Hormonal therapy or external-beam radiation with brachytherapy and the risk of death from prostate cancer in men with intermediate risk prostate cancer

Purpose

To determine whether external-beam radiotherapy (EBRT) improves disease control compared with supplemental androgen suppression therapy (AST) in men with intermediate-risk prostate cancer who are being treated with brachytherapy.

Patients and Methods

A total of 807 men with intermediate-risk prostate cancer (T2bNXM0, Gleason ≤7, prostate-specific antigen [PSA] <20 ng/mL; or cT1c-T2bNXM0, Gleason 7) were consecutively treated with either AST and brachytherapy or EBRT and brachytherapy, between 1997 and 2007, and were followed up until September 21, 2007. A Fine and Gray competing risks multivariable regression model was used to assess whether AST or radiotherapy dose escalation reduced the risk of prostate-cancer-specific mortality (PCSM) when adjusting for age, PSA, Gleason score, and tumor category.

Results

Treatment with brachytherapy and with EBRT was associated with a significant increase in the risk of PCSM compared with brachytherapy and AST (adjusted hazard ratio [HR] 4.027 [95% CI, 1.168-13.89]; P = .027) after adjusting for age and prostate cancer prognostic factors. A Gleason score of 4+3 and increasing PSA were associated with worse PCSM (adjusted HR 8.882 [95% CI, 1.095-72.04]; P = .041; and adjusted HR 8.029 [95% CI, 2.38-28.8]; P = .0014, respectively).

Conclusion

Supplemental AST use compared with EBRT is associated with a lower risk of PCSM in men with intermediate-risk PC undergoing brachytherapy. Prospective validation in a randomized controlled trial is needed.     

Hormonal profile of diabetic men and the potential link to prostate cancer

OBJECTIVE: Previous studies suggest men with diabetes may be at reduced risk for prostate cancer as compared to men without diabetes. To investigate potential biological mechanisms, hormonal profiles of diabetic men and non-diabetic controls were compared. METHODS: In the Health Professionals Follow-Up Study, plasma levels of C-peptide, testosterone, sex-hormone binding globulin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 were determined in 171 diabetic men and 3,001 non-diabetic controls. Multiple linear regression analysis was conducted and least square means were calculated for hormones of interest. RESULTS: Plasma levels of several hormones either /=15 years after diagnosis with diabetes were examined. As time since diabetes diagnosis increased, plasma levels of C-peptide and IGFBP-3 significantly decreased (p for trend: C-peptide =.05, IGFBP-3 =.03). While testosterone and SHBG levels both significantly increased with increasing time since diabetes diagnosis (p for trend: testosterone =.02, SHBG =.002), the ratio of testosterone to SHBG decreased, suggesting a reduction in bioavailable testosterone. Plasma IGF-1 levels were lower in diabetics than non-diabetics, but no significant time trend was noted. CONCLUSION: This study of hormonal profiles of diabetic versus non-diabetic men identified changes in diabetic men that may be consistent with reduced prostate cancer risk.     

Treatment patterns among Canadian men diagnosed with localized low-risk prostate cancer

In general, guideline-recommended treatment options for men with low-risk prostate cancer (pca) include active surveillance, radical prostatectomy, and external-beam radiation therapy or brachytherapy. Because of the concern about overdiagnosis and consequent overtreatment of pca, patients with low-risk disease are increasingly being managed with active surveillance. Using data from six provincial cancer registries, we examined treatment patterns within a year of a diagnosis of localized low-risk pca, and we assessed differences by age.Of patients diagnosed in 2010 in four of the six reporting provinces, most received surgery or radiation therapy within 1 year of diagnosis. Depending on the province, either surgery or radiation therapy was the most commonly used primary treatment. In the other two provinces, most patients had no record of treatment within a year of diagnosis. Examining treatment patterns by age demonstrated a lesser likelihood of receiving surgery or radiation therapy within 1 year of diagnosis among men more than 75 years of age than among men 75 years of age or younger (no record of treatment in 69.1% and 46.3% respectively).In conclusion, we observed interprovincial and age-specific variations in the patterns of care for men with low-risk pca. The findings presented in this report are intended to identify opportunities for improvement in clinical practice that could lead to improved care and experience.     

Dietary supplement use patterns in men with prostate cancer: the Cancer Prostate Sweden Study

BackgroundIn a European setting, we know little about the use of dietary supplements among men with prostate cancer (PCa) and to what extent lifestyle, disease or other factors influence such use.Patients and methodsWe evaluated supplement use in 1127 men with incident PCa and in 900 population controls in Sweden. Age-adjusted binary regression with an identity link was carried out to estimate prevalence differences and corresponding 95% confidence intervals (CIs). Modifying effects of lifestyle- and diet-related factors were explored by statistical assessment of additive interaction.ResultsAmong men with PCa, 542 individuals (48%) had used supplements, which was a 10% (95% CI: 5.9%–15%) higher prevalence than among population controls. Among individuals with high intake of fatty fish, vegetables, and phytoestrogens, but low intake of saturated fat, supplement use was 29% (95% CI: 18%–41%) more common in men with PCa than in population controls. We found no evidence of heterogeneity by categories of education, smoking history, body mass index, fiber, fruit, or phytoestrogen intake, treatment, or disease stage.ConclusionSupplement use is common in Swedish men with PCa, especially among those with a healthy dietary pattern.     

To tell or not to tell: patterns of disclosure among men with prostate cancer

This paper draws on the results of a longitudinal, qualitative study of men with prostate cancer (treated with prostatectomy) and their spouses. Interviews were conducted separately and simultaneously with men and their spouses, at three points in time (pre-surgery, 8-10 weeks post-surgery and 11-13 months post-surgery). The primary focus in the paper is on men's responses to questions about their decisions to share information (or not) with others about their diagnosis and ongoing medical situation. Most men with prostate cancer avoided disclosure about their illness where possible, and placed great importance on sustaining a normal life. Factors related to limiting disclosure included men's low perceived need for support, fear of stigmatization, the need to minimize the threat of illness to aid coping, practical necessities in the workplace, and the desire to avoid burdening others. This study contributes to an understanding of disclosure issues related to prostate cancer, and raises issues about how best to be helpful to men, given their tendency to minimize the impact of illness, and the need for support.     

Partnership and outcomes in men with prostate cancer

BACKGROUND:

Being in a supportive relationship may have improved the health‐related quality of life (HRQOL) of men with prostate cancer, if the support was strong and positive. In the current study, the authors sought to examine the impact of partnership status on the mental health of men treated for localized prostate cancer.

METHODS:

Participants had clinically localized prostate cancer and chose treatment with radical prostatectomy (n = 307), external?beam radiotherapy (n = 78), or brachytherapy (n = 91). The authors prospectively assessed subject characteristics and HRQOL outcomes and evaluated associations between partnership outcomes and HRQOL measures. Two multivariate linear regression models were then created, 1 for baseline HRQOL outcomes and 1 for change in HRQOL from baseline to 12 months, with partnership status as the main predictor and subject characteristics as covariates.

RESULTS:

Partnership status was not found to be associated with either baseline physical or mental health, but partnered participants had less bowel bother (P = .02) and a lower fear of recurrence (P = .03) at baseline than did unpartnered subjects. Men with fewer comorbid conditions scored better across almost all baseline HRQOL domains. Primary treatment type was significantly associated with changes in physical HRQOL, with men undergoing radical prostatectomy describing better changes in physical health than those treated with brachytherapy (P = .04) or those receiving external?beam radiotherapy (P ≤ .01).

CONCLUSIONS:

Physical and mental health was found to be comparable in the study cohort of partnered and unpartnered men treated for prostate cancer. The universally high socioeconomic status of the current study cohort may mitigate differences in HRQOL by partnership status. Cancer 2009. © 2009 American Cancer Society.     

Body fatness and sex steroid hormone concentrations in US men: results from NHANES III

Objective

Obesity is associated with a variety of chronic diseases, including cancer, which may partly be explained by its influence on sex steroid hormone concentrations. Whether different measures of obesity, i.e., body mass index (BMI), waist circumference, and percent body fat were differentially associated with circulating levels of sex steroid hormones was examined in 1,265 men, aged 20?C90+ years old, attending the morning examination session of the Third National Health and Nutrition Examination Survey (NHANES III).

Materials and methods

Serum hormones were measured by immunoassay. Weight, height, and waist circumference were measured by trained staff. Percent body fat was estimated from bioelectrical impedance. Multivariate linear regression was used to estimate associations between body fatness measures and hormone levels.

Results

Total and free testosterone and sex hormone binding globulin concentrations decreased, whereas total and free estradiol increased with increasing BMI, waist circumference, and percent body fat (all p trend < 0.05). The magnitude of change in these hormones was similar for a one-quartile increase in each body fatness measure.

Conclusion

Measured BMI, waist circumference, and percent body fat led to similar inferences about their association with hormone levels in men.     

Perceived barriers and facilitators to physical activity in men with prostate cancer: possible influence of androgen deprivation therapy

While physical activity is beneficial for men with prostate cancer, too few perform sufficient activity for such benefit. This study examined perceptions of men with prostate cancer of their barriers and facilitators to physical activity, and how androgen deprivation therapy (ADT) may influence these perceptions. Two focus groups were conducted, involving six ADT and eight non‐ADT patients respectively. Data were transcribed verbatim and themes developed using a general inductive thematic approach. Facilitators to physical activity common to both groups of cancer survivors included clinician and spousal involvement, with pre‐existing co‐morbidities and increased age cited as barriers by both groups. The ADT subgroup cited personal involvement as a facilitator to physical activity, with fatigue, reduced motivation and a relative lack of specific advice from their clinician as additional barriers. The non‐ADT subgroup had no additional facilitators to physical activity but cited time constraints as a barrier. These results highlight the important role that cancer clinicians and spouses play in promoting physical activity for men with prostate cancer and how ADT may influence their other facilitators and barriers. As physical activity is beneficial for prostate cancer survivors, especially those on ADT, cancer clinicians should regularly discuss physical activity with their patients.     

Permanent prostate brachytherapy in men with clinically localised prostate cancer

Permanent prostate brachytherapy techniques are associated with excellent biochemical control for patients with localised prostate cancer. Ten-year data show that permanent prostate brachytherapy is compatible with external beam irradiation or radical prostatectomy. However, treatment protocols and techniques for prostate brachytherapy vary between centres and there is little conformity of treatment protocols. The selection of patients for monotherapy or combined external beam irradiation and brachytherapy is controversial. The role of neoadjuvant androgen deprivation also remains unanswered in patients with localised prostate cancer. In addition, post-implant dosimetry may in fact be more significant for predicting outcome than the addition of adjuvant therapies, and should be a requirement when performing prostate brachytherapy. Data now seem to support specific computed tomography (CT)-based criteria to evaluate implant quality and delivered dose to the prostate. Unfortunately, prostate oedema and poor imaging techniques are limiting factors for evaluating implant dosimetry. Treatment planning techniques that use new treatment planning computers may assist in improving the implant procedure and dosimetry and are now available.     

Metformin significantly reduces incident prostate cancer risk in Taiwanese men with type 2 diabetes mellitus

BackgroundWhether metformin therapy affects incident prostate cancer risk in Asian patients with type 2 diabetes mellitus (T2DM) has not been investigated.MethodsThe National Health Insurance reimbursement database of Taiwanese male patients with new-onset T2DM between 1998 and 2002 and aged ⩾40 years (n = 395,481) were retrieved to follow up prostate cancer incidence until the end of 2009. Metformin was treated as a time-dependent variable. Of the patients studied, 209,269 were never-users and 186,212 were ever-users. A time-dependent approach was used to calculate prostate cancer incidence and estimate hazard ratios using Cox regression for ever-users, never-users and subgroups of metformin exposure (tertiles of cumulative duration and cumulative dose). Sensitivity analyses were conducted in various subgroups, using time-dependent and non-time-dependent approaches.ResultsDuring the follow-up, 2776 metformin ever-users and 9642 never-users developed prostate cancer, representing an incidence of 239.42 and 737.10 per 100,000 person-years, respectively. The hazard ratio (95% confidence intervals) after adjustment for propensity score (PS) for ever- versus never-users was 0.467 (0.446–0.488). The PS-adjusted hazard ratios for the first, second and third tertiles of cumulative duration of metformin therapy were 0.741 (0.698–0.786), 0.474 (0.441–0.508) and 0.231 (0.212–0.253), respectively (P-trend < 0.001); and were 0.742 (0.700–0.786), 0.436 (0.406–0.468) and 0.228 (0.208–0.251) for the respective cumulative dose (P-trend < 0.001). Sensitivity analyses consistently supported a protective effect of metformin on incident prostate cancer.ConclusionsMetformin use is associated with a decreased risk of incident prostate cancer in Taiwanese male patients with T2DM.     

Dietary patterns and risk of prostate cancer in U.S. men.

We prospectively investigated the associations between dietary patterns and risk of prostate cancer in the Health Professionals Follow-up Study. Between 1986 and 2000, 3,002 incident prostate cancer cases were identified in our cohort. Using factor analysis, two major dietary patterns were identified, a prudent and a western dietary pattern. Dietary patterns were not appreciably associated with risk of total prostate cancer. For the highest versus the lowest quintiles, the multivariable relative risk (RR) for the prudent pattern was 0.94 [95% confidence interval (CI), 0.83-1.06], and for the western pattern, the multivariable RR was 1.03 (95% CI, 0.92-1.17). Neither were these associated with risk of advanced prostate cancer [highest versus lowest quintile, prudent pattern (RR, 1.01; 95% CI, 0.68-1.49); western pattern (RR, 1.13; 95% CI, 0.77-1.67)]. Higher western pattern scores were suggestively associated with a greater risk of advanced prostate cancer among older men [highest versus lowest quintile (RR, 1.35; 95% CI, 0.97-1.90)], but not after adding processed meat to the model [highest versus lowest quintile (RR, 1.11; 95% CI, 0.75-1.65)]. We did not find any evidence for a protective association between prudent pattern and risk of prostate cancer. The lack of association between a western dietary pattern as identified by factor analysis in our cohort and prostate cancer risk suggests that dietary risk factors for prostate cancer are likely to differ from those for other conditions, such as cardiovascular disease and type 2 diabetes, that have been associated with a western dietary pattern in this cohort.     

Hormonal predictors of prostate cancer: a meta-analysis.

PURPOSE: Although there is strong circumstantial evidence that androgens are implicated in the etiology of prostate cancer, epidemiologic investigations have failed to demonstrate consistently that one or more steroid hormones are implicated. In contrast, recent epidemiologic studies unequivocally link serum insulin-like growth factor 1 (IGF-1) levels with risk for prostate cancer. METHODS: We have performed the first meta-analysis of all previously published studies on hormonal predictors of risk for prostate cancer. RESULTS: A meta-analysis restricted to studies that performed mutual adjustment for all measured serum hormones, age, and body mass index indicated that men whose total testosterone is in the highest quartile are 2.34 times more likely to develop prostate cancer (95% confidence interval, 1.30 to 4.20). In contrast, levels of dihydrotestosterone and estradiol do not seem to play a role of equal importance. The only study that provides multivariably adjusted sex hormone-binding globulin data indicates that this binding protein is inversely related to prostate cancer risk (odds ratio, 0.46; 95% confidence interval, 0.24 to 0.89). Finally, all three studies that examined the role of serum IGF-1 have consistently demonstrated a positive and significant association with prostate cancer risk that is similar in magnitude to that of testosterone. CONCLUSION: Men with either serum testosterone or IGF-1 levels in upper quartile of the population distribution have an approximately two-fold higher risk for developing prostate cancer.     

前列腺癌内分泌治疗及其全程管理

前列腺癌已成为我国男性常见病之一,内分泌治疗在前列腺癌（尤其是晚期前列腺癌）治疗中举足轻重,但在临床应用中出现的一系列分歧并没有解决。如何相对统一认识,进行合理的前列腺癌内分泌治疗的全程管理,让患者获得最佳疗效显得尤为重要。本文依据国内外指南以及临床试验结果,对目前前列腺癌内分泌治疗的一系列问题,如治疗时机、治疗方案、患者选择、预后随访等作了详细总结及分析。     

Association of serum cholesterol and cholesterol-lowering drug use with serum sex steroid hormones in men in NHANES III

Purpose  

Low cholesterol levels and statin drugs may protect against prostate cancer with a worse prognosis. Their protective mechanism is unknown, but has been hypothesized to be related to cholesterol’s role as a sex steroid hormone precursor. We evaluated whether serum testosterone and estradiol differ by cholesterol or cholesterol-lowering drug use.