Low to Moderate Load Power Training for Men With Metastatic Prostate Cancer.

Background and Rationale:

Prostate cancer is the most frequently diagnosed cancer among men worldwide, particularly affecting older populations, with increasing incidence and prevalence projected in the coming decades. While survival rates have improved substantially, these advances have not been matched by improvements in long-term quality of life. A significant proportion of patients with advanced prostate cancer undergo androgen deprivation therapy (ADT), which reduces testosterone levels to control tumor progression.

Despite its effectiveness, ADT is associated with multiple adverse effects, including loss of muscle mass and strength, increased adiposity, decreased bone mineral density, chronic fatigue, and metabolic alterations. These changes resemble an accelerated aging process and increase the risk of sarcopenia, osteoporosis, and functional dependency. In addition, ADT has been linked to psychological disturbances, including depression, anxiety, cognitive impairment, and reduced vitality.

Health-related quality of life (HRQoL) is a multidimensional construct encompassing physical, psychological, and social domains. In prostate cancer patients undergoing ADT, quality of life is significantly impaired due to the combined effects of disease burden and treatment-related side effects. Mental health plays a central role in this construct, as cancer diagnosis and treatment are highly stressful experiences that can disrupt identity, autonomy, and life continuity.

Exercise has been identified as an effective non-pharmacological intervention for mitigating many of the adverse effects of ADT. Systematic reviews and meta-analyses have demonstrated that exercise improves muscle strength, cardiorespiratory fitness, functional performance, fatigue, and body composition in this population. Exercise has also been associated with improvements in quality of life and emotional well-being, particularly when interventions are supervised and long-term.

The mechanisms underlying these benefits are multifactorial. Neurobiological processes include increased levels of neurotransmitters and brain-derived neurotrophic factor (BDNF), as well as reduced systemic inflammation. From a psychosocial perspective, exercise enhances self-efficacy, perceived control, and social interaction, all of which contribute to improved mental health.

However, most existing research has focused on aerobic or traditional resistance training protocols aimed at hypertrophy. There is a lack of studies examining power-oriented resistance training, which emphasizes rapid force production at moderate loads. Muscle power declines more rapidly than strength with aging and is a critical determinant of functional independence. It is particularly relevant for activities of daily living such as standing up, climbing stairs, or maintaining balance.

Given that ADT induces an accelerated decline in neuromuscular function, power-oriented training may be especially beneficial in this population. Furthermore, this type of training may use lower loads and avoid excessive fatigue, which may enhance adherence in patients experiencing chronic fatigue.

Additionally, previous studies have relied predominantly on quantitative measures, which may not fully capture the subjective and psychosocial dimensions of exercise participation. A mixed-methods approach is therefore necessary to understand how exercise influences identity, motivation, and psychological adaptation in men with prostate cancer.

Objectives:

Primary Objective

1. To determine the effects of a power-oriented resistance training program on health-related quality of life in older men with metastatic prostate cancer undergoing androgen deprivation therapy. 2. To assess improvements in functional capacity, including strength, balance, and performance in daily activities.

Secondary Objectives

1. To evaluate the effects on mental health outcomes, including anxiety, depression, emotional well-being and self-esteem. 2. To determine the safety and feasibility of power-oriented resistance training. 3. To explore participants' subjective experiences using qualitative methods.

Hypotheses:

1. The intervention will significantly improve quality of life compared to the control group. 2. Power-oriented resistance training will be safe and well tolerated. 3. Functional capacity will significantly improve following the intervention. 4. Participants will show improved mental health outcomes. 5. Qualitative findings will reveal improvements in self-efficacy, identity, and psychosocial adaptation.

Study Design:

This study is a randomized controlled trial (RCT) with a mixed-methods approach.

Participants will be randomly assigned to: * Experimental Group: Power-Oriented Resistance Training * Control Group: Usual care, with information and guidance on how to be physically active at home.

The intervention will last 24 weeks, with a 6-month follow-up.

Participants:

A total of 66 participants will be recruited, based on power analysis (α = 0.05; power = 0.80; effect size = 0.5). An attrition rate of 20% was also considered.

Inclusion Criteria: * Histopathologically confirmed diagnosis of prostate adenocarcinoma.

• Metastatic hormone-sensitive prostate cancer (mHSPC), defined as: * Presence of metastases at initial diagnosis (synchronous mHSPC), or * Development of metastatic disease following prior treatment with curative intent (surgery and/or radiotherapy) (metachronous mHSPC). • Evidence of progression to castration-resistant prostate cancer (CRPC).

* Ongoing treatment with a doublet regimen consisting of standard androgen deprivation therapy (ADT) in combination with an androgen receptor signaling inhibitor (ARSI), initiated prior to study enrollment. * Receipt of bone-protective therapy, including calcium and vitamin D supplementation in combination with bisphosphonates. * Presence of metastatic involvement limited to bone and/or lymph nodes. * Functionally independent in activities of daily living.

Exclusion Criteria: * Evidence of visceral metastatic disease. * Current or prior treatment with a triplet regimen that includes chemotherapy. * History of pathological fracture.

Intervention:

Power-Oriented Resistance Training

• Frequency: 2 sessions/week. * Intensity: 40-50% 1RM. * Execution: High-velocity concentric phase. * Volume: Low to moderate. * No training to failure. This model is designed to improve functional performance while minimizing fatigue and injury risk.

Control Group:

Participants will receive information and guidance for being physically active and perform strength training at home.

Outcome Measures:

Primary Outcome • Health-related quality of life (FACT-P).

Secondary Outcomes

• Functional capacity: (Rate of force development; Handgrip test; Timed up and go test; 6-Minute Walk Test; 10-meter walking speed; 5 times Sit to stand test).

• Mental health (anxiety, depression and stress): DASS-21.

• Self-esteem: Rosenberg scale.

• Physical activity levels: (IPAQ SF).

• Adverse events (field diary).

Qualitative Analysis

• Rate of Force Development [Time frame: From enrollment to the end of the exercise program at 6 months.]
• Lower-body strength [Time frame: From enrollment to the end of the exercise program at 6 months.]
• Handgrip strength [Time frame: From enrollment to the end of the exercise program at 6 months.]
• Functional mobility [Time frame: From enrollment to the end of the exercise program at 6 months.]
• Gait speed [Time frame: From enrollment to the end of the exercise program at 6 months.]
• Functional aerobic capacity [Time frame: From enrollment to the end of the exercise program at 6 months.]
• Static balance [Time frame: From enrollment to the end of the exercise program at 6 months.]
• Mental health [Time frame: From enrollment to the end of the exercise program at 6 months.]
• Self-esteem [Time frame: From enrollment to the end of the exercise program at 6 months.]
• Physical activity level [Time frame: From enrollment to the end of the exercise program at 6 months.]
• Body composition [Time frame: From enrollment to the end of the exercise program at 6 months.]