CRD summary

The authors’ concluded that the available evidence was insufficient to draw a firm conclusion with respect to lycopene supplementation in prostate cancer patients, but some evidence was provided for a reduction in disease progression. In view of the small sample sizes and poor quality of the included studies and potential for publication bias, the authors’ conclusions appear appropriate.

Authors' objectives

To evaluate the effect of lycopene supplementation on disease progression in men with prostate cancer.

Searching

MEDLINE, EMBASE, CINAHL, Web of Science, AMED and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to January 2009 for publications in any language. Search terms were reported. Bibliographies of relevant reviews were handsearched.

Study selection

Intervention studies that were randomised controlled trials (RCTs), non-randomised controlled trials and before-after studies of lycopene supplementation in any form (such as tablet/capsule, whole tomato, tomato sauce and tomato juice) in prostate cancer patients regardless of disease duration, stage and treatment modalities were eligible for inclusion. Studies of mixed supplementation with lycopene and other nutrients or supplements were excluded. The primary outcome was disease progression of prostrate cancer measured by change in prostrate-specific antigen level. Secondary outcomes were side effects/toxicity, complications associated with prostate cancer and its treatment (such as pain and urinary tract symptoms) and survival. Interventions in the included studies were lycopene capsules and tablets, tomato sauce and tomato paste/juice with a dose range of 4mg to 120mg per day and a duration of three weeks to two years. Participants were diverse and included those with stage T1 or T2, localised or metastatic, hormone refractory, or recurrent prostate cancer.

Three independent reviewers identified papers for inclusion from titles and abstracts of papers. When relevance was not clear, full text copies of papers were examined by two reviewers.

Assessment of study quality

Methodological quality was assessed using the method developed by Jadad and Schulz. The criteria used included randomisation, blinding, dropout and withdrawals. Quality scores ranged from 0 to 5. A score of 3 or less indicated a low-quality study. The authors did not report how many reviewers performed the quality assessment.

Data extraction

Two reviewers independently performed data extraction. Prostrate-specific antigen levels were extracted using the parameters of the published papers, which were chiefly means with standard deviations (SD) and also regression slopes, percentage changes and prostrate-specific antigen slope changes. Numbers of events were extracted for other outcomes.

Methods of synthesis

A narrative synthesis was provided as the included studies were heterogeneous.

Results of the review

Eight relevant studies were identified (n=317): two RCTs (n=26 and n=54); one non-RCT with an unmatched control group (n=66); and five before-after studies (n=171, range 20 to 46). Both RCTs were low quality (Jadad scores <3). One RCT had a high loss to follow-up (26%).

Change in prostrate-specific antigen levels: One RCT (n=54) found a significantly lower mean for prostrate-specific antigen in the treatment group versus controls of 3.0ngmL^-1 (SD 1.9) versus 9.0ngmL^-1 (SD 7.5) (p<0.001). The other RCT (n=26) found no significant difference between the treatment and control groups. For the non-RCT (n=66) there was a significant reduction in mean prostrate-specific antigen after treatment from 10.9ngmL^-1 (SD 1.1) to 8.7ngmL^-1 (SD 0.9) (p<0.001). These were also significantly lower than the control group endpoint 13.8 ng mL^-1 (SD 2.4). Three of the before-after studies also reported statistically significant reductions in prostrate-specific antigen level after the interventions. The remaining two before-after studies did not have significant results.

Evidence of progression from bone scans: There was a significantly higher number of patients with a normal bone scan (complete response) in the intervention versus the control group in one RCT (25% versus 15%, p<0.02) and progressive disease was significantly less common in the intervention group (p<0.02). One before-after study reported a 25% reduction in overall metastatic lesions.

One RCT reported longer overall survival in the intervention group compared to control at 25.5 months (p<0.001). None of the studies that examined toxicity/side effects (six studies) reported any severe toxicity or intolerance related to intervention. Two studies reported improvements in cancer-related symptoms (details in review).

Authors' conclusions

The evidence available was insufficient to draw a firm conclusion with respect to lycopene supplementation in prostate cancer patients.

CRD commentary

The review addressed a well-defined question in terms of participants, interventions, study design and relevant outcomes. Relevant databases were searched in any language. Minimal efforts were made to identify unpublished studies, so some relevant studies may have been missed. Publication bias was not assessed. Study quality was assessed using suitable criteria. Some efforts were made to reduce error and bias in the review process, but it was not reported how many reviewers performed the quality assessment. Relevant study details were reported, but no details of patient ages were reported. A narrative synthesis was provided due to the heterogeneity of the interventions and participants. All of the included studies were small and of low quality.

The authors' conclusions appeared appropriate, but the small sizes and poor quality of the included studies as well as potential for publication bias should be born in mind.

Implications of the review for practice and research

Practice: The authors stated that there was not sufficient evidence to recommend the use of lycopene supplements in routine clinical practice for patients diagnosed with prostate cancer, but lycopene was unlikely to be harmful to such patients.

Research: The authors stated that large robust RCTs in broader patient groups were needed to identify the patient group most likely to benefit from lycopene supplementation and the most appropriate dose, method of supplementation and duration. Research that focused on the effects of lycopene should also consider the effects of other carotenoids and phytochemical compounds present in tomato products. Double-blind RCTs were required to assess the ability of lycopene to slow down the progression of prostate cancer and increase survival.

Funding

Not stated. The authors declared no conflicts of interest.

Bibliographic details

Haseen F, Cantwell MM, O'Sullivan JM, Murray LJ. Is there a benefit from lycopene supplementation in men with prostate cancer? A systematic review Prostate Cancer and Prostatic Diseases 2009; 12(4): 325-332. [PubMed: 19901932]

Original Paper URL

http://www.nature.com/pcan/journal/v12/n4/full/pcan200938a.html

Indexing Status

Subject indexing assigned by NLM

MeSH

Anticarcinogenic Agents /therapeutic use; Carotenoids /therapeutic use; Dietary Supplements; Disease Progression; Humans; Male; Prostate-Specific Antigen /blood; Prostatic Neoplasms /drug therapy /prevention & control; Randomized Controlled Trials as Topic

AccessionNumber

12010000788

Database entry date

15/09/2010

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.