Timing of High-Dose Rate Brachytherapy With External Beam Radiotherapy in Intermediate and High-Risk Localized Prostate CAncer (THEPCA) Patients and Its Effects on Toxicity and Quality of Life: Protocol of a Randomized Feasibility Trial

Abstract

BackgroundProstate cancer is the most common cancer in males in the UK and affects around 105 men for every 100,000. The role of radiotherapy in the management of prostate cancer significantly changed over the last few decades with 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 localized prostate cancer is the development of acute and late genitourinary and gastrointestinal toxicities. The recent European guidelines suggest that there is no consensus regarding the timing of high-dose rate (HDR) brachytherapy and EBRT. The schedules vary in different institutions where an HDR boost can be given either before or after EBRT. Few centers deliver HDR in between the fractions of EBRT.ObjectiveAssessment of acute genitourinary and gastrointestinal toxicities at various time points to better understand if the order in which treatment modality is delivered (ie, HDR brachytherapy or EBRT first) has an effect on the toxicity profile.MethodsTiming of HDR brachytherapy with EBRT in Prostate CAncer (THEPCA) is a single-center, open, randomized controlled feasibility trial in patients with intermediate and high-risk localized prostate cancer. A group of 50 patients aged 18 years old and over with histological diagnosis of prostate cancer (stages T1b-T3BNOMO), will be randomized to one of two treatment arms (ratio 1:1), following explanation of the study and informed consent. Patients in both arms of the study will be treated with HDR brachytherapy and EBRT, however, the order in which they receive the treatments will vary. In Arm A, patients will receive HDR brachytherapy before EBRT. In Arm B (control arm), patients will receive EBRT before HDR brachytherapy. Study outcomes will look at prospective assessment of genitourinary and gastrointestinal toxicities. The primary endpoint will be grade 3 genitourinary toxicity and the secondary endpoints will be all other grades of genitourinary toxicities (grades 1 and 2), gastrointestinal toxicities (grades 1 to 4), prostate-specific antigen (PSA) recurrence-free survival, overall survival, and quality of life.ResultsResults from this feasibility trial will be available in mid-2016.ConclusionsIf the results from this feasibility trial show evidence that the sequence of treatment modality does affect the patients’ toxicity profiles, then funding would be sought to conduct a large, multicenter, randomized controlled trial.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 15835424; http://www.isrctn.com/ISRCTN15835424 (Archived by WebCite at http://www.webcitation.org/6Xz7jfg1u).

Does the sequence of high-dose rate brachytherapy boost and IMRT for prostate cancer impact early toxicity outcomes? Results from a single institution analysis

“…For example, one particular advantage of utilizing HDR-BT upfront is the ability to place fiducial markers and perform HDR-BT in one procedure, reducing patient burden to one preparation regimen. A similarly designed, prospective randomized trial titled THEPCA is currently underway in England with results pending [20] .…”

“…The NCCN, GEC-ESTRO, and ABS guidelines provides no recommendation and sequencing is institution and/or trial-dependent [17] , [18] , [19] . The Timing of HDR brachytherapy with EBRT in Prostate Cancer (THEPCA) study (NCT02618161) is an ongoing prospective trial designed to compare toxicity, quality of life, (QoL) and disease outcomes in 50 patients with intermediate or high-risk prostate cancer treated with single fraction HDR-BT boost delivered pre-EBRT versus post-EBRT in combination with ADT [20] .…”

Quality of Life in Patients with Clinically Localized Prostate Cancer Managed with Modern Radiotherapy: Impact on Bowel Habit, Sexual Function and Urinary Symptoms

“…Currently, there are several treatment modalities for localized cancer including radical prostatectomy, radiotherapy and active surveillance; with low specific cancer mortality rates, 3-4% and 2-10% at 10 and 15 years respectively, similar in all treatment modalities [1,3]. The increase in the diagnosis of tumors in early stages, associated with similar life expectations among the different treatments, create a challenge for both patients and treating doctors when choosing the best therapeutic option.…”

“…In the United States, 75% of patients with localized prostate cancer are treated with radiotherapy or radical prostatectomy [3]. The role of radiotherapy for the management of prostate cancer has changed in recent decades with the development of high and low-rate brachytherapy, modulated intensity radiotherapy and imageguided radiation therapy.…”