Clinical Practice Guideline
The Palliative Care of Patients With Incurable Cancer
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Background: The purpose of palliative medicine is to optimize the quality of life of patients with incurable, progressive diseases. The care delivered in actual clinical practice is not uniform and often takes insufficient account of the currently available scientific evidence.
Methods: In accordance with the methodological directives on systematic literature reviews and consensus-finding that have been issued by the German Oncology Guideline Program (Leitlinienprogramm Onkologie), a nationwide, representative group of experts updated the previously published seven chapters of the S3 (evidence-based and consensus-based) guideline and formulated new recommendations on a further eight topics in palliative care.
Results: Non-drug options for the treatment of fatigue include aerobic exercise and psycho-educative methods, particularly cognitive behavioral therapy. Sleep disturbances can be treated with improved sleep hygiene and relaxation techniques, as well as with drugs: Z substances for short-term and sedating antidepressants for intermediate-term treatment. For nausea and vomiting, the first line of treatment consists of antidopaminergic drugs, such as haloperidol, or drugs with an antidopaminergic effect combined with a further receptor affinity, such as metoclopramide. For patients suffering from malignant intestinal obstruction (MIO), an important consideration for further treatment is whether the obstruction is complete or incomplete. Psychotherapeutic interventions are indicated for the treatment of anxiety.
Conclusion: Multiple studies have confirmed the benefit of the early integration of palliative care for achieving the goals of better symptom control and maintenance of quality of life. There is currently a low or moderate quality of evidence supporting the management of certain symptoms in patients with incurable cancers.
In the palliative care of a patient with incurable cancer, the goal is to maintain the best possible quality of life. Palliative care starts when cancer has been diagnosed as incurable, and is delivered by primary care providers or by specialized palliative care professionals (general versus specialist palliative care).
The first version of the S3 Guideline for Palliative Care covered seven topics: breathlessness, cancer pain, constipation, depression, communication, the dying phase, and the organization of palliative care (1).
For the second version of the Guideline, eight new topics were chosen for their clinical relevance or their prevalence in the palliative situation (as detailed below). In addition, the seven existing sections were updated, giving a new, expanded, and updated S3 Guideline containing 15 sections, the principles of palliative care, a glossary, and a list of quality indicators (2). The aim of the Guideline is to ensure universal high-quality palliative care for all patients with incurable cancer in Germany. Moreover, many key recommendations can also be applied to other patient groups.
For this planned expansion and update of the S3 Guideline on Palliative Care, a representative group of experts was drawn from 61 medical specialty societies and institutions, including patient representatives. First, we searched for existing guidelines. Next, a literature search for systematic reviews and primary studies was conducted in the databases Medline, Cochrane Library, and—according to the topic—in Embase, PsycInfo and/or CINAHL, until 2016 or 2018, respectively. Publications were selected according to the PRISMA criteria (eFigure 1). The recommendations that were developed were formally agreed at consensus conferences by the elected representatives of the medical specialist societies.
A total of 212 key recommendations relating to the eight new topics were formulated and are summarized here. Overall, the expanded Guideline now contains 442 recommendations, 162 of which are evidence-based (recommendation grades and evidence levels as defined in eTable 1 are given in parentheses in the text). The remainder of the recommendations are based on expert consensus (EC). Eleven quality indicators were agreed on.
Identifying treatment goals and decision-making criteria
The process by which decisions are reached about treatment goals and carrying out medical interventions should be participatory—i.e., it should include the patient. It should be started early or even anticipatory (Advance Care Planning).
Goals of care
Goals of care should be set by the doctor and the patient together on the basis of the current state of the patient’s disease and the therapeutic options available (EC). The primary goal of care in palliative care is to maintain or improve of the patient’s quality of life. This includes symptom control and dying with dignity; it does not exclude the goal of prolonging life.
Decisions about starting, continuing, or ending medical interventions
The main criteria in reaching these decisions are medical indication and patient consent (EC statement). The decision to treat should be made on the basis that the goal of care is realistically achievable and that the benefits have been weighed against the harms (EC). For the patient or his or her personal representative to give consent, the medical intervention and its complications must first have been sufficiently explained and information given about other possible treatment options (EC). If the patient does not have capacity to give consent, close relatives should be involved (EC). The goals of care and interventions decided upon should be reviewed regularly (Figure 1).
If “fatigue” is not a word the patient can relate to, questions about “weakness” and “tiredness” can be used: for example, “Do you feel unusually tired and/or weak?” or “How tired are you? How weak are you?” (EC).
If fatigue has become a burden or is debilitating, the patient should be offered treatment (EC). The first step is to try to identify potentially treatable causes (EC). Secondary fatigue can be caused by, for example, anemia, infection, electrolyte imbalance, cachexia, depression, or the use of sedatives (eFigure 2).
Various evidence-based non-drug interventions are available for symptomatic management of fatigue. Regular aerobic exercise was given only a moderate recommendation (“should”), to allow the functional status of palliative patients to be taken into account (B/1−). Nine out of 13 randomized, controlled studies (RCTs) (n = 744) showed that physical activity significantly reduced fatigue in palliative patients, although no meta-analysis could be conducted (; Mochamat et al., personal communication). The largest RCT (n = 269) demonstrated a decrease of 6.6 points in a 100-point scale (EORTC QLQ-C30; 95% confidence interval [−12.3; −0.9]; p = 0.02; Cohen’s d = 0.33 [0.04; 0.61]) (4). Psychoeducational techniques, especially cognitive behavioral therapy, and energy management strategies are also given a weak recommendation (B/1−) because they are based on weak evidence (; Mochamat et al., personal communication).
Symptomatic drug therapy with psychostimulants and corticosteroids can be tried (0/1−). The efficacy of methylphenidate in patients with advanced cancer was confirmed in a systematic review with a meta-analysis of two RCTs (standardized mean difference = 0.49; [0.15; 0.83]) and in two other RCTs (6). Modafinil has only been investigated in two RCTs with contradictory findings (6). Finally, there is weak evidence for the efficacy of corticosteroids in the treatment of fatigue in patients with advanced cancer (6).
Sleep-related disorders/nocturnal restlessness
Patients with incurable cancer often do not spontaneously report difficulties in sleeping as the focus is on other symptoms (7). For this reason, patients should be actively asked about sleep disorders along with other symptoms (EC) (eTable 2). Any causes that can perhaps be addressed—pain, for instance, or drug side effects, fear (fear of dying), depression, or guilt feelings—should also be explored (EC), and, if appropriate, opportunities to talk or possible treatments should be offered (EC).
In addition to general sleep hygiene and stimulus control (EC), cognitive behavioral therapy for insomnia can be initiated (Guideline adaptation, 0/2++). Good indirect evidence for this in a general population has been shown in several meta-analyses (8). Relaxation techniques are also recommended (EC).
For short-term drug treatment of insomnia, Z-drugs such as zopiclone or zolpidem should be used (B/1−) (9), while sedating antidepressants should be used for medium-term treatment (B/1−) (10, 11). The evidence for this is available only for a general patient population with cancer and is very weak—apart from results for paroxetine versus placebo (n = 426; difference in sleep problems [Hamilton Depression Index] in intergroup comparison: χ2(1) = 5.97; p = 0.01; Cohen’s d = 0.23) (11). Benzodiazepines are not indicated primarily, except when there are other indications for their use (B/4). Sedating antipsychotics can also be given where there is another indication for their use or where there is no alternative (0/3) (12). Melatonin can also be used as last-line treatment (0/1+) (13).
Nausea and vomiting (not tumor-therapy-induced)
Every time a patient’s symptoms are assessed, nausea and vomiting should always be included (EC)—preferably using validated recording instruments such as MIDOS or IPOS (B/4).
Treatment options are many and varied (Figure 2). Fundamentally, aggravating factors such as stress or particular odors should be avoided, and if drugs are a trigger, consideration should be given to whether they can be reduced or stopped (EC). Where nausea and/or vomiting are opioid-induced, it may be possible to switch the opioid (0/1−) (14, 15). Mouth care should be offered after every episode of vomiting (EC). A choice of relaxation techniques should be offered (EC). If vomiting is refractory to treatment, a nasogastric tube may be considered (EC).
Regarding drug therapy, the evidence for patients in the palliative setting is limited. Thus, indirect evidence from patients undergoing tumour-specific therapy is mostly used. . Drug treatment should be etiology-based (EC). As first-line therapy, drugs with antidopaminergic (e.g., haloperidol) or antidopaminergic and other receptor affinity (e.g., metoclopramide) should be given (B/1−) (14, 16, 17). As second-line treatment options, other drug classes can be used: antipsychotics with a broad spectrum of action (e.g., levomepromazine) (B/3) (16, 18), antihistamines (e.g., dimenhydrinate) (0/4), and 5HT3-antagonists (0/1−) (19). Patients with brain metastases who have raised ICP should be given dexamethasone (B/1−) (20). Antiemetics with different receptor affinities should be combined if monotherapy is inadequate (B/4). Where vomiting is persistent, parenteral drug administration should be preferred (EC).
Malignant bowel obstruction
Malignant bowel obstruction (MBO) is the complete or partial obstruction of the bowel due to intra-abdominal tumor or intraperitoneal metastasis, diagnosed on the basis of clinical examination and imaging. Nonmechanical (paralytic) impairment of the passage of bowel contents is not covered in this section.
MBO-related symptoms such as nausea, vomiting, meteorism, and abdominal pain should be assessed together with any potentially treatable causes (EC). Further diagnostic investigations such as rectal digital palpation or computed tomography should be considered, depending among other things on the patient’s clinical condition and on other treatment options including surgery (EC).
Parenteral nutrition should be viewed with caution in patients whose predicted survival time is limited to a few weeks (B/3); for patients with a predicted survival of several weeks or months, it should be considered (A/3) (21, 22, 23).
The decision whether to place a stent or to operate to remove or bypass the obstruction should be made by an interdisciplinary team (EC). Placement of a PEG (percutaneous endoscopic gastrostomy) tube should be considered if nausea and vomiting can be effectively relieved by a nasogastric tube (EC).
The aim of symptomatic drug therapy of an incomplete MBO is to restore the passage of bowel contents; for this, prokinetic antiemetics such as metoclopramide are indicated (B/4), and glucocorticoids can be started to reduce edema over a few days (0/1+) (24). Softening laxatives may be given to treat constipation (EC). Enemas may be offered concomitantly (EC).
In patients with complete MBO, prokinetics should be avoided. For this reason, antipsychotics (B/3) (25) and/or antihistamines (B/4) are used for antiemesis; these may be combined with 5HT3-antagonists (0/4). Reducing intraluminal secretion can help to relieve nausea and vomiting, e.g., using an anticholinergic such as hyoscine butylbromide (0/3) and/or somatostatin analogs (0/1) (26) and ranitidine or a proton pump inhibitor (EC) (eTable 3). Colic-type pain should be treated with butylscopolamine (EC).
Malignant wounds are defined as wounds caused by a primary skin tumor, skin metastases, or breakthrough of a tumor in a deeper location. In addition to contributing factors, wound history-taking should cover impairment of the patient’s quality of life and the subjective lived experience of the patient and the patient’s relatives (EC) (eTable 4).
Alleviating psychosocial stress
Malignant wounds can have a powerful effect on quality of life. The change in the patient’s self-image and body image, and the social consequences of that change, should be touched upon empathetically (EC), and the patient’s self-management and sense of control should be supported (EC).
Before dressings are changed, analgesics should be given anticipatory to preempt any expected pain (EC). Treatment locally with a local anesthetic (0/4) or morphine gel (0/2−) (27) is recommended on the basis of indirect evidence relating to other types of wounds.
In addition to meticulous wound cleaning (EC), a variety of interventions are recommended (eFigure 3): the use of local antiseptics (0/3) (indirect evidence, e.g., ); wound dressing materials that have an antiseptic effect or absorb exudate and bind pathogens, e.g., those containing activated carbon (0/3) (29); metronidazole administered locally (0/1−) (29) or systemically (0/3) (30).
Prevention and management of bleeding
Slight bleeds require vasoconstrictive measures such as cooling or compression (EC). More copious bleeds should be treated with local or systemic antifibrinolytics such as tranexamic acid (B/2+) (31) or with local hemostatic agents (EC). The efficacy of topical tranexamic acid in comparison to placebo has been studied in a meta-analysis of mostly surgical patients (n = 6034, 67 RCTs) and is thus assessed as indirect evidence (weighted mean difference in mean blood loss: −276.6 mL; [−327.8; −225.4 mL]; p <0.0001) (31).
This section discusses subsyndromal and specific anxieties. Subsyndromal anxiety disorders are those that do not completely meet the ICD criteria for anxiety disorders (panic disorders, phobias, generalized anxiety disorders, adjustment disorders, and posttraumatic stress disorders).
Specific anxieties are triggered by the patient’s disease situation. They may relate to actual or feared symptoms, to treatment, to the end of life, or to relatives and loved ones, among others. Anxiety should be regularly recorded and assessed as necessary as to content and any need for treatment (EC).
The care team needs to have an attitude and choose words that avoid triggering anxiety (EC). Uncontrolled symptoms that cause anxiety should be treated in the best way possible (EC).
If anxiety is burdensome or impairing, non-drug measures should be used (EC). These include psychological and/or psychotherapeutic techniques (0/1+).
A meta-analysis of RCTs with moderate risks of bias that studied palliative patients with anxiety showed a moderate, significant effect of cognitive behavioral therapy (Cohen’s d = 0.44; p <0.001), mindfulness-based stress reduction, and acceptance and commitment therapy (−0.67; p <0.001) (32). Other techniques using social-work– or spirituality-based approaches or art therapy are recommended by expert consensus (EC).
Drug therapy is offered when other techniques are insufficiently effective or cannot be implemented (EC) (Table 1). The evidence base for the palliative setting is very weak. Based on clinical experience, short-acting benzodiazepines should be given to treat symptoms of acute anxiety (B/4). Alternatives that may be considered are antidepressants, antipsychotics, or other anxiolytics (B/1−) (33, 34).
The desire to die
Based on the international literature, the Guideline refers to the desire to die as a complex phenomenon, affecting palliative care patients and ranging from the acceptance of death (“satiety of life”) to acute suicidality (Figure 3). A desire to die can often exist alongside a will to live (35), and may be traced to a variety of causes: for example, physically or psychologically stressful symptoms, social problems such as isolation, worries about the future, and loss of autonomy (35). A desire to die may serve various different functions, such as opening up a way of escaping from an unbearable situation, having control over the end of one’s life, or as an expression of a sense of despair.
Proactiely addressing a desire to die
Patients with incurable cancer should be actively asked whether they feel a desire to die (B/4). There is no evidence that enquiring suicidal thoughts leads to their emergence or increase. In a meta-analysis of six studies, suicidal ideation was not significantly increased after participants were asked about suicidality or exposed to suicide-related content (overall effect, odds ratio = 0.973 [0.83; 1.15]; p = 0.749) (36).
Dealing with a desire to die
In conversations about a desire to die, the care team should maintain a basic attitude of openness and respect; this does not mean that they are assenting to the active ending of a life (EC). Based on various diagnostic and treatment considerations, strategies and techniques have been developed for use in dealing with a patient who desires to die; details are given in Table 2.
Updates to the seven original topics
Since the landmark study by Temel et al. (37), several new, high-quality RCTs have shown the advantages of early integration of palliative care, such that two central recommendations, previous consensus-based, can now be formulated as evidence-based (A/1− and A/3, respectively) (38). A new addition is that every patient who has been diagnosed with incurable cancer should be offered a needs assessment by a specialist palliative care team.
In regard to the other recommendations on the original seven topics, few changes were required. Recent studies have indicated that steroids can relieve breathlessness even in patients without lymphangitis carcinomatosa or tumor-related airway obstruction (0/1+) (39).
In view of recent results about adverse effects, haloperidol should be used much more cautiously in a patient with delirium during the dying phase; if restlessness increases, it may be combined with a benzodiazepine (B/1−) (40).
The expanded and updated S3 Guideline formulates recommendations for clinical practice in 15 core topics of palliative medicine. These recommendations should guide the actions of all those working in general and specialist palliative care who are involved in the management of patients with incurable cancer. A representative and multiprofessional group of experts together with patient representatives developed and agreed these recommendations on the basis of current, up-to-date evidence, with the goal of providing the best possible palliative care for patients and their relatives.
We are grateful to all the experts and elected representatives of medical specialist societies for their commitment and hard work in developing this Guideline. Grateful thanks are also due to Dr. Markus Follmann, Prof. Dr. Ina Kopp, Dr. Monika Nothacker, Thomas Langer, and Dr. Simone Wesselmann of the Cancer Guidelines Program for their advice on methods and constant support.
We are especially grateful to Verena Geffe, Dr. Susanne König, and Dr. Kerstin Kremeike of the Guideline Office. Finally, thanks go to the three supporting bodies of the Cancer Guidelines Program—the Association of Scientific Medical Societies in Germany (AWMF), the German Cancer Society (Deutsche Krebsgesellschaft), and German Cancer Aid (Deutsche Krebshilfe)—for creating the Guideline, and to German Cancer Aid for independent financial support.
Conflict of interest statement
Professor Voltz has received lecture fees from Novocure and MSD Sharp & Dohme, and from the National Health Academy Ltd. (Nationale Gesundheits-Akademie NGA GmbH).
The other authors declare that they have no conflict of interest. .
Manuscript received on 7 October 2019, revised version accepted on 3 December 2019.
Translated from the original German by Kersti Wagstaff.
Clinical guidelines in the Deutsches Ärzteblatt, as in numerous other
specialist journals, are not subject to a peer review procedure, since S3
guidelines represent texts that have already been evaluated, discussed,
and broadly agreed upon multiple times by experts (peers).
PD Dr. med. Steffen T. Simon
Zentrum für Palliativmedizin, Uniklinik Köln
Kerpener Str. 62, 50937 Köln, Germany
Cite this as:
Simon ST, Pralong A, Radbruch L, Bausewein C, Voltz R: Clinical practice guideline: The palliative care of patients with incurable cancers. Dtsch Arztebl Int 2020; 117: 108–15. DOI: 10.3238/arztebl.2020.0108
For eReferences please refer to:
*2 These two authors share the position of last author.
University of Cologne, Faculty of Medicine and University Hospital, Department of Palliative Medicine: PD Dr. med. Steffen T. Simon, Dr. med. Anne Pralong, Prof. Dr. med. Raymond Voltz
University of Cologne, Faculty of Medicine and University Hospital, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD): PD Dr. med. Steffen T. Simon, Dr. med. Anne Pralong, Prof. Dr. med. Raymond Voltz
Department of Palliative Medicine, University Hospital Bonn: Prof. Dr. med. Lukas Radbruch
Ludwig-Maximilians-University Munich, Munich University Hospital, Department of Palliative Medicine: Prof. Dr. med. Claudia Bausewein
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