Grant title: Exercise medicine as adjunct therapy during RADIation for CAncer of the prostaTE to improve treatment efficacy – the ERADICATE study: a phase II randomised controlled trial
We are very thankful to World Cancer Research Fund International for supporting our team to investigate whether targeted exercise can improve the response to radiotherapy by inducing short- and long-term changes in tumour blood flow and oxygen levels.
Our team recently found that acute exercise approximately tripled tumour blood flow, but it is unknown if this effect translates to increased tumour oxygen levels and whether chronic exercise can “normalise” tumour blood vessels, which would facilitate tumour blood flow and potentially further enhance the effectiveness of radiotherapy in patients with prostate cancer.
The impact of this study can be substantial. For example, demonstrating that exercise can modulate tumour blood flow and oxygen levels would highlight the utility of exercise medicine as an adjunct therapy that can enhance the effectiveness of cancer treatment – we are very excited to test these possibilities – Prof Daniel Galvão
Background
Radiotherapy is one of the main treatment options for men with localised and locally advanced prostate cancer. However, the biology of prostate cancer is complex and many of the blood vessels surrounding the tumour are structurally and functionally abnormal, which compromises tumour blood flow. This limits the delivery of oxygen to some parts of the tumour.
This lack of oxygen is a major limiting factor in radiotherapy that reduces the effectiveness of treatment. This is because cancer cells with low oxygen levels are more resistant to radiotherapy. Moreover, low tumour oxygen levels are associated with the growth and spread of the cancer, resulting in disease progression and mortality.
Importantly, up to 40% of prostate cancer patients show signs of cancer recurrence after radiotherapy. Strategies that aim to increase tumour oxygen levels therefore have excellent potential to sensitise cancer cells to radiotherapy, enhance treatment response, and improve overall patient outcomes, including survival.
We recently completed a pilot study in 5 men with prostate cancer scheduled for radiotherapy where we found that acute exercise approximately tripled tumour blood flow. However, it is unknown if this effect translates to increased tumour oxygen levels and whether chronic exercise can “normalise” tumour blood vessels, which would facilitate tumour blood flow and potentially further enhance the effectiveness of radiotherapy.
Aims and objectives
The purpose of this study is to investigate whether targeted exercise can improve the response to radiotherapy and enhance the effectiveness of treatment in men with prostate cancer. We will examine whether this effect may be explained by short- and long-term changes in tumour blood flow and oxygen levels induced by exercise. In addition, we will investigate whether exercise can reduce treatment-related side effects in men with prostate cancer undergoing radiotherapy compared with standard medical care.
How it will be done
Magnetic resonance imaging (MRI) will be used to assess markers for treatment response, tumour blood flow and tumour oxygen levels in 50 men with localised or locally advanced prostate cancer scheduled for radiotherapy. MRI will be performed before and after a single 15-minute exercise session at moderate-to-vigorous intensity (short-term effect) as well as before and after radiotherapy treatment (long-term effect). Participants will be randomly allocated to either usual care or usual care plus exercise, with targeted exercise performed 3 times per week (1 hour per session) during the 4–8 weeks of radiotherapy. Treatment-related side-effects will be assessed before, during and after the intervention using validated questionnaires.
Potential impact
The impact of this study, if exercise is proven effective, is enormous. For example, demonstrating that exercise can modulate tumour blood flow and oxygen levels would highlight the utility of exercise medicine as adjunct therapy that can enhance the effectiveness of radiotherapy. Furthermore, reducing treatment-related (eg urinary) side effects would address a major issue for men with prostate cancer during and after treatment. Finally, because limited tumour blood flow also impedes drug delivery in chemotherapy, for example, the findings from this study have important implications for other cancer types and translate to different treatments.