Navigating the Shadows: Understanding and Managing Persistent Somatic Symptoms in Cancer Survivors

Abstract

The purpose of this chapter is to provide healthcare professionals, researchers and caregivers with insights on persistent somatic symptoms afflicting cancer survivors. These symptoms, including pain, fatigue, gastrointestinal distress, sexual dysfunction, respiratory issues, and cardiovascular, neurological and musculoskeletal complications often endure long after treatment completion, negatively impacting quality of life. Certain populations like childhood cancer survivors and those receiving intensive chemotherapy have higher somatic symptom burden. Possible mechanisms include accelerated aging, somatization tendencies, treatment side effects, mood disorders, and comorbidities. Assessing patient-reported outcomes and screening tools can facilitate early detection and management. Treatment strategies encompass pharmacological and nonpharmacological modalities targeting specific symptoms. Overall somatic symptom burden correlates with psychological distress and disability among survivors. Tailored, patient-centric rehabilitation programs over the cancer trajectory, from pretreatment through long-term survivorship, can mitigate symptoms. More research on persistent somatic complications is warranted to optimize evidence-based care for survivors’ multifaceted needs.

1. Introduction

Imagine a cancer survivor, who, after undergoing rigorous treatments and conquering the disease, finds themself grappling with unexplained physical symptoms that persist long after their remission. Despite their triumph over cancer, they feel trapped in the shadows of persistent somatic symptoms, impacting their daily life. Unfortunately, this experience is not unique, as many cancer survivors face similar challenges even after their battle with the disease has ended. In this chapter, we delve into the often-overlooked aspect of persistent somatic symptoms in individuals who have emerged victorious against cancer. Survivors often face a range of physical, psychological, and emotional challenges that can persist long after treatment ends. These symptoms, which can manifest in various forms and intensities, significantly impact survivors’ daily functioning and overall quality of life.

By shedding light on this topic, we aim to provide healthcare professionals, researchers, and caregivers with valuable insights and evidence-based approaches to alleviate suffering and improve the lives of cancer survivors.

To ensure the depth and accuracy of our findings, we conducted a meticulous review of the existing literature on persistent somatic symptoms in cancer survivors. By examining a wide array of studies, we aim to present a comprehensive synthesis of current knowledge and identify gaps that warrant further investigation.

2. Prevalence and impact of persistent somatic symptoms in cancer survivors

Persistent somatic symptoms can substantially impact cancer survivors’ quality of life and well-being. These symptoms encompass physical and psychological issues like pain, fatigue, anxiety, depression, and sleep problems [1, 2, 3]. Long-term rare cancer survivors commonly report tiredness/lack of energy as the most prevalent and bothersome symptom [3]. Emotional distress symptoms like depression, anxiety, and somatization are common in childhood cancer survivors [4]. Notably, symptoms can persist long-term after treatment as late effects of cancer or therapy [5]. Comorbidities strongly predict early mortality in survivors [6]. Studies consistently link somatic symptom severity and frequency to fear of recurrence in childhood cancer survivors [7]. Symptom burden profoundly impacts health-related quality of life; survivors with high physical, somatic and psychological symptoms report remarkably poor physical and mental quality of life [8]. Somatic symptoms are associated with disability and increased healthcare use in cancer patients with pain/depression [9].

The prevalence and persistence of these symptoms can vary based on factors such as age, comorbidity, race, and cancer type. For instance, older breast cancer survivors commonly report symptoms such as cardiotoxic effects, peripheral neuropathy, cognitive problems, fatigue, anxiety, depression, and sleep disturbances [1]. Similarly, racial and ethnic disparities have been observed in the physical and mental health outcomes of cancer survivors, with Black, Hispanic, and Indigenous survivors experiencing poorer health outcomes [10]. Moreover, sexual orientation and racial/ethnic differences have been found to influence the physical and mental health outcomes of female and male cancer survivors [11]. For example, prostate cancer survivors with high symptom burden require more supportive information and tailored long-term survivorship care to address their needs effectively [12].

2.1 Factors contributing to higher risk of persistent somatic symptoms in certain survivor populations

Research suggests childhood cancer survivors may experience premature aging, potentially due to cancer therapy exposure leading to cellular senescence, reduced telomere length, epigenetic changes, somatic mutations, and mitochondrial DNA issues [13]. Biological pathways likely explain the occurrence of psychosomatic symptoms like pain, fatigue, and weakness in conditions such as somatization, depression, and chronic fatigue [14]. In cancer, somatization manifests as somatic symptoms including pain, fatigue, appetite changes, and low energy [15]. Minor bodily symptoms may be cognitively linked to fear of recurrence, influencing survivors’ well-being [16].

All survivors have poorer psychological health than cancer-free individuals, emphasizing the psychological impact of survivorship [17]. Childhood leukemia, Hodgkin’s disease, and lymphoma survivors who had intensive chemotherapy have an increased risk of depression and somatic distress [18]. Factors like female sex, low education, income, and unemployment are associated with increased physical distress in childhood cancer survivors [19]. Psychological distress persists in 20–40% of survivors, highlighting its enduring impact [20]. Long-term psychoactive drug use is associated with more somatic symptoms in psychiatric patients [21]. Worsening physical health, pain, and ending analgesics predict persistent distress in survivors [22]. Table 1 summarizes somatization aspects in survivors.

Factor	Description	Reference
High Prevalence	The manifestation of psychological distress through physical symptoms is a significant concern among 50% of cancer survivors.	[23]
Type of cancer	Survivors of childhood cancer may experience higher levels of depression, anxiety, and somatization	[24]
Psychosocial Factors	Immigrants have elevated levels of somatization and anxiety; Higher rates of depression and relationship difficulty in LGBTQ community	[17, 25]
Demographic Factors	Somatization is associated with higher age, male sex, low education, and living alone.	[26, 27]

Table 1.

Somatization in cancer survivors.

3. Characteristics of persistent somatic symptoms in cancer survivors

Somatic symptoms are prevalent among cancer survivors. These symptoms include pain, fatigue, anxiety, depression, and somatic distress. Cunningham et al. highlighted that somatic symptoms, such as pain and fatigue, are common after childhood cancer and are associated with greater fear of cancer recurrence and poorer health-related quality of life [7]. Moreover, Heathcote et al. emphasized the prevalence and burden of somatic symptoms, particularly pain and fatigue, in adult survivors of childhood cancer [28]. Tuman et al. also found that breast cancer survivors with a tendency to make threatening interpretations experienced overall problematic somatic symptoms [29]. Furthermore, fear of cancer recurrence has been linked to somatic symptoms and perceived stress among cancer survivors [30].

3.1 Chronic pain in cancer survivors

Chronic pain is a common issue among cancer survivors, significantly impacting their daily functioning [31]. Studies have shown that chronic pain is prevalent and disabling, affecting a substantial proportion of cancer survivors [32]. Pain is one of the most distressing symptoms experienced by cancer survivors, with a notable impact on their quality of life [33]. However, there is a lack of recognition among clinicians regarding the frequency of chronic pain in this population, which may lead to underestimation of its prevalence and severity [34, 35]. Therefore, tailored policies, guidelines, and comprehensive training for healthcare professionals in pain management are necessary to address the complexity of chronic pain in cancer survivors [36]. The management of pain in cancer survivors presents various challenges, including social and demographic inequalities in barriers to cancer pain management [37]. The use of opioids in cancer survivors with chronic pain raises concerns, and advanced therapeutic strategies may be necessary to ensure prolonged pain control [38]. Figure 1 summarizes the most common indications for opiates in this population.

Figure 1.

Indications for opioids in cancer survivors.

Additionally, cancer-specific psychosocial factors, such as pain catastrophizing and multisite pain, contribute to the pain experience in cancer survivors [39]. Healthcare professionals must manage the needs of cancer survivors in a manner that acknowledges the burden of pain in the context of other symptoms and morbidities experienced by long-term survivors [40]. Various interventions have been explored to address chronic pain in cancer survivors, including acupuncture, cognitive behavioral therapy, and breathing exercises, with some evidence of positive effects for pain relief [41, 42]. Moreover, the evaluation of medications and self-management techniques for controlling neuropathic symptoms in cancer survivors highlights the multifaceted approach required to address the complexities of pain management in this population [43]. Figure 2 summarizes pharmacological pain management in this population.

Figure 2.

World Health Organization (WHO) step ladder approach.

3.2 Chronic fatigue in cancer survivors

The prevalence of moderate to severe fatigue among cancer survivors has been reported to be as high as 66.1%, with a significant impact on their quality of life [44]. Studies have shown that fatigue is prevalent not only in breast cancer survivors but also in survivors of lung, colorectal, prostate, and other types of cancer [45]. Table 2 summarizes various instruments to screen or measure fatigue.

Screening Tool	Description
Brief Screening Tools	VAS 0–10 scales Multi-symptom screening scales: ESAS, MSAS
Unidimensional Scales (physical impact of CRF)	Functional Assessment of Cancer Therapy Fatigue (FACT-F) Brief Fatigue Inventory (BFI) EORTC QLQ C30
Multidimensional Scales (physical, cognitive, affective)	Fatigue Symptom Inventory (FSI) Revised Piper Fatigue Scale Chalder Fatigue Scale / Fatigue Questionnaire
ICD-10 Diagnostic Criteria Guided Clinical Diagnosis	Diagnosis if six or more of the following symptoms are present daily or nearly daily during same 2 weeks in past month and at least one of symptoms is significant fatigue: fatigue (diminished energy, increased need to rest disproportionate to change in activity) generalized weakness, limb heaviness diminished concentration, attention decreased motivation, interest in activities insomnia, hypersomnia non-restorative sleep struggle to overcome inactivity emotional reactivity to feeling fatigued (sadness, frustration, irritability) difficulty with daily tasks because of fatigue short-term memory problems post-exertional malaise lasting several hours Symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning Evidence from history, physical examination, or laboratory findings that symptoms are consequence of cancer or cancer therapy Symptoms not primarily consequence of comorbid psychiatric disorders such as major depression, somatization or somatoform disorder, or delirium

Table 2.

Screening for chronic fatigue syndrome.

ESAS: The Edmonton Symptom Assessment System.

VAS: Visual Analogue Scale.

MSAS: The Memorial Symptom Assessment Scale.

EORTC QLQ-C30: The EORTC Core Quality of Life questionnaire.

Furthermore, fatigue has been found to co-occur with other symptoms such as depression, insomnia, neuropathy, and pain, contributing to the overall burden experienced by cancer survivors [46]. It has also been noted that fatigue may persist for months after the completion of cancer treatment, affecting 30–60% of cancer survivors [47]. Table 3 summarizes possible underlying mechanisms behind chronic fatigue in cancer survivors.

Psychogenic	Organic disease
Mostly <6 months and fluctuates in severity	6 months
Related to various stressors	Obvious psychosocial sctressors are often absent
Sleeping disturbance with either insomnia or eary morning awakening	Varies. May be present but often related to the underlying illness
Worse in the morning, may be alleviated by activity	Less in the morning and worsened with activity
Multiple and nonspecific complaints along with a normal exam	Fewer and more specific symptoms. Exam may suggest potential underlying problem

Table 3.

Ethnology of cancer fatigue.

Furthermore, chronic fatigue has been found to be strongly associated with depression in cancer survivors, indicating a potential interplay between these two conditions [48]. While both fatigue and depression are prevalent among cancer survivors, it is essential to differentiate between these two conditions. Table 4 summarizes core findings and differences.

Chronic fatigue in cancer survivors	Depression in cancer survivors
Fatigue much more common than depression (60–90% vs. 20–25%)	Depression more likely in presence of; hopelessness, worthlessness, guilt history or family history of depression
Depressive symptoms due to fatigue are often less severe and are attributed to consequences of fatigue by patients	Suicidal ideations, desire for death are not common in patients with fatigue

Table 4.

Fatigue and depression in cancer survivors.

The management of fatigue in cancer survivors is a complex challenge, as there is currently no somatic strategy specifically tailored to address this issue [49]. Furthermore, the experience of chronic fatigue post-treatment can have a profound impact on the family and social dynamics of cancer survivors [50]. Table 5 summarizes the main treatment strategies.

Interventions for Fatigue	Description
Depression treatment	Typical antidepressants selective serotonin reuptake inhibitors (SSRIs) may be better tolerated than others bupropion may be more activating (similar in structure to stimulants) novel agents (venlafaxine, nefazodone, mirtazapine) Psychostimulants methylphenidate, dextroamphetamine, modafinil, amodafinil
Nonpharmacologic interventions	Physical Activity / Aerobic Exercise [51] Energy conservation and restoration Sleep restoration, UV Light Therapy Psychotherapies: Cognitive Behavioral Therapy Mindfulness Based Stress Reduction Psycho-educational, Supportive Counseling, journal [52, 53]. Meditation/Relaxation/Yoga Acupuncture, Quigong Nutritional Counseling/Supplements
Pharmacologic interventions	Psychostimulants methylphenidate (2.5 to 30 mg once or twice daily or higher) dextroamphetamine (2.5 to 30 mg once or twice daily or higher) modafinil (100 to 400 mg/day) amodafinil (150–250 mg/day) Corticosteroids dexamethasone (1 to 3 mg bid) prednisone (5 to 10 mg bid): limited data; at least transient symptom improvement; long-term benefit not demonstrated Pharmacologic interventions with L-carnitine Patients with advanced cancer are at risk for carnitine deficiency because of low intake and increased renal loss. Anticytokine agents (thalidomide, pentoxifylline, cox-2 inhibitors) Other agents (donepezil, megestrol acetate, amantadine, anabolic steroids, antidepressants, sleep aids) Supplements: ginseng, Vit D, others

Table 5.

Management of chronic fatigue.

3.3 Impact of cognitive impairment on somatic symptoms in cancer survivors

Research has shown that long-term survivors are at risk for neurocognitive impairment due to multiple sources of risk [54]. The lack of information regarding cognitive impairment has been found to negatively impact the work and work capacity of cancer survivors [55]. Chemotherapy has been implicated in cognitive abnormalities in cancer survivors, including impairments of memory, attention, processing speed, and executive function [56]. Moreover, aging cancer survivors may report new-onset neurocognitive impairments, and there is a need to identify risk factors associated with such impairments [57]. Table 6 outlines assessment and diagnosis of cognitive impairment in cancer survivors.

History	Time course of cognitive decline (correlation with cancer, chemo, hospitalization) Fluctuations/Sleep wake cycle Assess for pain and discomfort Cognitive, functional, behavioral history (current and baseline) with collateral from family and caregivers h/o delirium or dementia, seizures, falls, h/o ICU stay Medication list/ chemotherapy or other cancer therapies ETOH, benzodiazepines Vascular risk factors Family history of neurodegenerative disorders
Examination	Mental Status Examination and cognitive/neuropsychological testing Physical examination Neurological examination (frontal release signs, gait, asterixis, EPS, focal findings)
Diagnostic Work Up	Basic Metabolic Panel: Na, K, Ca, Mg/ BUN and creatinine/ LFTs/ Albumin CBC (WBC, Hemoglobin/Hematocrit, MCV, Platelets) Thyroid function tests, RPR, FTA-ABS, Vitamin B12 Thiamine EKG UA/Cultures ABG/CXR Ammonia EEG/ Brain Imaging/LP
Differential Diagnosis	Delirium, Depression, Anxiety, Adjustment disorders Fatigue, Sleep Disorders (insomnia, sleep apnea), Substance Use Disorders, Paraneoplastic syndromes, • Mild or Major Neurocognitive Disorder

Table 6.

Assessment of cognitive impairment in cancer survivors.

Cognitive rehabilitation has been proposed as a potential intervention, as concerns about impaired cognition are one of the most frequently reported post-treatment symptoms in cancer survivors [58]. Physical activity has been associated with better neurocognitive function in cancer survivors, suggesting a potential avenue for intervention [59]. The National Comprehensive Cancer Network recommends pharmacologic interventions as a last line of therapy:

• Psychostimulants: methylphenidate, dextroamphetamine

• Wakefulness-promoting agents: modafinil, armodafinil

• Cholinesterase inhibitors: Donepezil, rivastigmine

• NMDA-antagonists: Memantine

• Bupropion, atomoxetine

Table 7 summarizes neuromodulation strategies utilized in cancer survivors.

Strategy	Description
Neurofeedback	Promising results in breast cancer patients.
Repetitive transcranial magnetic stimulation	Currently, no studies in cancer patients.
Transcranial Direct Current Stimulation	Non-invasive brain stimulation technology Studied in patients with depression, pain syndromes, stroke, Alzheimer’s, and Parkinson’s disease in non-cancer settings with promising clinical evidence.

Table 7.

Neuromodulation strategies for cognitive difficulties in survivorship.

3.4 Impact of sleep disorders on somatic symptoms in survivors

Sleep disorders and somatic symptoms are prevalent among cancer survivors, impacting their quality of life and psychological well-being. Statistically, sleep medication use is prevalent among cancer survivors, with the prevalence of insomnia symptoms being nearly 40% in this population [60]. Research indicates that adult survivors of childhood cancer are more likely to experience fatigue, sleep disturbance, and daytime sleepiness [61]. For instance, a study by Schlarb et al. found that self-reported sleep quality, sleep onset latency, sleep disturbances, use of sleep medications, and daytime dysfunctioning were significant predictors of somatoform syndrome, while sleep efficiency and sleep duration indirectly influenced somatic complaints [62]. Insomnia severity is directly related to habitual somatic complaints and pain intensity [63]. Similarly, Sun et al. indicated that a high level of somatic symptoms exacerbates the adverse effects on sleep disturbance, emphasizing the bidirectional nature of the relationship [64]. Table 8 summarizes general principles and interventions in cancer patients and survivors with sleep problems.

Intervention	Characteristics
Nonpharmacological Interventions	Cognitive-behavioral therapy for insomnia (CBT-I) (+) strong evidence in cancer patients with therapeutic effects maintained long term. Exercise Interventions: regular aerobic exercises, even of different durations and weekly volumes, benefits patient sleep quality.
Pharmacological Interventions	The American Academy of Sleep Medicine does not recommend sleep medications for longer than 4 weeks. The NCCN Survivorship Guidelines recommends assessment every 1 to 3 months to determine ongoing need for medications. All medications have been shown to be more effective than placebo at improving short-term sleep outcomes in the general population. The potential benefits of pharmacologic therapy on sleep quality and daytime function are balanced against the risk of side effects and dependence with long-term use.

Table 8.

Management of sleep difficulties in cancer survivors.

3.5 Sexual dysfunction in cancer survivors

Research shows sexual dysfunction is a prevalent issue among cancer survivors, especially childhood and young adult survivors. A review highlighted adolescent and young adult survivors experience substantial sexual dysfunction [65]. Another review identified the prevalence and risk factors for sexual dysfunction in childhood cancer survivors, emphasizing its link to quality of life and psychosocial outcomes [18]. Studies show childhood cancer survivors may experience sexual difficulties and delays in milestones due to the cancer’s impact on psychosexual development [66]. Sexual dysfunction is prevalent among female childhood cancer survivors, significantly impacting their psychosexual functioning [67]. There is an increased risk of sexual dysfunction in young adult survivors of childhood cancer, indicating a need for support in this population [68]. Another study emphasized the lack of information on sexual health for male childhood cancer survivors, showing further research and support is needed [69]. Standardized nursing care interventions reduced sexual dysfunction in cervical cancer survivors, underscoring potential benefits of targeted interventions [70]. These findings demonstrate sexual dysfunction is a common issue among survivors that interventions may help address. Table 9 summarizes NCCN guidelines regarding sexual dysfunction.

ASK	About sexual function at regular intervals
ASSESS	Using the Brief Sexual Symptom Checklist as a primary screening tool
REVIEW	Present and past sexual history and sexual concerns
DISCUSS	How cancer treatment has affected sexual functioning, intimacy, treatment-associated infertility and, if indicated, provide appropriate referrals
DIRECT	Patients to needed resources

Table 9.

Guidelines of sexual dysfunction.

3.6 Weight loss in cancer survivors

Weight loss and poor appetite are significant concerns among cancer patients and survivors. Another study highlighted that intermittent claudication and appetite loss are common among breast cancer survivors and are associated with cardiac dysfunction and mood disorders [71]. Similarly, it was found that self-reported distress among older cancer survivors was associated with weight change and poor appetite [72]. Additionally, identified appetite changes as one of the indicators of physical wellbeing in cancer survivors, emphasizing its impact on quality of life [73]. Table 10 summarizes the differences between starvation and cancer/post-treatment weight loss.

Starvation	Cancer/Post-Treatment Weight Loss
Loss of adipose tissue	Loss of fat and lean muscles
Hunger is present, significant	No hunger, no concerns about food
Decreased resting energy	Increased resting energy expenditure
No specific mediators or markers	Pro-inflammatory cytokines

Table 10.

Weight and appetite loss and cancer cachexia.

Furthermore, emphasized the consequences of weight loss for cancer survivors as a crucial issue in survivorship research, highlighting the need for interventions to address this concern [74]. Other authors also identified appetite loss as a part of a cluster of symptoms in breast cancer survivors, indicating its impact on their quality of life [75]. Research highlighted the importance of maintaining a healthy weight for cancer survivors, emphasizing the potential benefits for their overall well-being [76]. In addition, weight loss interventions have been studied in the context of cancer survivorship. Reported that behaviorally based weight loss interventions for breast cancer survivors resulted in significant weight losses, indicating the potential effectiveness of such interventions. Table 11 summarizes pharmacological and nonpharmacological management of cancer and post-treatment weight loss in cancer survivors.

Strategy	Description
Counseling	The nutritional counseling: liberalizing diet restrictions, encouraging patients to eat frequent small meals with preferably the bulk of calorie intake occurring in the morning.
Nonpharmacological Management	Ensuring sufficient energy and protein intake (nutritional support, consultation with a nutritionist) Maintaining body weight, physical activity and muscle mass (exercise, PT)
Pharmacological Management	Appetite Stimulants corticosteroids, cannabinoids, progesterone analogs, and serotonin modulators (olanzapine, mirtazapine). Anabolic Agents anabolic steroids Growth hormone, ghrelin analogs Cytokine and metabolic inhibitors Eicosapentaenoic acid Thalidomide

Table 11.

Weight and appetite loss management.

3.7 Gastrointestinal distress in cancer survivors

Nausea and vomiting are very common in cancer patients, including survivors. Research shows 70–80% of chemotherapy patients experience these symptoms [77], which continue into survivorship and hurt quality of life [78]. Over 60% of terminally ill patients have nausea and vomiting in their last 6 weeks [79]. Managing these symptoms is crucial for survivors’ wellbeing. Studies suggest high protein intake can lessen nausea and vomiting [80]. Acupressure has been explored to treat chemotherapy-induced nausea and vomiting [81]. Aromatherapy with ginger may alleviate nausea and vomiting after cervical cancer chemotherapy [82].

Constipation and diarrhea persist as major issues for survivors versus healthy controls [83]. More extreme gastrointestinal symptoms correlate with poorer physical and mental health [84]. Colorectal cancer survivors specifically reported high levels of constipation and diarrhea [85]. Physical activity improved diarrhea in prostate cancer survivors [86]. Exercise motivation plans and doctor recommendations together could raise exercise levels in breast and colorectal survivors, potentially improving constipation and diarrhea [87]. Beyond exercise, dietary changes and probiotics have been explored. One study promoted exercise and avoiding sedentary lifestyles for breast cancer survivors [88]. Probiotics during or after cancer treatment may alleviate certain gastrointestinal issues like diarrhea and abdominal pain [89].

3.8 Cardiovascular complications and symptoms in cancer survivors

Cardiovascular complications are a major concern for cancer survivors, as they continue facing increased risk of death from cardiovascular problems after remission or cure [90]. Understanding the mechanisms and diagnostic strategies with risk prediction is key to preventing cardiovascular issues in patients and survivors [91]. Additionally, acquiring modifiable cardiovascular risk factors, especially hypertension, heightens the risk of severe, life-threatening, and fatal cardiac events in survivors, regardless of cancer treatment risks [92]. Long-term cardiovascular effects of cancer treatments like radiotherapy and chemotherapy are well-documented in adult survivors [93]. Furthermore, survivors have high cardiovascular disease risk, with those at risk having significantly higher mortality than those without risk [94]. Preexisting cardiovascular risks and older age associate with heart failure and other cardiovascular diseases in survivors, particularly those who had anthracyclines [95]. Notably, people diagnosed with highly survivable cancers are more likely to die from cardiovascular disease than cancer recurrence, yet cardiovascular risks may be overlooked during survivorship care [96]. This is especially concerning as many breast cancer survivors are more likely to die from cardiovascular disease than breast cancer [97]. Moreover, compared to the general population, survivors have increased risk of cardiovascular events, and the odds of several cardiovascular risk factors are higher among middle-aged survivors [98]. It’s estimated cardiovascular disease is the number one comorbidity in survivors and causes many non-cancer deaths among them [99]. Therefore, continuous monitoring and aggressive management of modifiable cardiovascular risks could reduce the cardiovascular burden in cancer survivors.

3.9 Other somatic problems

3.9.1 Osteopenia and osteoporosis in cancer survivors

Osteopenia and osteoporosis are significant concerns for cancer survivors, particularly for breast and prostate cancer survivors. Table 12 summarizes various mechanisms of bone loss in cancer survivors.

Factor (s)	Mechanism(s)
Medications	Glucocorticoids (PO + high dose inhaled) Excessive thyroid replacement Proton pump inhibitors Anticonvulsants Long-term heparin use GnRH agonists (Lupron): prostate cancer Aromatase inhibitors Thiazolidinediones Sedative hypnotics (FALL risk) Furosemide: falls ±calciuresis Opiates (cause hypogonadism)
Solid tumors	Hypogonadism; +/−secondary hyperparathyroid
Various	Weight loss, cachexia
Myeloma	OB inhibition, rarely osteomalacia
Leukemia/lymphoma	Steroids, TKIs
Stem cell transplant	Steroids/GVHD, malabsorption, immunosuppressives, chemo
Neuroendocrine cancer	Ectopic ACTH, Cug syndrome

Table 12.

Etiology of bone loss in cancer patients and survivors.

While osteoporosis or osteopenia may seem insignificant compared to other long-term side effects, these disorders can significantly restrict a survivor’s lifestyle [100]. Research has shown that younger breast cancer survivors, especially those aged ≤ 50 years, with estrogen receptor-positive tumors, and those treated with aromatase inhibitors alone or chemotherapy plus any hormone therapy, are at a higher risk for osteopenia and osteoporosis compared to cancer-free women [101]. Adult cancer survivors, including those with childhood leukemia, are also at risk, with approximately 50% of patients having osteopenia or osteoporosis [102]. Similarly, cancer survivors are at risk of developing osteoporosis and osteopenia due to cancer treatment [103]. These conditions often do not produce clinical symptoms until a fracture occurs—commonly seen in the wrist, hip, and spine from minimal trauma that would not typically break a healthy bone. Spinal compression fractures in particular may generate severe back pain, height loss, protruding abdomen, and reduced mobility. More general symptoms can include bone pain, joint aches, and difficulty with walking or daily tasks. Early detection and treatment can reduce fracture risk and related disability.

3.9.2 Respiratory problems in cancer survivors

It is evident that respiratory problems are a significant concern among cancer survivors. Research suggests that childhood cancer survivors had significant excesses in respiratory mortality, including pneumonia, fibrosis, pneumonitis, and other respiratory deaths, with standardized mortality ratios ranging from 7-fold to 17-fold higher than expected [104]. Similarly, highlighted that survivors of childhood and young adult cancer remain at a significantly increased risk of respiratory complications several decades after treatment, emphasizing the importance of clinical initiatives for prevention, early detection, and treatment [105]. Furthermore, reported that adverse health effects, including respiratory infections, were statistically significantly increased in breast cancer survivors, indicating the long-term impact of cancer and its treatment on respiratory health [106]. Additionally, compared the incidence of pulmonary outcomes among cancer survivors and found an increased risk of pulmonary complications, such as asthma, chronic cough, emphysema, lung fibrosis, and recurrent pneumonia, emphasizing the need for ongoing monitoring and management of respiratory health in this population [61].

4. Non-pharmacological approaches to alleviate persistent somatic symptoms

4.1 Physical therapy and rehabilitation

Physical therapy and rehabilitation play a vital role in the care and recovery of cancer survivors. Research has shown that cancer survivors are highly motivated to seek information about physical activity and dietary choices to enhance their response to treatment, expedite recovery, and improve their quality of life [107]. Cancer rehabilitation is a process that helps survivors achieve and maintain the highest possible physical, social, psychological, and vocational functioning within the limits created by cancer and its treatments [108]. In fact, a study evaluating survivors of the 10 most prevalent cancers found that 63% reported the need for at least one rehabilitation service, with physical therapy being the most frequently reported need [109]. Furthermore, investment in oncology physical therapy and the development of international standards of care can allow physical therapists to meet the rehabilitation needs of cancer survivors [110]. Rehabilitation intervention may be required at multiple time points along the cancer continuum, from prior to treatment to the early rehabilitation and long-term survivorship phases post-treatment [111]. Additionally, rehabilitation and exercise have been found to be effective for treating physical functional decline and addressing symptoms across multiple domains and at multiple points along the cancer disease continuum. Moreover, physical activity programs are recommended as part of cancer rehabilitation services [112]. However, there are challenges in implementing physical activity and rehabilitation guidelines in routine primary care cancer rehabilitation, and exploring professionals’ perceptions and preparedness to implement these guidelines is essential [113]. Rehabilitation is recommended to help cancer survivors regain functional independence and mitigate subsequent disability [114]. Home exercise programs have been found to be a useful adjunct to physical therapy programs for treating arm and shoulder morbidities in cancer survivors. The American College of Sports Medicine and the American Cancer Society have recommended physical activity as an intervention strategy to help cancer survivors manage symptoms, improve quality of life, and possibly even extend survival [115].

Furthermore, during re-entry after cancer treatment, clinicians can educate survivors on the benefits of healthy behaviors [116]. This period after the primary treatment for cancer ends requires support care for patients having physical, psychological, and social readjustments, making rehabilitation services crucial [117].

4.2 Psychological interventions for somatic symptoms in cancer survivors

Psychological interventions are crucial for addressing the somatic symptoms experienced by cancer survivors. Research shows that cognitive behavioral therapy and physical activity interventions effectively improve quality of life in survivors [118]. Cancer and its treatments can significantly influence psychological well-being and cause distress later in life [24]. Childhood cancer survivors have an increased risk of depression and somatic distress, exacerbated by intensive chemotherapy [18]. Psychological interventions like mindfulness and therapy reduce cancer-related fatigue [26]. Over 35% of survivors experience depressive symptoms during survivorship. Distress manifests as depression, anxiety, PTSD, worry, or anger [27]. Support interventions reduce distress in prostate cancer survivors [25]. Psychosocial interventions increasingly promote resilience and meaning to improve well-being [119, 120]. Disparities in rural survivors’ mental health indicate a need to increase their access to services [121]. In summary, a range of psychological interventions are vital to address survivors’ somatic symptoms and improve their overall quality of life.

4.3 Integrative therapies for somatic symptoms in cancer survivors

The use of complementary and alternative medicine (CAM) in cancer survivors is widespread and increasing [122]. Certain survivors, like childhood cancer survivors, have high psychological distress, cognitive dysfunction, and poor quality of life [18, 123]. CAM use is high among survivors, but reasons behind use and communication with doctors are not well understood [124]. Many survivors report somatic symptoms and stress. Elderly survivors may have more symptoms, distress, and unhealthy lifestyles [27]. However, lung cancer survivors reported fewer daily somatic symptoms than other survivors [125]. Use of complementary therapies has significantly increased, suggesting survivors are interested in supplementing treatment [126]. Most breast cancer survivors use CAM at some point [127]. Adult survivors of pediatric cancer had more affective, somatic and comorbid symptoms than sibling controls [128]. Even long-term survivors use healthcare differently than community controls [129]. Survivors with pain levels similar to people without cancer still engage more in CAM [130]. In summary, CAM use is increasing in survivors and tied to various symptoms, but reasons behind use and impact need further research.

5. Conclusion

Persistent somatic symptoms are highly prevalent in cancer survivors, negatively affecting quality of life across physical, psychological and social domains. Common symptoms include pain, fatigue, sexual dysfunction, cognitive changes, cardiovascular/gastrointestinal issues, respiratory problems, and musculoskeletal disorders. Risk factors like childhood cancer and intensive treatment can worsen burden. Proposed mechanisms involve accelerated aging, somatization, mood disorders, treatment side effects, and physical/psychosocial comorbidities.

Careful assessment of patient-reported outcomes is vital for early detection and management of somatic symptoms. Both drug and non-drug approaches help alleviate persistent symptoms. Evidence-based, patient-centered rehabilitation programs implemented early and continued long-term can significantly mitigate symptoms and improve functioning.

Acknowledgments

I would like to express my sincere gratitude to the faculty members at the Department of Psychiatry, University of Missouri-Kansas City School of Medicine for their guidance and support. Finally, the experiences and struggles of cancer survivors battling persistent somatic and psychological symptoms were the motivation behind this review. I hope my work can positively impact survivorship care and that emerging research continues to alleviate suffering among those courageously recovering from cancer.

Conflict of interest

The authors declares no conflict of interest.