A Randomised Feasibility Trial to Investigate the Timing of HDR Brachytherapy With EBRT in Intermediate and High Risk Localised Prostate CAncer Patients and Its Effects on Toxicity and Quality of Life

The role of radiotherapy in management of prostate cancer significantly changed over the last few decades with the developments in Brachytherapy, External Beam Radiotherapy (EBRT), Intensity modulated Radiotherapy (IMRT) and Image guided Radiotherapy (IGRT). One of the challenging factors of Radiotherapy treatment of localised prostate cancer is acute and late Genitourinary and Gastrointestinal toxicities. There are several studies and case series published in literature assessing the toxicities developed during EBRT and Brachytherapy treatment for prostate cancer EBRT and Brachytherapy emerged as the main stay of localised prostate cancer treatment in recent years. The low risk localised prostate cancers can be treated with low dose brachytherapy or by prostatectomy, whereas the intermediate and high risk localised prostate cancers are usually treated with EBRT alone or along with HDR brachytherapy. The recent European guidelines suggest that there is no consensus regarding the timing of HDR brachytherapy and EBRT. The schedules vary in different institutions where HDR boost can be given either before or after EBRT. Few centres deliver HDR in-between the fractions of EBRT.

The EBRT doses range from 37.5Gy in 15 fractions to 45Gy in 25 fractions when given with HDR. The total HDR brachytherapy dose can be delivered in fractions, however a single dose of 15Gy is gaining acceptance across the world due to its logistical advantage. The Time gap between the two Radiotherapy modes of delivery is generally within 21 days.

There is no consensus about the timing of HDR brachytherapy (BT) when treated along with EBRT. The advantages of using HDR Brachytherapy before EBRT are that the investigators could potentially identify patients who are not suitable for brachytherapy early in the treatment process. It is essential to know whether there is any significant difference in toxicities and treatment outcome especially acute urinary toxicity amongst the two treatment approaches. It will be done by a simple 1:1 ratio randomisation which will only be possible if a participant meets the inclusion and exclusion criteria.

Brachytherapy procedure Procedure will be carried out at the surgical theatres in Southend University Hospital.

1. Patients will undergo prostate implantation under general or spinal anesthetic using a Transrectal ultrasound guided transperineal technique.
2. Imaging according to local practice using ultrasound, CT and or MR will be undertaken
3. The CTVp is defined by the prostate capsule and extended to include any extra capsular or seminal vesicle disease. A volumetric expansion of 3mm constrained to the rectum posteriorly is then added. This defines the PTV.
4. Catheter reconstruction and dwell time definition is then undertaken to provide a treatment plan for approval by the treating clinician.
5. Treatment is delivered once an optimized plan has been approved
6. After completion of treatment in the brachytherapy room the implant catheters and urinary catheter are removed; no anesthesia is required for this procedure.
7. The patient will return to the ward and may be discharged home later the same day or the following day Dose prescription A dose of 15Gy in a single treatment exposure defined at the 100% isodose which is the minimum tumour isodose to cover the PTV.