Dr Pia Bader
Consultant urologist, FEBU Staedtisches Klinikum Karlsruhe
One of the main fields in urology is oncology, which includes pain management and palliative care in patients with cancer, particularly of the prostate. The four main goals of care for these patients are: prolonging survival, optimising comfort, optimising function, and relieving pain. Table 1 provides a hierarchy of treatment principles through which to achieve these goals.
Individualisation of therapy is the most important guiding principle of care. It is achieved by continually assessing each individual patient on the benefits of treatment for pain relief versus the side-effects of treatment (that is tolerability). In this way, the optimal outcome for pain relief versus side-effects – and therefore quality of life – will be achieved for each patient.
Local therapy is preferred to systemic treatment. However, if local therapy is neither feasible nor well tolerated, it is better to use symptomatic measures. In simple cases, such measures as stenting can make analgesic medication redundant. Examples include inserting a ureteral stent or a bladder catheter in case of obstruction, or performing an intestinal stoma in case of recurrent subileus caused by peritoneal carcinomatosis. The importance of physiotherapy and psychological counselling cannot be emphasised too strongly.
Non-pharmacological therapies of cancer pain
Surgery may help to relieve symptoms caused by specific problems, such as renal or bladder obstruction, unstable bony structures, spinal cord compression. Radical surgery to excise locally advanced disease in patients without evidence of metastatic spread may help prevent painful local problems.
Bone metastases are the commonest source of pain during the evolution of cancers, causing anxiety, isolation, immobility, depression and sleeplessness. Daily activities are disrupted and analgesia is required in about 30% of patients with osseous metastases.
Radiotherapy and radionuclide therapy
External beam radiotherapy may increase bone stability and reduce pain in single lesions. Radiopharmaceuticals may be an option in multiple painful metastases.
The most important radiopharmaceuticals are 89Sr (strontium-89), 153Sm (samarium-153) and, to a lesser extent, 186Re (renium-186). 89Sr and 153Sm are indicated for bone pain resulting from osteoblastic skeletal metastases, involving more than one site, but without spinal cord compression.1 The overall response rate is 60%–80%, but pain reduction is unlikely to occur within the first week and can occur as late as one month after injection. Analgesics should be continued until bone pain improves. Because of myelosuppression, the white blood cell count should be >3500/μL and platelets >100.000/μL. Warning: radiopharmaceuticals should not be administered if the glomerular filtration rate <30 mL/min.2
Radiotherapy is also well established for palliation of symptomatic bone metastases,3 with complete or partial pain relief in 20%–50% and in 50%–80% of patients, respectively. The onset of pain relief varies from a few days to four weeks. Single-fraction radiotherapy (recommended dose, 8 Gy) is as effective as multifraction radiotherapy.4
Metastatic epidural spinal cord compression is a severe complication affecting between 5%–10% of patients with cancer. Neurological function at the onset of treatment determines the functional outcome. Delayed treatment is the most common cause of an unfavourable outcome.5
Direct decompressive surgery is superior to radiotherapy alone with regard to regaining ambulatory function, pain relief and recovering sphincter function.6 Radiotherapy is recommended as the primary treatment for patients unsuitable for surgery (Table 2). A multifraction regimen is usually preferable.
For impending pathological fractures, a prophylactic orthopaedic procedure should be considered.
Pharmacological treatment of cancer pain
Successful pharmacological treatment of cancer pain depends on the clinician’s ability to assess the presenting problems, identify and evaluate pain syndromes, and formulate a plan for comprehensive continuing care.
According to the principle that “causal therapy is preferred to symptomatic therapy”, the following therapeutics must be considered:
- Antibiotics may be analgesic when the source of the pain involves infection (e.g. pyonephrosis, abscess, osteitis pubis)
- Chemotherapy and the likelihood of its successful effect on pain are generally related to the likelihood of tumour response. For example, in 2004, two randomised trials of docetaxel-based versus mitoxantrone-based chemotherapies in prostate cancer7,8 demonstrated a pain response of 31%–35% with docetaxel-based regimens versus 22% with a mitoxantrone-based approach.
Bisphosphonates are pyrophosphate analogues. Their clinical effects are:
- Decreased risk of skeletal-related events (e.g. hormone refractory prostate cancer with bone metastasis)9
- Pain response in 60%–85% of the patients.9
Choice of drugs
Systemic analgesic pharmacotherapy is the mainstay of cancer pain management. It is based on three main groups of analgesic drugs, which are non-opioid analgesics, opioid analgesics, and adjuvant analgesics (corticosteroids, neuroleptics, benzodiazepines). Application of the World Health Organization (WHO) ‘analgesic’ ladder (Table 3), together with appropriate dosage guidelines, results in adequate pain relief in 70%–90% of patients.
Non-opioid analgesics, such as aspirin, paracetamol, and non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, diclofenac or metamizole, are the drugs of choice for mild-to-moderate pain (Step 1 of Table 3). Aspirin and, to a lesser extent, ibuprofen and diclofenac, inhibit platelet aggregation and increase the risk of bleeding diathesis, especially when combined with corticosteroids.10 This fact should be considered in patients with myelosuppression due to cancer, radiotherapy or chemotherapy or after surgery.
Moderate-to-severe cancer pain should generally be treated with a systemically administered opioid analgesic in combination with a non-opioid. For moderate cancer pain, weak opioids, such as codeine, oxycodone or propoxyphene, may be sufficient (Step 2 of Table 3 ). Severe pain should be treated with a strong opioid from the onset of therapy (Step 3 of Table 3).
Opioids should be administered by the least invasive and safest route possible capable of providing adequate analgesia, ranging from oral, rectal, transdermal, or sublingual to parenteral route (intravenous or subcutaneous).
Patients with continuous or frequent pain, usually benefit from scheduled “around-the-clock” dosing, aimed at preventing the pain from recurring. And, they should be provided with a so-called “rescue dose”, which is a supplemental dose taken as required to treat pain that breaks through the regular schedule.
Respiratory depression is possibly the most serious adverse effect of opioid therapy. However, tolerance to respiratory depression rapidly develops in a patient repeatedly given opioids, so that opioid analgesics can be used for chronic cancer pain without significant risk of respiratory depression. Adjuvant analgesics (Table 4) may be combined with primary analgesics in any of the three steps of the analgesic ladder.
Treatment of neuropathic pain
Other therapies include tricyclic antidepressants (amitriptyline, imipramine), anticonvulsants (gabapentin, pregabalin), topical treatments (lidocaine patch, capsaicin), N-methyl-D-aspartate (NMDA) receptor antagonists (ketamine), baclofen, local anaesthetics, and clonidine.11 Gabapentin and pregabalin are first-line treatments for neuropathic pain, especially if tricyclic antidepressants are contraindicated.
Invasive analgesic techniques
Tumour infiltration or compression of a peripheral nerve or plexus can result in severe neuropathic pain. Between 10% and 30% of patients do not achieve a satisfactory balance between relief and side-effects using systemic pharmacotherapy. However, anaesthetic and neurosurgical techniques may reduce the need for systemically administered opioids for the achievement of adequate analgesia.
Available techniques are :
- Reversible regional anaesthetic techniques (such as intercostal blockade)
- Superior hypogastric plexus block to control pelvic pain refractory to pharmacological treatment.
Continuous intrathecal or epidural administration of morphine alone or in combination with clonidine or bupivavaine. A temporary trial of spinal opiod therapy will help to assess the benefits of this approach before implantation of a permanent catheter.
Postoperative pain management in urological patients
Undertreated postoperative pain may result in increased morbidity (for example, pneumonia, thrombembolism) and mortality. Careful pain assessment – before and after treatment – can lead to more efficient pain control and adequate dosages of the correct drugs (Table 5).
Choice of analgesic agents
Paracetamol (acetaminophen) or other non-opioid analgesics are often sufficient for mild-to-moderate postoperative pain.
Nonsteroidal anti-inflammatory drugs are non-selective cyclo-oxygenase (COX) inhibitors. They produce analgesia without respiratory depression or sedation and decrease opioid consumption.
COX-2 selective inhibitors are approved for short-term postoperative analgesia. Compared with NSAIDs, they have fewer gastrointestinal complications and improved bone healing. Their long-term use is contraindicated in patients with cardiovascular problems because this class of drugs has the potential to increase thromboembolic events compared with placebo.
Metamizol (dipyrone) is an effective antipyretic and analgesic drug for mild-to-moderate postoperative pain. It is considered a useful analgesic by several European countries such as Germany and Switzerland, despite its prohibition in the USA and other European countries following single, reported cases of neutropenia and agranulocytosis.
Opioids are the first-line treatment for severe acute postoperative pain and can be used safely and effectively with careful titration against pain relief. Co-administration of paracetamol (acetaminophen) reduces the consumption of opioids.12
Neural block (intermittent or continuous local anaesthetic) can be used after urological surgical procedures to supplement postoperative analgesia.13
Intra-operative wound infiltration with local anaesthetic provides some postoperative analgesia and may reduce the requirement for systematic analgesia.14
Patient-controlled analgesia (PCA) is the most effective mode of systemic administration of opioids. However, epidural analgesia enables reduced drug use, greater patient satisfaction and superior analgesia compared with intravenous PCA.15
Successful management of oncological pain and postoperative pain requires a multimodal approach involving careful, ongoing assessment and evaluation. The guiding principle is to balance benefits of treatment against side-effects to provide the best quality of life achievable in each individual patient.
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- McQuay HJ et al. Radiotherapy for the palliation of painful bone metastases. Cochrane Database Sys Rev 2000;2: CD001793
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