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CANCER

What is Cancer?

Cancer is a complex group of diseases characterised by the uncontrolled proliferation of abnormal cells. These malignant cells evade normal regulatory mechanisms, invade surrounding tissues, and, in many cases, metastasise to distant sites via the bloodstream or lymphatic system. Cancer arises due to genetic mutations that disrupt normal cell cycle control, enabling continuous division and growth. These mutations may be inherited or acquired due to environmental and lifestyle factors.

Cancers are classified based on their tissue of origin:

Carcinoma

The most common type, originating in epithelial cells, which line the body's surfaces and internal organs. Examples include breast, lung, prostate, and colorectal cancers.

Sarcoma

Develops in connective tissues such as bones, muscles, cartilage, and fat.

Leukemia

Arises from hematopoietic (blood-forming) tissues, resulting in abnormal proliferation of white blood cells.

Lymphoma

Begins in lymphatic tissues, including lymph nodes and the spleen, affecting the body's immune response.

Central Nervous System Cancers

Originates in the brain or spinal cord and can be highly aggressive.

Contributing Factors

Cancer development is influenced by multiple factors, broadly classified into genetic, environmental, and lifestyle components:

Genetic Predisposition: Individuals with a family history of certain cancers (e.g., breast, ovarian, colorectal) may inherit genetic mutations, such as BRCA1, BRCA2, TP53, or APC, which significantly increase their cancer risk.
Environmental Exposures: Prolonged exposure to carcinogens—such as tobacco smoke, asbestos, industrial chemicals, and ultraviolet (UV) radiation—can cause DNA damage and promote malignant transformation.
Lifestyle Factors: Unhealthy habits, including poor diet (high in processed foods and red meats), excessive alcohol consumption, obesity, and sedentary behavior and physical inactivity, are linked to an increased risk of developing cancer.
Chronic Infections: Persistent infections with oncogenic viruses, such as human papillomavirus (HPV), Epstein-Barr virus, and hepatitis B and C, can induce chronic inflammation and genetic alterations that contribute to carcinogenesis.
Hormonal Imbalances: Elevated estrogen, insulin, and insulin-like growth factor (IGF-1) levels have been implicated in hormone-sensitive cancers, including breast and prostate cancer.

General Signs and Symptoms of Cancer

While specific symptoms vary depending on the type and location of cancer, general warning signs include:

Unexplained weight loss
Unexplained fever
Persistent fatigue or breathlessness
Unusual, unexplained or chronic pain, particularly in bones or muscles
Skin changes, including jaundice or darkened patches
Unusual bleeding or discharge
Persistent cough or hoarseness, blood in sputum
Difficulty swallowing
Sores or ulcers that aren’t healing
Changes in bowel or bladder habits, or blood in bowel motion
Lumps or thickened areas under the skin (particularly in the neck or armpits

Early detection of these symptoms can improve treatment outcomes, emphasising the importance of routine medical check-ups.

Stages of Cancer

Stage	Characteristics
Stage III (Regional spread)	Cancer has grown significantly and spread more extensively to nearby lymph nodes and tissues but not yet to distant sites. More aggressive treatment, including chemotherapy, targeted therapy, and/or radiation, is often required.
Stage IV (Metastatic or advanced cancer)	Cancer has spread to distant organs (e.g, lungs, liver, bones). Treatment focuses on slowing progression, symptom management, and improving quality of life, often using systemic therapies like chemotherapy, immunotherapy, and/or targeted treatments.
Stage II (Localised spread)	The tumor is larger and may have spread to nearby tissues or lymph nodes but not to distant organs. Treatment typically involves a combination of surgery, chemotherapy, and/or radiation.
Stage I (Early-stage)	Cancer is localised to the primary site and has not spread to lymph nodes or distant areas. Tumor size is generally small, and treatment options like surgery and/or radiation can be highly effective.
Stage 0 (Carcinoma in situ)	Abnormal cells are present but have not spread to nearby tissues. This stage is considered precancerous and highly treatable if detected early.

Common Cancer Treatments

Traditional cancer treatment modalities include:

Surgery: The primary treatment for localised tumors, aimed at removing cancerous tissue before it spreads.
Radiation Therapy: Uses high-energy ionising radiation to destroy cancer cells by damaging their DNA. Side effects include fatigue, skin reactions, and damage to surrounding healthy tissues.
Chemotherapy: Involves the systemic administration of cytotoxic drugs targeting rapidly dividing cells. This treatment can lead to significant side effects, including nausea, immunosuppression, and neuropathy.
Immunotherapy: Stimulates the body's immune system to recognise and destroy cancer cells. Emerging research suggests that exercise may enhance immunotherapy efficacy by improving immune function.
Hormonal Therapy: Used in hormone-sensitive cancers, such as breast and prostate cancer, to block hormone production or receptor activity, thereby slowing tumor growth.

Exercise as an Adjunct Therapy

Research increasingly supports the role of exercise across all phases of cancer care—prevention, treatment, and survivorship:

Prevention: Regular physical activity is associated with a reduced risk of developing several cancers, including breast, colon, and prostate cancer, by modulating systemic inflammation, metabolism, immune function, and hormone balance/regulation.
During Treatment: Exercise helps mitigate treatment side effects, including fatigue, muscle wasting, bone density loss, and cardiovascular complications. It also preserves lean body mass and enhances functional capacity.
Prehabilitation (Before Surgery): Engaging in structured exercise programs prior to surgery has been shown to significantly improve postoperative recovery. A comprehensive analysis of 186 clinical trials involving approximately 15,700 patients revealed that those who exercised regularly before surgery experienced a 50% reduction in complication risks. Incorporating a healthy diet and social support into pre-surgery routines further minimised complications and shortened hospital stays.
Post-Treatment Survivorship: Structured exercise programs improve physical function, mental well-being, overall quality of life and long-term survival outcomes by reducing the likelihood of recurrence and secondary malignancies or other conditions.

Mechanisms Behind The Role of Exercise
in Cancer Care

Exercise influences cancer biology through multiple mechanisms:

Immune System Modulation: Regular exercise enhances natural killer (NK) cell activity, T-cell function, and macrophage response, improving immune surveillance against malignant cells.
Hormonal Regulation: Physical activity decreases circulating levels of insulin, insulin-like growth factors (IGFs), and estrogen, all of which are implicated in cancer growth and progression.
Reduction of Chronic Inflammation: Exercise reduces pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which play a role in tumor initiation and progression.
Oxidative Stress Adaptation: Moderate exercise promotes antioxidant defense mechanisms, protecting cells from oxidative DNA damage.
Enhanced Apoptosis: Exercise induces programmed cell death in precancerous and cancerous cells, aiding in the prevention of tumor proliferation.

Exercise Prescription in Cancer Care

Our CEPs collaborate with oncologists and physiotherapists to ensure your exercise plan complements your medical care. Whether at home, in a gym, or online, we’re here to guide you towards a healthier, more active lifestyle during and after cancer treatment. A structured exercise physiology program should be tailored based cancer type, treatment stage, and overall health status, as well as with consideration for co-occurring conditions and individual goals and preferences, however, general exercise prescription may follow the following framework:

Assessment: Comprehensive evaluation of current fitness levels, medical history, prognosis and treatment status.
Prescription: Designing a balanced regimen incorporating:
- Aerobic Exercise: 150-300 minutes of moderate-intensity or 75-150 minutes of vigorous-intensity exercise per week, such as walking, cycling, or swimming.
- Resistance Training: At least two days per week of moderate-intensity strength training to preserve muscle mass and bone density.
- Flexibility and Balance Training: Yoga, Pilates, and/or stretching to improve range of motion and prevent falls.
- Individualised Modifications: Consideration of treatment side effects, such as fatigue or neuropathy, with tailored progressions to accommodate functional limitations. Modification to prescription can be made to accommodate post-surgical protocols and/or considerations, e.g., reducing severity of lymphoedema following mastectomy.
Monitoring: Regular follow-ups to adjust the program as needed, ensuring safety and effectiveness.

Cancer, Exercise, Improved Outcomes
& Survivorship

Exercise has been shown to have a profound impact on cancer survivorship, improving both survival rates and quality of life across cancer care. Exercise has emerged as a critical component of cancer treatment and rehabilitation, providing both physiological and psychological benefits and overall outcomes. Exercise can positively influence various types of cancer, via various mechanisms, however research is particularly strong in the following areas:

Breast Cancer

Exercise has been widely studied in breast cancer patients, showing numerous benefits:

Fatigue Reduction: Exercise interventions help reduce cancer-related fatigue, a common side effect of both the disease and its treatment. Aerobic and resistance training have shown the ability to alleviate fatigue and improve energy levels in breast cancer survivors.
Survival and Recurrence: Physical activity is associated with improved survival rates and a reduced risk of recurrence. A meta-analysis by Schmid and Leitzmann (2014) found that higher levels of physical activity after diagnosis were linked to a 34% lower risk of breast cancer recurrence and a 41% reduced risk of mortality.
Reduction in Mortality: Holmes et al. (2005) conducted a large study in which breast cancer survivors who engaged in regular physical activity post-diagnosis had a 40-50% reduction in the risk of mortality compared to those who were less active. This was attributed to the combined benefits of exercise in reducing cancer recurrence and promoting overall health.
Mechanisms: Regular exercise helps regulate hormone levels (especially estrogen), which may contribute to a reduced risk of recurrence. Exercise also enhances immune function, reduces inflammation, and improves metabolic health—all of which can contribute to improved outcomes.

Prostate Cancer

Exercise plays a significant role in the recovery and management of prostate cancer:

Muscle mass maintenance: Resistance training is particularly beneficial in preventing muscle loss, which is common in prostate cancer patients undergoing androgen deprivation therapy.
Bone mineral density: Exercise prescription with a focus on resistance and impact training can assist in preserving bone mass and bone mineral density (BMD), which is particularly important for patients on androgen deprivation therapies (ADT) known to reduce BMD.
Cardiovascular health: Aerobic exercise improves cardiovascular health, which is crucial for overall cancer treatment tolerance.
Side effect reduction: Studies have shown that exercise can mitigate treatment-related side effects, such as fatigue and sexual dysfunction.
Disease-Specific Mortality: Kenfield et al. (2011) found that physical activity was associated with a 49% lower risk of prostate cancer-specific mortality. This reduction in risk was observed in men who maintained a moderate level of physical activity following diagnosis, highlighting the long-term benefits of staying active.
Benefits of Exercise: Physical activity helps mitigate the side effects of treatment, such as fatigue and muscle wasting, which are common in prostate cancer patients undergoing androgen deprivation therapy. Moreover, exercise has positive effects on cardiovascular health, which is critical as prostate cancer treatments can lead to an increased risk of heart disease.

Colorectal Cancer

Exercise contributes to both the prevention and treatment of colorectal cancer:

Bowel Function: Regular physical activity has a positive effect on bowel motility, reducing the likelihood of constipation and improving overall gastrointestinal function (Meyerhardt et al., 2006).
Prognosis and Recurrence: Exercise has been shown to improve prognosis and reduce recurrence rates. A study by Campbell et al. (2019) reported that physically active colorectal cancer survivors had a lower risk of mortality and recurrence compared to sedentary individuals.
Recurrence and Survival: Meyerhardt et al. (2006) showed that exercise can reduce the risk of colorectal cancer recurrence and improve survival by up to 50%. In this study, colorectal cancer survivors who engaged in regular physical activity had a substantially lower risk of recurrence and death compared to their sedentary counterparts.
Physiological Effects: Exercise improves insulin sensitivity, reduces inflammation, and aids in weight management—all of which are associated with lower risks of recurrence and better overall prognosis in colorectal cancer patients.

Lung Cancer

Lung cancer patients, particularly those undergoing chemotherapy or radiotherapy, benefit greatly from exercise:

Pulmonary Function: Exercise, including aerobic training, enhances pulmonary function, counteracting the decline in lung capacity caused by treatments.
Breathlessness and Quality of Life: Aerobic exercise helps to reduce the feeling of breathlessness (dyspnea) and enhances quality of life in lung cancer survivors. This is crucial for individuals recovering from surgery or undergoing treatment.
Postoperative Recovery and Survival: Cardiorespiratory fitness, a key outcome of aerobic exercise, is strongly linked to better postoperative recovery and longer survival in lung cancer patients. A study by Hwang et al. (2016) found that patients who maintained higher levels of fitness before and after lung cancer surgery had significantly improved recovery times and were more likely to survive longer.
Reduced Mortality: Regular exercise is associated with improved survival rates, likely due to its positive effects on immune function, reducing the risk of infection and complications, and enhancing cardiovascular health.

Ovarian Cancer

Exercise has significant effects on ovarian cancer patients:

Muscle Loss: Like breast and prostate cancer, ovarian cancer treatments can lead to muscle loss. Resistance training is particularly effective in preserving lean muscle mass and improving physical function.
Immune Function: Moderate-intensity exercise may enhance immune function, which is important for managing cancer-related fatigue and supporting treatment responses.

Pancreatic Cancer

While research is still emerging, there is some evidence to suggest that exercise can benefit pancreatic cancer patients:

Slows Disease Progression: Physical activity may contribute to slowing the progression of pancreatic cancer by improving metabolic and immune responses.
Quality of Life: Exercise interventions have been found to improve quality of life, particularly in reducing fatigue and improving physical functioning.

Leukemia and Lymphoma

Exercise has positive effects on patients with leukemia and lymphoma:

Cardiovascular Fitness: Maintaining cardiovascular fitness through exercise is crucial for leukemia and lymphoma patients, especially those undergoing chemotherapy.
Fatigue and Mental Health: Physical activity significantly reduces treatment-related fatigue, and also improves mood, anxiety, and depression, contributing to better overall mental health and emotional well-being.

The Impact of Exercise on Tumor Biology and Treatment Outcomes

Emerging research has highlighted the significant role of exercise in modifying the tumor microenvironment, thereby enhancing the efficacy of cancer treatments. Key findings include:

Improved Tumor Vascularisation and Drug Delivery: Studies using mouse models of cancer have demonstrated that exercise normalises tumor vasculature, reducing chaotic and dysfunctional blood vessel growth. This improved vascular structure enhances perfusion and oxygenation, leading to increased chemotherapy delivery and efficacy.
Enhanced Immune Response: Exercise has been shown to mobilise and activate immune cells, including natural killer (NK) cells, cytotoxic T cells, and macrophages, which infiltrate the tumor and aid in immune-mediated destruction of cancer cells. Increased circulation of immune cells during and after exercise enhances immune surveillance, reducing tumor progression.
Reduced Tumor Hypoxia and Increased Treatment Sensitivity: Tumor hypoxia—a condition of low oxygen within the tumor—contributes to aggressive cancer behavior and treatment resistance. Regular aerobic exercise improves oxygen delivery to the tumor, thereby increasing the effectiveness of radiotherapy and chemotherapy.
Regulation of Pro-Inflammatory Cytokines: Chronic inflammation is a key factor in cancer progression. Exercise reduces levels of pro-inflammatory cytokines such as TNF-α, IL-6, and C-reactive protein while increasing anti-inflammatory cytokines. This shift in the inflammatory profile can slow tumor growth and improve response to treatment.
Activation of Anti-Cancer Pathways: Exercise upregulates tumor-suppressing proteins, such as p53, which play a role in DNA repair and apoptosis (cell death) of cancerous cells. It also downregulates oncogenic signaling pathways such as the PI3K/AKT/mTOR pathway, which is implicated in tumor growth and survival.

These findings suggest that integrating structured exercise into cancer care can improve treatment outcomes by enhancing drug delivery, modulating the immune response, reducing hypoxia, and regulating inflammation. As research in this field progresses, exercise is increasingly being recognised as a valuable adjunct therapy in oncology.

Conclusion

Exercise is a crucial component in cancer prevention, treatment, and recovery. Evidence-based exercise programs tailored to individual needs significantly enhance quality of life, mitigate treatment side effects, and improve long-term survivorship. Encouraging patients to incorporate regular physical activity as part of their cancer care strategy can lead to better clinical outcomes and overall well-being.

The Vitruvian Team.

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