Resistance Exercise, IL-7 and Immune Phenotypes in Prostate Cancer

• Supervised Resistance Exercise Programme (Other): A 12-week, supervised resistance training programme delivered in small groups in a gym setting. Participants will train 3 times per week on non-consecutive days, with sessions lasting 45-60 minutes. The programme targets all major muscle groups, with volume and intensity gradually increasing throughout the intervention period.

Primary outcomes

• Change in Resting Interleukin-7 (IL-7) Concentration [Baseline and 12 weeks]: Assessed via enzyme-linked immunosorbent assay (ELISA) from resting, fasting blood samples to evaluate changes in baseline immune-supporting signaling proteins.

Secondary outcomes

• Change in Frequencies of Resting Immune Cell Phenotypes [Baseline and 12 weeks]: Assessed via flow cytometry from resting, fasting blood samples to evaluate key immune cell populations, specifically naïve CD4+ T-cells, naïve CD8+ T-cells, and naïve B-cells.
• Acute Circulating IL-7 Response to a Single Bout of Exercise [Week 12]: Quantified as the incremental Area Under the Curve (iAUC) of circulating IL-7 via ELISA. Blood samples are taken at rest, immediately post-exercise, and 30 minutes post-exercise.
• Change in Total Lean Mass [Baseline and 12 weeks]: Measured via Dual-Energy X-ray Absorptiometry (DEXA) to evaluate changes in lean tissue.
• Change in Total Fat Mass [Baseline and 12 weeks]: Measured via Dual-Energy X-ray Absorptiometry (DEXA) to evaluate changes in body fat.
• Change in Local Muscle Cross-Sectional Area (CSA) [Baseline and 12 weeks]: Local muscle cross-sectional area (CSA) assessed via peripheral Quantitative Computed Tomography (pQCT) to assess changes in specific muscle size.
• Change in Handgrip Strength [Baseline, 12 weeks]: Measured using a hand dynamometer to assess upper-body isometric strength
• Change in 30-Second Sit-to-Stand Test Performance [Baseline and 12 weeks]: Evaluated by the number of sit-to-stand repetitions completed in 30 seconds to assess lower-body functional strength.
• Change in Timed Up and Go (TUG) Test Performance [Baseline and 12 weeks]: Assessed using the Timed Up and Go Test (TUG) to evaluate changes in functional mobility and balance.
• Change in Leg Press Peak Power Output [Baseline and 12 weeks]: Assessed using a Keiser leg press to determine peak power output
• Change in Leg Press One-Repetition Maximum (1RM) [Baseline and 12 weeks]: Assessed using a Keiser leg press to determine 1-repetition maximum (1RM).
• Change in Glycated Haemoglobin (HbA1c) [Baseline and 12 weeks]: Analyzed from resting, fasting blood samples to monitor long-term glycemic control.
• Change in Fasting Insulin [Baseline and 12 weeks]: Analyzed from resting, fasting blood samples to evaluate insulin levels and metabolic health
• Change in Fasting Glucose [Baseline and 12 weeks]: Analyzed from resting, fasting blood samples to evaluate baseline glycemic control
• Change in C-Reactive Protein (CRP) [Baseline and 12 weeks]: Analyzed from resting, fasting blood samples to assess baseline systemic inflammation.
• Change in Cancer-Specific Quality of Life (EORTC QLQ-C30) [Baseline and 12 weeks]: Evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Scores range from 0 to 100, where higher scores represent a better quality of life.
• Change in Prostate Cancer-Specific Symptoms (EORTC QLQ-PR25) [Baseline and 12 weeks]: Evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module (EORTC QLQ-PR25). Scores range from 0 to 100, where higher scores represent higher symptom burden (worse outcome).
• Change in Fatigue Severity (FACIT-Fatigue) [Baseline and 12 weeks]: Evaluated using the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) scale. Scores range from 0 to 52, where higher scores represent lower levels of fatigue (better outcome).
• Uptake and Retention Rates [Through study completion]: Uptake is calculated as the percentage of invited eligible patients who consent to participate. Retention is the percentage of randomised participants who successfully complete the final post-intervention assessments.
• Incidence of Adverse Events [Throughout the 12-week intervention period]: Total number and percentage of participants experiencing adverse events, systematically tracked and evaluated for seriousness and causality.
• Exercise Session Attendance Rate [Throughout the 12-week intervention period]: Calculated as the percentage of the total prescribed supervised exercise sessions successfully attended by the participants in the intervention group.
• Resistance Exercise Dose Adherence [Throughout the 12-week intervention period]: Calculated as the percentage of total prescribed exercise sets completed by the participants in the intervention group
• Average Session Rate of Perceived Exertion (RPE) [Throughout the 12-week intervention period]: Evaluated using the Borg Rating of Perceived Exertion (RPE) Category-Ratio scale (CR10). Scores range from 0 (no exertion at all) to 10 (maximal exertion), recorded at the end of each session and averaged for participants in the intervention group. Higher scores represent a higher perceived physical effort.
• Frequency of Exercise Dose Reductions [Throughout the 12-week intervention period]: Calculated as the percentage of attended exercise sessions where the prescribed volume or intensity had to be modified or reduced due to fatigue or intolerance in the intervention group.
• Frequency of Exercise Interruptions [Throughout the 12-week intervention period]: The total count of instances where a participant in the intervention group missed 3 or more consecutive scheduled exercise sessions.

Sex: Male, ages: 18 Years to any

Inclusion Criteria:

* Histologically confirmed diagnosis of localised prostate cancer (clinical stage T1-3b, N0-1, M0 and a Gleason score of 6-10).
* Scheduled to undergo curative-intent treatment involving neoadjuvant androgen deprivation therapy (ADT) for a duration of at least 3 months, alongside radiotherapy.
* Recruited prior to, or within the first 2 weeks of, initiating ADT.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Written medical clearance to participate from the treating oncologist.
* Sufficient proficiency in English to comprehend study instructions.
* Provision of written informed consent.

Exclusion Criteria:

* Evidence of distant metastases (M1).
* Uncontrolled cardiovascular conditions (e.g., uncontrolled hypertension, unstable angina, or a myocardial infarction within the past 6 months).
* Musculoskeletal pathologies or conditions that would preclude the safe execution of resistance exercise.
* A known history of autoimmune disease.
* Current use of chronic systemic corticosteroids or other immunosuppressive agents.
* Engagement in structured resistance exercise within the preceding 3 months.