Pancreatic cancer in adults: diagnosis and management

This guideline covers diagnosing and managing pancreatic cancer in adults aged 18 and over. It aims to improve care by ensuring quicker and more accurate diagnosis, and by specifying the most effective treatments for people depending on how advanced their cancer is.

# Recommendations
People have the right to be involved in discussions and make informed decisions about their care, as described in NICE's information on making decisions about your care.
Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off-label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.

# Diagnosis

## People with obstructive jaundice
For people with obstructive jaundice and suspected pancreatic cancer, offer a pancreatic protocol CT scan before draining the bile duct.
If the diagnosis is still unclear, offer fluorodeoxyglucose-positron emission tomography/CT (FDGPET/CT) and/or endoscopic ultrasound (EUS) with EUSguided tissue sampling.
Take a biliary brushing for cytology if:
endoscopic retrograde cholangiopancreatography (ERCP) is being used to relieve the biliary obstruction and
there is no tissue diagnosis.

## People without jaundice who have pancreatic abnormalities on imaging
Offer a pancreatic protocol CT scan to people with pancreatic abnormalities but no jaundice.
If the diagnosis is still unclear, offer FDGPET/CT and/or EUS with EUSguided tissue sampling.
If cytological or histological samples are needed, offer EUS with EUSguided tissue sampling.

## People with pancreatic cysts
Offer a pancreatic protocol CT scan or magnetic resonance cholangiopancreatography (MRI/MRCP) to people with pancreatic cysts. If more information is needed after one of these tests, offer the other one.
Refer people with any of these high-risk features for resection:
-bstructive jaundice with cystic lesions in the head of the pancreas
enhancing solid component in the cyst
a main pancreatic duct that is 10 mm diameter or larger.
Offer EUS after CT and MRI/MRCP if more information on the likelihood of malignancy is needed, or if it is not clear whether surgery is needed.
Consider fine-needle aspiration during EUS if more information on the likelihood of malignancy is needed.
When using fine-needle aspiration, perform carcinoembryonic antigen (CEA) assay in addition to cytology if there is sufficient sample.
For people with cysts that are thought to be malignant, follow the recommendations on staging.

## People with inherited high risk of pancreatic cancer
Ask people with pancreatic cancer if any of their first-degree relatives has had it. Address any concerns the person has about inherited risk.
Offer surveillance for pancreatic cancer to people with:
hereditary pancreatitis and a PRSS1 mutation
BRCA1, BRCA2, PALB2 or CDKN2A (p16) mutations, and one or more first-degree relatives with pancreatic cancer
PeutzJeghers syndrome.
Consider surveillance for pancreatic cancer for people with:
-r more first-degree relatives with pancreatic cancer, across 2 or more generations
Lynch syndrome (mismatch repair gene  mutations) and any first-degree relatives with pancreatic cancer.
Consider an MRI/MRCP or EUS for pancreatic cancer surveillance in people without hereditary pancreatitis.
Consider a pancreatic protocol CT scan for pancreatic cancer surveillance in people with hereditary pancreatitis and a PRSS1 mutation.
Do not offer EUS to detect pancreatic cancer in people with hereditary pancreatitis.

# Specialist pancreatic multidisciplinary teams
A specialist pancreatic cancer multidisciplinary team should decide what care is needed, and involve the person with suspected or confirmed pancreatic cancer in the decision. Care should be delivered in partnership with local cancer units.

# Staging
For people with newly diagnosed pancreatic cancer who have not had a pancreatic protocol CT scan, offer a pancreatic protocol CT scan that includes the chest, abdomen and pelvis.
Offer fluorodeoxyglucose-positron emission tomography/CT (FDG-PET/CT) to people with localised disease on CT who will be having cancer treatment (surgery, radiotherapy or systemic therapy).
If more information is needed to decide the person's clinical management, consider one or more of the following:
MRI, for suspected liver metastases
endoscopic ultrasound, if more information is needed for tumour and node staging
laparoscopy with laparoscopic ultrasound, for suspected small-volume peritoneal and/or liver metastases if resectional surgery is a possibility. See recommendation 1.2.1 on how care should be agreed and delivered.

# Psychological support
Throughout the person's pancreatic cancer care pathway, specifically assess the psychological impact of:
fatigue
pain
gastrointestinal symptoms (including changes to appetite)
nutrition
anxiety
depression.
Provide people and their family members or carers (as appropriate) with information and support to help them manage the psychological impact of pancreatic cancer on their lives and daily activities. This should be:
available on an ongoing basis
relevant to the stage of the person's condition
tailored to the person's needs.
For more guidance on providing information and support, see the NICE guideline on patient experience in adult NHS services.

# Pain management
Consider EUS-guided or image-guided percutaneous neurolytic coeliac plexus block to manage pain for people with pancreatic cancer who:
have uncontrolled pancreatic pain or
are experiencing unacceptable opioid adverse effects or
are receiving escalating doses of analgesics.
Do not offer thoracic splanchnicectomy to people with pancreatic cancer.

# Nutritional management
Offer enteric-coated pancreatin for people with unresectable pancreatic cancer.
Consider enteric-coated pancreatin before and after pancreatic cancer resection.
Do not use fish oils as a nutritional intervention to manage weight loss in people with unresectable pancreatic cancer.
For people who have had pancreatoduodenectomy and who have a functioning gut, offer early enteral nutrition (including oral and tube feeding) rather than parenteral nutrition.
For more guidance on nutrition support, see the NICE guideline on nutrition support in adults.

# Relieving biliary and duodenal obstruction

## Biliary obstruction
Offer resectional surgery rather than preoperative biliary drainage to people who:
have resectable pancreatic cancer and obstructive jaundice and
are well enough for the procedure and
are not enrolled in a clinical trial that requires preoperative biliary drainage.
During attempted resection for pancreatic cancer, consider surgical biliary bypass if the cancer is found to be unresectable.
If biliary drainage is needed in a person who has resectable pancreatic cancer and obstructive jaundice and is not yet fit enough for resectional surgery, offer endoscopically placed selfexpanding metal stents.
For people with suspected pancreatic cancer who may need their stent removed later on, consider endoscopically placed self-expanding fully covered metal stents.
Offer endoscopically placed self-expanding metal stents rather than surgical biliary bypass to people with unresectable pancreatic cancer.

## Duodenal obstruction
During attempted resection for head of pancreas cancer, consider prophylactic gastrojejunostomy if the cancer is found to be unresectable.
If possible, relieve symptomatic duodenal obstruction caused by unresectable pancreatic cancer.
When deciding between gastrojejunostomy and duodenal stent placement, consider gastrojejunostomy for people with a more favourable prognosis.

# Managing resectable and borderline resectable pancreatic cancer

## Neoadjuvant therapy
Only consider neoadjuvant therapy for people with borderline resectable pancreatic cancer as part of a clinical trial.
Only consider neoadjuvant therapy for people with resectable pancreatic cancer as part of a clinical trial.

## Surgery
For people having surgery for head of pancreas cancer, consider pylorus-preserving resection if the tumour can be adequately resected.
Consider standard lymphadenectomy, rather than extended lymphadenectomy for people having head of pancreas resection.

## Adjuvant treatment
Give people time to recover from surgery before starting adjuvant therapy. Start adjuvant therapy as soon as they are well enough to tolerate all 6 cycles.
Offer adjuvant gemcitabine plus capecitabine to people who have had sufficient time to recover after pancreatic cancer resection.In February 2018, this was an off-label use. See NICE's information on prescribing medicines.
Consider adjuvant gemcitabine for people who are not well enough to tolerate combination chemotherapy.In February 2018, this was an off-label use. See NICE's information on prescribing medicines.

## Follow-up for resected pancreatic cancer
For people who have had resection, offer ongoing specialist assessment and care to identify and manage any problems resulting from surgery.
For people who have new, unexplained or unresolved symptoms after treatment, provide access to specialist investigation and support services.

# Managing unresectable pancreatic cancer

## Locally advanced pancreatic cancer
Offer systemic combination chemotherapy to people with locally advanced pancreatic cancer who are well enough to tolerate it.
Consider gemcitabine for people with locally advanced pancreatic cancer who are not well enough to tolerate combination chemotherapy.
When using chemoradiotherapy, consider capecitabine as the radiosensitiser.

## Metastatic pancreatic cancer
Offer FOLFIRINOX to people with metastatic pancreatic cancer and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.In February 2018, this was an off-label use. See NICE's information on prescribing medicines.
Consider gemcitabine combination therapy for people who are not well enough to tolerate FOLFIRINOX. For guidance on combination therapy with gemcitabine and nabpaclitaxel, see NICE's  technology appraisal guidance on paclitaxel as albumin-bound nanoparticles with gemcitabine for untreated metastatic pancreatic cancer.In February 2018, this was an off-label use of many gemcitabine combination therapies. See NICE's information on prescribing medicines.
Offer gemcitabine to people who are not well enough to tolerate combination chemotherapy.
Consider oxaliplatin-based chemotherapy as second-line treatment for people who have not had first-line oxaliplatin.In February 2018, this was an off-label use. See NICE's information on prescribing medicines.
Consider gemcitabine-based chemotherapy as second-line treatment for people whose cancer has progressed after first-line FOLFIRINOX.In February 2018, this was an off-label use. See NICE's information on prescribing medicines.
For recommendations on venous thromboembolism prophylaxis for people with pancreatic cancer, see the NICE guideline on reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism in over 16s.

## Genomic biomarker-based treatment
The point at which to use genomic biomarker-based therapy in solid tumour treatment pathways is uncertain. See our topic page on genomic biomarker-based cancer treatments.

# Terms used in this guideline

## Standard lymphadenectomy
As defined by Tol et al. (2014) Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS)Tol et al. (2014) Definition of a standard lymphadenectomy in surgery for pancreatic ductal adenocarcinoma: a consensus statement by the International Study Group on Pancreatic Surgery (ISGPS). Surgery 156(3): 591600# Context
Pancreatic cancer is the fifth most common cause of cancer death in the UK, with an annual incidence of nearly 9,600. On average, 23 people die each day from the disease. The UK has one of the worst survival rates in Europe, with average life expectancy on diagnosis just 4 to 6 months and a relative survival to 1 year of approximately 20%.
Only 3% of people survive for 5 years or longer. This figure has not improved much in over 40 years, and it is not yet clear how the more recent trend of increased surgery and adjuvant chemotherapy will affect survival.
Because of late diagnosis, only approximately 8% of people with pancreatic cancer are eligible for potentially curative surgery. However, people have up to a 30% chance of surviving 5 years if their tumour can be surgically removed and they have adjuvant chemotherapy.
The symptoms of pancreatic cancer are non-specific. One survey found that 40% of people diagnosed with pancreatic cancer in England had visited their GP 3 or more times before the diagnosis was made. Fifty per cent of people are diagnosed as an emergency in A&E. Even after diagnosis, there is evidence from the National Cancer Intelligence Network of wide variation in practice throughout England.
There are often delays in access to diagnosis and treatment (as highlighted in the NHS England Five Year Forward View), and this guideline will help to improve this.# Recommendations for research
The guideline committee has made the following recommendations for research. The committee's full set of research recommendations is detailed in the full guideline.

# Neoadjuvant therapy
Prospective randomised trials should be undertaken to compare preoperative (neoadjuvant) therapy with standard postoperative therapy in people with resectable pancreatic cancer.

## Why this is important
The survival rate of pancreatic cancer after surgical resection is very low, which suggests that most patients have metastatic disease at the time of surgery. In addition, complications of surgery may stop people from having adjuvant therapy. This makes neoadjuvant therapy an attractive option. However, the evidence for neoadjuvant therapy is limited and low quality. Using neoadjuvant therapy means delaying surgery, and it is possible that during this delay pancreatic cancer will progress and become unresectable in some people, negating any benefit of neoadjuvant therapy.
Research is needed to compare neoadjuvant treatments (which might be chemotherapy, radiotherapy or both) with surgery followed by adjuvant chemotherapy. The outcomes of interest are:
feasibility of delivering neoadjuvant treatment
feasibility of randomising patients
-bjective response rate of neoadjuvant therapy
R0 resection rate
surgical complications, length of hospital stay, mortality of surgery
delivery of planned treatment
disease-free survival and overall survival after surgery
quality of life, patient experience and patient-reported outcome measures.

# Cachexia interventions
A cohort study followed by phase 2 and 3 studies should be undertaken in people with pancreatic cancer and cachexia or pre-cachexia, to compare cachexia assessment methods and anti-cachexia interventions with standard care.

## Why this is important
Most people with advanced and metastatic pancreatic cancer also have cachexia. This causes severe reductions in their quality of life and is associated with reduced overall survival. Cachexia has 3 phases: precachexia, cachexia and refractory cachexia. The condition cannot be stopped by conventional nutritional support and leads to progressive functional impairment. Complete or partial reversal of cachexia would cause major improvements in quality of life, and potentially improve survival if people recover enough to have more effective cancer treatments. The outcomes of interest are:
prevention or reversal of cachexia
-verall survival
quality of life
pain relief
lean tissue mass
tolerance to treatment.

# Minimally invasive pancreatectomy
Prospective randomised trials should be undertaken to compare the effectiveness of minimally invasive pancreatectomy or pancreatoduodenectomy (laparoscopic or robotic) with open pancreatectomy or pancreatoduodenectomy in people with pancreatic cancer.

## Why this is important
Minimally invasive surgery is generally considered to be more acceptable to patients than open surgery. It has been introduced successfully for several other types of cancer and has been shown to improve quality of life. However, there is not enough evidence to determine whether minimally invasive surgery improves morbidity and mortality for people with pancreatic cancer, compared with open surgery. Prospective randomised trials are therefore needed in this area. The outcomes of interest are:
conversion rate to open surgery
R0 resection rate
lymph node yield
blood loss
duration of surgery
complications
need for critical care
length of hospital stay
time to return to normal activity
mortality of surgery
long-term survival after surgery
quality of life, patient experience and patient-reported outcome measures.

# Pain management
A randomised trial should be undertaken comparing early endoscopic ultrasound-guided neurolytic coeliac plexus (EUSguided NCP) interventions with ondemand EUSguided NCP interventions in people with unresectable pancreatic cancer.

## Why this is important
There is a limited number of randomised trials in this area, and the methods used to perform NCP intervention are heterogeneous. It is not clear if early NCP intervention is superior to ondemand NCP intervention in terms of the important outcomes for the patient and duration of effect of the procedure. Ondemand NCP intervention may benefit people with uncontrolled pain, people receiving escalating doses of analgesia, people experiencing unacceptable analgesic side effects, and others. However, people who receive early NCP intervention may not need ondemand NCP intervention later on. Further research should clarify if the timing of the intervention confers any advantage. The outcomes of interest are:
reduction in pain
patient experience (including nutritional status)
health-related quality of life
adverse events
analgesic use
survival.

# Psychological support needs
A qualitative study should be undertaken to evaluate information and support interventions to address psychological needs at different points in the care pathway for people with pancreatic cancer.

## Why this is important
People with pancreatic cancer often have unmet psychological support needs that impact on their quality of life. These can be related to anxiety and depression, and to the psychological impact of fatigue, pain, gastrointestinal symptoms (particularly changes to appetite) and nutritional status. There has been very little research into the information and support interventions that would meet these needs. Research would help identify effective information and support interventions that would improve quality of life for people with pancreatic cancer and their family members or carers. Outcomes of interest are:
quality of life
psychological wellbeing
ability to carry out normal activities
patient experience and patient-reported outcome measures.