Peutz-Jeghers syndrome.
  • MRI and EUS in combination are the preferred screening modalities for pancreas cancer screening.
  • Screening intervals of 12 months should be considered when there are no concerning pancreas lesions, with shortened intervals and/or the performance of EUS in 6-12 months directed towards lesions determined to be low risk (by a multidisciplinary team). EUS evaluation within 3-6 months for indeterminate lesions and within 3 months for high-risk lesions, if surgical resection is not planned. New-onset diabetes in a high-risk patient should lead to additional diagnostic studies or change in surveillance interval.
  • Decisions regarding therapy directed towards abnormal findings detected during screening should be made by a dedicated multi-disciplinary team together with the high risk individual and their family.
  • Surgical resection should be performed at high volume centers.
  • Consider discontinuing pancreas cancer screening in high-risk individuals when they are more likely to die of causes unrelated to pancreas cancer, due to co-morbidity and/or are not candidates for pancreas resection.
  • The limitations and potential risks of pancreas cancer screening should be discussed with patients prior to initiating a screening program.

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 [44] :

  • 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. [63, 2]

Diabetes Mellitus as Risk Factor 

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. [2]

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Diagnosis

The European Society of Medical Oncology (ESMO) recommendations for diagnosis of pancreatic cancer include the following [63] :

  • 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 [2] :

  • 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.

  • If no mass is evident in the pancreas on CT protocol imaging, EUS is recommended before other evaluation options.

  • 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 [2] :

  • 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.

The NCCN guidelines recommend that clinicians consider germline testing in any patient diagnosed with pancreatic cancer and consider a molecular analysis of tumors in those with metastatic disease. The NCCN panel has also strongly recommended somatic profiling of tumor tissue. [2]

In patients diagnosed with metastatic pancreatic cancer, American Society of Clinical Oncology (ASCO) guidelines recommend the following as part of the initial assessment [95] :

  • Perform a multiphase CT scan of the chest, abdomen, and pelvis to assess the extent of disease. Perform other staging studies only as dictated by symptoms.
  • Evaluate the patient’s baseline performance status (PS), symptom burden, and comorbidity profile.
  • Discuss the goals of care (including an advance directive), patient preferences, and support systems.

Multidisciplinary collaboration to formulate treatment and care plans and disease management should be the standard of care.

Early testing for actionable genomic alterations is recommended to guide treatment decisions for patients who are likely to be potential candidates for additional treatment after first-line therapy. Both germline and somatic testing for the following are recommended:

  • Microsatellite instability (MSI)/mismatch repair deficiency (dMMR)
  • BRCA mutations with known significance
  • NTRK gene fusions
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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 [2] :

  • 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 [96] :

  • 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 [96] :

  • 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 [96] :

  • 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.

Postoperative recommendations include the following [96] :

  • 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 [63] :

  • 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 [63] :

  • 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 incurably advanced disease. Key recommendations for treatment of localized disease include the following [2] :

  • 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.

  • Postoperative adjuvant therapy improves outcomes but no definite standard has been set. Options for patients who did not 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 therapy for patients with resectable or borderline resectable tumors, but notes that "there is limited evidence to recommend specific neoadjuvant regimens off-study, and practices vary with regard to the use of chemotherapy and radiation." NCCN recommendations on neoadjuvant therapy in pancreatic carcinoma are as follows [2] :

  • Consult with a high-volume center when neoadjuvant therapy is being considered\.
  • If neoadjuvant therapy is recommended, treat at or coordinate through a high-volume center, when feasible. 
  • Participation in a clinical trial is encouraged.
  •  Subsequent chemoradiation is sometimes included.

Neoadjuvant regimen options include the following [2] :

  • FOLFIRINOX/modified FOLFIRINOX, with or without subsequent chemoradiation
  • Gemcitabine + albumin-bound paclitaxel, with or without subsequent chemoradiation
  • Gemcitabine + cisplatin (≥2–6 cycles) followed by chemoradiation (only for known BRCA1/2 mutations)

 

 

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Locally Advanced Disease

The 2016 ASCO guidelines include the following recommendations for treatment of locally advanced, unresectable disease [97] :

  • 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. [97]

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. [97]

In patients with locally advanced (unresectable) tumors, ESMO recommendations are as follows [63] :

  • 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 [2] :

  • FOLFIRINOX/modified 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 and Palliative Care

American Society of Clinical Oncology recommendations

For first-line treatment of metastatic pancreatic cancer, ASCO guidelines recommend FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) for patients who meet all of the following criteria [98, 95] :

Gemcitabine plus nab-paclitaxel is recommended for patients who meet all of the following criteria:

  • ECOG performance status  0-1
  • Relatively favorable comorbidity profile
  • Patient preference and a support system for relatively aggressive medical therapy 

Gemcitabine alone is recommended for patients who have either an ECOG performance status of 2 or a comorbidity profile that precludes more aggressive regimens and for patients who wish to pursue cancer-directed therapy. The addition of nab-paclitaxel or capecitabine or erlotinib to gemcitabine may be offered, with proactive dose and schedule adjustments to minimize toxicities.

In patients with an ECOG performance status of 3 or with poorly controlled comorbid conditions despite ongoing active medical care, cancer-directed therapy should be offered only on a case-by-case basis. Major emphasis should be on optimizing supportive care measures. 

Treatment options after first-line therapy:

  • In patients with tumors harboring NTRK fusions, treatment with larotrectinib or entrectinib is recommended.
  • The programmed death–1 immune checkpoint inhibitor pembrolizumab is recommended as second-line therapy for patients who have tested positive for mismatch repair-deficient or microsatellite instability-high tumors.
  • In patients who have a germline BRCA1 or BRCA2 mutation and who have received first-line platinum-based chemotherapy without disease progression for at least 16 weeks, options for continued treatment include chemotherapy or the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib.

Gemcitabine plus nab-paclitaxel may be offered as second-line therapy to patients who meet all of the following criteria:

  • First-line treatment with FOLFIRINOX
  • ECOG performance status 0-1
  • Relatively favorable comorbidity profile
  • Patient preference and a support system for aggressive medical therapy

Fluorouracil plus nanoliposomal irinotecan, or fluorouracil plus irinotecan when the former combination is unavailable, is preferred as a second-line therapy for patients who meet all of the following criteria:

  • First-line treatment with a gemcitabine-based regimen
  • ECOG performance status 0-1
  • Relatively favorable comorbidity profile
  • Patient preference and a support system for aggressive medical therapy
  • Access to chemotherapy port and infusion pump management services

Fluorouracil plus oxaliplatin may be considered as second-line therapy for patients who meet all of the following criteria:

  • First-line treatment with gemcitabine plus nab-paclitaxel
  • ECOG performance status 0-1
  • Relatively favorable comorbidity profile
  • Patient preference and a support system for aggressive medical therapy
  • Access to chemotherapy port and infusion pump management services

Gemcitabine or fluorouracil can be considered as second-line therapy for patients who have either an ECOG performance status of 2 or a comorbidity profile that precludes more aggressive regimens and who wish to pursue cancer-directed therapy (the addition of nab-paclitaxel to gemcitabine or nanoliposomal irinotecan to fluorouracil may be offered, with proactive dose and schedule adjustments to minimize toxicities).

No data are available to recommend third-line or further therapy with a cytotoxic agent. Clinical trial participation is encouraged.

Follow-up and surveillance

For patients on active cancer-directed therapy outside of a clinical trial, imaging to assess first response should be offered at 2 to 3 months from the initiation of therapy. Computed tomography scans with contrast are the preferred modality. Thereafter, clinical assessment, conducted frequently during visits for cancer-directed therapy, should supplant imaging assessment. Routine use of positron emission tomography scans is not recommended. CA19-9 is not considered an optimal substitute for imaging for the assessment of treatment response.

No data exist on the duration of cancer-directed therapy. An ongoing discussion of the goals of care and assessment of treatment response and tolerability should guide decisions to continue or to hold or terminate cancer-directed therapy.

European Society for Medical Oncology recommendations

For patients with advanced/metastatic disease, ESMO recommendations are as follows [63] :

  • 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 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

National Comprehensive Cancer Network recommendations

NCCN treatment guidelines include the following recommendations [2] :

  • 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/modified 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

Palliative Care

The NCCN guidelines for palliative care include the following [2] :

  • 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 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. [63]

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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 [99] :

  • 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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