Adaptive radiotherapy for high-risk prostate cancer using multiparametric MRI (ARPC-MRI) – a feasibility study

It is well known that cancer is a leading cause of death (World Health Organization, 2015), in the UK prostate cancer is the most common cancer to affect men with 47,151 new diagnoses (Cancer Research UK) and 11,819 deaths (Prostate Cancer UK) recorded during 2015. Radiotherapy offers an effective treatment for prostate cancer and is consequently a standard treatment option with approximately 35% of prostate cancer patients receiving radiotherapy. Although this has contributed to a significant improvement in ten-year survival over the last 40 years, with Cancer Research UK reporting that 84% of men diagnosed with prostate cancer now survive for ten years or more, reports suggest that following radiotherapy up to 50% of patients experience a further prostate-specific antigen (PSA) level rise suggesting recurrence (Dal Pra and Souhami, 2016; Alonzo et al., 2016). Alonzo et al. (2016) suggest that this recurrence is local, i.e. confined to the prostate, in roughly half of these instances implying that the original radiotherapy treatment delivered was inadequate. Radiotherapy treatments are designed to precisely deliver a high radiation dose to the tumour, to cause DNA (deoxyribonucleic acid) damage and cell death, whilst minimising damage to surrounding normal tissues to reduce toxicity and treatment side-effects. Modern prostate radiotherapy combines dose modulation, using IMRT (intensity modulated radiotherapy) or VMAT (volumetric modulated arc therapy), with image guidance (IGRT) to accurately deliver a highly conformal dose to the target area(s) whilst minimising organ at risk (OAR) and normal tissues doses. Image guidance facilities can also be used to deliver adaptive radiotherapy (ART) to further improve dose conformity and OAR sparing. At the author’s cancer centre ART is available to patients undergoing treatment for head and neck, bladder and cervix/uterus cancers. ART for head and neck cancer involves the patients receiving weekly cone-beam CT (CBCT) imaging, if any significant changes, typically due to weight loss or tumour shrinkage, are seen the treatment is adapted by re-optimising the dosimetry for the remainder of the treatment. A plan-of-the-day adaptive approach is taken for bladder and cervix/uterus treatments where knowledge of the way the diseased organ changes shape and/or position allows the creation of three radiotherapy treatment plans to accommodate a range of bladder or uterus positions. For plan-of-the-day ART a CBCT is acquired before each daily treatment (fraction) and the most appropriate of the three plans is selected to closely accommodate the treatment area whilst minimising the dose to OARs such as the rectum and bowel. Movement of the prostate, although minimal, tends to result from rectal changes which can’t be predicted or easily captured at the planning stage so current adaptive radiotherapy techniques are not appropriate. However, many radiotherapy departments are beginning to invest in MR-linacs or MRI units specifically for radiotherapy use, consequently there is likely to be gradual development of magnetic resonance guided radiotherapy. This study will recruit 15 high-risk prostate cancer patients to receive additional MP-MRI imaging before, during and after their radiotherapy treatment course. Seven sets of MP-MRIs will be acquired across four timepoints for each patient in the radiotherapy treatment position to provide prospective data. These timepoints are:

1. before commencement of androgen deprivation therapy;
2. at time of the radiotherapy planning CT appointment;
3. during week 4 of the radiotherapy treatment course;
4. 1 month after completion of radiotherapy.

The study will determine if changes observed using MP-MRI before and during radiotherapy treatment courses for high-risk prostate cancer are significant enough to support radiotherapy treatment plan adaption.