VOL: 97, ISSUE: 41, PAGE NO: 32
Ursula O'Leary, MSc, DipPainManagement, RN, was nurse manager at St John's Hospice at the Hospital of St John and St Elizabeth, London, at the time of writingA primary cancerous tumour often leads to secondary deposits of diseased cells. In many cases it is these secondary lesions (metastases) that cause the symptoms leading to diagnosis. Cancer can be devastating in itself, affecting the physical, psychological and social aspects of life. However, secondary spread can compound this by causing more problems.
A primary cancerous tumour often leads to secondary deposits of diseased cells. In many cases it is these secondary lesions (metastases) that cause the symptoms leading to diagnosis. Cancer can be devastating in itself, affecting the physical, psychological and social aspects of life. However, secondary spread can compound this by causing more problems.
Bone metastasis has been described as the most common type of bone lesion seen in adults (Mundy, 1987). Although it is difficult to determine accurately its incidence and prevalence, it has been estimated that 15-20% of patients with cancer develop secondary bone disease (Richardson, 1989; Welch-McCaffrey, 1988). This article discusses the effects of bone metastasis on patients' quality of life.
Certain cancers are thought to spread to bone more easily than others and are associated with a higher incidence. Hanks (1995) and Neilsen et al (1991) suggest that the primary cancers most likely to metastasise to bone are those of the breast, prostate, kidney, thyroid and lung.
Welch-McCaffrey (1988) proposes that 80% of all patients who develop secondary bone disease have tumours originating in the breast, prostate or lung. This is not surprising as these are the most common cancers. The remaining 20% have primary tumours of the kidney, thyroid, liver, bowel, cervix, uterus and pancreas. Needham and Hoskin (1994) and Mundy (1987) appear to agree with this, stating that solid tumours, such as those found in the breast, lung and prostate, are most commonly associated with bone metastasis.
It is difficult to present an accurate account of the affinity of primary tumours for particular secondary sites, because some authors have relied on information gathered at autopsy (Neilsen et al, 1991). This data does not take into account the many patients living with the condition. Also, post-mortems are no longer routinely carried out on UK patients with a confirmed cancer diagnosis, so current figures are not representative and the incidence of bone metastasis may be significantly higher.
This could have serious ethical and financial implications for patients with metastatic disease, as underfunding could delay vital research, prevent early detection and compromise health care.
Mechanisms of metastatic spread
The mechanism of metastatic spread from a primary tumour is not fully understood, but it is a complex process that depends on an interaction between host and tumour cells.
A number of theories exist, for example that metastasis develops in the first organ that a tumour cell encounters: tumours that drain through the portal vein will metastasise to the liver while those that drain systemically will metastasise to the lungs. But some authorities have disputed this theory. For example, Whyte (1996), Piasecki (1996) and Richardson (1989) claim that certain cancers, such as breast, prostate, thyroid, lung and kidney cancer, appear to have a unique affinity to bone.
Cells from primary tumours travel via the bloodstream and precipitate in the bone marrow, which provides a rich source of nutrition and a suitable growing environment for cell deposits. This theory has been validated, to some extent, by the use of histological grading in prostatic cancer and the discovery of a positive oestrogen receptor in the case of breast tumours.
The trabeculae (dividing platelets of bone), which are sparse in the bone marrow, allow the deposit to enlarge before any change in or destruction of the bone deposition, or both. Metastatic cells do not destroy bone directly but promote the stimulation of osteoclasts, the cells responsible for bone resorption (Pemberton, 1995), causing a release of lysozyme. This enzyme digests the protein portion of the bone and splits the salts deposited in the bone matrix. The phosphates and calcium salts are then absorbed into the surrounding extracellular fluid in the bone canaliculi (Pemberton, 1995).
While some authors support the theory that a primary cancer will invade the first organ encountered (Whyte, 1996; Pemberton, 1995; Needham and Hoskin, 1994), it is more probable that, in the case of bone metastasis, the principal mode of spread is via the bloodstream. The rationale for this theory is that the axial skeleton and the more proximal bones of the appendicular skeleton, which are lacking in red marrow, are not usually affected.
Tranin (1994) suggests that primary cancers and metastatic spread may be genetically influenced. Oncogenes are already known to induce cancer and/or metastatic spread, while tumour suppressor genes are thought to be responsible for the presence, or absence, of metastatic development.
It appears that the mechanism of metastatic spread remains a complex issue. As scientific research continues, albeit slowly, to discover more about this process and cancer itself, curative and preventative treatment become a realistic possibility.
Effects of metastatic bone spread
Metastatic bone disease can have serious physical, psychological and social implications for patients and their carers. It is worth noting that any physical effects should not be viewed in isolation from the psychological and social effects. It is important to recognise each as an integral part of the total experience.
Several mechanisms associated with bone metastasis can precipitate pain (see Box 1, overleaf). There are conflicting views on the prevalence of pain as a result of metastatic bone disease.
Bonica (1990) speculates that 35-45% is a reasonable estimate of the incidence of pain due to tumour invasion of bone. However, no evidence is cited to support this assumption.
Some authors merely state that pain is a frequent symptom of secondary bone disease (Coleman et al, 1995; Needham and Hoskin, 1994; Robinson, 1993), while others maintain that some patients do not experience any pain whatsoever (Twycross, 1995; Pemberton, 1995).
However, none of these authors appear to have based their opinions on valid research. The implications of this may be that although the physiological processes producing pain are the same, the perceived experience of this phenomenon is a complex issue that may be influenced by non-physiological factors.
Hypercalcaemia is often associated with widespread osteolytic metastases. It is reported to affect 10-40% of the oncological population during the course of their illness (McCloskey, 1997; Gaich and Burtis, 1991; Mundy, 1987).
Hypercalcaemia results from a combination of increased osteoclastic bone resorption, poor renal perfusion and reduced glomerular filtration. This can lead to increased plasma calcium concentrations, which appear to precipitate or exacerbate pain by modifying the pain threshold (Fleisch, 1991). This appears to be a plausible explanation because some patients experience a reduction in, or complete relief of, bone pain once calcium levels are corrected (Richardson, 1989).
In addition to pain, hypercalcaemia can cause a variety of other symptoms, such as confusion, drowsiness, thirst and vomiting, which can have serious implications for cancer patients and their carers. If left untreated, hypercalcaemia can lead to death (Fleisch, 1991).
Anaemia and bone marrow depression
Chronic inflammatory changes within the body, often associated with bone metastases, can inhibit the mobilisation of iron from body stores and cause chronic anaemia (Foley, 1993). This can result in increased lethargy and reduced mobility, precipitating the incidence of deep vein thrombosis and the formation of pressure ulcers leading, in turn, to increased pain.
In metastatic bone disease, bone marrow function can often become depressed due to tumour invasion (Coleman et al, 1995). This necessitates decreased doses of cytotoxic drugs and compromises life expectancy. It can have drastic implications for patients, leading to psychological distress and an overall increase in the pain experienced.
Spinal cord compression
When patients with advanced cancer develop spinal cord compression (SCC), 85% can attribute it to bony metastases of the vertebral body or pedicle (Richardson, 1989). Only 1-2% of all patients with cancer will develop this potentially serious condition (Twycross, 1995; Foley, 1993).
Tumour invasion leads to increased pressure on the spinal cord and vascular supply, which can result in mechanical injury, vasostasis and infarction. This can have catastrophic implications, including both motor and sensory loss, sphincter anomalies and even paraplegia.
Kramer (1992) argues that SCC does not necessarily indicate a poor prognosis, but success in this situation is achieved only after early detection and treatment.
The overall cancer pain experience can be increased in SCC as a result of muscle spasm, nerve-root compression and visceral pain caused by bladder and bowel distension. Both increased pain and disease progression can have psychological and social implications for patients.
A lack of research prevents a full assessment of the incidence of pathological fracture. Mercadante (1997) claims that bone fragility can lead to this condition in 8-30% of patients with bone metastases, while Richardson (1989) states that fewer than 1% of patients with bone metastases will develop a pathological fracture. However, neither author outlines how their information was obtained.
It may be that these particular studies accounted only for fractures confirmed by X-ray or bone scan, whereas it may be inappropriate for some patients who have cancer to undergo such investigations. If this theory is correct it could dramatically affect the stated statistics.
As a result of the mechanism of metastatic bone disease, it appears that the trunk and limbs are more commonly affected (Whyte, 1996). This may result in pain, debilitation and decreased mobility which can have serious implications for patients.
Metastatic bone disease poses significant problems for patients, their carers and the health care professionals who assist in the management of its effects. Statistically it may fail to attract serious concern, but secondary bone disease can be associated with distressing symptoms and may compromise life expectancy as well as quality of life. There appears to be some ignorance among health care professionals regarding some of the complications associated with this disease, such as the incidence of pain.
Although it is often considered a minor complication of primary cancer, secondary bone disease can be fatal. It may also have a considerable effect on social and psychological aspects of a patient's life. Health care professionals need to be aware of the consequences of such a diagnosis and to devise strategies that will minimise not only the possible physical complications but also its negative effects on their patients' quality of life.