Purpose
Observational studies and randomized controlled trials (RCTs) have shown an association between vitamin D levels and prostate cancer progression. However, evidence of direct causality is ...sparse and studies have not examined biological mechanisms, which can provide information on plausibility and strengthen the evidence for causality.
Methods
We used the World Cancer Research Fund International/University of Bristol two-stage framework for mechanistic systematic reviews. In stage one, both text mining of published literature and expert opinion identified testosterone as a plausible biological mechanism. In stage two, we performed a systematic review and meta-analysis to assess the evidence from both human and animal studies examining the effect of vitamin D on testosterone, and testosterone on advanced prostate cancer (diagnostic Gleason score of ≥ 8, development of metastasis) or prostate cancer-specific mortality.
Results
A meta-analysis of ten human RCTs showed evidence of an effect of vitamin D on total testosterone (standardised mean difference (SMD) = 0.133, 95% CI = − 0.003–0.269, I
2
= 0.0%,
p
= 0.056). Five human RCTs showed evidence of an effect of vitamin D on free testosterone (SMD = 0.173, 95% CI = − 0.104–0.450, I
2
= 52.4%,
p
= 0.220). Three human cohort studies of testosterone on advanced prostate cancer or prostate cancer-specific mortality provided inconsistent results. In one study, higher levels of calculated free testosterone were positively associated with advanced prostate cancer or prostate cancer-specific mortality. In contrast, higher levels of dihydrotestosterone were associated with lowering prostate cancer-specific mortality in another study. No animal studies met the study eligibility criteria.
Conclusion
There is some evidence that vitamin D increases levels of total and free testosterone, although the effect of testosterone levels within the normal range on prostate cancer progression is unclear. The role of testosterone as a mechanism between vitamin D and prostate cancer progression remains inconclusive.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
AbstractObjectiveTo determine whether a standardised and manualised care intervention in men in primary care could achieve superior improvement of lower urinary tract symptoms (LUTS) compared with ...usual care.DesignCluster randomised controlled trial.Setting30 National Health Service general practice sites in England.ParticipantsSites were randomised 1:1 to the intervention and control arms. 1077 men (≥18 years) with bothersome LUTS recruited between June 2018 and August 2019: 524 were assigned to the intervention arm (n=17 sites) and 553 were assigned to the usual care arm (n=13 sites).InterventionStandardised information booklet developed with patient and expert input, providing guidance on conservative and lifestyle interventions for LUTS in men. After assessment of urinary symptoms (manualised element), general practice nurses and healthcare assistants or research nurses directed participants to relevant sections of the manual and provided contact over 12 weeks to assist with adherence.Main outcome measuresThe primary outcome was patient reported International Prostate Symptom Score (IPSS) measured 12 months after participants had consented to take part in the study. The target reduction of 2.0 points on which the study was powered reflects the minimal clinically important difference where baseline IPSS is <20. Secondary outcomes were patient reported quality of life, urinary symptoms and perception of LUTS, hospital referrals, and adverse events. The primary intention-to-treat analysis included 887 participants (82% of those recruited) and used a mixed effects multilevel linear regression model adjusted for site level variables used in the randomisation and baseline scores.ResultsParticipants in the intervention arm had a lower mean IPSS at 12 months (adjusted mean difference −1.81 points, 95% confidence interval −2.66 to −0.95) indicating less severe urinary symptoms than those in the usual care arm. LUTS specific quality of life, incontinence, and perception of LUTS also improved more in the intervention arm than usual care arm at 12 months. The proportion of urology referrals (intervention 7.3%, usual care 7.9%) and adverse events (intervention seven events, usual care eight events) were comparable between the arms.ConclusionsA standardised and manualised intervention in primary care showed a sustained reduction in LUTS in men at 12 months. The mean difference of −1.81 points (95% confidence interval −0.95 to −2.66) on the IPSS was less than the predefined target reduction of 2.0 points.Trial registrationISRCTN Registry ISRCTN11669964.
ObjectivesTo estimate the cost-effectiveness of a primary care intervention for male lower urinary tract symptoms (LUTS) compared with usual care.DesignEconomic evaluation alongside a cluster ...randomised controlled trial from a UK National Health Service (NHS) perspective with a 12-month time horizon.SettingThirty NHS general practice sites in England.Participants1077 men aged 18 or older identified in primary care with bothersome LUTS.InterventionsA standardised and manualised intervention for the treatment of bothersome LUTS was compared with usual care. The intervention group (n=524) received a standardised information booklet with guidance on conservative treatment for LUTS, urinary symptom assessment and follow-up contacts for 12 weeks. The usual care group (n=553) followed local guidelines between general practice sites.MeasuresResource use was obtained from electronic health records, trial staff and participants, and valued using UK reference costs. Quality-adjusted life-years (QALYs) were calculated from the EQ-5D-5L questionnaire. Adjusted mean differences in costs and QALYs and incremental net monetary benefit were estimated.Results866 of 1077 (80.4%) participants had complete data and were included in the base-case analysis. Over the 12-month follow-up period, intervention and usual care arms had similar mean adjusted costs and QALYs. Mean differences were lower in the intervention arm for adjusted costs −£29.99 (95% CI −£109.84 to £22.63) while higher in the intervention arm for adjusted QALYs 0.001 (95% CI −0.011 to 0.014). The incremental net monetary benefit statistic was £48.01 (95% CI −£225.83 to £321.85) at the National Institute for Health and Care Excellence UK threshold of £20 000 per QALY. The cost-effectiveness acceptability curve showed a 63% probability of the intervention arm being cost-effective at this threshold.ConclusionsCosts and QALYs were similar between the two arms at 12 months follow-up. This indicates that the intervention can be implemented in general practice at neutral cost.Trial registration numberISRCTN11669964.
ObjectivesInterventions designed to improve men’s diet and physical activity (PA) have been recommended as methods of cancer prevention. However, little is known about specific factors that support ...men’s adherence to these health behaviour changes, which could inform theory-led diet and PA interventions. We aimed to explore these factors in men following prostatectomy for prostate cancer (PCa).Design, setting and participantsA qualitative study using semistructured interviews with men, who made changes to their diet and/or PA as part of a factorial randomised controlled trial conducted at a single hospital in South West England. Participants were 17 men aged 66 years, diagnosed with localised PCa and underwent prostatectomy. Interview transcripts underwent thematic analysis.ResultsMen were ambivalent about the relationship of nutrition and PA with PCa risk. They believed their diet and level of PA were reasonable before being randomised to their interventions. Men identified several barriers and facilitators to performing these new behaviours. Barriers included tolerance to dietary changes, PA limitations and external obstacles. Facilitators included partner involvement in diet, habit formation and brisk walking as an individual activity. Men discussed positive effects associated with brisk walking, such as feeling healthier, but not with nutrition interventions.ConclusionsThe facilitators to behaviour change suggest that adherence to trial interventions can be supported using well-established behaviour change models. Future studies may benefit from theory-based interventions to support adherence to diet and PA behaviour changes in men diagnosed with PCa.
Lower urinary tract symptoms (LUTS) constitute a substantial burden on males due to their high prevalence (up to 30% of males aged >65 years)1 and significant impact on quality of life. Prevalence ...and severity of LUTS increase with age; therefore, the burden on the NHS and primary care (where most males with LUTS are managed) is expected to grow, alongside population ageing. Yet a comparatively small proportion of affected males seek advice or treatment for their symptoms; reported as between 19% and 24% in studies conducted in Europe and the US. There is a perception among males that LUTS is a normal sign of ageing, which may be related to a lack of knowledge of the condition and available treatments. Indeed, qualitative research reported in the current issue of the BJGP suggests that GPs find it difficult to decide on the mechanism of LUTS in males. Remarkably, the situation is also problematic after referral for urological management, where incomplete discussions and misperceptions of LUTS and its treatment have also been identified. Unfortunately, this can lead to a situation where treatment seems to be a case of 'trial and error'.
Background
Smoking and alcohol increase the risk of head and neck cancer and affect treatment outcomes. Interventions modifying these behaviors may improve posttreatment outcomes and survival. We ...systematically reviewed evidence of the effectiveness of smoking/alcohol interventions in head and neck cancer and oral dysplasia.
Methods
The AMED, CINAHL, Embase, MEDLINE, and Web of Science databases were searched for randomized controlled trials (RCTs) of smoking/alcohol interventions in people with head and neck cancer. A qualitative synthesis of the studies was conducted.
Results
Three RCTs were identified: 2 smoking interventions and 1 smoking and alcohol intervention. One intervention, which was comprised of a smoking intervention based on Cognitive Behavioral Therapy and pharmacologic management compared to usual care, reduced smoking prevalence.
Conclusion
Further research is required into the underlying mechanisms that lead to cessation and interventions that include both pharmacological and behavioral therapy. Future RCTs should include suitable control conditions and sufficient power to assess clinical outcomes.
Full text
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background Evidence from observational studies have shown that moderate intensity physical activity can reduce risk of progression and cancer-specific mortality in participants with prostate cancer. ...Epidemiological studies have also shown participants taking metformin to have a reduced risk of prostate cancer. However, data from randomised controlled trials supporting the use of these interventions are limited. The Prostate cancer-Exercise and Metformin Trial examines that feasibility of randomising participants diagnosed with localised or locally advanced prostate cancer to interventions that modify physical activity and blood glucose levels. The primary outcomes are randomisation rates and adherence to the interventions over 6 months. The secondary outcomes include intervention tolerability and retention rates, measures of insulin-like growth factor I, prostate-specific antigen, physical activity, symptom-reporting, and quality of life. Methods Participants are randomised in a 2 x 2 factorial design to both a physical activity (brisk walking or control) and a pharmacological (metformin or control) intervention. Participants perform the interventions for 6 months with final measures collected at 12 months follow-up. Discussion Our trial will determine whether participants diagnosed with localised or locally advanced prostate cancer, who are scheduled for radical treatments or being monitored for signs of cancer progression, can be randomised to a 6 months physical activity and metformin intervention. The findings from our trial will inform a larger trial powered to examine the clinical benefits of these interventions. Trial registration Prostate Cancer Exercise and Metformin Trial (Pre-EMpT) is registered on the ISRCTN registry, reference number ISRCTN13543667. Date of registration 2nd August 2018-retrospectively registered. First participant was recruited on 11th September 2018. Keywords: Prostate cancer, Metformin, Physical activity, Feasibility randomised controlled trial, Localised, Locally advanced, Radiotherapy, Prostatectomy, Active surveillance
Evidence from studies on prostate cancer progression have identified vitamin D to be a potentially important nutrient. However, the World Cancer Research Fund and American Institute for Cancer ...Research have reported the quality of this evidence to be limited and warrant further investigation. We plan to use the recently developed WCRF International/University of Bristol mechanistic systematic review framework to determine whether the observed association between vitamin D and prostate cancer exists through a plausible biological pathway.
This protocol sets out how we will perform a systematic review of the literature in human and animal studies. We will search the electronic databases MEDLINE, EMBASE, PubMed, and BIOSIS Citation Index without restrictions on year of publication or language. We will extract data from observational and experimental studies examining two inter-linked pathways in the relationship between vitamin D and prostate cancer progression: (1) vitamin D and testosterone, and (2) testosterone and prostate cancer progression. We focus on testosterone as its actions form a potentially novel intermediate mechanism that was identified via our online literature mining tools. The outcomes of interest include incidence or prevalence of prostate cancer, measures of prostate cancer progression (including biochemical recurrence, local, or distal metastases), and prostate cancer-specific mortality. We will assess study quality and the level of certainty of the evidence. We will analyse data where possible, using meta-analysis with forest plots or albatross plots; otherwise, a narrative synthesis will be performed.
To our knowledge, this will be the first systematic synthesis of the evidence underpinning the vitamin D-testosterone-prostate cancer mechanistic pathway. The results of the review may inform future research, intervention trials, and public health messages.
Lifestyle factors, including diet and physical activity, are associated with prostate cancer progression and mortality. However, it is unclear how men would like lifestyle information to be delivered ...following primary treatment. This study aimed to identify men's preferences for receiving lifestyle information.
We conducted a cross-sectional pilot best-worst discrete choice experiment which was nested within a feasibility randomised controlled trial. Our aim was to explore men's preferences of receiving diet and physical activity advice following surgery for localised prostate cancer. Thirty-eight men with a mean age of 65 years completed best-worst scenarios based on four attributes: (1) how information is provided; (2) where information is provided; (3) who provides information; and (4) the indirect cost of receiving information. Data was analysed using conditional logistic regression. Men's willingness to pay (WTP) for aspects of the service was calculated using an out-of-pocket cost attribute.
The combined best-worst analysis suggested that men preferred information through one-to-one discussion
= 1.07, CI = 0.88 to 1.26) and not by email (
= - 1.02, CI = - 1.23 to - 0.80). They preferred information provided by specialist nurses followed by dietitians (
= 0.76, CI = 0.63 to 0.90 and - 0.16, CI = - 0.27 to - 0.05 respectively) then general nurses (
= - 0.60, CI = - 0.73 to - 0.48). Three groups were identified based on their preferences. The largest group preferred information through individual face-to-face or group discussions (
= 1.35, CI = 1.05 to 1.63 and 0.70, CI = 0.38 to 1.03 respectively). The second group wanted information via one-to-one discussions or telephone calls (
= 1.89, CI = 1.41 to 2.37 and 1.03, CI = 0.58 to 1.48 respectively), and did not want information at community centres (
= - 0.50, CI = - 0.88 to - 0.13). The final group preferred individual face-to-face discussions (
= 0.45, CI = 0.03 to 0.88) but had a lower WTP value (£17).
Men mostly valued personalised methods of receiving diet and physical activity information over impersonal methods. The out-of-pocket value of receiving lifestyle information was important to some men. These findings could help inform future interventions using tailored dietary and physical activity advice given to men by clinicians following treatment for prostate cancer, such as mode of delivery, context, and person delivering the intervention. Future studies should consider using discrete choice experiments to examine information delivery to cancer survivor populations.
Head and neck cancers include malignancies of the mouth, larynx and oropharynx. Tobacco use and alcohol consumption are associated with increased risks of developing and dying from head and neck ...cancer. The aim of this review is to examine the effectiveness of smoking and alcohol cessation interventions on disease-related outcomes, quality of life and behavioural change in adults with head and neck cancer and oral dysplasia.
The Cochrane library, CINAHL, Embase, MEDLINE, PsycINFO and Web of Science databases will be searched for randomised controlled trials investigating the effects of smoking or alcohol interventions on patients with either head and neck cancer or oral dysplasia. The primary outcomes are disease-free survival and, for participants with oral dysplasia, malignant transformation to cancer. Secondary outcomes are disease recurrence and progression, quality of life and behavioural change. The quality of included studies will be assessed using the 'Cochrane Collaborations tool for assessing risk of bias'. A qualitative synthesis of the results will be reported, and a meta-analysis of the outcome data conducted, where appropriate.
This systematic review will identify the extent of the current research on smoking and alcohol cessation interventions in patients with head and neck cancer and oral epithelial dysplasia. The findings have the potential to inform which interventions have been successful and how future behavioural change interventions should be conducted within these populations.
PROSPERO CRD42016038237.
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