Timing of High-Dose Rate Brachytherapy with External Beam Radiotherapy in intermediate and high-risk localised Prostate Cancer (THEPCA): a randomised trial

Background
HDR brachytherapy(HDR-BT) and external beam radiotherapy(EBRT) are effective treatments for prostate cancer(PC) but cause genitourinary(GU) and gastrointestinal(GI) toxicities. There is no consensus on the timing of HDR-BT in relation to EBRT and the effect of sequencing on patients.
Objective
The primary objective was to assess differences, if any, in the incidence of Grade 3 or higher GU toxicities from treatment. We also aimed to explore the incidence of G1-4 GI toxicities, quality of life and patient satisfaction. Suppression of PSA and signals for survival differences were also analysed.
Methodology
A single-centre randomised trial in intermediate and high-risk localised PC patients to receive HDR-BT before (Arm A) or after (Arm B) EBRT. Toxicities were graded using CTCAE. IIEF and FACT-P were used to assess erectile dysfunction and QOL at 0, 3, 9 and 12 months.
Results
50 patients were recruited to each arm, with 48 and 46 patients completing treatment and follow up in each arm. 81.5% had high-risk disease. There were no G3 or G4 GU or GI toxicities. G1 urinary frequency was the most common adverse event experienced in both arms, peaking in incidence 3 months after commencing treatment (45.7 and 42.2% in Arm A and B, respectively). Up to 11 % of patients reported G1 urinary frequency at 12 months.
Other G1 GU toxicities experienced by >10% of patients were urinary tract obstruction, tract pain and urgency. These symptoms also peaked in incidence at 3 months. G2 GU toxicities were uncommon and experienced in a maximum of 2 patients within each arm at any time point.
Over 30% of patients had G1 flatulence at baseline and this remained the most frequently occurring G1 GI toxicity throughout the study, peaking at 12months (21.4% and 25.6% in Arm A and Arm B, respectively). Other GI toxicities experienced by more than 10% of patients were GI pain, proctitis and rectal mucositis, most of which demonstrated a peak incidence at 3 or 9 months. G2 GI toxicities were uncommon, except G2 flatulence. No significant difference was found in CTCAE, IPSS, IIEF, FACT-P and QOL scores between the arms.