chapter 24 Cancer
INTRODUCTION AND OVERVIEW
It is estimated that up to 80% of patients with cancer seek complementary and alternative therapies, almost entirely as adjunctive treatment. A study published in the Journal of Clinical Oncology reported that 88% of 102 people with cancer who were enrolled in phase I clinical trials (research studies in people) at the Mayo Comprehensive Cancer Center had used at least one CAM therapy.1 Of those, 93% had used supplements (such as vitamins or minerals), 53% had used non-supplement forms of CAM (such as prayer/spiritual practices or chiropractic care), and almost 47% had used both.
CANCER AND THE ESSENCE MODEL
Although it has just been said that cancer is different from other diseases, the ESSENCE principles of cancer prevention and management2 (see Ch 6) are very similar whatever the cancer type. The important thing is to understand the principles, which are largely the same whatever the cancer, and not get concerned because there might be less information on one particular type of cancer. Although most research data is drawn from the more common cancers, the same rules apply for others.
PATIENT EDUCATION
In the most general sense, cancer is a disease in which a cell changes in such a way that it:
Staging
Cancers can be largely divided into two groups: solid and blood-borne malignancies.
Cancers are generally staged according to their level of spread and how aggressive or mutated they are. The TNM system is one of the most commonly used staging systems.3 This system has been accepted by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Most medical facilities use the TNM system as their main method of cancer reporting.
The TNM system is based on the extent of the tumour (T), the extent of spread to the lymph nodes (N) and the presence of metastasis (M). A number is added to each letter to indicate the size or extent of the tumour and the extent of spread (Box 24.1).
BOX 24.1 TNM staging system
Source: National Cancer Institute 20043
Primary tumour (T) | |
TX | Primary tumour cannot be evaluated |
T0 | No evidence of primary tumour |
Tis | Carcinoma in situ (early cancer that has not spread to neighbouring tissue) |
T1, T2, T3, T4 | Size and/or extent of the primary tumour |
Regional lymph nodes (N) | |
NX | Regional lymph nodes cannot be evaluated |
N0 | No regional lymph node involvement (no cancer found in the lymph nodes) |
N1, N2, N3 | Involvement of regional lymph nodes (number and/or extent of spread) |
Distant metastasis (M) | |
MX | Distant metastasis cannot be evaluated |
M0 | No distant metastasis (cancer has not spread to other parts of the body) |
M1 | Distant metastasis (cancer has spread to distant parts of the body) |
Hence, it is not just the primary prevention of cancer through healthy lifestyle that is important, but also secondary prevention through early detection and screening. There are many forms of screening for particular cancers, such as breast self-examination and mammography for breast cancer, faecal occult blood or colonoscopy for bowel cancer, digital rectal examination and prostate-specific antigen (PSA) for prostate cancer and chest X-ray for lung cancer. Cancers picked up on routine screening are more likely to be in an earlier stage of growth and of a lower level of malignancy than cancers detected because they have produced symptoms.
Treatment
This having been said, if a patient feels obstructed, undermined or disempowered in their cancer management, if they are told there is nothing they can do for themselves, if they are told that lifestyle doesn’t matter or that there is nothing outside the medical model that can help them, then they need to think seriously about finding another practitioner. Quality information and respectful and open lines of communication are much needed for both practitioner and patient, so that neither is making uninformed decisions and so that outcomes can be optimised. The Australian Senate Inquiry into the management of cancer made a number of findings and clearly indicated that the ‘cancer establishment’ should be doing a far better job in this regard.4
MIND–BODY THERAPIES
In an authoritative review, Professor David Spiegel concluded that chronic and severe depression is probably associated with an increased risk of cancer, but that there is ‘stronger evidence that depression predicts cancer progression and mortality’.5a Of all the emotional factors, depression is probably the most important.6 Further, providing psychosocial support, through a support group for example, ‘reduces depression, anxiety, and pain, and may increase survival time with cancer’.5a The longer the depression has existed, say for longer than 6 years, the greater the risk factor it is. The risk is nearly doubled, independent of other lifestyle variables, and is not related to any particular cancer.7,8 The most recent review of the effect of depression on survival for patients who already have cancer concluded that clinical depression played a causal role in cancer mortality and was associated with a 39% increased mortality rate.9
Poor coping, distress and depression have been linked to poor survival for various cancers, including cancer of liver and bile duct (hepatobiliary),10 lung cancer,11 breast cancer12, malignant melanoma13 and bowel cancer. Some studies have not confirmed a link.14 Having a good global quality of life is associated with better survival for a variety of cancers.15–18 Other factors, including the perceived aim of treatment, minimisation, quality of life and anger, all influence survival.19 Minimisation refers to a person minimising the importance or impact of the cancer. It is not denial, but reflects an ability to adapt or to see the illness in a larger perspective.
If psychological and social factors do play a role in the cause and prognosis of cancer, the important question is whether psychosocial interventions such as group support, relaxation and meditation and CBT produce better survival chances. That they can improve quality of life for cancer patients is clear, but unfortunately there are very few completed controlled trials examining the survival outcomes of such interventions. A number of studies have shown a significant improvement in both quality of life and survival time, but others have not.20
The most noted and first study of its type was done by David Spiegel, who studied women with metastatic breast cancer. His results showed a doubling of average survival time from 18.9 months to 36.6 months for the women who received the support program, compared with those who didn’t. The intervention included group support focused on improving emotional expression, some simple relaxation and self-hypnosis techniques, plus the usual medical management.21 Ten years after the study, three women in the intervention group were still alive but none in the group that had had the usual medical management alone were.
Another well-performed study by Fawzy and colleagues looked at outcomes for 68 patients with early-stage malignant melanoma.22 The patients were divided into two groups and followed for 6 years, at which time those who had had the usual surgical care and monitoring plus stress management showed a halving of the recurrence rate (7/34 vs 13/34) and much lower death rate (3/34 vs 10/34) than the group who had had the usual surgical management and monitoring alone. The intervention on this occasion was only 6 weeks of stress management. In this study, immune function was also followed. Originally the two groups were comparable but the stress management group had significantly better immune function 6 months into the study. We know that melanoma is one of the cancers that is aggressively attacked by natural killer (NK) cells and this probably contributed to the major difference in survival rates—that is, the immune system, monitoring for any cancer spread, was able to deal with it before the cancer had a chance to grow. Ten-year follow-up on the Fawzy program still shows a positive survival effect, although this has weakened a little over time,23 so it may be that people lose motivation over time, and ‘boosters’ may be required to maintain the therapeutic effect.
Other studies have also yielded promising results in terms of survival, for cancer of the liver,24 gastrointestinal tract25 and lymphoma.26 A number of trials have shown equivocal or negative results from a psychosocial support program, in terms of improved survival.27–31 One of these trials was an attempt to replicate the Spiegel study but the results showed that, despite some improvements in mental health and quality of life, there was no significant effect on survival. An even more recent study of group support for breast cancer survival showed that the intervention did not statistically significantly prolong survival, although the average survival time in the support group was 24.0 months, compared with 18.3 months in the control group. The support program did, however, help to treat and prevented new depressive disorders, reduced hopeless-helplessness and trauma symptoms, and improved social functioning.32 Another recent study on psychotherapeutic support for gastrointestinal malignancies like stomach and bowel cancer showed a clinically and statistically significant survival benefit. This hospital-based psychosocial support program was delivered to individuals rather than in a group format. Over twice the number of gastrointestinal cancer patients were alive at 10 years if they had a psychotherapeutic intervention.33 The work by the Ornish group on support programs and cancer is probably the best researched and has shown excellent results, but this included a range of other lifestyle factors apart from psychosocial support.
Support programs vary enormously in content, duration and delivery, thus many questions in the area of psychosocial support and cancer survival will need to be answered in future research.34 For example: What kinds of programs work best? Who should they be run by? How long is the optimal duration for such a program? What are the essential ingredients? What advice should a doctor give to a patient regarding whether or not to attend a support group? To what extent does compliance affect the outcome? Does having a residential component improve outcomes?
It is likely that it is not just being in a program that is protective but also the level to which a person participates in it and lives by it. This was demonstrated by one of the studies referred to above, showing that high involvement in the program was associated with better survival, and that there was no benefit from just ‘going through the motions’.35 One paper suggested that programs of 12 weeks or longer duration were more likely to be effective.36 Those that use validated forms of meditation and also foster positive emotional responses including humour and hope are more likely to be successful. Although programs attempting to deal with psychological factors need to take into account the fact that personality traits and coping styles can affect quality of survival, there are mixed results from research on whether things such as ‘helplessness’,37,38 ‘fighting spirit’ and ‘optimism’39 affect survival. Despite the fact that a number of studies suggest that they do, other studies throw this into doubt.40
If improving mental health does indeed have survival benefits, the potential mechanisms explaining that longer survival are worth considering.41 Below is a summary of key points, followed by a more extensive discussion of each.
Direct physiological and metabolic effects
Indirect effects
The original belief in psycho-oncology circles was that immune cells were the main explanation for why the mind has effects on cancer outcomes, but there is much more to it than that. Immunity may explain some of the beneficial effects of stress management for some tumours, but not all. In some cancers, such as malignant melanoma or those where viral infections are an important cause, the immune system may be the main defence, but it is probably less important for cancers that are primarily caused by chemical injury, such as lung cancer. Many cancers do not wear their mutated antigens on their surface and therefore the immune system cannot recognise and attack them.56
Some hormones can also suppress cancer growth and even induce cancer cell apoptosis. The ability to change the activity of such chemical mediators may in part explain why various activities prolong a healthy lifespan in humans, such as cognitive behaviour therapy, meditation-based therapies, stress reduction, anti-inflammatory techniques, dietary (calorie) restriction and aerobic exercise. These all affect molecular mediators including dehydroepiandrosterone (DHEA), interleukins and especially melatonin.57
Chronic inflammation is not a good combination with cancer. Even the inflammation associated with major surgery has been shown to increase the growth of tumour metastases at distant sites via these hormones,58 so it is important for patients with disseminated cancer only to have surgery if it is really necessary. Reducing stress hormones59 and inducing hormones associated with wellbeing and relaxation, such as melatonin, may be part of the reason that stress reduction and psychosocial interventions help cancer survival.60
Some immune mediators (e.g. TNF-alpha) can kill tumour cells and have anti-tumour effects. We now know that many tumours are ‘dormant’ through a balance between cell division, cell death and the body’s defences.61 Upsetting this balance may explain why the occurrence and recurrence of cancer often follow recent traumatic events that were not well dealt with.62 In such a case it may be more accurate to say that emotional disturbance is a contributing or precipitating factor accelerating the cancer’s growth, rather than it being the cause of the cancer.
Apart from having significant effects on immunity63 and ageing,64 melatonin also has anti-tumour effects. It slows cancer cell replication, helps to switch off cancer genes, and inhibits the release and activity of cancer growth factors, promotes better sleep and helps to enhance the immune response.65,66 Because of the biological activity of melatonin, this has a number of implications for cancer therapy.67,68 Helping the body to stimulate its own melatonin production has many beneficial effects. Among the things which stimulate melatonin endogenously are many of the interventions that are part of holistic cancer support programs (Box 24.2).
Melatonin regulates our body clock, and therefore sleep is intimately linked with melatonin levels and thereby with cancer progression.75 This may partly explain why things that affect melatonin (e.g. doing shift work or working in the airline industry) may also be risk factors for cancer.76 Body-clock alterations commonly occur in cancer patients, with greater disruption seen in more advanced cases. Emotional and social factors as well as many symptoms associated with cancer can have a significantly negative effect on sleep rhythms. From a therapeutic perspective, using behavioural interventions to enhance sleep is a vital part of coping with cancer but it also helps to improve cancer defences and prognosis. The chapter on sleep strategies (see Ch 43) would be useful to read if sleep is a problem.
Psychological states affect genetics. We can have a genetic disposition to cancer but, equally, DNA has protective genes such as ‘cancer suppressor genes’. It has been shown that stress impairs repair of genetic mutations77 and causes oxidative damage to DNA. In experiments on workers, perceived workload, perceived stress and the ‘impossibility of alleviating stress’ were all associated with high levels of DNA damage.78,79 Personality factors were also linked to oxidative DNA damage, with high ‘tension-anxiety’, particularly for males, or ‘depression-rejection’, particularly for females, correlating with the level of DNA damage.80 A low level of closeness to parents during childhood, or bereavement in the previous 3 years, were also associated with greater DNA damage. Psychological stress reduces the ability of immune cells to initiate genetically programmed cancer cell suicide.81
Angiogenesis, which is the process of new blood vessel formation, is vital for tissue repair but also for the growth of tumours. Solid tumours can only grow into other tissues because they are able to lay down new blood vessels. Blood vessel growth is also mediated via various cytokines. One particularly important one is vascular endothelial growth factor (VEGF), and in cancer patients high levels of this cytokine are associated with poor prognosis. Sympathetic nervous system activation, a vital part of the stress response, increases the level of VEGF, and cancer patients who report higher levels of social wellbeing have lower levels of VEGF, a good prognostic sign. ‘Helplessness’ and ‘worthlessness’ are also associated with higher levels of VEGF.82 Other studies emphasising the importance of angiogenesis in tumour progression have found links with depression.83 Tumours in stressed animals showed markedly increased vascularisation (angiogenesis) and increased levels of the hormones that produce these effects.84
As ever, we are more interested in the therapeutic potential of strategies for improving psychological wellbeing. Support groups have already been discussed but other research with bearing on this topic is also of interest. A study has been performed on the effects of mindfulness-based stress reduction (MBSR) on quality of life, stress, mood, hormonal and immune function in early-stage breast and prostate cancer patients.85 The 8-week MBSR program included relaxation, meditation, gentle yoga and daily home practice, and followed patients for 12 months. The participants showed and maintained significant improvements in symptoms of stress, their cortisol levels decreased (a good prognostic sign) and physiological markers of stress reduced, as did pro-inflammatory cytokines: ‘MBSR program participation was associated with enhanced quality of life and decreased stress symptoms, altered cortisol and immune patterns consistent with less stress and mood disturbance, and decreased blood pressure’.85a
SPIRITUALITY
Cancer, more than most illnesses, raises the prospect of one’s own mortality. As such it is a common catalyst for looking at one’s life and reconsidering what is important. Cancer can therefore be a powerful stimulus for personal growth, but for many it will lead to an emotional implosion unless motivation is positive and adequate support is given. Much has already been said in the chapter on spirituality (Ch 12) about how having an active search for meaning or a spiritual dimension in one’s life:
These are all reasons in themselves to consider ‘spirituality’, however one relates to it, as an important part of the management of cancer. Indeed, it has already been mentioned in the chapter on spirituality (Ch 12) that approximately 80% of patients dealing with major illness wished to discuss spiritual issues with their doctor. Among cancer survivors, the relationship between social functioning and distress was significantly affected by having a sense of meaning in life, whereas the relationship between physical functioning and distress was partially mediated by meaning.86 There have been precious few studies on whether spirituality or religion is protective against cancer. The only well-performed trial found a significantly lower incidence of bowel cancer among those with a religious dimension to their lives, and this could not be explained by other risk factors.87 This study also found longer survival in those with bowel cancer.
A related issue is whether various forms of ‘distant healing’ can assist in healing or in symptom control. A review showed that there was some evidence, albeit a little sparse and inconsistent, to suggest that forms of healing including therapeutic touch, faith healing and reiki may be helpful.88 Most of the results demonstrated so far, however, are reduction in pain and anxiety, and improvement in function. Grander claims, such as effects on tumour regression through prayer, therapeutic touch and faith healing, are mainly anecdotal and have not been rigorously investigated or proved.
CONNECTEDNESS
As has been discussed, social isolation predisposes a person to a whole range of illnesses including cancer and is associated with a higher mortality rate.89 Population studies of adults demonstrated that socially isolated males were 2 to 3 times more likely to die over the following 9 to 12 years and that socially isolated women were 1.5 times as likely to die.90 This is not explained by other lifestyle factors, although our social context has a significant influence on our lifestyle. This influence can be positive or negative. Having support to give up smoking, for example, makes it much easier, whereas a lack of support can make it all but impossible.
The most common sources of social support are family and friends. It has been shown that cancer patients who are married or have a stable relationship survive for longer than would otherwise be expected. Reviews of the studies have shown an ‘association between at least one psychosocial variable and disease outcome. Parameters associated with better breast cancer prognosis are social support, marriage, and minimising and denial, while depression and constraint of emotions are associated with decreased breast cancer survival’.91
EXERCISE THERAPY
Reviewing the vast body of evidence, the World Cancer Research Fund has declared that physical inactivity is clearly a risk factor for cancer.92 This can be illustrated by examining some of the studies reviewed.
Over 30 studies have shown a protective relationship between physical activity and colon cancer mortality.93,94 This protective effect also extends to precancerous bowel polyps. The reduction of bowel cancer risk is around 50%.
Large-scale Norwegian studies show a 37% reduction in the risk of breast cancer in all women who exercise regularly, particularly in those less than 45 years of age, for whom the risk was 62% lower. In those who were lean, exercised approximately 4 hours per week and were premenopausal, the risk was reduced by 72%.95 Similar findings have been found for lung cancer.95 This is confirmed in an analysis of the Nurses’ Health Study.96 In postmenopausal women, brisk walking has been shown to reduce breast cancer risk. Another study looked at 75,000 postmenopausal women aged between 50 and 79 years, and showed that those who exercised at a level equivalent to brisk walking for 1¼ to 2½ hours per week had a significant breast cancer risk reduction of 18%.97 This increased to 22% in those who exercised up to 10 hours per week. A past history of strenuous exercise at age 35 or 50 was associated with a breast cancer risk reduction. Independent of smoking and nutritional status, the Norwegian study mentioned above also showed a reduced risk of lung cancer in those who exercised. Aerobic exercise seems to be the best protection against cancer, and the suggested reasons as to why exercise protects against cancer include: