Ali Stunt and Dr Ellie Cannon discuss the current state of care for people with pancreatic cancer and the expected impact of new recommendations from NICE
Read this article to learn more about:
- the current state of pancreatic cancer care in the UK
- diagnosing pancreatic cancer, including diagnostic tests and when to use them
- management options for pancreatic cancer including support needs, pain management, and nutritional needs.
Inequality of care and access to diagnosis has long been a problem in pancreatic cancer, with treatment delays experienced by many patients. Pancreatic cancer is the fifth largest cause of cancer death in the UK1 and it is set to become the fourth largest by 20262 as survival rates for other cancers continue to improve. The survival statistics for pancreatic cancer have not changed markedly in nearly 50 years.
From 2010 to 2015, the incidence of pancreatic cancer in the UK increased by 17%, 3–6 exceeding the World Health Organization’s Globocan7 project predictions for the year, and mortality8–10 increased by 13% over the same period. National Cancer Intelligence Network data for 201511 show that 44% of pancreatic cancer cases are diagnosed as emergency presentations. Of those patients diagnosed as an emergency, only 12% will survive 1 year.11
A patient’s chance of surviving a year is around three times greater if they are referred to a specialist from primary care (see Figure 1),11 but too few patients are diagnosed in this way. Patients diagnosed via emergency admission have much worse survival outcomes than those diagnosed following a GP referral.11
In February 2018, the CONCORD-3 study reported that the UK ranks 46th out of 57 countries surveyed for 5-year survival rates for pancreatic cancer.12 Pancreatic cancer continues to be diagnosed late and consequently more people are dying from the disease.
The All-Party Parliamentary Group on Pancreatic Cancer published a report in November 2017 following an inquiry into early diagnosis of pancreatic cancer.13 The report recommended increasing research funding, launching a Public Health England awareness campaign, increased GP support, and faster diagnostic pathways.
Problems with diagnosis
As with many other cancers, diagnosing pancreatic cancer before it has spread is critical to achieving long-term survival. In the early stages, pancreatic cancer has symptoms that are subtle, insidious, or nonspecific to pancreatic cancer, both for patients and GPs, which means that it is particularly difficult to detect and diagnose. Box 1 lists some of the most common symptoms of pancreatic cancer.
Box 1: Common symptoms of pancreatic cancer14
- Upper abdominal pain that radiates around the back
- Mid-back pain that may be eased by leaning forward
- Significant weight loss
- Pale, smelly stools
A UK study found that around one-third of patients with pancreatic cancer require three or more visits to their GP before they are referred to a specialist.15,16 The more GP visits the patient had to make, the longer their diagnosis was delayed; for patients with pancreatic cancer who visited their GP five times or more, their diagnosis was delayed on average by 93 days.15
In the UK, only 10–20% of patients with pancreatic cancer are diagnosed at a stage when curative surgery remains an option, largely due to late diagnosis (almost one-half of patients with pancreatic cancer are diagnosed via emergency admission11). Only 8% of patients go on to receive surgery.17 Delays in getting the patient to surgery can lead to an operable patient becoming inoperable.
Later diagnosis of pancreatic cancer also incurs a significant cost to the health service. Research shows that the average cost of an emergency admission where pancreatic cancer is the primary diagnosis is nearly £5000 in England, which is around three times the average cost per patient (about £1500), of all emergency hospital admissions combined.18
As the symptoms of pancreatic cancer can often be nonspecific, it is vital that when pancreatic cancer is suspected, GPs have adequate access to diagnostic tests. From 2004 to 2014, the use of imaging tests for the diagnosis of conditions such as cancer increased (in this period the volume of magnetic resonance imaging [MRI] scans increased by 220%, and computed tomography [CT] scans by 160%).19 However, some GPs consider that access to diagnostic testing is a barrier to early diagnosis of pancreatic cancer. In a survey of GPs, commissioned by Pancreatic Cancer Action, the majority stated that they found it difficult to access CT scans. The main difficulties they cited were a lack of direct access to CT scans and having to justify the need to request a scan.
In February 2018, NICE published NICE Guideline (NG) 85 on Pancreatic cancer in adults: diagnosis and management. It is hoped that publication of the guideline will lead to a reduction in variation of care, and a shorter time to diagnosis and treatment.
Surveillance for pancreatic cancer
People with hereditary pancreatitis have a 50-fold increased risk of pancreatic cancer.21
NICE Guideline 85 recommends that patients with pancreatic cancer should be asked if any of their first-degree relatives have had pancreatic cancer, and that any concerns they have about inherited risk are addressed.20
NICE Guideline 85 recommends surveillance for pancreatic cancer in people with the following genetic/hereditary conditions:20
- hereditary pancreatitis and a PRSS1 mutation
- BRCA1, BRCA2, PALB2, or CDKN2A (p16) mutations, and one or more first-degree relatives with pancreatic cancer
- Peutz–Jeghers syndrome.
Approximately 5% of all patients with pancreatic cancer carry the BRCA1 and BRCA2 mutations in the UK.22BRCA2 mutation carriers have a 3.5-fold risk of developing pancreatic cancer.23 Women with BRCA1 or BRCA2 mutations have been shown to have a 2.4-fold increase in incidence of pancreatic cancer.24
Research indicates that patients with pancreatic cancer who have BRCA1 or BRCA2 mutations have improved survival when treated with poly-ADP ribose polymerases (PARP) inhibitors (a family of nuclear enzymes that regulate the repair of DNA) and/or platinum chemotherapy drugs.25 These treatments are still only available in clinical trials but, if they prove successful, they could offer further treatment options for this subgroup of patients with pancreatic cancer.
Surveillance for pancreatic cancer should also be considered for people with:20
- two or more first-degree relatives with pancreatic cancer, across two or more generations
- Lynch syndrome (mismatch repair gene [MLH1, MSH2, MSH6, or PMS2] mutations) and any first-degree relatives with pancreatic cancer.
NICE Guideline 85 recommends that the following surveillance methods are considered:20
- MRI/magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) for people without hereditary pancreatitis
- a pancreatic protocol CT scan for people with hereditary pancreatitis and a PRSS1 mutation.
Endoscopic ultrasound should not be used to detect pancreatic cancer if the person has hereditary pancreatitis because fibrosis, distortion, and calcium deposits caused by hereditary pancreatitis prevent the detection of small pancreatic tumours by EUS.20
NICE Guideline 85 makes recommendations for further research around the differing surveillance methods, and frequency of surveillance for people with an inherited risk of pancreatic cancer. Research will need to take into account the fact that these people will have widely differing levels of risk depending on their genotype or phenotype.20
The increased use of CT scanning and other imaging techniques has led to a rise in the numbers of pancreatic cysts being discovered.20 Not all cysts are malignant, but some are and some will have the potential to become malignant. NG85 makes recommendations about the techniques required to monitor those with cystic lesions; however, the guidance does not clarify how often people with cystic lesions with a potential for malignancy need to be followed up.
A pancreatic protocol CT scan or magnetic resonance cholangiopancreatography (MRI/MRCP) should be offered to people with pancreatic cysts. If more information is needed after one of these tests, then the other one should be offered.20
People with any of the following high-risk features should be referred for resection:20
- obstructive 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.
EUS can be offered 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.20
Fine-needle aspiration can be considered during EUS if more information on the likelihood of malignancy is needed.20
When using fine-needle aspiration, carcinoembryonic antigen assay can be done in addition to cytology if there is sufficient sample.20
For people with cysts that are thought to be malignant, the recommendations on staging should be followed.20
Diagnosis of pancreatic cancer
The focus of NG85 is on the management of pancreatic cancer; however, recommendations diagnosing pancreatic cancer are also included, which complement those in NICE NG12 on Referral for suspected cancer.26
For people with obstructive jaundice and suspected pancreatic cancer, routine practice is to stent and drain the bile duct before offering a pancreatic protocol CT scan; however, NG85 recommends that a CT scan is offered before draining the bile duct, in order to speed up the diagnosis.20
If the diagnosis is still unclear, the patient should be offered fluorodeoxyglucose-positron emission tomography/CT (FDG-PET)/CT and/or EUS with EUS-guided tissue sampling.20
Biliary brushings for cytology are to be taken if:20
- endoscopic retrograde cholangiopancreatography is being used to relieve the biliary obstruction and
- there is no tissue diagnosis.
Pancreatic abnormalities but no jaundice
Patients found to have pancreatic abnormalities but no jaundice after imaging (ultrasound) are to be offered a pancreatic protocol CT scan.20 If the diagnosis is still unclear, a FDG-PET/CT and/or EUS with EUS-guided tissue sampling is to be offered.20 If cytological or histological samples are needed, EUS with EUS-guided tissue sampling should be offered.20
Multidisciplinary specialist teams
High-volume centres with specialist clinicians have been found to offer better outcomes for patients with pancreatic cancer.20 In these centres, surgery is centralised and specialist multidisciplinary teams that include clinicians with pancreatic cancer-specific expertise can provide a wider range of options for patients, with more access to novel treatments and a greater knowledge of recruitment for ongoing clinical trials. They also provide an opportunity for people to access specialist pancreatic cancer nutritional assessment and intervention.
Staging of disease
One of the key recommendations from NG85 is that FDG-PET/CT is offered to people with localised disease that has been confirmed by CT, and who will be having cancer treatment (surgery, radiotherapy, or systemic therapy) so that patients can be staged more accurately.20
Accurate staging is especially pertinent for patients who are potential candidates for resectional surgery as it helps to determine their eligibility for surgery more accurately and, in some cases, prevents unnecessary surgery that cannot cure the patient’s disease. NICE estimates that the FDG-PET/CT scan will result in a 20% reduction in surgery to remove the cancer, which should enable the patient to receive the right treatment at the right time.27
Relieving biliary and duodenal obstruction
NICE Guideline 85 recommends that patients who have resectable pancreatic cancer and obstructive jaundice should be offered surgery, rather than preoperative biliary drainage, as long as they are well enough.20 The Manchester Cancer Jaundice Pathway Study found that fast-tracking surgery reduced the time from ultrasound and CT scan to potentially curative surgery from a median of 57 and 33 days pre-pathway to 13 and 9 days post-pathway, respectively.28 In a similar study in Birmingham, the time from CT scan to surgery was reduced from 65 days to 16 days and significantly more patients underwent potentially curative surgery in the ‘fast track’ group, 31/32 [97%] versus 46/61 [74%].17
Common support needs of patients with pancreatic cancer reported in the evidence given to NICE included pain, fatigue, and gastrointestinal symptoms, as well as issues around food and nutrition. People with pancreatic cancer often report anxiety and depression; these additional support needs are often overlooked in the treatment of patients with pancreatic cancer, despite the great need.20
While it was recognised that more research is needed in this area, NG85 includes recommendations relating to the support needs of patients. Throughout the person’s pancreatic cancer care pathway, the psychological impact of the following areas should be specifically assessed:20
- gastrointestinal symptoms (including changes to appetite)
Information and support should be given to patients and their families or carers to help them manage the psychological impact of pancreatic cancer on their lives and daily activities. This information should be ongoing, relevant to the stage of disease, and should address patients’ specific needs.20
Specific guidance is now given for pain management with the use of coeliac plexus block. EUS-guided or image-guided percutaneous neurolytic coeliac plexus block should be considered to manage pain for people with pancreatic cancer who:20
- have uncontrolled pancreatic pain or
- are experiencing unacceptable opioid adverse effects or
- are receiving escalating doses of analgesics.
Specifically, patients with pancreatic cancer should not be offered thoracic splanchnicectomy.20
Because of the potential for pancreatic exocrine insufficiency, there is now specific guidance on the use of pancreatic enzyme replacement therapy:20
- enteric-coated pancreatin should be offered for people with unresectable pancreatic cancer
- for those resectable patients, enteric-coated pancreatin should be considered before and after pancreatic cancer resection
- fish oils should not be used 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, early enteral nutrition (including oral and tube feeding) should be offered rather than parenteral nutrition.
Chemotherapy and radiotherapy treatments
It is useful for GPs to be able to advise patients on the treatments available in secondary care. Here is an overview of the chemotherapy and radiotherapy treatments that are currently available (NB not all treatments discussed are licensed for the treatment of pancreatic cancer).
NICE Guideline 85 recommends that any neoadjuvant treatment for patients with resectable or borderline resectable pancreatic cancer should only be given as part of a clinical trial.20
Locally advanced disease
Systemic combination chemotherapy should be offered to people with locally advanced pancreatic cancer who are well enough to tolerate it. For those not able to tolerate combination chemotherapy, then gemcitabine alone should be considered.20
For patients receiving chemoradiotherapy, then capecitabine should be considered as the radiosensitiser.B
Irreversible electroporation should only be used in the context of a clinical trial.20,29
Metastatic pancreatic cancer
For patients with a very high performance status (Eastern Cooperative Oncology Group status 0–1), the guidance is to offer the FOLFIRINOX combination.20 (It should be noted that at the time of publication (May 2018) FOLFIRINOX did not have a UK marketing authorisation for this indication, although its use is common in UK practice.)
Gemcitabine combination therapy (including gemcitabine and paclitaxel as albumin-bound nanoparticles) should be considered for people who are not well enough to tolerate FOLFIRINOX.20,30
Gemcitabine should be offered as monotherapy to people who are not well enough to tolerate combination chemotherapy.20
Oxaliplatin-based chemotherapy should be considered as second-line treatment for people who have not had first-line oxaliplatin.20 For those who have already had first-line FOLFIRINOX and whose cancer has progressed, then a gemcitabine-based chemotherapy should be considered as second-line treatment.20
It is encouraging to see a NICE guideline published for the diagnosis and management of pancreatic cancer, and recommended guidance in areas such as fast-track surgery will undoubtedly have an impact on patient outcomes.
However, there are great inequalities in the standard of care for patients with pancreatic cancer across England and it is hoped that NG85 will help inform clinicians and patients of what they should expect/be entitled to. A recent study by Pancreatic Cancer UK31 found that only 34% of all patients received any form of surgery, chemotherapy, or radiotherapy. An online survey of resectable patients conducted by Pancreatic Cancer Action (n=63) found that 27% were not offered adjuvant chemotherapy when they were eligible to receive it.32
Going forward, it will be useful to evaluate the nationwide implementation of NG85. An annual audit of pancreatic cancer services, perhaps led by the Department of Health, would help highlight examples of best practice and identify areas that are failing to improve standards of care for people with pancreatic cancer.
Founder and Chief Executive, Pancreatic Cancer Action
Dr Ellie Cannon
Resident GP at Sky News and GP Ambassador for Pancreatic Cancer Action
- Symptoms of pancreatic cancer may be nonspecific but include upper abdominal pain, mid-back pain, jaundice, indigestion, weight loss, pale smelly stools, and depression
- Consider surveillance for pancreatic cancer for people with risk factors and related genetic/hereditary conditions
- Offer a pancreatic protocol CT scan or MRI/MRCP to people with pancreatic cysts. If more information is needed after one of these tests, then offer the other one
- For people with obstructive jaundice and suspected pancreatic cancer, it is now recommended to offer a CT scan before draining the bile duct, to speed up diagnosis
- Offer patients with pancreatic abnormalities but no jaundice after ultrasound imaging a pancreatic protocol CT scan
- Offer FDG-PET/CT to patients with localised disease who will be having cancer treatment to stage their cancer more accurately and prevent unnecessary surgery for some
- Surgery is preferable to preoperative biliary drainage for patients with resectable pancreatic cancer and obstructive jaundice, as long as they are well enough
- Assess the psychological impact of fatigue, pain, gastrointestinal symptoms, nutritional needs, anxiety, and depression throughout a patient’s pancreatic cancer care pathway, and give information and support to patients and families/carers
- Pain can be managed with coeliac plexus block in patients who have uncontrolled pancreatic pain, unacceptable opioid adverse effects, or who require escalating doses of analgesics
- Offer enteric-coated pancreatin to patients with unresectable pancreatic cancer and consider giving it to patients before and after pancreatic cancer resection
- Systemic combination chemotherapy is first-line treatment for patients with locally advanced pancreatic cancer, with gemcitabine given alone to patients not well enough to tolerate combination therapy.
CT=computed tomography; MRI/MRCP= magnetic resonance cholangiopancreatography
Implementation actions for STPs and ICSs
written by Dr David Jenner, GP, Cullompton, Devon
The following implementation actions are designed to support STPs and ICSs with the challenges involved with implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources.
- Establish a local multidisciplinary working group to look at the challenge of pancreatic cancer locally
- Ensure GPs are aware of NICE guidance on when to suspect pancreatic cancer and how to investigate these cases
- Enable GPs to refer direct for urgent CT scan of the abdomen under local protocols to meet 2-week wait standards
- Define local MDT arrangements for the management of pancreatic cancer, ensuring all key specialties are represented
- Collaborate with specialist oncology and palliative care services to provide post-diagnostic support to individuals.
CT=computed tomography; MDT=multidisciplinary team
- Cancer Research UK. Pancreatic cancer statistics. www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/pancreatic-cancer#heading-One (accessed 28 March 2018).
- Pancreatic Cancer UK (PCUK). Pancreatic cancer is to be one of ‘big four’ cancer killers in less than ten years, new analysis reveals. PCUK, 2017. Available at: www.pancreaticcancer.org.uk/latest-news/2017/february/pancreatic-cancer-to-become-big-four-killer
- Office for National Statistics (ONS). Cancer registration statistics, England (2016). ONS, 2018. Available at: www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/cancerregistrationstatisticscancerregistrationstatisticsengland
- Welsh Cancer Intelligence and Surveillance Unit (WCISU). Incidence (2015 data) dashboard. WCISU, 2017. Available at: public.tableau.com/profile/welsh.cancer.intelligence.and.surveillance.unit#!/vizhome/Incidence2015data/Homepage
- Information Services Division (ISD). Cancer of the pancreas. Scotland: trends in incidence 1991–2015. ISD, 2017. Available at: www.isdscotland.org/Health-Topics/Cancer/Publications/2017-04-25/i_cancer_pancreas.xls
- Northern Ireland Cancer Registry (NICR). Pancreas cancer. NICR, 2015. Available at: www.qub.ac.uk/research-centres/nicr/FileStore/PDF/FactSheets/2011-2015/Filetoupload,756674,en.pdf
- International Agency for Research on Cancer. GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. globocan.iarc.fr/Pages/burden_sel.aspx (accessed 28 March 2018).
- ONS. Deaths registered in England and Wales (series DR). Available at: www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/datasets/deathsregisteredinenglandandwalesseriesdrreferencetables
- ISD. Cancer of the pancreas. Scotland: trends in mortality 1991–2016. ISD, 2017. Available at: www.isdscotland.org/Health-Topics/Cancer/Publications/2017-10-31/m_cancer_pancreas.xls
- Queen’s University Belfast, NICR. Cancer mortality statistics for Northern Ireland: 1993–2016—pancreatic cancer (C25). Available at: www.qub.ac.uk/research-centres/nicr/FileStore/OfficialStats2016/Mortality2016/Filetoupload,810434,en.xls
- National Cancer Intelligence Network (NCIN), Public Health England. Routes to diagnosis 2006–2015 workbook. Available at: www.ncin.org.uk/view?rid=3549
- Allemani C, Matsuda T, Di Carlo V et al. Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 2018; 391 (10125): 1023–1075.
- All-Party Parliamentary Group on Pancreatic Cancer (APPGPC), PCUK. The need for speed—diagnosing pancreatic cancer earlier, giving patients a chance of living better for longer. APPGPC, 2017. Available at: www.pancanappg.org.uk/wp-content/uploads/2017/11/5934_PCUK_APPG_Report_HR4.pdf
- Pancreatic Cancer Action. Pancreatic cancer symptoms. pancreaticcanceraction.org/about-pancreatic-cancer/symptoms/ (accessed 28 March 2018).
- Lyratzopoulos G, Abel G, McPhail S et al. Measures of promptness of cancer diagnosis in primary care: secondary analysis of national audit data on patients with 18 common and rarer cancers. Br J Cancer 2013; 108 (3): 686–690.
- Lyratzopoulos G, Neal R, Barbiere J et al. Variation in number of general practitioner consultations before hospital referral for cancer: findings from the 2010 National Cancer Patient Experience Survey in England. Lancet Oncol 2012; 13 (4): 353–365.
- Roberts K, Prasad P, Steele Y et al. A reduced time to surgery within a ‘fast track’ pathway for periampullary malignancy is associated with an increased rate of pancreatoduodenectomy. HPB (Oxford) 2017; 19 (8): 713–720.
- Laudicella M. Pancreatic cancer UK policy briefing—appendix 1: estimating the cost of inpatient care in patients diagnosed with pancreatic cancer as a result of an emergency admission. PCUK, 2013. Available at: www.pancreaticcancer.org.uk/media/86662/every-lm_policybriefing-final.pdf
- NHS England. NHS imaging and radiodiagnostic activity. NHS England, 2014. Available at: www.england.nhs.uk/statistics/wp-content/uploads/sites/2/2013/04/KH12-release-2013-14.pdf
- NICE. Pancreatic cancer in adults: diagnosis and management. NICE Guideline 85. NICE, 2018. Available at: www.nice.org.uk/ng85
- Haddad A, Kowdley G, Pawlik T, Cunningham S. Hereditary pancreatic and hepatobiliary cancers. Int J Surg Oncol 2011; 2011: 154673.
- Holter S, Borgida A, Dodd A et al. Germline BRCA mutations in a large clinic-based cohort of patients with pancreatic adenocarcinoma. J Clin Oncol 2015; 33 (28): 3124–3129.
- The Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 1999; 91 (15): 1310–1316.
- Iqbal J, Ragone A, Lubinski J et al. The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer 2012;107 (12): 2005–2009.
- Brennan G, Relias V, Saif M. BRCA and pancreatic cancer—highlights from the 2013 ASCO annual meeting. J Pancreas 2013; 14 (4): 325–328.
- NICE. Suspected cancer: recognition and referral. NICE Guideline 12. NICE, 2015. Available at: www.nice.org.uk/guidance/ng12
- NICE website. Pancreatic cancer patients should be offered early scans to avoid unnecessary surgery, says NICE. NICE News and Features, 2018. Available at: www.nice.org.uk/news/article/pancreatic-cancer-patients-should-be-offered-early-scans-to-avoid-unnecessary-surgery-says-nice
- O’Reilly D. The Manchester cancer jaundice pathway. Available at: www.cancerresearchuk.org/sites/default/files/the_manchester_cancer_jaundice_pathway_oct_2016.pdf
- NICE. Irreversible electroporation for treating pancreatic cancer. NICE Interventional Procedures Guidance 579. NICE, 2017. Available at: www.nice.org.uk/ipg579
- NICE. Paclitaxel as albumin-bound nanoparticles with gemcitabine for untreated metastatic pancreatic cancer. NICE Technology Appraisal 476. NICE, 2017. Available at: www.nice.org.uk/ta476
- PCUK. Urgent change needed in pancreatic cancer care. PCUK, 2018. Available at: www.pancreaticcancer.org.uk/latest-news/2018/march/urgent-change-needed-in-pancreatic-cancer-care/
- Research Now, for Pancreatic Cancer Action. Topline report of pancreatic cancer survey. November 2015. Available at:pancreaticcanceraction.org/wp-content/uploads/2018/05/Research-Now-Pancreatic-Cancer-Summary-Report-16-11-15.pptx