Cranberry capsules for acute radiation induced cystitis: The Kathleen Kilgour Centre experience

Abstract

Acute cystitis is a common radiation side effect in prostate cancer patients undergoing radiation therapy treatment which results from radiation damage to the bladder. Acute cystitis symptoms can occur within weeks of starting radiation therapy treatment and symptoms include frequency, nocturia, haematuria, urgency, pain and a reduced capacity to store urine. Current standard of care focuses on symptom management and not on treating cystitis. Previous research had shown that the incidence of radiation cystitis and pain/burning was lower and urinary flow stronger in men taking daily cranberry capsules, compared with men taking placebo capsules. The aim of the current study was to validate these findings in a 100 patient multicentre stage III double blinded randomized controlled clinical trial. Here, I present the analysis of data collected from the Kathleen Kilgour Centre (KKC) between January 2018 and January 2019. Prostate cancer patients were randomised to take either 2 cranberry capsules containing 72mg of proanthocyanidins or 2 placebo capsules per day; these capsules were indistinguishable from each other. The capsules were taken daily starting on day 1 of radiation treatment and finishing two weeks after completion of radiation treatment. Three assessment scales were used measure the severity of acute radiation induced cystitis on day 1 of radiation treatment and once weekly after that until 2 weeks after completion of radiation treatment. Two of the scales are validated (the Modified Radiation Therapy and Oncology Group Scores and Interstitial Cystitis Symptom/Problem Scores) and one novel scale (Radiation Induced Cystitis Assessment Scale) was used to assess acute radiation induced cystitis. Participants filled out the Interstitial Cystitis Symptom/Problem Scores and the Radiation Induced Cystitis Assessment Scale themselves with the research radiation therapist (the author of this thesis) completing the Modified Radiation Therapy and Oncology Group Scores. These assessment scales included items on severity and frequency of symptoms as well as the impact of these symptoms on daily life for participants. Between December 2016 and February 2019, 34 men were recruited, and 33 men completed the trial (16 men in the cranberry arm and 17 in the placebo arm). This thesis reports on those that were recruited during enrolment of BRT Hons. A total of 19 men were recruited between January 2018 and January 2019 (9 men in cranberry arm and 10 men in the placebo arm). There was no statistically significant difference between the severity of cystitis symptoms of patients who took cranberry capsules compared with patients who took placebo capsules, using any of the cystitis severity scales. Prostate cancer can lead to cystitis-like symptoms; therefore, it was anticipated that some men would present with these symptoms at baseline. Randomisation evenly distributed these men with baseline symptoms between the cranberry and placebo arms therefore minimising any potential confounding of the results. To further ensure that the baseline symptoms did not confound the results, the maximum score minus the baseline score was determined and used in the statistical analysis. This allowed for the assessment of any worsening of cystitis symptoms as participants went through their radiation treatment. Therefore, the results will most accurately depict any effect cranberry capsules might have on the change in the severity of cystitis that the participants experience as they undergo radiation therapy treatment. Participants were allocated to one of three treatment regimens; a conventional regimen of 74Gy in 37 fractions, a hypofractionated CHHiP regimen of 60Gy in 20 fractions, or the prostate bed regimen of 66Gy in 33 fractions. A lower total dose or a higher dose per fraction could affect cystitis severity. Randomisation between these three treatment regimens was stratified to minimise the confounding that the different treatment regimens could have on any potential differences in cystitis severity between men taking cranberry or placebo capsules. The placebo capsules used in this study contained red beetroot powder to make them indistinguishable from the cranberry capsules. This aided in successfully blinding the participants from visually assessing and knowing if they were on the cranberry or placebo capsules. However, beetroot contains antioxidants such as betalains, which also have anti-inflammatory properties. Both cranberry and placebo capsules were tested and compared to cranberry capsules, the placebo capsules had very low anti-inflammatory activity and no antioxidant activity. Therefore, the placebo capsules could be used in this trial as true inactive placebos. Participants are required to have a full bladder daily for their radiation therapy treatment. A full bladder reduces the irradiated volume of the bladder, therefore reducing the severity of the side effects. The bladder volumes and bladder doses received were similar between the cranberry and placebo arms and were not likely to confound the results of this study. Bladder volume is likely to be inconsistent from day to day and participants’ bladder volumes were checked daily on cone beam CT and participants were encouraged to hydrate to fill their bladder as full as when they did their planning CT scan. Daily variation in bladder volume is a potential unavoidable confounder in the study. In conclusion, this study found that cranberry capsules were not superior to capsules containing beetroot for managing acute radiation induced cystitis in this small KKC cohort.