Exercise Oncology: Prostate and Colon Cancer Study Notes

Acknowledgment of Country

• Acknowledgment is paid to the traditional owners of the land: the Gadigal people of the Eora Nation.

• Respect is extended to the knowledge embedded within the Aboriginal Custodianship of Country, as knowledge and practices are shared within the Chris O’Brien Lifehouse.

The Exercise Medicine Continuum in Oncology

• Continuum Phases:

  • Primary Prevention: Exercise used to reduce the initial risk of developing cancer.

  • Diagnosis: The point of clinical identification of the disease.

  • Pre-hab (Pre-habilitation): Exercise interventions occurring after diagnosis but prior to the start of acute treatment (e.g., surgery) to optimize physical function.

  • Treatment/s (Intra/Inter-hab): Exercise during active treatment (Acute/Chronic phases) to manage side effects and maintain function.

  • Post-treatment (Re-hab): Rehabilitation following the completion of primary treatments to address acute and chronic side effects.

  • Secondary Prevention: Long-term exercise to prevent recurrence or the development of new primary cancers.

  • Living with Incurable Cancer: Exercise focused on quality of life (QOL) and symptom management for patients with advanced disease.

ACSM Roundtable: Moving Through Cancer Guidelines

• General Recommendation: Avoid inactivity. Moving more and sitting less benefits nearly everyone.

• Guidelines for Overall Health:

  • Moderate Aerobic Exercise: At least $150$–$300\,min/week$.

  • Vigorous Aerobic Exercise: At least $75$–$150\,min/week$ (or an equivalent combination).

  • Resistance Exercise: At least $2$ times per week.

• Guidelines for Symptom Management (During and Following Treatment):

  • Research indicates lower amounts of exercise can improve: Cancer-related fatigue, health-related quality of life, physical function, anxiety, depression, sleep, lymphedema, and bone health.

  • Aerobic Focus: $3$ times per week for $30$–$60\,min$ to manage fatigue, QOL, and anxiety/depression.

  • Resistance Focus: $2$ times per week, $2$ sets of $8$–$15$ reps to manage fatigue, QoL, and bone health.

  • Combined Approach: Aerobic $2$–$3$ times per week ($20$–$40\,min$) plus Resistance $2$ times per week ($2$ sets, $8$–$15$ reps).

Individualization of Exercise Prescription (ExRx)

• A "one size fits all" approach is insufficient. Prescription must consider:

  • Cancer type, stage, prognosis, and oncogenic factors.

  • Treatment (Tx) type, dose, and schedules.

  • Acute and chronic side effects of each treatment.

  • Patient age and co-morbidities.

  • Exercise history, personal preferences, and access to facilities.

Prostate Cancer (PrCa): Incidence and Pathophysiology

• The Prostate: A walnut-sized gland in adults located below the bladder and in front of the rectum, surrounding the urethra.

• Cancer Definition: Abnormal cells in the prostate gland growing in an uncontrolled way.

• Infection and Demographic Statistics:

  • Over $28,000$ men diagnosed annually in Australia (approx. $79$ per day).

  • Represents $17\%$ of all newly diagnosed cancers; lifetime risk is $1$ in $5$.

  • Age Distribution:

    • Under $49$ years: $458$ ($1.58\%$).

    • $50$–$59$ years: $3,760$ ($13.02\%$).

    • $60$–$69$ years: $10,191$ ($35.30\%$).

    • $70$–$79$ years: $10,548$ ($36.53\%$).

    • Over $80$ years: $3,911$ ($13.54\%$).

  • Vulnerable Populations: Anyone with a prostate can get prostate cancer, including transgender women, non-binary, or intersex people.

Prostate Cancer Symptoms and Screening

• Early Stage Symptoms: Frequent urination, pain during urination, and poor urinary flow.

• Later Stage Symptoms: Blood in urine or semen, fatigue, unexplained weight loss, pain in the back, pelvis, lower thighs, penis, or testicles, and weakness in legs or feet.

• Screening Tools:

  • PSA (Prostate Specific Antigen): Monitoring levels; note that elevations can occur for reasons other than cancer.

  • PSA Guidelines: Recommended every $2$ years for men aged $50$–$69$ who wish to be tested.

  • Digital Rectal Exam (DRE): Can detect some physical abnormalities.

  • Imaging: MRI and PSMA (Prostate Specific Membrane Antigen) scans; bone scans (+ SPECT CT) are used to detect metastases.

Risk Factors and Classification of PrCa

• Risk Factors: Genetic mutations in $BRCA1$ and $BRCA2$ genes; family history.

• Staging and Grading:

  • Gleason Score: Based on the two most prominent patterns in biopsy; e.g., $3 + 4 = 7$.

  • ISUP Grades: Grade $1$ (least aggressive) to Grade $5$ (most aggressive).

  • Tumour Stage: Classified by size and spread (Local, Regional, Metastatic).

Treatment Strategies for PrCa

• Active Surveillance: Closely monitoring low-risk cancer (PSA < $10\,ng/mL$, Stage $T1$–$2$, Gleason $6$ or less). Includes PSA tests every $3$–$6$ months and DRE every $6$ months. Approximately $70\%$ of Australians with low-risk PrCa choose this.

• Watchful Waiting: Primarily for older patients when the cancer is unlikely to cause problems during their lifetime or when they cannot tolerate aggressive treatment. Focused on maintaining QOL.

• Surgery: Prostatectomy (Abdominal, Laparoscopic, or Robotic). Side effects include libido changes, erectile dysfunction, and urinary/fecal incontinence.

• Radiation Therapy (RaTh): External beam radiation or Brachytherapy. Side effects include fatigue and urinary changes.

• Hormone Therapy: Androgen Deprivation Therapy (ADT) and Androgen Receptor Pathway Inhibitors (ARPIs). Blocks testosterones/androgens that stimulate cancer growth.

Exercise and Tumour Biology in Prostate Cancer

• Monotherapy: Exercise is NOT a monotherapy and cannot cure cancer.

• Epidemiology: Physical activity (PA) is not associated with primary PrCa prevention but is associated with reduced risk of recurrence.

• Neoadjuvant Exercise Therapy (Jones et al., 2024):

  • Phase $1$ Decentralized Trial for treatment-naive patients scheduled for surgery.

  • Experimental Doses: Ranged from $90\,min/week$ to $450\,min/week$ (walking at $60\%$–$85\%$ capacity).

  • Findings: Doses of $225$–$375\,min/week$ of moderate aerobic exercise directly impacted tumour biology (absolute change in $Ki-67$ proliferation and PSA) in some men. This dose exceeds standard guidelines ($150\,min/week$).

• The ERASE Trial (Kang et al., 2021):

  • High-Intensity Interval Training (HIIT) $3$ times per week for men on active surveillance.

  • Findings: HIIT impacted PSA levels and PSA doubling time (PSADT), suggesting a synergistic effect with later pharmacological treatments.

Physiological Impact of Androgen Deprivation Therapy (ADT)

• Testosterone Withdrawal Effects:

  • Decreased bone mass and muscle mass.

  • Increased fat mass (central/trunk fat).

  • Metabolic dysregulation: Altered lipid profile, increased risk of Cardiovascular Disease (CVD), and obesity.

  • Reduced resting metabolic rate.

• Exercise Benefits for ADT Patients:

  • A $6$-month RCT (Wall et al., 2017) using supervised AEX + progressive RT showed:

    • Increased $VO_{2}max$ by $0.11\,L/min$.

    • Increased lean tissue mass by $0.8\,kg$.

    • Decreased total fat mass by $1.1\,kg$ and trunk fat by $1.0\,kg$.

    • Increased resting fat oxidation by $12.0\,mg/min$.

  • Specific Recommendations: Minimum $2$ strength sessions per week; aerobic training target $150\,min/week$ (general) or $300\,min/week$ (weight loss).

Colorectal Cancer: Incidence and Symptoms

• Incidence: ~$15,542$ people diagnosed in 2024. Fourth most common cancer in Australia.

• Pathology: Develops from inner bowel lining; preceded by polyps. $90\%$ are adenocarcinomas.

• Demographics: Average age at diagnosis is $69$, but young-onset colorectal cancer (CRC) is increasing.

• Symptoms:

  • Changes in bowel habits (diarrhea, constipation, thin stools).

  • Blood in stools or urine.

  • Abdominal pain, bloating, or cramping; anal/rectal pain.

  • Unexplained weight loss and fatigue/anemia (pale complexion, breathlessness).

Colorectal Cancer Risk Factors and Screening

• Risk Factors: Age, family history, Lynch syndrome (genetic), history of Inflammatory Bowel Disease (IBD) or Adenomas.

• Modifiable Factors: Inactivity, obesity/"abesity", alcohol, high energy intake, and high intake of red or processed meats.

• Screening: Faecal Occult Blood Test (FOBT) every $2$ years for ages $50$–$74$.

Colorectal Cancer Treatment and Side Effects

• Surgery: Hemicolectomy; may result in a stoma. Post-surgery patients are often advised against heavy lifting for $6$ weeks.

• Chemotherapy (5-FU, Oxaliplatin, Folforinox):

  • 5-Fluorouracil (5-FU) / Capecitabine: Hand-foot syndrome (erythema/redness).

  • Oxaliplatin: Chemotherapy-Induced Peripheral Neuropathy (CIPN). Often cold-sensitive.

  • Irinotecan: Gastrointestinal (GI) symptoms.

• Radiation Therapy: Can cause tissue fibrosis, nerve damage, and fecal incontinence.

• Targeted Therapy: BEGF inhibitors (Bevacizumab/Avastin) causing HTN/rashes; BRAF inhibitors (Encorafinib).

• Fatigue Causes: Treatment-related, anemia, neutropenia, sleep disturbance, or disease progression.

Chemotherapy-Induced Peripheral Neuropathy (CIPN)

• Pattern: Often bilateral, affecting knees down (feet/toes) and hands/fingers.

• Toxicity Mechanism: Affects distal nerve terminals, myelin, microtubules, mitochondria, and ion channels.

• Prevention and Management (STOP RCT):

  • Interventions include Sensorimotor Training (SMT/Balance) and Whole-Body Vibration (WBV).

  • SMT facilitates functional adaptations and regeneration of the neuromuscular system, reducing falls.

• Exercise Prescription for CIPN:

  • Lower Limb: Plantar/dorsiflexion, Mexican toe waves, squats, and obstacle courses for dynamic balance.

  • Upper Limb: Finger flexion/extension, throwing/catching. Use gloves or wrist straps if grip or cold sensitivity is a factor.

Biological Mechanisms of Exercise in Colon Cancer

• Primary Prevention: Pre-diagnosis PA is associated with a $23\%$–$25\%$ reduction in risk.

• Recurrence: Post-diagnosis PA associated with a $30\%$–$38\%$ reduction in risk.

• The SPARC Myokine:

  • Exercise induces the release of SPARC (Secreted Protein Acidic and Rich in Cysteine).

  • In animal models, SPARC-positive mice showed a decrease in precancerous colon cells with exercise; SPARC-negative mice did not respond.

  • Exercise interacts with intrinsic host factors to influence tumour progression via insulin, IGF (Insulin-like Growth Factor), and immune pathways.

Exercise Prescription (ExRx) Design and Autoregulation

• Fatigue and SOB (Shortness of Breath): For anemia or lung inflammation, use low-dose resistance exercise with cluster sets (e.g., $4 \times 5$ or $6 \times 5$) with long recoveries.

• Stoma Considerations: Teach bracing (seated/standing). Progress from seated pelvic tilts to planks. Use "Bird-Dog" exercises to safely manage trunk flexion/extension.

• Decisional Balance: Adjust exercise dose based on symptom severity. Higher symptom severity may require reduced volume/intensity (Autoregulation).