A Randomised Trial of Cranberry Versus Apple Juice in the Management of Urinary Symptoms During External Beam Radiation Therapy for Prostate Cancer

doi:10.1016/S0936-6555(03)00161-4

Clinical Oncology

Volume 15, Issue 6, September 2003, Pages 322-328

https://doi.org/10.1016/S0936-6555(03)00161-4 Get rights and content

Abstract

Aims: The aim of the study was to assess whether the oral intake of cranberry juice cocktail compared with apple juice was associated with a significant difference in urinary symptoms experienced during radical external beam radiation therapy (EBRT) for prostate carcinoma.

Materials and methods: One hundred and twelve men with prostate cancer were randomised to either 354 ml cranberry juice or apple juice a day. Stratification was based on a history of a previous transurethral resection of prostate (TURP yes/no) and baseline International Prostate Symptom Score (IPSS <6 or ≥6) of urinary symptoms.

Results: The maximum IPSS (MRT) and the maximum change in IPSS from baseline (DRT) are used to report the results. We analysed the effects of juice allocation on DRT and MRT using analysis of covariates (ANCOVA). We observed no significant difference for DRT (P=0.39) or MRT (P=0.76) related to the consumption of cranberry compared with apple juice. However, we found a significant relationship between the history of a previous TURP and both DRT (P=0.01) and MRT (P=0.01). The history of a previous TURP was associated with lower values for both end points. Baseline IPSS was significant for DRT (P=0.004) and MRT (P≤0.001). We found a significant relationship between the baseline IPSS <6 or ≥6 cut point on MRT (P≤0.001) but not on DRT (P=0.43). The use of neoadjuvant hormones had no significant effect on DRT (P=0.64) or MRT (P=0.76). The use of additional symptomatic medication during the study was not significantly different between the two arms.

Conclusions: This study shows no significant difference in the urinary symptoms experienced during EBRT related to the consumption of cranberry juice compared with apple juice.

Introduction

In British Columbia, a province of Canada, 3000 men are diagnosed with prostate cancer each year and about 750 men a year are treated with external beam radiation therapy (EBRT) [1]. The main acute side-effects to the prostate experienced during EBRT are bladder and bowel-specific. There is also the constitutional symptom of fatigue. The acute side-effects are generally self-limiting and are related to the reaction of normal tissues to radiation. The proposed underlying pathophysiological response of the bladder to radiation has also been described [2]. The specific urinary side-effects associated with radiation to the prostate are frequency and urgency of micturition, dysuria, nocturia and a change in strength of stream. The acute symptoms experienced by patients during radiation therapy to the prostate have been reported using, for example, the RTOG grading system [3].

Patient assessment of how ‘bothersome’ these symptoms are on quality of life vary [4]. Management of these symptoms should initially include reassurance and general symptomatic advice, such as maintaining a high fluid intake. If more specific intervention is required, a number of different medications are often tried, which include urinary antiseptics, analgesics, smooth muscle relaxants, such as terazosin, or anti-spasmodics, such as oxybutynin. These medications allow some symptomatic improvement while waiting for the course of radiation to be completed and the side-effects to spontaneously resolve. Occasionally, catheterisation may be the only way to alleviate severe urinary symptoms. The assessment of urinary symptoms can be achieved by the use of self-administered questionnaires. The International Prostate Symptom Score (IPSS) is a self-administered, validated seven-point questionnaire, which was originally designed to assess symptoms of the lower urinary tract related to benign prostatic hypertrophy. It has, however, been used in the assessment of symptoms related to prostate cancer and its treatment [5]. The IPSS produces a single figure score of urinary symptoms ranging from 0–40, with scores of 20 or more suggestive of ‘moderate’ to ‘severe’ symptoms [5]. Usually, there is a final question related to overall quality of life scored from 0–6. The IPSS questionnaire has previously been modified to include a question on ‘painful urination’, which is felt to be particularly relevant in the assessment of side-effects associated with radiation [6].

Patients anecdotally report a beneficial effect during radiation therapy from the ingestion of cranberry juice. The aim of this study was to assess whether the oral intake of cranberry juice cocktail with a control group of apple juice was associated with a significant difference in the urinary symptoms experienced during EBRT.

Section snippets

Methods

The Ethics Review Board of the University of British Columbia, Canada, approved the study.

Eligibility Criteria

The patients had prostate cancer and were due to be treated with radical EBRT (dose prescription 64–70 Gy). The treatment plans used a three-dimensional conformal four-field technique, with the clinical target volume encompassing the prostate (plus or minus the seminal vesicles). The ability to complete the IPSS questionnaires, either independently or with the help of a friend or relative, was also required. We used the modified IPSS questionnaire, developed by Barry [6]. The questionnaire was

Exclusion Criteria

Patients unable to complete questionnaires owing to physical or mental disability, poorly controlled ‘brittle’ diabetes or a known allergy to any component of cranberry or apple juice were ineligible. Criteria for exclusion also included previous radical prostatectomy or treatment plans for large field (whole pelvis) radiation. Patients with a urinary catheter before starting radiation therapy were excluded from the study. The insertion of a catheter during EBRT would result in their withdrawal

Data Collection

We collected the following data: the 1997 (UICC) T stage of the patients’ prostate cancer, use of neoadjuvant hormones, presence or absence of a previous transurethral resection of prostate (TURP), use of any additional symptomatic medication, total radiation dose/fractionation and the presence or absence of diabetes. We collected IPSS values twice a week during the course of radiation therapy and for 2 weeks after completing radiation, hence each week has two IPSS values.

Statistics

The study statistician generated the randomisation sequence and a system of sealed envelopes was used for the juice allocation. Data from the British Columbia Prostate Cohort Outcomes Initiative revealed that a previous TURP is a significant factor for increased acute bladder toxicity. It was assumed that patients in the study cohort would have a similar median baseline IPSS. These data also indicated that 50% of patients would score between 0–5 for their baseline IPSS (median score of 6.0;

Results

One hundred and twelve patients entered the study and their stratified allocation is shown in Table 1. Twelve participants withdrew; the reasons and timing of withdrawal are listed in Table 2. We found no significant association between juice allocation and the rate (Chi-square P=0.71) or the timing (t-test P=0.12) of withdrawal from the study. IPSS score was similar between the two arms at baseline (used as a stratum at randomisation, P=0.76). The baseline IPSS values are displayed in Fig. 1.

Discussion

According to Eisenberg et al. [8], 34% of North American people use at least one complementary therapy, which translates into US $228 spent per person per year on dietary supplements. This reflects the considerable public interest in the use of alternative products. Preliminary results from studies in mice suggest that cranberry, orange and grapefruit juices may have an anti-neoplastic activity [9]. Cranberry juice is also promoted as having a role in maintaining urinary tract health. In vitro,

Study Limitations

The use of a sealed envelope system for randomisation is acknowledged as being suboptimal, but was a practical solution for the study. It is unknown how well the patients complied with the consumption of the allocated juice and if they abstained from the consumption of other fruit juices during the study period, which might confound the results. The knowledge of a potentially beneficial effect of cranberry juice on urinary tract health is publicly well-known. A typical response rate for

Conclusion

This study does not show a significant difference between the urinary symptoms experienced during EBRT between patients consuming cranberry juice cocktail and apple juice. Baseline IPSS and previous TURP were factors associated with significant differences in urinary symptoms during radiation treatment.

Acknowledgments

We would like to thank Ocean Spray Cranberries Incorporated for providing the cranberry juice cocktail and apple juice free of charge to the patients during the trial period. Marge Leahy was especially helpful in organising delivery of the product. We would like to thank the radiation therapists at the Vancouver Cancer Agency, particularly Suzie Gagnon and Bil Whiteside, as well as Cheri Van Patten, nutritionist, and the Genitourinary Tumour Group at the Vancouver Cancer Centre.

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Original ArticleA Randomised Trial of Cranberry Versus Apple Juice in the Management of Urinary Symptoms During External Beam Radiation Therapy for Prostate Cancer

Abstract

Introduction

Section snippets

Methods

Eligibility Criteria

Exclusion Criteria

Data Collection

Statistics

Results

Discussion

Study Limitations

Conclusion

Acknowledgments

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Urology

J Urol

J Urol

J Urol

J Urol

Lancet

Clin Oncol

Int J Radiat Oncol Biol Phys

Am J Cardiol

The changing face of prostate cancer in British Columbia 1988–2000

Can J Urol

Random-effects models for longitudinal data

Biometrics

Unconventional medicine in the United States

N Engl J Med

Original Article
A Randomised Trial of Cranberry Versus Apple Juice in the Management of Urinary Symptoms During External Beam Radiation Therapy for Prostate Cancer