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178 Chapter 13
Symptoms and Clinical Diagnosis
Patients with lung cancer, especially right-sided, are at
particular risk of SVCO. Symptom onset is often insidious,
over weeks, allowing collateral blood vessels to develop,
resulting in visibly engorged subcutaneous veins on the
chest, neck and upper abdomen. Two-thirds of patients
complain of breathlessness and half of facial swelling or a
feeling of fullness in the head. The symptoms (see Table 3)
may be exacerbated by bending forwards or lying down.
Occasionally symptoms of SVCO may develop acutely due
to sudden occlusion. In these cases, the patient may
become acutely unwell.
Investigations and Initial Management
Although symptoms are often uncomfortable, SVCO is
rarely life-threatening unless oxygenation is severely com-
promised. For patients without a known cancer diagnosis,
urgent referral to the respiratory or acute oncology team is
required. For those with a known cancer, urgent contact
should be made with their existing oncology team. A con-
trast-enhanced CT thorax confirms the diagnosis.
The role of steroids is unproven although they are
often given; dexamethasone 16 mg daily (with gastric
protection) may help. Steroids should not be given
“blind” without specialist guidance if the underlying
diagnosis is not known. Rarely, high-grade mediastinal
lymphoma may present as SVCO, in which case steroids
may induce tumour lysis syndrome, threatening renal
function, and obscuring a histological diagnosis.
Anticoagulants are only indicated where associated
thrombosis is demonstrated.
Active treatment of SVCO may provide relief from dis-
tressing symptoms and is indicated in all but the frailest,
terminally ill patients who may be helped more by pallia-
tive symptomatic measures alone.
If the patient is breathless, bed rest and elevation of the
bed head may be helpful. Oxygen should be used only if it
gives symptomatic relief or when the patient is hypoxic.
Analgesia and antitussives may help patients who have
headache and cough.
Subsequent Treatment
The aim of treatment is to relieve symptoms and, if pos-
sible, reverse the underlying process. Treatment decisions
are based upon an understanding of the underlying malig-
nant diagnosis, prognosis and likely sensitivity to chemo-
therapy and radiotherapy.
Where response to chemotherapy or radiotherapy may
be delayed or insufficient, insertion of a stent under
radiological control gives rapid and often immediate
relief of symptoms, most resolving within 72 hours [17].
Urgent referral for stenting should be considered for
severe symptoms or for relapse following treatment with
other modalities. Caution must be exercised however,
with the placement of stents in patients with a good prog-
nosis, especially those with curable disease, as fibrosis
and narrowing occurring some months after stenting may
require further intervention with the risk of intractable
symptoms. Following stenting, treatment with chemo-
therapy or radiotherapy can be considered for patients
who remain fit enough.
Outcome
The average survival of patients diagnosed with a malig-
nant cause of SVCO is eight months, but the prognosis
depends heavily on the underlying histology and stage of
disease at presentation. In lung cancer, relapse occurs fol-
lowing radiotherapy and/or chemotherapy in approxi-
mately 17% of patients over a period of 1–16 months
following treatment [16].
Follow-up
Where anti-cancer treatment is undertaken, care should be
centred at the specialist unit providing the treatment until
toxicity has settled. Following treatment, patients with
incurable disease should be cared for in a home setting
with GP and palliative care support, with oncology avail-
able as an “SOS” option.
Table 3 Symptoms and signs of SVCO.
Symptoms Physical Signs
• Breathlessness
• Head fullness
• Headache
• Nasal congestion
• Epistaxis
• Cough
• Chest pain
• Dizziness
• Dysphagia
• Hoarse voice
• Neck vein distension
• Facial/arm swelling
• Dyspnoea
• Distension of superficial
veins (chest/abdominal wall)
• Plethora
• Facial or conjunctival
oedema
• Central or peripheral
cyanosis
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Managing Complications of Cancer 179
a sudden increase in pain, makes a pathological fracture
likely. Spinal cord compression should also be considered
and urgent specialist referral for investigation is indicated
(see MSCC section).
Management
The management of bone metastases depends upon the
symptoms arising, disease trajectory, patient condition and
wishes, and, importantly, the presence/risk of pathological
fracture.
The Mirel’s score is a well-established scoring system to
estimate the probability of a given metastatic lesion result-
ing in fracture [22] (Table 4). A score of eight or more indi-
cates a high risk of fracture and orthopaedic review should
be sought to consider prophylactic fixation with weight-
bearing minimized through the affected region until defin-
itive treatment is complete. Good results are anticipated in
all but the frailest patient. Where surgical stabilisation is
not possible the risks and benefits of weight-bearing
should be discussed with the patient.
Treatment of Uncomplicated Bone
Metastases
General Measures
The initial priority is analgesia. While nonsteroidal
anti-inflammatory drugs (NSAIDs) are routinely used in
practice, the evidence supporting their role was found to
be weak in a systematic review of the available literature
[23]. Steroids, for example dexamethasone 4–6 mg daily,
can be helpful as a short-term adjunct to other analgesics
but, if not helpful after a week’s trial, should be discontin-
ued. If NSAIDs or steroids are continued, gastric protec-
tion should be prescribed. The mainstay of managing
severe pain from bony metastases is, however, strong
Bone Metastases
Bone metastases are common, especially in cancers of the
breast, prostate, lung, and kidney. Widespread bone lesions
are also a feature of multiple myeloma. Up to 70% of
women dying of breast cancer have been found to have
radiological evidence of bone metastases while these are
present in almost all men dying of prostate cancer [18, 19].
Although many patients will be asymptomatic, around a
third present with pain [20]. Other complications of bone
metastases include pathological fracture, nerve compres-
sion, and hypercalcaemia.
Symptoms and Clinical Diagnosis
Pain due to bone metastases is commonly unrelenting,
nagging and progressive. It may be present at rest, is often
exacerbated by movement (functional pain) and can be
associated with referred pain, restriction of movement,
and neurological impairment.
Investigations
Initial investigation with plain X-rays of the affected area is
required to confirm the diagnosis and rule out patholog-
ical fracture ahead of specialist review. Orthogonal (i.e.
perpendicular) views of long bones are required as some
metastases may be visible only on one view. Lesions may be
sclerotic (with areas of increased bone density due to bone
deposition) or lytic (with areas of increased bone lucency
due to bone destruction). Prostate cancer classically results
in sclerotic metastases although lytic disease may occur,
whereas myeloma causes marked lysis of the bone. Breast
and lung cancer often give a mixed picture of sclerotic and
lytic metastases. Renal cancer metastases are often large
and vascular.
An isotope bone scan is more sensitive than a plain
radiograph for the investigation of bone metastases and
can be considered where suspicion remains despite an
unremarkable plain radiograph. In cases of difficulty, or if
surgery is contemplated, an MRI scan of the affected area
may be helpful.
Pathological Fracture
Approximately 20–50% of patients with bone metastases
will experience a pathological fracture [21]. These are usu-
ally associated with lytic bone metastases, particularly in
weight-bearing bones, including both spinal and long
bones. Sudden loss of function or mobility, especially with
Table 4 Mirels’ score for impending pathological fracture [22].
Score
1 2 3
Site Upper limb Lower limb Peritrochanteric
Pain Mild Moderate Functional
Lesion Blastic Mixed Lytic
Size <1/3 1/3–2/3 >2/3
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180 Chapter 13
opioids [20]. Pre-emptive analgesia is helpful for incident
pain (pain on movement). Pain may also be reduced by
resting the affected area. Consultation with physiothera-
pists and occupational therapists may be helpful, particu-
larly if aids and adaptations are required.
Radiotherapy
For uncomplicated, painful bony metastases requiring
strong opioids, local radiotherapy is the treatment of
choice [24]. In bone metastases, approximately 60% of
patients will experience pain relief with a complete
response in 24%, a median of 2-4 weeks after a single dose
of radiotherapy [25]. Palliative radiotherapy given in this
way can be repeated if the pain recurs with a good chance
of a second response and little added toxicity [26].
A flare of pain is experienced by approximately one third
of patients during the first week following radiotherapy.
This can be reduced from one in three to one in four
patients by dexamethasone, 8 mg OD, taken at least one
hour prior to radiotherapy and for the following four days
[27]. Concurrent gastric protection should be considered.
“Hemibody radiotherapy” in which a single dose is
delivered either to the upper or to the lower half of the
skeleton [28] is rarely used in current practice due to the
availability of systemic therapy options.
Systemic Anticancer Treatments
Systemic anti-cancer treatments, including hormones for
breast and prostate cancer, chemotherapy, targeted agents,
and immunotherapy may be beneficial in appropriately
selected patients.
Bone-targeted Agents
Bone-targeted agents such as bisphosphonates and deno-
sumab inhibit bone resorption and have been shown to
reduce skeletal-related events (SREs) across a range of can-
cer diagnoses [29]. SREs include pathologic long bone
fracture, spinal cord compression, radiotherapy for pain
relief, requirement for surgery and episodes of malignancy
associated hypercalcaemia. Bisphosphonates can be deliv-
ered intravenously or orally and although oral prepara-
tions improve the convenience of treatment they are less
well-tolerated. Denosumab is delivered subcutaneously
under specialist guidance. In both cases specific side-
effects include flu-like symptoms, hypocalcaemia (the risk
of which is reduced by checking for and correcting vitamin
D deficiency prior to commencement) and osteonecrosis
of the jaw (a rare but painful event, minimized by under-
taking dental checks and completing preventative den-
tistry prior to commencement).
Bisphosphonates can also be used to manage malignant
bone pain for patients with myeloma, breast, lung, and
prostate cancer [30]. This approach is particularly valuable
for patients with multi-focal bone pain and those with
relapse beyond radiotherapy. In this situation they are usu-
ally delivered as an intravenous (IV) infusion. In bone
metastases from prostate cancer, a single trial has demon-
strated the non-inferiority of intravenous ibandronate to a
single fraction of palliative radiotherapy [31].
Percutaneous Ablation
Where conventional treatments are unsuccessful, radiofre-
quency ablation (RFA) or cryotherapy can be used to
destroy bone metastases, with or without the subsequent
injection of cement into the bone to consolidate bone
structure. This is particularly useful for lytic lesions of the
pelvis that are not amenable to prophylactic surgical fixa-
tion. These techniques require operator expertise, are not
available in all centres and are supported by very limited
randomized data.
Outcome
For bony metastases not complicated by nerve compres-
sion, fracture, or hypercalcaemia, treatment outcomes are
relatively good. Many patients will be able to reduce their
analgesic requirement and/or improve their mobility
following treatment. Prognosis is strongly influenced by
primary diagnosis, performance status, and the presence of
visceral metastases.
Follow-up
Patients with bony metastases often have several sites of
pain and more will usually reveal themselves with time.
Close follow-up is therefore required in the community to
ensure adequate analgesia and appropriate, prompt referral
back to specialist services when needed. Social services,
occupational and physiotherapy services may also be
needed to allow patients with reduced mobility to return
safely and comfortably to their own homes.
Treatment of Impending or Completed
Pathological Fracture
Surgical Fixation
An established pathological fracture in a weight-bearing
long bone is treated surgically in all but the frailest patient.
Those of the upper limb may be fixed surgically but in
unfit patients immobilisation will usually provide
improved pain control and radiotherapy can be consid-
ered. The decision to pursue surgery in those near the
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Managing Complications of Cancer 181
Diagnosis and Early Suspicion
Brain metastases frequently present with headaches,
although approximately 18% present with seizures [39,
40]. Brain metastases should be considered in all those
known to have cancer presenting with any of the symp-
toms listed in Table 5. Initial investigation is usually with
neurological examination and CT scan.
Management
In many patients, the presence of cerebral metastases is a
component of widely disseminated disease. The focus of
management for this group is symptomatic care and
consideration of psychosocial needs. For a selected group
of patients with a better prognosis, anti-cancer treatments
may be appropriate.
General Symptomatic Measures
Cerebral Oedema and Raised Intracranial Pressure
Acute treatment with steroids is guided by symptom severity
and associated oedema on imaging. An initial dose of 8 mg
dexamethasone is reasonable and should be given parenter-
ally only when absorption is uncertain (e.g. in the presence
of vomiting). Concurrent gastric protection is required. This
should be followed by regular dexamethasone (up to 16 mg
daily in one or two doses, the later dose given before 2 p.m. to
avoid night-time wakefulness (though this should not pre-
clude emergency administration of the first day’s dose)). The
steroid dose can be swiftly decreased, over days to weeks, to
the minimum dose necessary to manage symptoms. IV man-
nitol is rarely needed to reduce intracranial pressure in
patients whose condition is worsening rapidly.
end-of-life requires careful multi-disciplinary conside-
ration of the risks and benefits of intervention and
discussion with the patient. Functional outcome after sur-
gical fixation of an impending pathological fracture is usu-
ally excellent although overall outcome will depend on the
patient’s general state of health and performance status.
Vertebroplasty
For spinal lesions, vertebroplasty is frequently used in the
treatment of osteoporotic vertebral fractures and can be
considered for the treatment of painful spinal metastases
not responsive to conservative approaches [32, 33]. A ver-
tebra that contains a painful metastasis is injected with bone
cement under sedation and radiological screening. If there
is loss of bony height, there is also an option to restore some
of the lost height by the use of a balloon, termed a kypho-
plasty [34]. A randomized study demonstrates this approach
offers superior pain control to non-surgical treatment [35].
Radiotherapy
Following surgery for either an impending or established
fracture, postoperative radiotherapy is usually offered 4–6
weeks after the surgery to allow for soft-tissue healing. This
aims to prevent local progression and reduce the need for
further surgical intervention although the evidence support-
ing this is extremely limited [36]. The role of post-operative
radiotherapy should be considered in the context of expected
prognosis; local progression and implant failure take time to
occur. A pathological fracture can be managed with radio-
therapy alone, although reduction in functional pain is very
uncertain and significant risk of fracture non-union exists.
Rehabilitation and Discharge Planning
The chances of a patient rehabilitating successfully will
depend on many factors, particularly their general health
and performance status. Other painful bony metastases
may slow progress, especially if they occur in a limb that is
required to take more weight following surgery. As for
spinal cord compression, discharge planning may require
the coordinated action of several teams.
Brain Metastases
Metastases to the brain affect 5–20% of patients with cancer
[37, 38]. They are common in lung cancer (affecting approxi-
mately 20% of patients), with markedly lower rates in other
diagnoses; renal cancer (6–10%), melanoma (7%), breast can-
cer (5%) and colorectal carcinoma (<2%). In most patients,
the diagnosis of cerebral metastases carries a poor prognosis.
Table 5 Common symptoms and signs of brain metastases.
Common Symptoms and Signs of Brain
Metastases %
Headache
Nausea/vomiting
Focal weakness/hemiparesis
Confusion
Unsteadiness
Seizures
Dysphasia
Visual disturbance
49
30
32
21
18
12
6
6
Source Tsao et al. [40].
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182 Chapter 13
expertise, fitness for surgery, the size and site of the metas-
tasis, and patient choice [42]. Surgery may be considered
more appropriate where there is no known primary cancer,
when the metastasis is too large for SRS, and when raised
intracranial pressure causes severe symptoms, especially
with hydrocephalus due to posterior fossa lesions.
The addition of whole brain radiotherapy to either of
these local treatments reduces the risk of relapse in the
brain but does not impact on overall survival and is associ-
ated with more side-effects [40, 43].
Extensive Brain Metastases
Whole Brain Radiotherapy (WBRT)
WBRT has previously been a common treatment for brain
metastases. With the increasing availability of SRS, WBRT
use has declined dramatically to only those who would be
eligible for SRS but whose cerebral disease is too extensive.
It is usually delivered over 1 to 2 weeks. Steroids are
continued throughout and reduced once treatment is
complete as determined by symptoms. Cessation is not
possible for many patients.
Recent studies using patient-rated scales suggest that
symptomatic benefit following WBRT is the exception
(approximately 20% at 1 month), with benefit often out-
weighed by side-effects (Table 6) [44, 45]. Indeed, the prac-
tice-changing QUARTZ randomised trial in non-small cell
lung cancer demonstrated radiotherapy offered no benefit
over steroids alone, in terms of survival, quality of life or
steroid sparing effect [46]. For patients with a poor
performance status and poor prognosis, treatment with
steroids, concentrating on end-of-life care, symptom con-
trol, and supportive measures may be the best option.
Headache
Headache usually responds to steroids. Regular
paracetamol with the addition of a weak or strong opioid
(with concurrent laxatives) may be required.
Seizures
Once intracranial pressure is reduced, seizures may sub-
side, however some patients require regular anticonvulsant
medication (e.g. levetiracetam). Advice can be sought
from the patient’s oncology team or local neurology ser-
vices. For terminally ill patients with cerebral metastases
and uncontrolled fitting parenteral benzodiazepines may
be required, for example, midazolam by continuous subcu-
taneous infusion (CSCI) (see Chapter 20: Care in the Last
Days of Life and after Death). This can cause drowsiness,
and levetiracetam via CSCI is an option where avoidance
of sedation is preferred.
For patients whose seizures have previously been well
controlled, consideration should be given to the role of
concurrent medications which can lower the seizure
threshold. Prophylactic use of anti-epileptic medications
(before seizures have occurred) has not been shown to
reduce seizure incidence [41].
Nausea and Vomiting
This usually responds to measures which reduce intracra-
nial pressure, but anti-emetics, such as cyclizine, may be
required and may need to be given parenterally at first.
Confusion, Agitation, or Psychosis
The introduction of steroids may reverse acute problems but
occasionally sedation may be required until the steroids take
effect or as part of the management of terminal agitation.
Specific Anti-cancer Treatment Options
Limited Brain Metastases
Surgical resection or stereotactic radiosurgery (SRS) are
both used widely for the treatment of patients with a limited
volume and small number of brain metastases, diagnosis of
which requires MRI confirmation. Patients also need to have
controlled/controllable extra-cranial disease and a good
performance status and prognosis. Decision-making is
guided by the local neuro-oncology multi-disciplinary team.
SRS uses finely focused beams of radiation, very
restrictive immobilisation, and image guidance to pre-
cisely treat metastases and limit toxicity. This is available in
the United Kingdom in several larger radiotherapy centres.
Limited data are available to inform the comparison bet-
ween surgery and SRS. The choice depends on local
Table 6 Side effects of whole brain radiotherapy.
Acute
Late (>6 Months after
Completion of Treatment)
Temporary alopecia Difficulties with memory and
concentration
Headache Deterioration on neurocognitive
testing
Nausea Persistent alopecia
Redness and soreness
of the skin
Tiredness and
sleepiness
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Managing Complications of Cancer 183
disease. Close follow-up should be arranged in the
community where care is usually centred for those without
further anti-cancer treatment options.
Hypercalcaemia of Malignancy (HCM)
HCM is a usually reversible, potentially life threatening
condition with a significant symptom burden. Around
20% of patients with cancer develop hypercalcaemia [48],
making it a differential diagnosis for patients presenting
with symptoms of unknown origin. A mean survival of
2–3 months identifies HCM as a condition of advanced
disease [49].
HCM is most associated with: myeloma, breast, lung,
renal, and bladder cancers and squamous cell carcinomas
(SCC) – including head and neck, and cervix cancers.
“Red flags” for HCM are a diagnosis of SCC and the
presence of bone metastases (particularly in breast cancer
and myeloma) [49, 50]. Alternative causes of hypercal-
cemia should be considered, including endocrine and
pharmaceutical causes.
Hypercalcaemia is defined as a raised level of corrected
calcium [51]. As calcium binds to albumin, frail, cachexic
patients with low albumin level will present with artifi-
cially low calcium levels, hence the use of corrected
calcium levels. Severity of hypercalcaemia is defined in
Table 8 [51].
HCM is life threatening if untreated and, for a
proportion of presenting patients, this will be a “terminal
event.” In this situation, patients presenting with
“refractory HCM” (recurrent episodes of increasing fre-
quency on a background of extensive disease) may choose
to remain at home rather than seek hospital admission
and treatment. Open, honest discussions with patients
and families about the clinical picture, prognosis,
treatment burden, and wishes about place of care and
death will guide shared decision-making. Patients unable
Chemotherapy
Systemic chemotherapy is useful for some chemo-sensitive
tumours, such as small-cell lung cancer, germ cell tumours
and cerebral lymphoma. It may also be valuable in patients
with breast cancer. This is often part of multi-modality care
(including radiotherapy) and the benefits and side-effects
of its addition need careful consideration in the context of
the patient’s expected prognosis and other disease.
Rehabilitation and Discharge Planning
Many patients with brain metastases have a dramatic
change in their functional ability, independence and,
sometimes, personality. Their rehabilitation needs are sim-
ilar to those outlined for patients with MSCC. In addition,
some patients may need speech and language therapy.
Where swallowing is compromised, route of nutrition
should be considered and discussed with the patient with
input from dietetics team. For many patients, remaining at
home may be challenging due to loss of independence,
cognitive decline, and need for nursing care. Changes in
cognitive function can make the safe delivery of care at
home problematic while often causing distress for rela-
tives. There is a need for psychological support for both the
patient and their carers.
Outcome
The survival of patients with cerebral metastases is usually
limited. Performance status is the strongest predictor of
survival although patients with non-small-cell lung cancer
have a particularly poor prognosis with a median survival
of 2–3 months. Table 7 summarises the factors influencing
survival [47].
Follow-up
Symptomatic progression of brain metastases is common
and is often accompanied by progressive extra-cranial
Table 7 Factors affecting survival in patients with brain
metastases.
Factors that Improve
Survival
Factors that Reduce
Survival
Solitary metastasis Poor performance status
Long disease-free interval
before relapse
Uncontrolled extra-cranial
disease
Primary site breast Meningeal disease
Younger age
Table 8 Severity of hypercalcaemia.
Corrected Serum
Concentration
Mild Hypercalcaemia 2.60 – 3.00 mmol/l
Moderate Hypercalcaemia 3.01 – 3.40 mmol/l
Severe Hypercalcaemia Greater than 3.40 mmol/l
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184 Chapter 13
to make their wishes known because of a loss of capacity
may have an Advance Care Plan that can guide decision
making alongside discussion with family or significant
others.
Symptoms and Clinical Diagnosis
Clinical manifestations of hypercalcaemia are detailed in
Box 1. Symptoms may be subtle and slow to manifest or
present acutely with a rapid physical and cognitive decline
related to rising calcium levels. The more quickly levels
have risen the greater the severity of symptoms [52].
Management of Associated Symptoms
Until normocalcaemia is established it may be necessary to
palliate associated symptoms. Anti-emetics and laxatives
administered via an appropriate route may be required.
Local management guidelines for delirium should be fol-
lowed with support from the palliative care team or psychi-
atry colleagues as necessary. Monitoring fluid balance,
serial blood tests, and ECGs can add to the clinical
picture.
Treatment
First line treatment is rehydration with intravenous normal
saline (rate dictated by clinical condition and comorbidi-
ties). Nephrotoxic medications (e.g. NSAIDs) and drugs
that inhibit urinary calcium secretion, for example, thia-
zide diuretics should be discontinued.
Intravenous bisphosphonates (e.g. zoledronic acid,
pamidronate, and ibandronate) are the mainstay of
treatment as they inhibit the action of osteoclasts and
reduce bone resorption and calcium release. Side-effects
are discussed earlier in the section on Bone Metastases and
locally agreed guidelines on dosing and treatment regi-
mens should be consulted with dose modifications for
patients with renal impairment. Denosumab (a human
monoclonal antibody that inactivates RANK-L) and cina-
calcet are available but not widely used for management of
HCM [53, 54].
An episode of hypercalcaemia may precipitate a change
in anti-cancer treatment, reducing the risk of subsequent
recurrence.
Follow Up
A robust management plan incorporating regular moni-
toring of calcium levels and early identification of symp-
toms should be agreed [51]. This may be coordinated by
the GP, community palliative care team, or oncology team.
Advance Care Plans should be regularly reviewed in the
context of the individual’s clinical situation. While for
many, regular bisphosphonate treatment is appropriate, for
some the increasing burden of hospital admission or reg-
ular out-patient visits in the face of increasing frailty and
symptom burden from advanced cancer becomes unac-
ceptable, and a plan for end-of-life care will be made.
Urinary Tract Obstruction
Obstruction of either the upper or lower urinary tract can
occur. The level of obstruction dictates management.
Severe obstruction can result in obstructive nephropathy
(ON) with subsequent deterioration in renal function
leading to acute kidney injury (AKI) and, potentially,
death if both kidneys are affected [55].
Lower urinary tract obstruction is precipitated by
bladder outflow obstruction, detrusor muscle dysfunction
or urethral obstruction (Table 9) [55, 56]. Symptoms
include urinary retention, supra-pubic, or abdominal pain.
Upper urinary tract obstruction involves obstruction
of the renal collecting system, usually at the level of the
Box 1: Clinical Manifestations
of Hypercalcaemia
Clinical Manifestations
Neurological Fatigue and drowsiness;
cognitive changes ranging
from poor concentration,
forgetfulness, mood changes
to delirium, stupor and coma
Gastrointestinal Nausea, vomiting, anorexia,
constipation, and with more
insidious onset, gastric
ulcers, and pancreatitis
Renal Polyuria (excessive diuresis),
polydipsia (thirst),
dehydration, renal function
impairment. Less commonly
in HCM – nephrolithiasis
(stone formation)
Cardiac Arrythmias, shortened QT,
Prolonged PR, wide T,
bradycardia and potentially,
cardiac arrest
Other Bone pain, hypotension, dry
mouth, itch
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Managing Complications of Cancer 185
ureter (see Table 10). Symptoms include abdominal or
flank pain, nausea, and vomiting.
Investigations
Initial management is guided by the severity of obstruc-
tion, degree of urinary retention, and renal impairment.
Assessment may include urinalysis, abdominal examina-
tion, neurological assessment, medication review, serial
blood tests – particularly urea and electrolytes to gauge
the degree, and progression of renal impairment. A
urinary tract Ultra Sound Scan (USS) will confirm urinary
retention, megaureter, and hydronephrosis. Abdominal/
pelvic CT can identify underlying causes of obstruction.
Malignant Spinal Cord Compression should be consid-
ered as a cause of urinary retention.
Management
The primary aim of any intervention is to relieve the
obstruction [55]. Prompt discussion with urology col-
leagues is advised as management options, including sur-
gery, stenting, or bladder irrigation, may be considered
before anti-cancer treatments. Where renal function dete-
rioration is life threatening, discussion with renal physi-
cians should be considered to assess the role of temporary
renal replacement therapy.
Early management of lower urinary tract obstruction
can include urethral or supra-pubic catheterization, which
also ensures accurate fluid balance measurement, particu-
larly important in the management of AKI.
The two commonest management options for upper
tract ON are placement of percutaneous nephrostomy or
insertion of internal ureteric stents [55, 57]. Percutaneous
nephrostomy placement is radiologically guided: a tube is
placed through the skin into the kidney. Urine then drains
into a bag placed on the skin. Sedation is required and
patients may experience discomfort and pain during and
after the procedure.
Insertion of ureteric stents requires general anaesthesia
but avoids the requirement for external drains. Post-
procedure discomfort is possible.
There is little consensus on which approach is best. Both
bring risks of bleeding, infection/sepsis, tube, or stent
blockage and pain. Tube/stent replacement every 3–4
Table 9 Causes of Lower Urinary Tract Obstruction [55, 56].
Bladder outlet obstruction Tumour mass – pelvic, abdominal, or retroperitoneal mass/es;
lymphadenopathy
Calculi
Blood clot – “clot retention”
Benign Prostatic Hypertrophy
Prostate Cancer
Constipation
Drug induced (commonly caused by drugs with anti-cholinergic activity)
Indwelling or supra-pubic catheter blockage
Bladder dysfunction Neurogenic bladder dysfunction
Detrusor muscle dysfunction
Drug induced dysfunction – opioids; calcium channel antagonists;
“anticholinergics” and others
Urethral obstruction Obstructing tumour or lesions
Fibrosis (secondary to radiotherapy)
Urethral stricture
Paraphimosis
Table 10 Causes of Upper Urinary Tract Obstruction.
Intraluminal sources Obstructing tumour or lesions
Calculi
Ureteric stricture
Blood clot
Extraluminal source Tumour mass- pelvic, abdominal,
or retroperitoneal mass/es;
lymphadenopathy
Fibrosis
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186 Chapter 13
months is required to reduce complications and necessi-
tates hospital attendance.
Decision-Making and Outcomes
For patients with extensive or rapidly progressive disease
and no anti-cancer treatment options, it is essential to dis-
cuss the implications of interventions. Evidence of the ben-
efits of an interventional approach for patients with
advanced cancer and metastases is mixed. Some studies
demonstrate no significant difference in outcomes bet-
ween observation and intervention; others demonstrate
poor survival outcomes alongside complications affecting
quality of life if the interventional approach is adopted [57,
58].
In the palliative phase, quality of life concerns must be
balanced against the inherent risks of invasive interven-
tions. Reversing an AKI/ON may prolong life in the short
term, however, the patient may continue to deteriorate
from widespread cancer, or develop further distressing
symptoms. A purely palliative approach to symptom
management and emotional/spiritual support may be
more appropriate.
Follow Up
An interventional approach requires patients to be fol-
lowed up by urologists alongside their oncologist.
Community nursing and palliative care support may be
required, particularly for those electing for a conservative
management approach.
For information on the management of renal impair-
ment please see Chapter 18: Palliative Care in Advanced
Renal Disease.
Haemorrhage
Patients with cancer may develop bleeding for several
reasons:
• bleeding directly from a tumour or metastasis, including
malignant wounds (see the following section)
• invasion of tumour into blood vessels
• bleeding tendency due to thrombocytopenia, dissemi-
nated intravascular coagulopathy (DIC), uraemia, or
anticoagulants
• post radiotherapy telangiectasia (especially bladder and
GI tract)
• non-cancer causes, for example gastric ulceration due to
steroids or NSAIDs.
Where tumour invades a major vessel, a risk of life-threat-
ening “catastrophic” bleeding exists. Given the anxiety
associated with bleeding, this risk should be identified and
discussed calmly and sensitively with the patient and those
important to them. Patients should be prepared that a
small bleed may herald a subsequent larger event. Dark
coloured towels should be available and anticipatory pre-
scribing completed (acknowledging that, during the event,
this may not be used and staying with the patient may be
best) [59]. Management can be detailed in a bleeding crisis
plan. After such an event occurs all involved may require
an opportunity to de-brief.
The management of massive, terminal haemorrhage is
discussed separately in Chapter 20: Care in the Last Days
of Life and after Death.
Initial Assessment and Management
Initial assessment includes identification of bleeding
source and systemic impact by review of observations, Full
Blood Count (FBC), and clotting. Acute intervention
decisions are taken in the context of the patient’s prognosis
and advance care plan. Intravenous fluid, blood and
platelet transfusions maybe necessary.
Early medication review is required to identify the
prescription of drugs that increase risk of bleeding such as
NSAIDS, SSRIs, corticosteroids, and anticoagulant therapy.
A risk versus benefit approach to their use may be required,
necessitating discussion with the patient about their
choices. For example, balancing the risk of further bleeding
against that of thromboembolic events. Patients with
gastric bleeding should be commenced on a proton pump
inhibitor if this is not already in place.
Where bleeding is persistent and accessible, packing
may aid haemostasis in the short-term. In the case of epi-
staxis this is best carried out by an ENT surgeon. Similarly,
packing to reduce bleeding due to locally advanced cervical
cancer should be carried out by a gynaecologist or appro-
priately trained clinical oncologist. Topical therapies are
detailed in Table 11.
Drugs that reduce bleeding tendency may be helpful, for
example, tranexamic acid. Given as a dose of 500 mg-1 g
three times daily (orally or intravenously), this reduces
bleeding due to cancer without increasing the risk of
venous-thrombosis [60]. It should be continued for one
week after cessation of bleeding but can be re-trialled sub-
sequently if necessary. The risk of clot retention where
tranexamic acid is used for the treatment of haematuria
requires careful monitoring. DIC is a contraindication to
use of tranexamic acid.
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Managing Complications of Cancer 187
Subsequent management is determined following
discussion with the patient, recognising their preference
for further intervention, expected prognosis, prior treat-
ments, and extent of persistent bleeding.
Radiotherapy
Palliative radiotherapy is used to control bleeding from
both primary and metastatic cancers. Reduction in bleeding
is reported in 80–100% of patients depending upon diag-
nosis [61–65]. Treatment is usually restricted to a short
course; typically 1–5 days. Previous radiotherapy to the
area does not necessarily preclude further treatment – this
is an oncological decision.
Endoscopic Procedures
Endoscopic procedures, including bronchoscopy, oesoph-
ago-gastroscopy, cystoscopy, and colonoscopy offer visu-
alisation and treatment of a range of bleeding sites.
Improvement is frequently observed but rebleeding
remains a problem [65]. These invasive procedures require
careful consideration and discussion with the patient in
the context of prognosis.
Vascular Embolisation
Occasionally, bleeding from a vascular tumour can be
reduced by embolisation of its blood supply. The type of
bleeding and vasculature of the tumour and surrounding
normal tissues are critical to the decision to proceed.
Patients must be able to lie flat throughout the procedure.
An interventional radiologist can advise on the suitability
of the procedure, including further investigations to define
this. Post-procedure rebleeding can occur early (due to
incomplete embolization) and late (due to re-vascularisa-
tion). Tumour necrosis may occur, leading to pain and flu-
like symptoms [65].
Symptomatic Measures
Where initial management, radiotherapy, endoscopy, and
embolization are unsuccessful bleeding from a range of
sites can be managed as detailed in Table 11 in the malig-
nant wounds section.
Malignant Wounds
Primarily arising from skin neoplasms, malignant
wounds are also caused by localised or metastatic infil-
tration of tissue and vasculature from other primary
cancer sites [66]. Prevalence may be up to 14.5% in
patients with advanced cancer, with malignant wounds
most seen in patients with breast, head and neck, and
primary skin cancers [67]. Classification of the wound
dictates management.
Distinct from pressure sores or ulcers, malignant
wounds may be classified as:
• Sub-cutaneous nodules (including metastatic deposits,
primary tumours, and sub/cutaneous lymphoma)
•
Malignant ulcers (Marjolin’s ulcers)
Table 11 Management of symptoms related to malignant wounds [72–74, 77].
Symptom Management
Bleeding (including from
sub-cutaneous, rectal,
bladder, gynaecological,
or oral cancers)
Topical dressings soaked in adrenaline (epinephrine) 1/1000 – short term use for superficial
wounds
Haemostatic alginate dressings (with caution)
Intravesical (bladder instillation) of tranexamic acid
Topical administration of tranexamic acid or sucralfate as soaks, pastes/gels, mouthwash
Wound dressings / packs (+/- haemostatic medication as above)
Silver nitrate sticks to cauterise bleeding points
Radiotherapy
Wound pain Regular analgesia
Appropriate non-adherent dressings
Morphine 0.1%: Mix 1 mL of Morphine Sulfate 10mg/mL with 8g of Intrasite gel
(Continued)
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