A randomised controlled trial of regular MRI scans compared to standard care in patients with prostate cancer managed using active surveillance

Research question

In patients on active surveillance for prostate cancer, can regular MRI scans better detect prostate cancer progression, defined as grade or stage progression, than standard care over a 5-year follow-up period? Background

Two NICE and 3 James Lind Alliance research priorities for prostate cancer relate to improving active surveillance. Every year, ~7,600 patients with low-medium risk prostate cancer choose active surveillance rather than treatment. This is because these cancers have a low risk of progression and immediate radical treatments can cause genito-urinary side-effects.

However, a quarter of cancers do progress to higher risk over 5-years. For active surveillance, NICE recommends prostate specific antigen (PSA) blood tests and rectal exams every 3-6 months, and an MRI and biopsy at 1-year. After 1-year, PSA and rectal exams every 3-6 months and a biopsy if PSA increases or the prostate feels abnormal.

This has problems. First, half the cancers that progress are detected late. Second, patients can have unnecessary repeat biopsies which carry risks of infection, pain and bleeding.

Report show that 10-40% of patients decide to have treatment in the absence of progression. Regular MRI scans might be more accurate at detecting progression but a definitive randomised controlled trial is required. Methods

We will conduct an RCT in 30 UK centres recruiting from diverse ethnic, socio-economic and vulnerable groups. After consent, patients with localised prostate cancer who have chosen active surveillance will be randomly allocated to either NICE defined surveillance or regular MRI based surveillance. Annual biparametric MRI scans for visible or GG2 cancers and every two years for others.

Suspicious changes on MRI will require biopsy. The primary outcome will be progression in each group defined as higher risk cancer on biopsy (Grade Group >/=3) or higher stage (>/=T3 or >/=N or >/=M1) over 5-years. We will also measure number having MRI, biopsies and cancer treatment, complications and side-effects, and patient reported outcome measures on health-related quality-of-life, anxiety, urinary, sexual and bowel function.

The costs and cost savings for the NHS will be measured. We will have regular engagement with PPI co-applicants and focus groups. Timelines

The study will last 9-years in total. After 6-9 months of study set-up and site opening, a pilot for 12 months will be conducted to evaluate recruitment and if necessary mitigation plans to increase accrual. The main phase will recruit over 24 months with 5-years follow-up. The final months of the study will be for database queries and database lock as well as analyses and writing reports.

Impact and Dissemination

a) The regular use of MRI in active surveillance will lead to greater confidence in active surveillance for patients with low and medium risk prostate cancer. Compliance to surveillance will be high when this strategy is used. This is because such a strategy is likely to detect cancer progression earlier with fewer invasive biopsies. In our studies, <2% patients chose treatment during surveillance due to anxiety.

b) An additional ~2000 patients with intermediate risk cancer could be managed with active surveillance in future as a result of greater patient and physician confidence in active surveillance to detect progression when it occurs. c) Fewer NHS resources for clinic follow-ups, PSA tests and biopsies and their resultant harms.