Evaluation and Management of Lower Back Pain in Oncological Patients (Pathogenesis) Part 1

Introduction

Back pain is one of the most common complaints that brings patients to be examined by a physician (Moore, 2010). Pain may originate from a variety of tissues, including intervertebral disks, vertebrae, ligaments, neural structures, muscles, and fascia, or present as referred pain from adjacent pathology, such as peptic ulcers, pancreatitis, pyelonephritis, aortic aneurysm, and more (Henschke, et al., 2009). Nonspecific low back pain is typically managed with symptomatic care and physical therapy, with up to 90% of patients improving substantially over 3 months. It is such a common condition that the American College of Physicians has issued guidelines with a mandate against imaging patients for the first month after pain onset (Chou, 2010).

Serious, life-threatening diseases are uncommon causes of back pain; malignancy, ankylosing spondylitis, and infection together account for less than 5% of back pain cases in a typical primary care practice (Dagenais, et al., 2010). However, missing such a critical diagnosis represents a serious concern for every practitioner; thus complaints of back pain often lead to multiple imaging studies and consultations (Venkitaraman, et al., 2010).

The spine is one of the most common sites of metastasis with close to 20,000 cases of spine metastases arising each year in the United States (Sciubba, et al., 2009). The most common primary tumors in patients with metastases are breast, lung, prostate, and kidney cancer (Guillevin, et al., 2007). In close to 15% of oncology patients, the primary presenting symptoms of malignancy are related to spinal metastases. In these patients, the most common underlying pathology is lung cancer, followed by breast cancer in females and prostate cancer in male patients (Chamberlain & Kormanik, 1999).


When the patient’s history is taken properly, a thorough physical examination is conducted, and appropriate diagnostic tests are performed, the physician can determine with a high level of accuracy whether an individual patient is suffering from nonspecific ("simple") back pain, or whether an underlying, potentially catastrophic disease is triggering the pain (Bach, et al., 1990).

In taking the patient’s history, one should try to define specific characteristics of the pain. Is this radicular or axial back pain? Is the pain worse at night or in the morning? Is the pain mechanical in nature or constant? Is it progressing? The examining physician should also look for signs and symptoms of systemic disease, such as fatigue, night sweats, weight loss, and changes in bowel habits. Personal habits such as smoking, alcohol consumption, or drug use should be identified as a potential clue to the underlying pathology.

In a patient with a known history of cancer, the situation is quite different. Each new ache and bump might lead to the fear of a metastasis, and patients will thus be highly sensitive to changes. On the other hand, ignoring symptoms or assuming that they are normal side effects of medical treatment may lead a missed diagnosis and delayed treatment, with the potential of significantly shortening a patient’s life expectancy or greatly reducing the quality of remaining life (Verbeeck, 2004). Sadly, although the awareness to the risk of spinal metastases is high, even in patients at high risk, progression, with catastrophic consequences can occur during a drawn out diagnostic process (Cole & Patchell, 2008; Hagelberg & Allan, 1990; Loblaw, et al., 2005). Although a high level of suspicion may lead to higher rates of imaging in these patients, any back pain in a patient with a history of malignancy should be considered as suspicious for spinal metastases and should be fully investigated.

We aimed to review the essential skills required for diagnosis of the etiology of back pain, and to outline basic elements of treatment in patients presenting with metastatic disease to the spine.

Making the diagnosis

Characteristics of benign back pain

Defining a patient’s pain is a hard task. Pain is subjective. The way in which pain is experienced, tolerance for pain, the language used to describe it, and its impact on quality of life differ from patient to patient and from culture to culture. Pain can be affected by medications, comorbidities, prior treatments, and by the patient’s life situation and mental state (Florence, 1981). With these points in mind, specific information can enable a skilled diagnostician to differentiate metastatic pain from benign back pain.

Benign back pain often arises from a specific event, is relieved by rest and lying down, and increases with activity such as lifting, sneezing, laughing, and the Valsalva maneuver (Lishchyna & Henderson, 2004). It is most commonly focal, with adjacent spasm of the lumbar muscles and buttocks. Benign back pain generally subsides several weeks after injury, and can be managed effectively with non-narcotic analgesics and physical therapy (Ladeira, 2011). Patients with benign pain may experience several relapses, but generally pain remits between attacks. In a portion of patients (up to 7%) benign pain becomes chronic, however a discussion of chronic back pain is beyond the scope of this topic.

Characteristics of metastatic back pain

In contrast, pain caused by spinal metastases is typically persistent and progressive, and is not alleviated by rest. Often pain is worse at night, awakening the patient from sleep. This pain is typically focal at the level of the lesion, progresses over several days or weeks, and may be associated with neurological signs indicating pressure on the neural spinal elements (Bach, et al., 1990).

A spinal mass can cause one of several forms of back pain. Localized pain is confined to the region of the spine affected by the tumor. This type of pain presents when a metastasis that originally developed in the bone marrow extends to stretch the periosteum or invades soft tissues, triggering pain from the nerve roots or signaling instability in a specific spine segment (Cole & Patchell, 2008).

A second form of pain is radicular pain due to nerve root compression or invasion. This pain is also typically worse at night and when the patient is recumbent, due to lengthening of the spine and distension of the spinal epidural venous plexus. This pain is often made worse by a Valsalva maneuver or other stretching movement of the spine or lower limb. The pain is usually dermatome-linked and may be associated with weakness of the muscles innervated by this nerve root (Cole & Patchell, 2008). If more than one nerve root is involved, the pain might extend to more than one dermatome.

A third type of pain appears when a pathologic fracture is present. This pain is generally focal, associated with instability, and progressive. It will worsen with movement. In the case of a fracture, the patient may remember a specific event or time when the pain began. It can be debilitating, necessitating the use of large doses of narcotics or preventing the patient from sitting or walking (Smith, 2011). These fractures may also lead to neurological changes due to neural element compression (Shaw, et al., 1989).

Sadly, not all patients with spinal metastasis present with early back pain. Many times a metastasis, like other slowly evolving conditions, becomes symptomatic only when there is neural compression. In this case, the patient will come to medical care only when there is cord compression, with imminent risk of losing mobility and control of the bowels. This late presentation is associated with a lower probability of neurological recovery, and a high rate of morbidity and mortality (Sundaresan, et al., 1995).

Physical examination

As is the case with any diagnostic process, the physical examination begins when the patient walks through the door. The patient’s general appearance, nutritional state, walking pattern, and general habitus can be assessed during the walk to the examination bed. It is thus important for the physician to be positioned to watch the patient’s entry, and to be alert to these details.

A general examination should be performed, including clinical examination of the breasts, lungs, abdomen, thyroid, and prostate, in the appropriate setting. After the general examination, a thorough orthopedic examination should be performed to evaluate any limitation in movement or impairment due to metastatic disease in other locations. The spine should be examined to identify sites of focal tenderness and assess range of motion. Signs of spinal instability or neural compression should be evaluated, and a full neurological examination should be performed, including assessment of strength, deep and superficial sensation, and proprioception, as well as deep tendon and pathological reflexes (Winters, et al., 2006). In order to try to locate the specific location of the lesion, sensory and motor levels should be assessed and documented.

Physical examination should be repeated periodically to allow early detection of any pathological motor or sensory findings or abnormal reflexes or any signs suggesting spinal instability or pathological fracture (Bates & Reuler, 1988).

With findings from the physical examination in hand, the physician should have an understanding of the pathology, and whether it is pointing towards metastatic spread of the primary disease to the spine. The next steps in diagnosis or treatment are determined by these findings.

Blood work

If the history and physical examination leads to the suspicion that the patient’s pain could originate from something more severe than common backache, blood work is mandated. If cancer is suspected, initial tests should include a complete blood count, a full chemistry panel including calcium and phosphate levels (de Mello, et al., 1983), evaluation of the erythrocyte sedimentation rate, and C-reactive protein levels (Elsberger, et al., 2011). If laboratory studies reveal anemia, thrombocytopenia hypercalcaemia, or elevated levels of alkaline phosphatase, concern should increase (Nieder, et al., 2010). Specific markers for prostate and breast cancer should be tested, as well as urine and blood protein electrophoresis if gammopathy (multiple myeloma or plasmacytoma) is suspected (Scharschmidt, et al., 2011).

A blood smear or a bone marrow biopsy may be indicated if hematological disease is suspected (Raje & Roodman, 2011).

Imaging

Metastases generally appear in more than one anatomic location. They can be in the brain, soft liver, lungs, or lymph nodes. In the skeleton, the third most common location for tumor spread, lesions may be found in the vertebrae, pelvis, proximal parts of the femur, ribs, proximal part of the humerus, and skull (Ratanatharathorn, et al., 1999). If a spinal metastasis is suspected, it is important to perform a full workup, both to identify the primary lesion and to detect other metastases.

X-ray

Simple X-rays of the spine are considered to be the first and most attainable imaging study. If obtained, they should be complimented with a chest X-ray for a preliminary search for lung involvement, however neither spinal nor lung tumors are well visualized on radiographs until the malignancy has advanced significantly (Nielsen, et al., 1991). Lateral X-ray may show vertebral body collapse. AP views may demonstrate pedicle erosion (the "winking owl" sign) or evidence of a paraspinal mass (Fehlings & Rao, 2000).

In cases where the physician has a high degree of suspicion towards metastatic spine disease, a more expeditious approach to diagnosis should be taken using advance imaging techniques such as CT or MRI (Black, et al., 1996). In these patients X-ray may be used as a complimentary study, since images obtained standing and dynamic X-rays can provide a better understanding of sagittal balance and stability of the diseased spine.

Computed Tomography

Computerized tomography (CT) has higher sensitivity and specificity than X-ray. Multislice CT (MDCT) systems facilitate a single rapid study of the chest-abdomen-pelvis. Osteolytic, sclerotic, and mixed lesions are depicted well on CT scans, as are lesions involving the viscera and vascular anatomy. However, while 16/64 row MDCT provides excellent image quality and clear assessment of bony structures, metastatic lesions without significant bone destruction may be missed (Buhmann-Kirchhoff, et al., 2009). CT scans are also associated with relatively high quantities of radiation, limiting the number of screening studies that should be performed, especially in a younger population (Huda & He, 2011). In addition, the differential diagnosis between a malignant process versus osteoporotic or degenerative disease can be challenging in the spinal column (Chassang, et al., 2007). CT findings that suggest metastatic disease include destruction of the anterolateral or posterior vertebral cortex, destruction of one or both pedicles, an epidural mass, and presence of a focal paraspinal soft tissue mass (Fehlings & Rao, 2000; Laredo, et al., 1995).

Spinal metastasis to the thoracic and lumbar spine. A 74-year-old female with a history of gastrointestinal stromal tumor (GIST) presented with right leg sciatic pain and weakness. (A) Sagittal CT revealed an osteolytic metastasis in the vertebral body of T7, L1, and L2 (arrows). The L2 metastasis was most prominent, producing compression of the cauda equina. (B) Axial CT through the body of L2 demonstrating the soft tissue mass, which has created a cavity in the vertebral body, narrowed the spinal canal and created pressure on the cauda equina. (C) X-ray after transpedicular excision of the lesion shows reconstruction of the vertebral body with polymethylmethacrylate (PMMA) and L1-L3 posterolateral fixation with transpedicular screws and rods. The patient experienced immediate and sustained pain relief, with recovery of her previous strength. Two weeks after surgery she was treated with adjuvant EBRT.

Fig. 1. Spinal metastasis to the thoracic and lumbar spine. A 74-year-old female with a history of gastrointestinal stromal tumor (GIST) presented with right leg sciatic pain and weakness. (A) Sagittal CT revealed an osteolytic metastasis in the vertebral body of T7, L1, and L2 (arrows). The L2 metastasis was most prominent, producing compression of the cauda equina. (B) Axial CT through the body of L2 demonstrating the soft tissue mass, which has created a cavity in the vertebral body, narrowed the spinal canal and created pressure on the cauda equina. (C) X-ray after transpedicular excision of the lesion shows reconstruction of the vertebral body with polymethylmethacrylate (PMMA) and L1-L3 posterolateral fixation with transpedicular screws and rods. The patient experienced immediate and sustained pain relief, with recovery of her previous strength. Two weeks after surgery she was treated with adjuvant EBRT.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is gold standard for evaluating spinal tumors. It depicts vertebral bone marrow infiltration by tumor cells as well as soft tissue masses in and around the spinal column. Bone marrow invaded by a neoplasm is characterized by increased cellularity, resulting in a decreased signal on T1-weighted images and a high signal on T2-weighted images, thus differentiating it from normal marrow tissue (Loblaw, et al., 2005). Intravenous gadolinium further increases the contrast between tumor and normal tissues (Loughrey, et al., 2000). MRI has been shown to detect up to 98.5% of vertebrae with metastatic disease, including both osteolyitic and osteoblastic lesions. This high level of detection is not compromised by osteoporosity (Buhmann-Kirchhoff, et al., 2009).

However, MRI is a costly, time consuming exam, limiting its efficacy in patients who have difficulty lying down without moving for long periods of time and those who are claustrophobic or morbid (Eshed, et al., 2007). In addition, it may be difficult to differentiate between osteoporotic compression fracture and metastatic disease, especially if a fracture co-exists. Signs that characterize malignant vertebral collapse include ill-defined vertebral margins, abnormal signal involvement of the pedicle, a marked and heterogeneous MR enhancement pattern, and the presence of an irregular nodular-type paraspinal vertebral lesion (Shih, et al., 1999). Using of different diffusion coefficients may assist correctly identifying this deferential diagnosis (Chan, et al., 2002).

MRI of the lumbar spine. A 42-year-old male presented with cauda equina syndrome due to an epidural metastasis to the lumbar spine from a synovial sarcoma originating in the left lower limb. (A) Preoperative T2-weighted sagittal MRI demonstrating a metastasis to the L4 vertebral body invading the epidural space and compressing the thecal sac (arrow). The patient underwent laminectomy and resection of the epidural mass. (B) Postoperative T2-weighted sagittal MRI showing post-laminectomy decompression of the thecal sac.

Fig. 2. MRI of the lumbar spine. A 42-year-old male presented with cauda equina syndrome due to an epidural metastasis to the lumbar spine from a synovial sarcoma originating in the left lower limb. (A) Preoperative T2-weighted sagittal MRI demonstrating a metastasis to the L4 vertebral body invading the epidural space and compressing the thecal sac (arrow). The patient underwent laminectomy and resection of the epidural mass. (B) Postoperative T2-weighted sagittal MRI showing post-laminectomy decompression of the thecal sac. 

99Tc bone scan

With the exception of purely lytic tumors such as myeloma, eosinophilic granuloma, and renal cell carcinoma, 99mTc-methylene diphosphonate (MDP) bone scan has good sensitivity to tumors, is widely available, and has a relatively low cost, with the ability to scan the entire skeleton in a single study. It can be performed as a flat two dimensional exam or, incorporating more advanced single-photon emission computed tomography (SPECT) technology, with true 3D information. Bone scans have moderate sensitivity in the spine and pelvis (Steinborn, et al., 1999). Sensitivity to detection of spine metastasis can be significantly improved by the combination of bone scan and SPECT imaging capabilities (Schirrmeister, et al., 2001). Bone scans combined with SPECT may depict spinal lesions as well as metastases in other bones or organs, and provide some indication of the site of the primary tumor in cases where this is not known. The main drawback to these studies is exposure to high levels of ionizing radiation and a lower rate of detection when compared with MRI (Sedonja & Budihna, 1999).

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