Ute Goerling (ed.)Recent Results in Cancer ResearchPsycho-Oncology201410.1007/978-3-642-40187-9_8
© Springer-Verlag Berlin Heidelberg 2014
Cancer Survivorship in Adults
(1)
National Resource Center for late effects after Cancer Treatment, Oslo University Hospital, Radiumhospitalet, 4953 Nydalen, 0424 Oslo, Norway
Abstract
With the favorable trend regarding survival of cancer in the Western world, there is an increasing focus among patients, clinicians, researchers, and politicians regarding cancer survivors’ health and well-being. Their number is rapidly growing and more than 3 % of the adult populations in Western countries have survived cancer for 5 years or more. Cancer survivors are at increased risk for a variety of late effects after treatment, some life-threatening such as secondary cancer and cardiac diseases, others might negatively impact on their daily functioning and quality of life. The latter might include fatigue, anxiety disorders and difficulties returning to work while depression does not seem to be more common among survivors than in the general population. Still, the majority of survivors regain their health and social functioning. The field of cancer survivorship research has been rapidly growing. Models for follow-up care of cancer survivors have been proposed, but how to best integrate the knowledge of the field into clinical practice with adequate follow-up of cancer survivors at risk for developing late effects is still an unsolved question.
1 General Aspects
The number of cancer survivors has been steadily increasing in the Western world during the last decades due to increasing cancer incidence, better diagnostic procedures, and more effective treatment modalities. Today, the relative 5-year survival is 60–65 % for patients diagnosed with cancer (American Cancer Society 2012, Verdecchia et al. 2007). In Norway, cancer survivors alive ≥5 years from diagnosis represent 3.3 % of the total population (The Cancer Registry of Norway 2010). For some cancer types such as testicular cancer, breast cancer, and Hodgkin’s lymphoma, the 5-year relative survival exceeds 90 %. According to cancer types the most common survivor groups are survivors of female breast, prostate, colorectal, and gynecologic cancer (American Cancer Society 2012).
Cancer survivorship can be defined differently according to time since diagnosis and state of the tumor, and for this chapter we define a cancer survivor as a person who has lived at least 5 year beyond diagnosis and is regarded as tumor-free.
The favorable development as to survival after a cancer diagnosis has been followed by a growing clinical and scientific interest concerning health and quality of life among cancer survivors.
Chemotherapy, radiotherapy, surgery, and hormone therapies are the mainstay of cancer treatment, and they are often combined in various multimodal treatments. Adverse effects may occur during these treatments, and eventually continue for a long time after treatment or become permanent. Other adverse effects have their onset some time after treatment has been terminated, but then continue for a long time. Thus, cancer survivors are at increased risk of various medical and psychosocial complications (Fossa et al. 2008, Fosså and Vassilopoulou et al. 2008). Some late effects might be life-threatening, such as second cancer or cardiovascular disorders, while others such as hypogonadism, infertility, sexual dysfunctions, or chronic fatigue (CF) might have negative impact of the survivors’ daily function and quality of life, but do not threaten their lives.
One of the challenges related to studies of late effects is that some late effects like second cancer and cardiovascular diseases typically emerge many years after the termination of treatment. Results of such studies might not completely reflect the risk experienced by patients diagnosed today, since they undergo therapies which have been modified compared to those used 10–20 years ago. Therefore, the studies of late effects by its nature most often lag behind treatment currently given. Concerning new and improved treatments we will have to wait 10–30 years in order to identify their adverse effects. And so the chase for late effects will go on.
Many of the conditions that are described as late effects, like sexual dysfunction, cardiovascular disorders, and fatigue, are also prevalent in the general population. The prevalence of these conditions increase with older age and cancer is primarily a disease of older age since two-third of cancers is diagnosed after 60 years of age.
The goals of survivorship care are twofold: (1) To reduce the risk or cancer recurrence, second cancer and other severe diseases, and adverse effects. (2) To alleviate existing and expected physical and psychological adverse effects. These goals have several challenging implications: (1) To what extent shall cured cancer patients be informed of risks far in the future? (2) How often and how intensively shall survivors be screened for possibly upcoming severe adverse effects? (3) Considering the rapidly growing number of cancer survivors, how shall their health care be organized? To our knowledge there are no countries yet that have found the definite answers to these challenges.
In this chapter we will give an overview of the field of cancer survivorship, including the most important somatic, psychological, and psychosocial late effects and aspects regarding follow-care of cancer survivors and challenges for research in survivorship issues.
2 Somatic Late Effects
Approximately 15 % of cancer survivors will be bothered with treatment-related somatic late effects. An overview of the most important is presented here.
2.1 Second Cancer
Selected groups of cancer survivors are shown to have increased risk for development of a second cancer, which might be related to an iatrogenic effect of the cancer therapy and/or a genetic predisposition. Treatment-related solid second cancers are usually diagnosed at a latency of 10–30 years after radiotherapy, and their development is related to the radiation dose within the target field, but also to scattered irradiation beyond the field borders. A typical example is development of breast cancer after mediastinal irradiation/mantle field irradiation for Hodgkin’s lymphoma (Swerdlow et al. 2000) and esophageal cancer after thoracic radiotherapy in women with breast cancer (Morton et al. 2012).
During the last two, decades increasing documentation has emerged that cytotoxic drugs in a dose-dependent manner are carcinogenic leading to an increased risk of leukemia (Travis et al. 1999; Kollmannsberger et al. 1998), but also of solid tumors (Swerdlow et al. 2001, Fung et al. 2013)
The association between second cancer and cytotoxic treatment (radiotherapy, cytostatics) has been one of the strongest arguments for the development of risk-adapted strategies in order to reduce the treatment burden as much as possible, while maintaining the highest possible cure rate.
2.2 Cardiotoxicity
Dependent of their previous treatment long-term cancer survivors may develop asymptomatic or symptomatic left ventricle dysfunction, heart failure, premature coronary atherosclerosis, arrhythmia, or sudden cardiac death, most often due to myocardial infarction (Lenihan et al. 2013). Mediastinal radiotherapy and treatment with certain cytotoxic drugs (antracyclines, trastuzumab) represent well-known cardiotoxic risk factors, with clear dose–effect associations to cardiac dysfunction. Age below 15 years at primary treatment increases the risk. Increased risk of late cardiotoxicity (after 5–30 years) is also reported in breast cancer survivors who have undergone adjuvant cytotoxic treatment (thoracic radiotherapy, systemic cytostatics) (Darby et al. 2013). The European Society of Medical Oncology has recently published recommendations regarding the early detection of cardiotoxicity in patients at risk (Curigliano et al. 2012), but currently there is no international consensus about the optimal procedure for early detection or follow-up of cancer survivors at increased risk of cardiotoxicity.
In addition to a direct cardiac injury due to cytotoxic treatment, the development of metabolic syndrome (overweight, hyperlipidemia, hypertension, hyperglycosuria) represents a risk to the heart. This syndrome is described in long-term testicular (Haugnes et al. 2010, Willemse et al. 2013) and ovarian cancer survivors after cisplatin-based chemotherapy (Liavaag et al. 2009), but is also responsible for the increased risk of cardiac mortality in prostate cancer patients in particular after long-term androgen deprivation therapy (Kenney et al. 2012). Patients at risk should therefore be educated about the importance of a healthy life style (physical activity, healthy diet, no smoking, and moderate use of alcohol).
2.3 Gonadal Dysfunction and Infertility
All surgery, radiotherapy, chemotherapy, and long-term hormone treatment can lead to primary or secondary hypogonadism dependent on whether the damage primarily affects the testicles/ovaries or the pituitary gland/hypothalamus. In addition, the transport of the ovum or the sperm cells may be impeded by fibrosis or stenosis of the ducts because of surgery or radiotherapy.
There are important gender-related differences as to development, prevention, and possible therapy of treatment-related hypogonadism in cancer survivors. After low or intermediate doses of most cytotoxic drugs or after testicular irradiation of less than 2 Gy the sperm cell production can recover as long as spermatogonial stem cells are preserved. The testosterone producing Leydig cells are relatively resistant to chemotherapy and radiotherapy. Severe endocrine hypogonadism is therefore rare after cancer treatment in males. However, clinicians should keep in mind that long-term cancer survivors’ testosterone production appears to decrease faster than observed during physiological aging in the male general population.
The situation as to recovery of gonadal function is different in female survivors. At birth the ovaries contain approximately 10 million follicles. This number decreases along with aging up to menopause without replacement of follicles lost each month. After radiotherapy and chemotherapy the loss of follicles is accelerated. As no recovery is possible, female survivors are at risk of premature endocrine and exocrine ovarian failure (menopause before the age of 40).
Treatment of endocrine gonadal failure is based on the application of testosterone or estrogens, however, with important contra-indications in survivors after prostate and breastcancer. Prevention is the best way to limit infertility problems in cancer survivors. Updated guidelines are repeatedly published (Kenney et al. 2012; Metzger et al. 2013). Pretreatment sperm cell cryopreservation has been used for many years in adult male cancer patients, but is problematic in pre-pubertal boys. Pretreatment ovarian or testicular tissue cryoconservation is still experimental, but reimplantation of thawed ovarian tissue has been followed by pregnancies in a few cancer survivors after reimplantation of cryopreserved ovarian tissue. Overall pregnancy rates after adult-onset cancer are decreased by 26 % in male and by 39 % in female cancer patients compared to the general population. After implementation of risk-adapted cancer therapy, this discrepancy has been reduced for selected cancer types during the last three decades (e.g., in testicular cancer survivors or male survivors after Hodgkin`s lymphoma) (Stensheim et al. 2011).
2.4 Peripheral Neuropathy
One of the most common late effects (20–30 %) is peripheral neuropathy caused by chemotherapy containing vinca alkaloids, cisplatin, or taxanes (Windebank and Grisold 2008). For some patients the complaints are limited to numbness of soles of the feet, whereas others suffer from pain in the legs that might cause severe sleeping problems. Cisplatin is in addition ototoxic and can lead to tinnitus and hearing loss (Brydøy et al. 2009, Oldenburg et al. 2007). Though the latter toxicity most often is restricted to decibel frequencies of >4000 Hz, severe ototoxicity has a negative impact on a person’s social and professional life.
2.5 Muscle and Skeletal Effects
As proliferating cells are particularly sensitive to any cytotoxic treatment, radiotherapy to the skeleton and muscles in young adults can be followed by severe muscle atrophy and retarded growth of bones. The negative impact of the target dose is increased by chemotherapy with radiosensitizing drugs (Actinomycin D, Anthracyclines, Cisplatin) often applied as a part of multimodal therapy.
In breast cancer survivors reduced function of the ipsilateral arm/shoulder, pain and/or lymphoedema have represented frequent complaints, but the incidence of these late effects has been reduced after the introduction of breast conserving surgery and improved radiotherapy techniques (Nesvold et al. 2011)
Osteoporosis related to male and female endocrine hypogonadism may become a problem in all cancer survivors (Lustberg et al. 2012). Prostate cancer and breast cancer survivors are at particular high risk of developing this late effect as complete intermittent or permanent hypogonadism is an important part of their treatment. Today several drugs are available which together with Vitamin D, calcium application and physical activity reduce the risk of osteoporosis by nonhormonal mechanisms (Zoledronic acid, Denosumab).
3 Fatigue
Fatigue is defined as a subjective experience of tiredness, exhaustion, and lack of energy (Radbruch et al. 2008). Formal diagnostic criteria for “cancer-related fatigue” (CRF) as a syndrome were proposed in 1998, but has attracted relatively little attention in the scientific community (Donovan et al. 2013). In this context fatigue is regarded as a symptom.
For most cancer patients, fatigue is experienced as a side-effect during treatment and resolves by recovery from therapy. This can be conceptualized as acute fatigue. However, for some patients, fatigue may persist for years after completed cancer therapy and without any signs of active cancer disease. The term CF, defined as fatigue lasting for 6 months or more or after the stimuli has ended, applies well to such fatigue because the term differentiates between fatigue as part of everyday strains such as acute infections or psychosocial strains and the feeling of being chronically exhausted. Such a distinction is also supported by the fact that fatigue is a very common symptom in the general population (Loge et al. 1998).
The prevalence of fatigue among cancer survivors vary by assessment method, cancer type and definitions, but most prevalence figures vary between 19 and 38 % (Stone and Minton 2008). Survivors of Hodgkin lymphoma and breast cancer are the types most studied. Recent data also indicate that fatigue is common among long-term survivors of cancer in childhood and adolescence (Hamre et al. 2013). Fatigue is therefore probably the commonest late effect across all cancer survivors.
The present knowledge about etiology and mechanisms of fatigue among disease-free cancer survivors is limited (Stone and Minton 2008). It is also unlikely that any single mechanism will be identified because fatigue is multifactorial in origin and is also observed across a variety of noncancer diseases and illnesses. The etiology is therefore best considered as multifactorial, involving both physical and psychological factors. Psychological distress, pain, sleep disturbance, depression, anxiety, inactivity, late medical effects, inflammation, and anemia have all been associated with CRF (Stone and Minton 2008). Except for anemia, all are relevant in relation to CRF among cancer survivors.
Interventions to improve CRF among cancer survivors broadly fall into three categories; drug interventions, exercise interventions, and psychosocial interventions (Stone and Minton 2008). A recent update of a 2008 Cochrane review on drug therapy concluded that psychostimulants are promising but large-scaled randomized controlled trials are warranted (Minton et al. 2010). However, many of the reviewed studies included cancer patients with active disease, and the administration of psychostimulants to disease-free cancer survivors has ethical and legal aspects that need to be clarified. Exercise interventions, mostly consisting of graded aerobic exercise, have slightly to moderate positive effects upon CRF among cancer patients in general (Cramp and Daniel 2008). The strongest effects were observed among cancer survivors, but optimal type, amount and timing of interventions need to be sorted out. Psychosocial interventions include education, coping strategy training, behavioral therapy, cognitive therapy, and supportive therapy. These interventions have slight to moderate effects (Pachman et al. 2012). Education about fatigue, teaching self-care, energy conservation and activity management are easily applied in ordinary clinical contexts. In combination with sleep regulation focusing on night-time sleep, rest without sleeping during day-time, and graded physical exercise, are the best documented interventions that are applicable in ordinary clinical practice.
4 Anxiety and Depression
Longitudinal studies of depression and anxiety after cancer diagnosis suggest that the high early prevalence rates fall slowly over time. The prevalence of depression in long-term cancer survivors was similar to that of healthy controls (Mitchell et al. 2013). The proportion of depressed individuals among spouses of cancer survivors was similar to that of survivors.
Some studies have observed low levels of depression and distress as well as good quality of life (QOL) in long-term cancer survivors. In several studies QOL in long-term cancer survivors is similar to that of the general population (Mykletun et al. 2005).
In contrast, the risk of anxiety disorders is significantly higher among cancer survivors than among healthy controls. Anxiety has also been reported to be as common in spouses as in survivors (Mitchell et al. 2013). In the time frame of 10 years since diagnosis, anxiety shows a more persistent pattern than depression. The distribution of anxiety disorders among cancer survivors did not differ from that of the general population (Greer et al. 2011). In general, presence of anxiety has a negative effect on QOL. The common factor may be distressed (type D) personality, which is the conjoint effect of negative affectivity and social inhibition. The prevalence of type D personality among cancer survivors (19 %) is similar to the general population (13–24 %), but such survivors are at increased risk for impaired QOL and mental health problems (Mols et al. 2012).
4.1 Fear of Recurrence
Recently, more empirical studies have addressed fear of recurrence (Simard et al. 2013). Although defined in various ways, increasing consensus focuses on a fear that cancer could return or progress in the same place or in another part of the body. Various definitions have lead to multiple self-report measures for assessment of fear of recurrence without international recommendations so far (Thewes et al. 2012). This situation may also explain the wide range of prevalence rates reported. According to the review of Simard et al. (Simard et al. 2013) based on 130 papers, across cancer sites, 39–97 % of cancer survivors reported fear of recurrence, 22–87 % reported moderate to high degree, and 0–15 % high degree of such fear. Fear of recurrence seems to remain stable over time, even if the risk of recurrence decreases as time goes on. This finding points to an element of irrationality in fear of recurrence which is common to all kinds of pathological anxiety. The risk of recurrence among long-term testicular cancer survivors is minimal, but still 7 % reported ‘very high’ and 24 % ‘quite a bit’ fear of recurrence in our national Norwegian follow-up study (Skaali et al. 2009). This finding has to be considered in the light of the ‘focusing illusion’ phenomenon which implies considerable exaggeration if people are asked to focus on just one factor concerning their well-being (Kahneman et al. 2006).
4.2 Posttraumatic Stress Disorder
Posttraumatic Stress Disorder (PTSD) is a mental disorder due to exposure to a life-threatening event either personally or as a bystander. Since 1994 “being diagnosed with a life-threatening illness” has been defined as such a potentially traumatic event, and the studies of PTSD among cancer patients have flourished since then. The PTSD symptoms are quite specific with intrusion in the mind of experiences of cancer diagnosis and treatment, and avoidance and hypervigilance in relation to all associations with cancer. The level of PTSD symptoms is regularly high during diagnosis and treatment and then the level gradually tapers off.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
