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: Results of a randomized feasibility trial

Background: Advances in brachytherapy, external beam radiotherapy (EBRT) and image-guided radiotherapy have revolutionized radiotherapy delivery. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities remain a significant issue. Currently there is no European consensus on the timing of high-dose rate (HDR) brachytherapy in relation to EBRT. Schedules of HDR boost before or after EBRT vary significantly between institutions.The incidence of GI and GU toxicities was assessed in patients receiving HDR brachytherapy before and after EBRT. Methods: Men with Intermediate/high risk localized prostate cancer were randomized to Arm A (HDR brachytherapy before EBRT) or Arm B (HDR brachytherapy after EBRT). Both arms received a HDR boost of 15Gy and 46Gy in 23 fractions of EBRT. All patients received neoadjuvant and adjuvant hormone therapy for up to 2 years. Patients were followed quarterly up to a year. CTCAE scores for GU and GI toxicities were taken. IPSS, IEFL and FACT-P scores were collected. Fisher’s exact test was used to analyze the association between GU and GI toxicities. The T-test compared the mean differences in IPSS total scores at each follow-up. Analysis of variance evaluated the difference at follow up. Post-hoc testing and Bonferroni correction was applied. Results: 100 patients were randomized between 2015 and 2017. Data for 88 patients was available at cutoff. Mean age was 69 years (SD: 4.6). Age, Gleason score, TNM and clinical staging were similar in each arm. Mean IPSS Score was similar between both arms at baseline Arm A (6.52) & Arm B (6.57). 12 months follow up showed mild worsening of symptoms in both arms, but no significant difference noticed between Arm A (8.02) & Arm B (8.14) p=0.55. At 12 months, Grade 1 and 2 GU toxicities were more frequent in Arm A (22.88% & 5.28%, p=0.669) compared to Arm B (19.36% and 2.64%, p=0.485). Grade 1 GI toxicity was more common in Arm B (23.76%) than Arm A (21.2%), p=0.396. Grade 2 GI toxicities were more common in Arm A 5.28% vs 3.52%, p=0.739. Baseline mean IIEF scores were 10.9 and 10.53 in Arm A and B respectively. At 12 months this was 6.6 in Arm A and 7.11 in Arm B, but not statistically significant. FACT-P scores were not different in either arm, with good QOL scores maintained throughout. Mean score at baseline (125.18) was observed to be similar at 12 months follow up at (126.10). The PTV, CTV & OAR dose were compared and no significant differences were found. Conclusions: There were no significant differences in GI and GU related toxicities up to a year between patients receiving HDR brachytherapy before or after EBRT. There were no grade 3 or 4 toxicities. Treatment was well tolerated in both arms with good QOL scores. Longer follow up and a phase III multicenter RCT would be needed to validate findings. Clinical trial information: NCT02618161.