Reviewed: Hamilton K, Bennett NC, Purdie G, Herst PM. Standardized cranberry capsules for radiation cystitis in prostate cancer patients in New Zealand: a randomized double blinded, placebo controlled pilot study [published online July 4, 2014]. Support Care Cancer. 2014;23(1):95-102. doi: 10.1007/s00520-014-2335-8.
Patients with prostate cancer undergoing radiation therapy often experience acute radiation-induced cystitis (inflammation of the bladder). Although the symptoms of this condition can be treated, there are no preventative therapies available. Cranberry (Vaccinium macrocarpon, Ericaceae) supplements have been associated with urinary tract health and therefore may beneficial for patients with radiation-induced cystitis. The aim of this randomized, double-blinded, placebo-controlled pilot trial was to evaluate the effects of a standardized cranberry supplement on the incidence and severity of radiation cystitis in patients with prostate cancer.
The men participating in this study received radiation therapy for cancer of their prostate and regional lymph nodes at the Southern Blood and Cancer Centre in Dunedin, New Zealand. Eligible patients were identified from planning computed tomography (CT) scans that assessed the prostate, bladder, and bowel. Excluded patients included men who had previous radiation therapy, metastatic disease, consumed the anticoagulant drug warfarin, had a Karnofsky performance status score of less than 70 (a scoring index that classifies functional ability of cancer patients; patients with scores under 70 required at least some assistance for personal care), had kidney stones, or had an allergy to cranberries.
In terms of radiation treatment, the patients were prescribed a dose of 74 Gy (Gray units) in 37 fractions or 64 Gy in 32 fractions to the prostate and prostate bed, respectively. The patients all received intensity-modulated radiation therapy (6 MV [megavolt] photon beam). Radiation treatment was directed to the prostate, prostate bed, and/or regional lymph nodes. There was a nine-week radiation treatment period for the prostate bed and a 10-week treatment for the prostate and prostate nodes. Patients (n=41) were randomly assigned to take one capsule per day with breakfast of either a cranberry extract (Naturo Pharm LTD; Rotorua, New Zealand) (n=20) or a placebo (n=21) during the radiation treatment period and for two weeks post-treatment. The cranberry capsules contained 72 mg proanthocyanidins (PACs), determined by UV-VISEP/CN standard method, and the placebo capsules were nearly identical in taste, color, and smell.
Patients were advised to limit or not consume wine, grapes (Vitis vinifera, Vitaceae), cranberries, or other berries during the study. Treatment effects were evaluated by assessing the Modified Expanded Prostate Index Composite (EPIC) scores both at the beginning and the end of the study. In particular, this study focused on five urinary symptoms and the degree to which seven urinary tract symptoms bothered the patients.
The results of this study were analyzed on an intent-to-treat basis for 40 patients (20 in both groups). A total of two patients did not comply with the study, including one that left the study after two weeks. Most of the men (mean age: 68 years) in this study were of European descent (93%) and had a mid-range Gleason score (grading system for prostate cancer) of six or seven. In addition, nearly half of the patients had stage T1 disease (beginning of disease). Furthermore, all patient-related factors were distributed evenly between the two groups.
Based on symptom scoring, the researchers found that the incidence of cystitis was 65% for the patients in the cranberry treatment group and 90% for the patients in the placebo group (P=0.058). Moreover, 30% of the patients in the cranberry group and 45% of the patients in the placebo group had severe cystitis (P=0.30). No men in the study developed a urinary tract infection (UTI). All EPIC scores were consistently lower for the cranberry cohort. In particular, the cranberry cohort had significantly lower mean (P=0.045) and maximum (P=0.019) scores for pain/burning urination symptoms. The cranberry cohort also had better mean scores for urine stream, although this was not significant when accounting for baseline symptoms (P=0.14).
Patients that presented with baseline urinary symptoms had worse EPIC scores for most symptoms. Less pain/burning (P=0.042), better control (P=0.034), stronger urine stream (P=0.036), and less leaking/dribbling (P=0.024), in comparison to the placebo group, were found to be significant only in the cranberry treatment group with baseline urinary symptoms. Additionally, patients in the cranberry cohort that followed the low-hydration regimen had significant effects on symptoms for pain/burning (P=0.038), stronger urine stream (P=0.038), and less frequent use of pads/liners (P=0.042). There were no significant differences found in the high-hydration regimen.
The authors conclude, “Men receiving radiation therapy for prostate cancer may benefit from using cranberry capsules, particularly those on low hydration regimens or presenting with urinary symptoms before radiation treatment.” Although the results are promising, one of the limitations of this study was that the improvements were based only on a questionnaire. This study also could have evaluated inflammation markers or other diagnostic features of cystitis. Despite this shortcoming, the interesting results of this pilot study warrant further investigations of the use of cranberry supplements for radiation-induced cystitis in both men and women.
—Laura M. Bystrom, PhD