Abstract
Women with gynaecological malignancies often suffer significant physical and psychological symptom burden throughout the course of their disease. Despite advances in treatment, up to 25% of women diagnosed with a gynaecological cancers will die from recurrent disease. A palliative approach – delivered by the Gynaecology team, supported by a Specialist Palliative Care team as needed – can be offered alongside curative or life prolonging treatment as well as at end of life. This article reviews the management of common physical symptoms and complications experienced by patients with advanced gynaecological malignancies, including pain, nausea and vomiting, malignant bowel obstruction, constipation, malignant ascites, fistulating and fungating disease, anaemia and bleeding, and ureteric obstruction.
Introduction
Over 22,000 women are diagnosed with a gynaecological malignancy in the UK each year, accounting for approximately 12% of all female cancer diagnoses ( Table 1 ). Despite improvements in prevention, diagnosis and treatment (notably, cervical cancer incidence has fallen since the 1990s), many gynaecological cancers are more prevalent today due to increasing longevity and lifestyle factors such as rising obesity. Over 7500 women die annually from gynaecological cancers in the UK.
| Cancer site | Incidence per year | Deaths per year (% total cancer deaths in women) | Median 5-year survival (all stages) |
|---|---|---|---|
| Uterine | 9400 | 2300 (3%) | 75% |
| Ovarian | 7500 | 4100 (5%) | 45% |
| Cervical | 3300 | 850 (1%) | 61% |
| Vulval | 1300 | 440 (<1%) | 67% |
| Vaginal | 250 | 100 (<1%) | 65% |
Prognoses for patients with ovarian cancer are significantly worse compared to other gynaecological malignancies, as over two-thirds of cases present with advanced disease. If diagnosed at an early stage, up to 90% of women with ovarian cancer survive at least five years; however, five-year survival is under 5% when diagnosed at a late stage.
This article focuses on the clinical management of common physical symptoms and complications experienced by patients with advanced gynaecological malignancies. Box 1 gives an overview of key components of palliative care as outlined by NICE and the WHO.
National Institute for Clinical Excellence (NICE):
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The active holistic care of patients with advanced, progressive illness
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Management of pain and other symptoms and provision of psychological, social and spiritual support is paramount
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The goal of palliative care is achievement of the best quality of life for patients and their families
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Many aspects of palliative care are also applicable earlier in the course of the illness in conjunction with other treatments
World Health Organization (WHO):
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Palliative care affirms life and regards dying as a natural process
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It intends neither to hasten nor postpone death
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It enhances quality of life and uses a team approach to address patient and family needs
It is beyond the scope of this article to review advance care planning, provision of end of life care or dealing with psychological concerns. As per GMC guidance on treatment and care towards end of life, all doctors regardless of professional role must have the knowledge and skills to address these topics and thus ensure excellent provision of person-centred care. The Universal Principles of Advance Care Planning (2022) and NICE Guidance NG31 (Care of Dying Adults in the Last Days of Life) provide helpful overviews of key principles. The SPIKES communication model is widely used for addressing psychological concerns in the oncology and palliative care settings.
Common symptoms experienced by patients with advanced gynaecological malignancy
Pain
Pain is commonly experienced by women with gynaecological cancers, affecting more women as disease advances in the last months of life. Pain may relate to malignancy, treatment of malignancy, debility, other comorbidities, unrelated causes, or often a combination of these. Women with cervical cancer often experience neuropathic pain secondary to sacral nerve infiltration, whereas women with ovarian cancer may describe non-specific abdominal pain and distension arising from peritoneal disease, ascites or bowel obstruction. Patients with vulval cancer develop metastases less commonly, and may live for many years with distressing pain caused by local, fungating or fistulating disease. Cancer treatments may induce pain, e.g. chemotherapy-induced peripheral neuropathy, radiation fibrosis, and chronic post-surgical pain. It is important to note that female pain and pain experienced specifically by those from Black populations is more often under-investigated and undertreated. Timely and effective assessment and management of pain is crucial.
Assessment: thorough clinical assessment using a standardized pain assessment tool helps to identify aetiology and guide management. The choice of tool is important; for most people, a simple 11-point Numerical Rating Scale is appropriate, however specific groups may benefit from other tools such as the LANSS score for assessment of neuropathic pain, or the Abbey Pain Scale for those with cognitive impairment. The well-known SOCRATES acronym provides a structure for assessment of pain through history-taking, to determine the site, pattern of onset, character, radiation, associated symptoms, time course, exacerbating and relieving factors, and severity. The ‘Stanford Five’ questions are more patient-centred and are useful in a palliative care setting ( Box 2 ).
Cause – What the patient believes to be the cause of the problem
Meaning – What they believe the pain means (e.g. ‘my cancer must have come back’)
Impact – How the pain affects their quality of life, activities of daily living, etc.
Goals – What they expect from further medical treatments
Treatment – What they believe needs to be done next
Rather than being a sensory phenomenon involving nerve transmission via spinal pathways, pain is modulated by cortical factors; thus, pain which may be worsened by patients’ unaddressed concerns, fears and difficulties in psychological, emotional, social and spiritual domains. For this reason, purely pharmacological management plans are often insufficient to adequately address pain. Therefore, holistic assessment of unmet needs is key; this may lead to onward referral to clinical psychology, social care, chaplaincy or other supportive services.
Standard pharmacological treatment: analgesia should be commenced at a level appropriate for the patient’s severity of pain. The 3-step WHO analgesic ladder ( Figure 1 ) has been used for nearly 40 years; while it has the advantage of simplicity, it omits any role for non-pharmacological management, self-management or interventional techniques. Specialist clinicians treating cancer pain often choose to omit step 2, preferring to commence small doses of strong opioids rather than use equivalent doses of weak opioids. Analgesia should be regularly reviewed and titrated depending on the severity of pain, including down-titration to avoid or reduce side effects when possible.
Oral morphine is a strong opioid and is the first-line treatment of choice for severe cancer-related pain, in the absence of renal failure. When starting a strong opioid, any weak opioid should be discontinued and either a 4-hourly immediate release or a 12-hourly modified release strong opioid preparation commenced. In addition to a regular strong opioid, immediate-release PRN medication (dose usually prescribed as 1/6th of the total 24-hour background opioid dose) should be available for breakthrough pain, defined as an escalation in pain of moderate to severe intensity on a background of controlled pain. Incident pain is a specific type of breakthrough pain which occurs predictably when related to a specific activity, e.g. passing urine in the context of vulval cancer. Patients experiencing incident pain may benefit from a rapid-acting opioid such as fentanyl administered via the sublingual route – this should be initiated following advice from a specialist in palliative medicine.
Patients should be counselled on side effects of opioid medication when initiated, using method(s) of communication most suited to that patient’s needs, including written information if required. A discussion of driving while taking prescribed opioid medications should be held, in line with Department of Transport guidance. Nausea is typically transient and wears off after a few days, and can be managed with anti-emetics. Constipation and drowsiness are long-term side effects. Chronic opioid use can be associated with immune dysfunction and the development of drug tolerance. This should be kept in mind for patients with longer prognoses.
Symptoms and signs such as hallucinations and myoclonic jerks are indicators of early opioid toxicity, not side effects. These usually occur prior to respiratory depression and impaired consciousness, and should prompt urgent medication chart review, dose reduction, and investigation of possible causes which may include recent dose increase, new renal or hepatic failure, or other stressors such as infection or steroid withdrawal. Regular assessment for hallucinations and myoclonus should take place when up-titrating opioid doses. Naloxone may be required in cases of severe toxicity with reduced respiratory rate and impaired consciousness.
Patients with a viable oral route should receive oral analgesia where possible. Women with gynaecological cancer may experience nausea or vomiting which results in poor tolerance of oral medication or poor absorption from the gastrointestinal tract. These patients may benefit from the use of transdermal opioids (useful for stable pain) or subcutaneous opioids (e.g. in a syringe driver).
Adjuvant (non-opioid) medications can be used to manage pain at any step of the WHO analgesia ladder. When used in combination, their effect can be synergistic and may provide enhanced analgesia at lower doses of opioid, potentially reducing side effects. Non-opioids such as paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs) are widely accepted as useful treatment options for cancer-related pain, and should be considered if there are no contraindications. Patients should be made aware of the side effects of NSAIDs, including gastrointestinal bleeding, renal impairment and fluid retention. Celecoxib is the first-line NSAID of choice owing to a favourable side-effect profile and reduced risk of gastrointestinal bleeding. Anticonvulsant or antidepressant medications like amitriptyline and gabapentin are useful adjuvant medications in the management of neuropathic pain, which is often only partially opioid responsive. Muscle relaxants like diazepam or baclofen can be used for painful muscle spasm. Specialist palliative care referral is advised for difficult-to-treat pain when first- or second-line treatments are ineffective.
Specialist management: gynaecological cancers can metastasize to bones, although less commonly than other cancers. Radiotherapy is the treatment of choice for bone pain caused by bone metastases. Surgery can provide relief from bone pain due to a pathological fracture; prophylactic fixation surgery may be indicated where fracture risk is high, as indicated by Mirel’s score. Bisphosphonates can be valuable in the management of patients with pain related to hypercalcaemia and metastatic bone disease. Corticosteroids are also useful in the management of bone pain, as well as having wider uses in palliative management for patients with symptoms of metastatic spinal cord compression, raised intracranial pressure, liver capsular pain, peripheral nerve involvement, visceral organ invasion, bowel obstruction, fatigue and anorexia.
If pain control remains inadequate then interventions such as neurolytic blocks, cordotomy, spinal cord stimulation, intrathecal opioid, and local anaesthetic administration may be considered. Intrathecal administration of opioid with local anaesthetic can improve pain control whilst reducing side effects, especially drowsiness and constipation. Interventional pain specialist services are geographically variable; patients may need referral out of area to access these procedures.
Non-pharmacological management: non-pharmacological options can be used together with medication to aid pain management and include reflexology, massage and aromatherapy, acupuncture, hypnotherapy, hydrotherapy, visualization and relaxation techniques, talking therapies such as cognitive-behavioural therapy, and transcutaneous electrical nerve stimulation (TENS).
Practice points: pain:
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Accurate clinical assessment of cancer-related pain as part of a wider holistic assessment will help determine aetiology of pain and guide management with a combination of pharmacological, interventional and non-pharmacological approaches.
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Gynaecologists should be confident and competent to initiate cancer pain management, referring to specialist palliative care teams when required in more complex cases.
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If pain control remains inadequate despite optimization, interventional techniques may be considered.
Nausea and vomiting
Nausea and vomiting affects 50–70% of patients with advanced malignancy and is severely debilitating when untreated. Nausea and vomiting are triggered by activation of central receptors throughout the cerebral cortex, vomiting centre, chemoreceptor trigger zone (CTZ) and vestibular apparatus, and/or peripheral receptors in the gastrointestinal tract. Patients experiencing nausea and vomiting are at risk of other poorly controlled symptoms as well as pain and dehydration.
Specific causes of nausea and vomiting which commonly affect women with gynaecological malignancy include chemotherapy, opioid medication, constipation, bowel obstruction and metabolic abnormalities such as uraemia, hypercalcaemia and deranged liver function.
Assessment: establishing the cause of nausea is central to guiding management ( Table 2 ). Important features from the history include the pattern, quantity, exacerbating and relieving factors, bowel habit and previously trialled medications and route of administration. Clinical examination may reveal evidence of dehydration, sepsis or drug toxicity. For instance, patients with advanced ovarian cancer may present with vomiting secondary to bowel obstruction or ascites which may be evident on abdominal examination. Biochemical abnormalities such as hypercalcaemia, uraemia and deranged liver function should be excluded.
