Almost 1.4 million Americans were newly diagnosed with cancer in 2004, approximately 4,000 per day (1). In the same year, 564,000 U.S. deaths were attributed to cancer, about 22% of all deaths. It is estimated that over 10 million people in the United States are living with cancer at present, around 3% of the population. The demographic of cancer continues to slowly evolve with the overall number of cases slowly trending upward, and the number of long-term survivors, including those with chronic pain issues, continuing to grow (2).

The diagnosis of cancer is distressing to the patient in many ways. First, the patient fears that cancer will shorten his life. Second, the patient is apprehensive that the cancer will bring with its progression significant pain and suffering. Indeed, pain is already experienced by 20% to 50% of cancer patients initially at time of diagnosis. With cancer progression, 75% of patients with advanced cancer will experience pain (3). Up to 80% of cancer patients described their pain as having moderate to severe intensity.

According to the World Health Organization (WHO), an estimated 6.6 million people worldwide die from cancer every year (4). Recent WHO studies pointed out that cancer-related pain continued to be a significant source of global health concern. With advances in therapeutic modalities, about 80% of cancer pain can be controlled easily (5). Unfortunately, even with these advances, cancer pain remains widely undertreated even in developed countries (6). In the United States, the reasons for undertreatment of cancer pain are complex and encompasses many barriers, as outlined in Table 45-1.

Recently, there is a growing awareness that pain control is an essential part of comprehensive cancer care. Some studies have showed a direct correlation between good pain control and cancer patient’s length of survival, as well as responsiveness to timely oncologic treatment (7,8). In addition to problems stemming from immobility (deep venous thrombosis, pneumonia), uncontrolled pain has also proven to be major risk factor in cancer-related suicides (9,10). Further, issues of long-term survival with increasing treatment options prolonging survival add to the complexity of care required. The landscape of “cancer pain” is shifting quickly into a chronic pain situation in many instances, thereby blurring previous lines of distinction in treatment strategies most suited for “noncancer” versus “cancer” pain (2).

Many pain clinics utilize a questionnaire to aid in and standardize assessment.

Objective observations of grimacing, limping, and vital signs (tachycardia) may be useful in assessing the patient, but these signs are often absent in patients with chronic pain (see Chapter 37). Pain evaluation should be integrated with a detailed oncologic, medical, and psychological history. The initial evaluation should include evaluation of the patient’s feelings and attitudes about the pain and disease, family concerns, and the premorbid psychological history. A comprehensive but objective approach to assessment instills confidence in the patient and family that will be valuable throughout treatment.

A comprehensive evaluation of the patients with cancer pain includes the following:

The physical examination must be thorough, although at times it is appropriate to perform a focused examination. In patients
with spinal pain and known or suspected metastatic disease, a complete neurologic examination is mandatory. When cognitive impairment is suspected, a mini-mental status examination will clarify the level of impairment and allow tracking over time (see Chapter 37). Gonzales et al. found new evidence of metastatic disease in 64% of patients, and this finding resulted in new antitumor therapy for 18% of patients evaluated by their pain service (21).

The clinical plan of care is developed after all items of the history are evaluated.

The large majority of acute cancer pain is due to tumor invasion of pain-sensitive structures. This invasion causes a derangement of physiologic processes including inflammation, edema, acidosis, and necrosis of pain-sensitive tissues. Further pathologic processes may include invasion of bone or soft tissues, obstruction of lymphatic or vascular vessels, distention of hollow organs, distortion of solid organs, and compression of nervous system structures (22). All of these cause typical acute cancer pain syndromes, most of which are diagnosable during the oncologic workup (see also Chapter 31, Tables 31-5,31-6,31-7,31-8,31-9). Many of these same pains improve with successful treatment of the tumor, thus reassessment is important because of the dynamic nature of tumor-related pain.

A significant source of pain can also be related to the cancer treatments. Most of the time, this pain is more chronic, with a gradual onset and often delayed diagnosis and treatment. Certain types of chemotherapy often cause painful peripheral neuropathy including the taxanes, platinum compounds, vincristine and its analogs, and some newer agents such as bortezomib (23). Often, this neuropathy is dose-related and resolves with a lowering of the dose of the offending agent in subsequent courses of chemotherapy. However, in some patients, the painful neuropathy is permanent, severe, and very disabling. It can lead to problems with gait or fine motor tasks of the hands. Radiation treatment may also cause neural injury in the form of plexopathy, chronic radiation myelopathy, and chronic radiation enteritis and proctitis, as well as nonspecific postradiation head and neck pain, most likely a myofascial pain syndrome (24). Other postradiation problems include an increase in long-term pelvic fractures (25).

Surgical treatment also can lead to chronic postoperative pain syndromes. For example, the post–radical mastectomy patient often has pain in the posterior upper arm, axilla, and anterior chest wall secondary to damage of the intercostobrachial nerve (26). Similarly, nerve damages during thoracotomy and radical neck dissection can cause pain in the distribution of the affected nerves (27). Phantom limb pain is especially common after amputation procedures, with burning and cramping sensation in the area of the amputated limb (28) (see also Chapter 31 and Tables 31-5,31-6,31-7,31-8,31-9).

The increasing use of combination treatments in numerous cancers, such as combined chemoradiation prior to surgical resection of head and neck or breast tumors for example, have increased cure rates. However, they may also increase the toxicity and long-term sequelae of treatment. In such cases, chronic pain may not be attributable to one or another of the therapies, and the term treatment–related toxicity has been coined to describe this new phenomenon (29).

As the pain syndromes become chronic—defined as lasting beyond the expected healing time course—the treatment algorithms become similar to those used for noncancer chronic pain. Many confusing issues may develop within this patient population, such as those patients with very slowly progressive cancer and associated pain that may last many years. In many cases the lines between treating cancer pain versus noncancer pain syndromes are blurring (2,30).

In any assessment of cancer pain, an understanding of pain classification is helpful in delineating both the mechanism of pain and its responsiveness to therapeutic interventions. Pain can be broadly classified into nociceptive and neuropathic pain; however, in many patients, both mechanisms may be operating, and in all patients, psychological and environmental factors contribute to pain.

Opioid analgesics are a mainstay of treatment for cancer pain. In the WHO three-step analgesic ladder, “weak” opioids are recommended for treatment of moderate cancer pain, whereas “strong” opioids are prescribed for severe cancer pain. The weak opioids have slightly less potency and also fewer side effects. Some common oral weak opioids are listed in Table 45-5.

These weak opioids are produced in combination with acetaminophen or aspirin, thus they are “weak” because of the limitation imposed by acetaminophen or aspirin ceiling doses, above which the patient is at higher risk of renal and liver toxicity.

The “strong” opioids are more potent because they are made in pure form, without addition of aspirin or acetaminophen. These opioids do not have a maximum ceiling dose, but at higher dosages, the patient tends to experience more frequent and significant side effects of nausea and vomiting, constipation, pruritus, somnolence, and cognitive impairment. Some common strong opioids are listed in Table 45-6.

It has been claimed that 70% to 90% of patients with cancer pain have satisfactory pain relief from pharmacologic therapies alone, following the WHO guidelines (36). This means, however, that 10% to 30% of these patients have pain that cannot be effectively managed with medications alone. Additionally, it must be pointed out that the standard 70% to 90% success rates using the WHO step-ladder include patients with mild, moderate, and severe pain grouped together, with higher success rates in the mild pain group. Thus, the 70% to 90% adequate cancer pain treatment almost certainly overestimates WHO approach success in the most severe cancer pain syndromes. The reasons for this failure of pharmacologic treatment are variable (37), varying from physician- to patient-related factors. The physician-related reasons for pharmacologic failure include inaccurate assessment of pain and deficiency in knowledge of current analgesics and adjuvant medications. Patient-related reasons range from fear of addiction to appearance of adverse side effects (38,39). Failure of pharmacologic control of cancer pain due to lack of efficacy of existing drugs in some patients is also commonly seen with cancer progression. Patients with advanced disease can present with intractable pain from multiple metastases and multiple pain sites (see Chapter 31, Tables 31-5,31-6,31-7,31-8,31-9).

Patients who fail to respond to conservative pharmacologic treatments may be candidates for interventional therapies. A large armamentarium of invasive procedures is available to achieve better control of cancer pain. However, the role of interventional therapies must be placed in the proper context. Usually, these procedures cannot be employed as the sole
treatment for cancer pain, especially for advanced cancer patients. Rather, they should be used as part of a multimodality approach in the treatment of cancer pain (40,41). However, in cases in which the risk–benefit ratio is favorable and outcome evidence is strong (i.e., celiac plexus block), the patient need not “fail” WHO ladder therapy to be a candidate for interventional pain therapy. As discussed previously, the etiologies of cancer pain are diverse, and pain is interrelated with the constellation of symptoms experienced by the cancer patient. Consequently, a global, multimodal approach to treatment of cancer pain is necessary. It includes the appropriate antineoplastic therapy, management of analgesics and adjuvant pain medications, behavioral and psychiatric support, and finally interventional therapies. Most often, interventional pain procedures will not completely eliminate the need for pain medications. The therapeutic goal of such procedures is to help alleviate cancer pain, reduce the overall analgesic need, and thereby minimize associated opioid-related side effects, with the overall aim of enhancing quality of life.

Prior to proceeding with any invasive pain procedure, communication between the pain physician and the relevant parties is absolutely essential. The patient must first be educated about the risks and benefits of the interventional procedure. He must be allowed an opportunity to have questions about the procedure extensively and satisfactorily answered. He must, at the same time, be grounded in realistic expectations in terms of outcomes and possible complications from the chosen procedure. The patient should be made aware of the efficacy of the procedure, duration of effectiveness, and possibility of failure of the procedure to provide complete or even partial pain relief. He must understand that the interventional procedure is part of a multimodal approach to pain control.

With cancer patients, especially those critically ill or preterminal, family members and caregivers are often involved in the decision-making process. Family support helps the patient cope emotionally with cancer disease and with procedural interventions. Like the patient, the family must also be educated and have realistic expectations about the procedure.

Effective communication with other professional members of the care team is also important. These include the patient’s oncologists, primary care providers, and all the relevant consultants. Treatment of cancer is a multidisciplinary effort. The interventional procedure should be planned in coordination with the overall cancer treatment. For example, the cancer patient may undergo chemotherapy with resultant thrombocytopenia. In such case, the interventional procedure must be carried out prior to or following chemoinduction, when the patient’s platelet count is normalized. Typically, other members of the patient’s care team are informed about the planned interventional procedure and given a chance to voice any input or concern.

A thorough physical examination of the patient prior to the procedure is also critical. This entails a complete neurologic evaluation. Interventional procedures for pain control involve neurologically sensitive tissues such as nerves and CNS structures. The objective of intervention is to disrupt or modulate pain pathways involved in nociception. Interventional procedures like neurolysis of peripheral nerves will not only block pain transmission but also block sensory and motor innervations as well. Consequently, it is important to document before and after the procedure a complete and thorough physical examination, with focus especially on pain and neurologic changes. Changes such as sensory and motor blockade are closely monitored after procedures.

Interventional therapies can be categorized into three groups: neurolytic techniques, neuromodulatory techniques, and surgical techniques. Neurolytic or neuroablative techniques are procedures that target the destruction of those nerves or neural structures that are involved in the generation or transmission of pain signals. Neurolytic lesions can be created using a variety of agents. Lysis is achieved with chemicals (glycerol, alcohol, or phenol), heat (radiofrequency coagulation), or cold (cryotherapy) (see also Chapters 39, 42, and 44).

Neuromodulatory techniques have as their basis Wall and Melzack’s gate control theory of pain (42) (see Chapters 40 and 41), which is also discussed in light of current knowledge in Chapter 51. Regardless of the exact locus of such a gate, the concept is accurate in describing how afferent input of all types is heavily modulated along the route of transmission into the brain. All of these modulation sites become therapeutic targets when discussing the treatment of pain (43). Neuromodulative techniques aim to modulate pain signals along the transmission pathway. These techniques include local anesthetic blockade or regional infusion of drugs at epidural, intrathecal, intraventricular, or perineural sites, and the electrical stimulation of the CNS and peripheral nervous system (PNS).

Surgical techniques are another class of interventional pain procedures, ranging from minimally invasive percutaneous vertebroplasty to highly invasive neurosurgical destructive techniques, including percutaneous cordotomy, dorsal root entry zone (DREZ) lesions, thalamotomy, cingulotomy, hypophysectomy, and trigeminal tractomy. Most of these procedures are done stereotactically under monitored anesthesia care (MAC) and fluoroscopic or computed tomography (CT) guidance. Nondestructive neurosurgical techniques include deep brain stimulation and motor cortex stimulation; both of these are currently experimental.

Over 40,000 patients are diagnosed with head and neck cancer each year in the United States, and over 500,000 are diagnosed worldwide (55). Cancer of the head and neck constitutes about 5% of all malignant diseases in the United States, and affects about 6.6 million worldwide (56). Because of dense facial and neck innervations, cancer commonly causes not only disfiguring facial lesions but also disabling pain in face and neck. The incidence of pain following treatment for head and neck cancer may be as high as 50%, with more than 50% disabled 1 year after diagnosis, highly correlated to pain scores (57,58,59). Blocking relevant trigeminal or cervical nerve branches can control such pain. Efficacy of interventional nerve block, however, can be affected by tumor distortion of anatomy, radiation-induced fibrosis of local tissues, and possible overlapping sensory innervations of neighboring cranial nerves V, VII, IX, X, and upper cervical nerves (see Chapter 17). Careful anatomic evaluation of facial pain and proper selection of nerve block with a local anesthetic test block is indicated prior to consideration of neurolytic blockade in these patients.