Comprehensive Exercise Oncology: Prostate and Colorectal Cancer Study Notes

Acknowledgement and Institutional Context

• Acknowledgment of Country: Respect is paid to the traditional owners of the land, the Gadigal people of the Eora Nation, upon whose land the Chris O’Brien Lifehouse hospital is built. The hospital recognizes the knowledge embedded within Aboriginal Custodianship of Country.
• Institutional Identity: Chris O’Brien Lifehouse is cited as the primary institution for academic and clinical practice in exercise oncology.

The Continuum of Exercise Medicine in Oncology

• Exercise Medicine Phases: Exercise is integrated through the following clinical stages:     * Primary Prevention: Reducing the initial risk of cancer development.     * Diagnosis: The period immediately following the identification of cancer.     * Pre-hab: Exercise intervention prior to primary treatment (e.g., surgery) to optimize patient outcomes.     * Treatment (Intra/Inter-hab): Exercise during acute treatment phases (chemotherapy, radiation).     * Re-hab: Recovery following the completion of primary treatments.     * Secondary Prevention: Minimizing the risk of recurrence or new cancers.     * Living with Incurable Cancer: Enhancing quality of life (QOL) and managing symptoms in advanced disease.
• Symptom Management: Exercise addresses both acute and chronic side-effects across the continuum.

ACSM Roundtable Guidelines: Moving Through Cancer

• General Advice: Avoid inactivity. Moving more and sitting less benefits nearly everyone regardless of cancer status.
• Guidelines for Overall Health (Adults):     * Moderate Aerobic Exercise: At least $150-300\,\text{mins}$ per week.     * Vigorous Aerobic Exercise: At least $75-150\,\text{mins}$ per week.     * Resistance Exercise: At least $2\times$ per week.
• Specific Symptom Management (During and Following Treatment):     * Lower amounts of exercise can still alleviate: Cancer-related fatigue, Health-related Quality of Life (HRQoL), Physical function, Anxiety, Depression, Sleep disturbances, Lymphedema, and Bone health.
• Aerobic Exercise Plan: $3\times$ per week for $30-60\,\text{mins}$ helps manage anxiety, depression, fatigue, HRQoL, and physical function.
• Resistance Exercise Plan: $2\times$ per week, comprising $2\,\text{sets}$ of $8-15\,\text{reps}$ helps manage the same symptom list as aerobic exercise.
• Combination Plan: $2-3\times$ per week of aerobic exercise ($20-40\,\text{mins}$) plus $2\times$ per week of resistance exercise helps manage the listed symptoms plus lymphedema and bone health.
• Tailoring beyond "One Size Fits All": Prescription must consider:     * Cancer Type, stage, prognosis, and oncogenic factors.     * Treatment (Tx) type, dose, and schedule.     * Side effects (acute and chronic).     * Age and co-morbidities.     * Exercise history, personal preferences, and access to facilities.

Clinical Profile of Prostate Cancer

• Anatomy of the Prostate:     * A small gland ($size \text{ of a walnut}$ in adults) located below the bladder and in front of the rectum.     * It surrounds the urethra.
• Incidence Statistics:     * Over $28,000$ men diagnosed annually in Australia ($\approx 79\,\text{each day}$).     * Represents $17\%$ of all newly diagnosed cancers; lifetime risk is $1\,\text{in}\,5$.     * Average age at diagnosis is $70\,\text{years old}$.
• Age-Based Demographics (Annual diagnostics):     * Under $49\,\text{years old}$: $458\,(1.58\%)$     * $50-59\,\text{years old}$: $3,760\,(13.02\%)$     * $60-69\,\text{years old}$: $10,191\,(35.3\%)$     * $70-79\,\text{years old}$: $10,548\,(36.53\%)$     * Over $80\,\text{years old}$: $3,911\,(13.54\%)$
• Inclusivity Note: Anyone with a prostate can develop prostate cancer, including transgender women, non-binary people, and intersex individuals.

Screening and Classification of Prostate Cancer

• Symptoms of Early Stage: Frequent urination, pain with urination, and poor urine flow.
• Symptoms of Later Stage: Blood in urine or semen, fatigue, weight loss, pain in the back, pelvis, lower thighs, penis or testicles, and weak legs/feet.
• Screening Tools:     * PSA (Prostate Specific Antigen): Monitored every $2\,\text{years}$ for men aged $50-69$ who wish to test. High levels do not always equal cancer.     * Digital Rectal Exam (DRE): Physical manual inspection.     * Imaging: MRI and PSMA (Prostate Specific Membrane Antigen) scans.
• Risk Factors: Age, family history, and BRCA1 and BRCA2 gene mutations.
• Staging and Grade:     * Stage: Size and spread of the tumor.     * Grade (Gleason Score): Measures aggressiveness. Sum of the two most prominent grades (e.g., $3+4=7$).     * ISUP Grades: Grade 1 (least aggressive) to Grade 5 (most aggressive).

Management Strategies: Active Surveillance and Watchful Waiting

• Active Surveillance: Closely monitoring low-risk cancer to avoid unnecessary treatment.     * Eligibility: PSA level under $10\,\text{ng/mL}$, Stage T1–2, Gleason 6 or less.     * Protocol: PSA tests every $3–6\,\text{months}$, DRE every $6\,\text{months}$, and repeat biopsies/scans.     * Prevalence: $70\%$ of Australians with low-risk PrCa choose this.     * Exercise Opportunity: Focus on "treatment naive" patients to investigate exercise effects on tumor biology.
• Watchful Waiting: Used primarily for older patients where cancer is unlikely to impact lifetime or if treatment isn't tolerated.     * Goal: Maintain Quality of Life (QOL) rather than cure.

Exercise Medicine Interventions for Prostate Cancer

• Epidemiological Findings: Physical Activity (PA) is not strongly associated with primary prevention of prostate cancer but is strongly associated with reduced recurrence and mortality post-diagnosis.
• Exercise as Monotherapy: Exercise cannot cure cancer and should not be used as a monotherapy.
• Neoadjuvant Exercise Therapy (Jones et al., 2024):     * 6 exercise (walking) doses tested: $90,\,150,\,225,\,300,\,375,\,\text{and}\,450\,\text{mins/week}$.     * Intensity: $60\%$ to $85\%$ submaximal capacity.     * Findings: Doses of $225\,\text{to}\,375\,\text{mins/week}$ directly impacted tumor cell proliferation ($Ki-67$) and PSA levels.
• HIIT and Active Surveillance (ERASE Trial):     * High-intensity aerobic exercise ($HIIT$) $3\times$ per week.     * Results: Impacts tumor markers (PSA) and PSA Doubling Time (PSADT), indicating a delay in chemical progression.

Androgen Deprivation Therapy (ADT) and Physiological Impact

• Mechanism: Hormonal therapy blocks androgens (e.g., testosterone) and receptors to slow cancer progression.
• Androgen Sensitive Cancers: Side effects occur because testosterone is a growth factor for muscle.
• ADT Side Effects:     * Metabolic dysregulation and increased fat mass.     * Reduced muscle mass and strength.     * Osteoporosis (bone loss).     * Hot flushes and mood changes.     * Libido changes and erectile dysfunction (ED).

Clinical Trial Evidence: Exercise and Body Composition in ADT

• Wall et al. (2017) RCT: 6 months of supervised aerobic and progressive resistance training ($AEX + RT$) vs. usual care.     * Intervention: $2/\text{week}$ supervised ($6\,\text{RTX} + 20-30\,\text{min AEX}$ at $70-90\%\,VO_{2}max\,HR$) plus home AEX.     * Results:         * $VO_{2}max$ increase: $0.11\,L/min$ ($P = 0.033$).         * Resting fat oxidation increase: $12.0\,mg/min$ ($P = 0.037$).         * Glucose decrease: $-0.5\,mmol/L$.         * Lean tissue mass increase: $0.8\,kg$ ($P = 0.015$).         * Total fat mass decrease: $1.1\,kg$ ($P = 0.020$).         * Trunk fat mass decrease: $1.0\,kg$ ($P < 0.001$).
• Responder Variability: Individual data for $VO_{2}peak$ change ranged from $-18\%$ to $+32\%$, highlighting the impact of co-morbidities and treatment types.

Bone Mineral Density and Osteogenic Specificity

• Osteogenic Exercise: Specificity is required to preserve spine and hip Bone Mineral Density (BMD) in prostate cancer patients.
• Variables: Exercise must be high-impact or involve high-load resistance to stimulate bone growth effectively.

Medical Oncology and Lymphoedema in Prostate Cancer

• Lymphedema: Resulting from sampling, radiation, or damage to lymph nodes. Monitored through SOZO (limb volumes).
• Docetaxel Side Effects: Fatigue, Chemotherapy-Induced Peripheral Neuropathy (CIPN), arthralgias, and myalgias.
• Prednisolone Effects: Often given with Docetaxel; causes increased appetite, puffiness, and increased body fat.

Clinical Profile of Colorectal Cancer

• Incidence: Approximately $15,542$ people diagnosed in 2024; average age of $69$.
• Risk: Fourth most common cancer in Australia; $1\,\text{in}\,20$ diagnosed by age $85$.
• Type: $90\%$ are adenocarcinomas (glandular lining).
• Locations: Rectal vs. Colon (different locations have different prognoses).
• Polyp Progression: Usually preceded by growths called polyps.

Risk Factors and Young-Onset Colorectal Cancer

• Young Onset Trends: Increasing rates of colorectal cancer (CRC) in younger populations linked to sedentary behavior (TV viewing time).
• Biological Mechanism: Epigenetic changes (altered DNA methylation). Short bursts of activity can alter skeletal muscle gene expression related to cellular growth and proliferation.
• Nutritional Risks: High intake of red meat, processed meat, and high overall energy intake.
• Biological Risks: Obesity (Abesity), Alcohol, Inactivity, IBD (Inflammatory Bowel Disease), Adenomas, and Lynch syndrome (genetic mutation).

Symptoms and Diagnostic Screening for Colorectal Cancer

• Symptoms: Change in bowel habits (diarrhea/constipation), abdominal pain/bloating, blood in stools, rectal pain, weight loss, unexplained fatigue, and anemia.
• Urinary Symptoms: Changes in urine color or frequency can occur if the tumor is large.
• Screening: Faecal Occult Blood Test (FOBT) every $2\,\text{years}$ for ages $50-74$. Surveillance colonoscopy for high-risk families.

Management and Treatment of Colorectal Cancer

• Surgery: Left hemicolectomy or rectal resection.
• Chemotherapy: Folforinox, 5-Fluorouracil ($5-FU$), Capecitabine (Xeloda), and Oxaliplatin.
• Radiation Therapy: Often used for rectal cancer; causes DNA damage to prevent cell division but side effects include tissue fibrosis and faecal incontinence.
• Targeted Therapy:     * Bevacizumab (Avastin): VEGF inhibitor; side effects include headache, rash, and hypertension (HTN).     * EGFR Inhibitors: Target specific proteins on cancer cell surfaces.     * Encorafinib: Specifically for BRAF mutations.

Exercise Considerations for Colorectal Surgery and Stomas

• Pre-surgery (Pre-hab): Some patients require a Cardiopulmonary Exercise Test (CPET).
• Post-surgery:     * Traditionally 6 weeks of "no heavy lifting" (which does not exclude light/moderate movement).     * Focus on seated bracing, seated pelvic tilts, and progress to planks.     * Stoma Exercise: Avoid direct pressure. Progress through Bird-Dog sequences (e.g., Bird, then Dog, then Bird-Dog).

Chemotherapy Toxicity and Exercise Interventions (CIPN)

• 5-FU/Capecitabine Side Effects: Hand-foot syndrome (erythema/redness).
• Oxaliplatin Specificity: Causes cold-sensitive Peripheral Neuropathy (CIPN).
• Mechanism of CIPN: Damage to myelin, microtubules, mitochondria, and ion channels in the peripheral nervous system.
• Exercise Strategy (STOP RCT):     * Combined Aerobic, Resistance, Fine Motor, and Progressive Balance Training.     * Sensorimotor training ($SMT$) for functional adaptations and regeneration.     * Adaptations: Using gloves for cold sensitivity, using wrist straps for grip issues, and exercises like "Mexican toe waves," tandem walks, or catching balls.

Biological Mechanisms and Mortality Benefits of Exercise in Oncology

• Mortality Reduction: Post-diagnosis physical activity associated with $30-38\%\,\text{reduction}$ in cancer-specific and all-cause mortality (Patel et al., 2019).
• Survival Benefit: In colon cancer, exercise can show a $28-37\%\,\text{disease-free survival benefit}$, sometimes superior to chemo after surgery.
• SPARC Myokine: Exercise induces the secretion of SPARC (Secreted Protein Acidic and Rich in Cysteine).     * Research: SPARC-positive mice saw a decrease in precancerous colon cells with exercise; SPARC-negative mice did not.     * Significance: Exercise interacts with intrinsic host factors to influence tumor progression through insulin-glucose and inflammation pathways.
• Fatigue Management: Differentiate between treatment-related fatigue vs. anemia or disease progression. Modify exercises (e.g., cluster sets of $4 \times 5$ with long recoveries) for Shortness of Breath ($SOB$).

Questions & Discussion

• Exercise Specificity for Body Composition: Discussion on whether position statement guidelines are enough for high-risk patients or those on ADT ($150\,\text{min}\,\text{vs.}\,300\,\text{min/week}$).
• Non-Responders: Discussion on what to do if an individual does not respond to the exercise stimulus ($VO_{2}peak$ range $-18\%\,\text{to}\,32\%$).
• Masculinity in Prostate Cancer: Exercise provides a "men-centered approach," working synergistically with masculine values to assist recovery from a psychological perspective.