Introduction: The mainstay of bladder preservation treatment is radiotherapy, and hypoxia modification has been shown to improve outcomes. This thesis aims to (1) investigated the long-term outcomes of hypoxia modification associated with biological features in muscle-invasive bladder cancer; (2) investigate the relationship of parameters on radiotherapy planning (RTP) scan with clinical outcomes of patients following radical radiotherapy for bladder cancer; (3) quantify and compare inter-fraction bladder motion between men and women; (4) prospectively evaluate the association of intra-fraction motion of tumour bed and bladder. Method: (1) Examine the long-term outcomes of the BCON study and explore the biological features that may aid in patient selection for hypoxia modification including necrosis status, hypoxia gene signature score and molecular subtypes; (2) Conduct a retrospective study on patients who had completed radical chemoradiotherapy, assessing bladder and rectum dimensions on RTP scans and relating that to patients' outcomes; (3) Compare the differences in inter-fraction bladder motion between male and female bladders by measuring motion in six directions. (4) Evaluate the motion of tumour bed and bladder on MRI scans over a time period required to deliver a fraction of MRI guided treatment, and assess potential correlation between the motion of tumour bed and bladder Results: (1) The long-term benefit of hypoxia modification is sustained and necrosis and hypoxia gene signature score have the potential to select patients who would benefit most. (2) Bladder size is associated with survival outcomes. (3) Mean male and female bladder inter-fraction motion are similar. (4) There is an association between tumour bed and bladder motion in anterior-posterior and superior-inferior directions. Conclusion: The long-term benefit of hypoxia modification in the presence of necrosis and hypoxia suggest that a biomarker driven study will enable better patient selection for treatment in future. The bladder varies in size, moves in all direction intra- and inter-fraction. The current standard of care of a single treatment plan is not ideal. Adaptive radiotherapy with a library of plans that take into consideration tumour bed and bladder motion will allow for more accurate treatment to be delivered.
