STEP 4: Treatment
Step 4 describes the optimal treatments for pancreatic cancer, the training and experience required of the treating clinicians and the health service characteristics required for optimal cancer care.
All health services must have clinical governance systems that meet the following integral requirements:
- identifying safety and quality measures
- monitoring and reporting on performance and outcomes
- identifying areas for improvement in safety and quality (ACSQHC 2020).
Step 4 outlines the treatment options for pancreatic cancer. For detailed clinical information on treatment options refer to these resources:
- the National Comprehensive Cancer Network’s 2019 Clinical practice guidelines for pancreatic cancer
- the National Institute for Health and Care Excellence’s 2018 Pancreatic cancer in adults: diagnosis and management
- the National Cancer Institute’s 2020 Pancreatic cancer treatment (adult)(PDQ) – Health professional version
- the European Society for Medical Oncology’s 2015 Cancer of the pancreas: ESMO clinical practice guidelines and the 2019 eUpdate
The intent of treatment can be defined as one of the following:
- curative
- anti-cancer therapy to improve quality of life and/or longevity without expectation of cure
- symptom palliation.
The treatment intent should be established in a multidisciplinary setting, documented in the patient’s medical record and conveyed to the patient and carer as appropriate.
The potential benefits need to be balanced against the morbidity and risks of treatment.
The lead clinician should discuss the advantages and disadvantages of each treatment and associated potential side effects with the patient and their carer or family before treatment consent is obtained and begins so the patient can make an informed decision. Supportive care services should also be considered during this decision-making process. Patients should be asked about their use of (current or intended) complementary therapies (see Appendix D).
Timeframes for starting treatment should be informed by evidence-based guidelines where they exist. The treatment team should recognise that shorter timeframes for appropriate consultations and treatment can promote a better experience for patients.
Initiate advance care planning discussions with patients before treatment begins (this could include appointing a substitute decision-maker and completing an advance care directive). Formally involving a palliative care team/service may benefit any patient, so it is important to know and respect each person’s preference (AHMAC 2011).
The potential for curative surgery depends on the staging of the tumour, and only 10–20 per cent of patients have clearly resectable disease after careful pretherapeutic staging. This potential is assessed by the multidisciplinary team.
Patients who undergo surgical resection for localised pancreatic cancer have a median survival of 15–20 months and a five-year survival of 8–15 per cent (Lambert et al. 2019). Unfortunately, 80 per cent of patients present with metastatic or locally advanced disease, by which time the tumour is unresectable (Lambert et al. 2019).
Unresectable tumours are defined based on the presence of metastases including non-regional lymph node involvement, more than 180 degrees of contact with the major vessels, or tumoural invasion of the major vessels (Elbanna et al. 2020).
Curative surgery includes the following options with or without chemotherapy (adjuvant or neoadjuvant chemotherapy or neoadjuvant chemoradiation):
- Whipple procedure (pancreaticoduodenal resection)
- distal pancreatectomy
- total pancreatectomy.
Timeframe for starting treatment
Surgery should be undertaken within four weeks of the initial diagnosis, depending on urgency and modality.
Training and experience required of the surgeon
Surgeon (FRACS or equivalent) with adequate training and experience in hepatobiliary surgery with institutional credentialing and agreed scope of practice within this area.
There is strong evidence to suggest that surgeons who undertake a high volume of resections have better clinical outcomes for complex cancer surgery such as pancreatic resections (Toomey et al. 2016).
Documented evidence of the surgeon’s training and experience, including their specific (sub-specialty) experience with pancreatic cancer and procedures to be undertaken, should be available.
Health service characteristics
To provide safe and quality care for patients having surgery, health services should have these features:
- critical care support
- 24-hour medical staff availability
- 24-hour operating room access and intensive care unit
- diagnostic imaging
- endoscopic retrograde cholangiopancreatography (ERCP)
- 24-hour access to interventional radiology
- access to endoscopic ultrasound
- nuclear medicine imaging
- pathology
- full support from other surgical specialties.
There is strong evidence to suggest that high-volume hospitals have better clinical outcomes for complex cancer surgery such as pancreatic resections (Hata et al. 2016). Centres that do not have sufficient caseloads should establish processes to routinely refer surgical cases to high-volume centres.
Even if the cancer is deemed surgically curable the following should be considered (NCI 2019a):
- neoadjuvant chemotherapy for all high-risk patients
- neoadjuvant chemotherapy or chemoradiation therapy, especially in patients with borderline resectable disease or delay in surgery
- adjuvant chemotherapy in the postoperative setting
- chemoradiation therapy (or SBRT on a trial) for borderline resectable or locally advanced patients who are still potentially operable
- adjuvant chemotherapy within 12 weeks following resection.
Timeframes for starting treatment
Neoadjuvant chemotherapy should begin within four weeks of the initial diagnosis, depending on urgency and modality.
Adjuvant chemotherapy in the postoperative setting should begin within 12 weeks of surgery.
Training and experience required of the appropriate specialists
Medical oncologists must have training and experience of this standard:
- Fellow of the Royal Australian College of Physicians (or equivalent)
- adequate training and experience that enables institutional credentialing and agreed scope of practice within this area (ACSQHC 2015).
Cancer nurses should have accredited training in these areas:
- anti-cancer treatment administration
- specialised nursing care for patients undergoing cancer treatments, including side effects and symptom management
- the handling and disposal of cytotoxic waste (ACSQHC 2020).
Systemic therapy should be prepared by a pharmacist whose background includes this experience:
- adequate training in systemic therapy medication, including dosing calculations according to protocols, formulations and/or preparation.
In a setting where no medical oncologist is locally available (e.g. regional or remote areas), some components of less complex therapies may be delivered by a general practitioner or nurse with training and experience that enables credentialing and agreed scope of practice within this area. This should be in accordance with a detailed treatment plan or agreed protocol, and with communication as agreed with the medical oncologist or as clinically required.
The training and experience of the appropriate specialist should be documented.
Health service characteristics (systemic therapy)
To provide safe and quality care for patients having systemic therapy, health services should have these features:
- a clearly defined path to emergency care and advice after hours
- access to diagnostic pathology including basic haematology and biochemistry, and imaging
- cytotoxic medicines prepared in a pharmacy with appropriate facilities or externally sourced from Therapeutics Goods Association–licensed manufacturers
- occupational health and safety guidelines regarding handling of cytotoxic drugs, including preparation, waste procedures and spill kits (eviQ 2019;)
- guidelines and protocols to deliver treatment safely (including dealing with extravasation of drugs)
- coordination for combined therapy with radiation therapy, especially where facilities are not co-located
- appropriate molecular pathology access.
Training and experience required of radiation oncologists
Radiation oncologists must have training and experience of this standard:
- Fellowship of the Royal Australian and New Zealand College of Radiologists (or equivalent)
- adequate training and experience, institutional credentialing and agreed scope of practice in pancreatic cancer (ACSQHC 2015).
The training and experience of the radiation oncologist should be documented.
Health service unit characteristics (radiation therapy)
To provide safe and quality care for patients having radiation therapy, health services should have these features:
- linear accelerator (LINAC) capable of image-guided radiation therapy (IGRT)
- dedicated CT planning
- access to MRI and PET imaging
- automatic record-verify of all radiation treatments delivered
- a treatment planning system
- trained medical physicists, radiation therapists and nurses with radiation therapy experience
- coordination for combined therapy with systemic therapy, especially where facilities are not co-located
- participation in Australian Clinical Dosimetry Service audits
- an incident management system linked with a quality management system.
If the cancer is deemed unresectable, any other treatment is almost certainly palliative because pancreatic cancer is unlikely to be cured by chemotherapy and radiation therapy. Palliative therapy may be indicated for:
- nutritional assessment and support (including enzyme support therapy)
- surgical or radiological biliary decompression
- relief of gastric outlet obstruction
- pain control
- psychological care to address the potentially disabling psychological events associated with the diagnosis and treatment of pancreatic cancer.
The most commonly used therapies in unresectable pancreatic cancer include:
- endoscopic or radiological intervention
- surgical interventions – endoscopic biliary stent placement, percutaneous radiological biliary stent placement, palliative surgical biliary and/or gastric bypass
- chemotherapy
- chemotherapy followed by chemoradiation therapy for those without metastatic disease
- chemotherapy, followed by radiotherapy in selected cases
- coeliac plexus or intrapleural block.
For patients who are too unwell to undergo curative therapy, radiotherapy has been shown to improve survival, pain control and hospital admissions compared with the best supportive care.
Endoscopic stenting is recommended as initial palliation for biliary obstruction. Percutaneous transhepatic biliary stenting may be required for failed endoscopic stenting. For patients with gastric outlet obstruction, either surgical bypass or endoscopic stenting would be appropriate.
It is important to weigh up the risks versus benefits of any palliative therapy if the patient’s prognosis is not changed with implementation.
Timeframes for starting treatment
Treatment should begin within four weeks of initial diagnosis, depending on urgency and modality.
There is currently one approved targeted therapy available to treat patients with locally advanced, unresectable or metastatic pancreatic cancer.
Maintenance therapy with the PARP inhibitor olaparib (Lynparza) has been shown to significantly delay the progression of metastatic pancreatic cancer in patients with BRCA gene mutations compared with placebo (ASCO 2019).
A number of emerging therapies are being investigated for pancreatic cancer. Areas of interest for emerging therapies include identifying molecular targets, targeting cancer stem cells and stromal modulation, immunotherapies such as cancer vaccines, adoptive cell therapy and stemness inhibitors (Amanam & Chung 2018; Lambert et al. 2019).
The key principle for precision medicine is prompt and clinically oriented communication and coordination with an accredited laboratory and pathologist. Tissue analysis is integral for access to emerging therapies and, as such, tissue specimens should be treated carefully to enable additional histopathological or molecular diagnostic tests in certain scenarios.
Early referral to palliative care can improve the quality of life for people with cancer (Haines 2011; Temel at al. 2010; Zimmermann et al. 2014). This is particularly true for cancers with poor prognosis.
In general, all patients with pancreatic cancer, given the poor prognosis, should be offered referral to palliative care assessment as an integrated aspect of their overall oncology care (Gaertner et al. 2011).
In particular, referral to palliative care services is required when:
- symptoms affect quality of life
- ECOG ≥ 2
- estimated likely survival is less than a year and/or the patient/carer has increasing difficulty managing care needs
- complex psychosocial needs, including those of carers
- patient/family wishes for palliative care support, especially in the community setting
- bereavement support for carers.
Emphasise the value of palliative care in improving symptom management and quality of life to patients and their carers.
The ‘Dying to Talk’ resource may help health professionals when initiating discussions with patients about future care needs (see ‘More information’). Ensure that carers and families receive information, support and guidance about their role in palliative care (Palliative Care Australia 2018).
Patients, with support from their family or carer and treating team, should be encouraged to consider appointing a substitute decision-maker and to complete an advance care directive.
Refer to Step 6 for a more detailed description of managing patients with recurrent, residual or metastatic disease.
These online resources are useful:
The team should support the patient to participate in research or clinical trials where available and appropriate. Many emerging treatments are only available on clinical trials that may require referral to certain trial centres.
For more information visit the Cancer Australia website.
See validated screening tools mentioned in Principle 4 ‘Supportive care’.
A number of specific challenges and needs may arise for patients at this time:
- assistance for dealing with emotional and psychological issues, including body image concerns, fatigue, quitting smoking, traumatic experiences, existential anxiety, treatment phobias, anxiety/depression, interpersonal problems and sexuality concerns
- potential isolation from normal support networks, particularly for rural patients who are staying away from home for treatment
- management of physical symptoms such as chronic pain and fatigue
- nutritional assessment and support
- gastrointestinal symptoms (such as nausea, vomiting, mucositis, loss of appetite) as a result of chemotherapy treatment, requiring optimal symptom control with medication and referral to a dietitian if dietary intake is affected
- assistance with managing complex medication regimens, multiple medications, assessment of side effects and assistance with difficulties swallowing medications – referral to a pharmacist may be required
- decline in mobility or functional status as a result of treatment
- assistance with beginning or resuming regular exercise with referral to an exercise physiologist or physiotherapist (COSA 2018; Hayes et al. 2019).
Early involvement of general practitioners may lead to improved cancer survivorship care following acute treatment. General practitioners can address many supportive care needs through good communication and clear guidance from the specialist team (Emery 2014).
Patients, carers and families may have these additional issues and needs:
- financial issues related to loss of income (through reduced capacity to work or loss of work) and additional expenses as a result of illness or treatment
- advance care planning, which may involve appointing a substitute decision-maker and completing an advance care directive
- legal issues (completing a will, care of dependent children) or making an insurance, superannuation or social security claim on the basis of terminal illness or permanent disability.
Cancer Council’s 13 11 20 information and support line can assist with information and referral to local support services.
For more information on supportive care and needs that may arise for different population groups, see Appendices A and B, and special population groups.
Rehabilitation may be required at any point of the care pathway. If it is required before treatment, it is referred to as prehabilitation (see section 3.6.1).
All members of the multidisciplinary team have an important role in promoting rehabilitation. Team members may include occupational therapists, speech pathologists, dietitians, social workers, psychologists, physiotherapists, exercise physiologists and rehabilitation specialists.
To maximise the safety and therapeutic effect of exercise for people with cancer, all team members should recommend that people with cancer work towards achieving, and then maintaining, recommended levels of exercise and physical activity as per relevant guidelines. Exercise should be prescribed and delivered under the direction of an accredited exercise physiologist or physiotherapist with experience in cancer care (Vardy et al. 2019). The focus of intervention from these health professionals is tailoring evidence-based exercise recommendations to the individual patient’s needs and abilities, with a focus on the patient transitioning to ongoing self-managed exercise.
Other issues that may need to be dealt with include managing cancer-related fatigue, improving physical endurance, achieving independence in daily tasks, optimising nutritional intake, returning to work and ongoing adjustment to cancer and its sequels. Referrals to dietitians, psychosocial support, return-to-work programs and community support organisations can help in managing these issues.
The lead or nominated clinician should take responsibility for these tasks:
- discussing treatment options with patients and carers, including the treatment intent and expected outcomes, and providing a written version of the plan and any referrals
- providing patients and carers with information about the possible side effects of treatment, managing symptoms between active treatments, how to access care, self-management strategies and emergency contacts
- encouraging patients to use question prompt lists and audio recordings, and to have a support person present to aid informed decision making
- initiating a discussion about advance care planning and involving carers or family if the patient wishes
The general practitioner plays an important role in coordinating care for patients, including helping to manage side effects and other comorbidities, and offering support when patients have questions or worries. For most patients, simultaneous care provided by their general practitioner is very important.
The lead clinician, in discussion with the patient’s general practitioner, should consider these points:
- the general practitioner’s role in symptom management, supportive care and referral to local services
- using a chronic disease management plan and mental health care management plan
- how to ensure regular and timely two-way communication about:
- the treatment plan, including intent and potential side effects
- supportive and palliative care requirements
- the patient’s prognosis and their understanding of this
- enrolment in research or clinical trials
- changes in treatment or medications
- the presence of an advance care directive or appointment of a substitute decision-maker
- recommendations from the multidisciplinary team.
Refer to Principle 6 ‘Communication’ for communication skills training programs and resources.