Reduction In Prostate Cancer-specific Mortality Research Articles

Mortality Risk for Docetaxel-Treated, High-Grade Prostate Cancer With Low PSA Levels

Patients with high-grade prostate cancer with low levels of prostate-specific antigen (PSA; <4 ng/mL) are at high risk of mortality, necessitating an improved treatment paradigm. To assess for these patients whether adding docetaxel to standard of care (SOC) treatment is associated with decreased prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). PubMed search from 2000 to 2022. Five prospective randomized clinical trials (RCTs) performed in the US, France, and the United Kingdom evaluating SOC treatment with radiotherapy and androgen deprivation therapy (ADT) or with radical prostatectomy vs SOC plus docetaxel. Individual data were included from patients with nonmetastatic prostate cancer, a PSA level of less than 4 ng/mL, and a Gleason score of 8 to 10. Patients initiated treatment between February 21, 2006, and December 31, 2015 (median follow-up, 7.1 [IQR, 5.4-9.9] years). Data were analyzed on December 16, 2022. Hazard ratio (HR) of ACM and subdistribution HR (sHR) of PCSM adjusted for performance status (1 vs 0 or good health), Gleason score (9 or 10 vs 8), tumor category (T3-T4 vs T1-T2 or TX), and duration of ADT (2 years vs 4-6 months). From a cohort of 2184 patients, 145 patients (6.6%) in 4 RCTs were eligible (median age, 63 [IQR, 46-67] years). Thirty-one patients died, and of these deaths, 22 were due to prostate cancer. Performance status was 0 for 139 patients (95.9%) and 1 for 6 patients (4.1%). A reduced but nonsignificant risk of ACM (HR, 0.51 [95% CI, 0.24-1.09]) and PCSM (sHR, 0.42 [95% CI, 0.17-1.02]) was associated with patients randomized to SOC plus docetaxel compared with SOC. The risk reduction in ACM (HR, 0.46 [95% CI, 0.21-1.02]) was more pronounced among patients with a performance status of 0 and was significant for PCSM (sHR, 0.30 [95% CI, 0.11-0.86]). Adding docetaxel to SOC treatment for patients who are in otherwise good health with a PSA level of less than 4 ng/mL and a Gleason score of 8 to 10 was associated with a significant reduction in PCSM and therefore has the potential to improve prognosis.

Prostate cancer screening: controversies and suggested solutions

Prostate cancer is the most common cancer among men in industrialized countries. The annual incidence rate in Germany is about 60,000. Every year, 13,000 men die of this disease. Nevertheless, the 10-year survival rate is relatively favorable compared to other carcinomas.Prostate cancer screening is discussed controversially both nationally and internationally. This is due to the fact that the determination of the prostate-specific antigen (PSA) for tumor detection beginning in the 1980s led to over-diagnosis of clinically insignificant prostate cancer and consequently to over-therapy-usually by radical prostatectomy or radiotherapy.This review article will discuss the largest randomized controlled trials of PSA-based prostate cancer screening to date. It will highlight the advantages and disadvantages of this screening and give an outlook on the development of future strategies for prostate cancer screening.For PSA screening, the European Randomized Study for Screening of Prostate Cancer (ERSPC) study showed arelative reduction in prostate cancer-specific mortality of approximately 21% after amedian follow-up period of 13years. However, in absolute figures, relatively few men will benefit from population-based screening and the rate of over-diagnosed men remains high.The procedure in aSwedish long-term study, in which risk-adapted screening intervals were applied on the basis of the assessment of abaseline PSA level at ayoung age (40-50) showed promising results and may provide asolution to this dilemma. This strategy is the basis for the currently largest study on risk-adapted prostate cancer screening ( www.PROBASE.de ), which evaluates this concept for the first time with arandomized design.

Digoxin use after diagnosis of prostate cancer and survival: a population-based cohort study.

Preclinical studies have shown that digoxin exerts anticancer effects on different cancer cell lines including prostate cancer. A recent observational study has shown that digoxin use was associated with a 25% reduction in prostate cancer risk. The aim of this study was to investigate whether digoxin use after diagnosis of prostate cancer was associated with decreased prostate cancer-specific mortality. A cohort of 13 134 patients with prostate cancer newly diagnosed from 1998 to 2009 was identified from English cancer registries and linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify 2010 prostate cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were calculated for the association between post-diagnostic exposure to digoxin and prostate cancer-specific mortality. Overall, 701 (5%) patients with prostate cancer used digoxin after diagnosis. Digoxin use was associated with an increase in prostate cancer-specific mortality before adjustment (HR = 1.59; 95% CI 1.32-1.91), but after adjustment for confounders, the association was attenuated (adjusted HR = 1.13; 95% CI 0.93-1.37) and there was no evidence of a dose response. In this large population-based prostate cancer cohort, there was no evidence of a reduction in prostate cancer-specific mortality with digoxin use after diagnosis. Copyright © 2016 John Wiley & Sons, Ltd.

The Memorial Sloan Kettering Cancer Center Recommendations for Prostate Cancer Screening

The Memorial Sloan Kettering Cancer Center (MSKCC) recommendations on prostate cancer screening were developed in response to three limitations of previous screening guidelines: insufficient evidence base, failure to link screening with treatment, and lack of risk stratification. The objective of the recommendations is to provide a schema for prostate cancer screening that maximizes the benefits, in terms of reduction in prostate cancer-specific mortality, and minimizes the harms, in terms of overdiagnosis and overtreatment. We recommend the following schema for men choosing to be screened following informed decision-making: starting at age 45, prostate-specific antigen (PSA) without digital rectal examination. If PSA ≥ 3 ng/mL: consider prostate biopsy; if PSA ≥ 1 but < 3 ng/mL: return for PSA testing every 2-4 years; if PSA < 1 ng/mL: return for PSA testing at 6-10 years. PSA testing should end at age 60 for men with PSA ≤ 1 ng/ mL; at 70, unless a man is very healthy and has a higher than average PSA; at 75 for all men. The decision to biopsy a man with a PSA > 3 ng/mL should be based on a variety of factors including repeat blood draw for confirmatory testing of the PSA level, digital rectal examination results, and workup for benign disease. Additional reflex tests in blood such as a free-to-total PSA ratio, the Prostate Health Index, or 4Kscore, or urinary testing of PCA3, can also be informative in some patients. The best evidence suggests that more restricted indication for prostate biopsy and a more focused approach to pursue screening in men at highest risk of lethal cancer would retain most of the mortality benefits of aggressive screening schema, while importantly reducing harms from overdetection and overtreatment.

Aspirin use and mortality in men with localised prostate cancer: A cohort study.

5084 Background: Cyclooxygenase-2 (COX-2) expression in prostate cancer has been associated with high grade tumours and poorer prognosis. Use of aspirin, a COX-2 inhibitor, has been associated with reduced prostate cancer mortality in some studies. These studies have not, however, provided information on the dose and timing of aspirin use. Methods: National Cancer Registry Ireland data was used to identify men with stage I-III prostate cancer (ICD10 C61) diagnosed 2001-2006. Aspirin use in the year preceding prostate cancer diagnosis was identified from linked prescription refill data (General Medical Services) and stratified by dose (low ≤75mg, high &gt;75mg) and dosing intensity (proportion of days in that year with aspirin supply available). Cox proportional hazards models, adjusted for age, smoking status, year of incidence, comorbidity score, Gleason score, tumour size, pre-diagnostic statin use, and receipt of radiation (time varying) were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between aspirin use and all-cause and prostate cancer-specific mortality. Interactions with tumour characteristics were examined. Results: 2,936 men with stage I-III prostate cancer were identified (aspirin users, N=1,131; 38.5%). Median patient follow-up was 5.5 years. In multivariate analyses, aspirin use was not associated with a significant reduction in prostate cancer-specific (HR 0.90, 95% CI 0.68-1.20) or all-cause mortality (HR 0.98, 95% CI 0.84-1.15). In dose response analyses aspirin use was associated with a significantly lower risk of prostate cancer-specific mortality in men receiving &gt;75mg of aspirin (HR 0.59, 95% CI 0.35-1.00, p=0.048) but not ≤75mg aspirin (HR 1.01, 95% CI 0.75-1.37, p=0.938). Stronger associations were also observed in men with higher aspirin dosing intensity or a Gleason score &gt;7. Conclusions: Pre-diagnostic aspirin use, measured using objective prescription refill data, was associated with a significant reduction in prostate cancer-specific mortality in men with stage I-III prostate cancer receiving &gt;75mg of aspirin. These results confirm previous findings, and provide important new information regarding the dose of aspirin associated with survival benefit.

Aspirin Use and the Risk of Prostate Cancer Mortality in Men Treated With Prostatectomy or Radiotherapy

Experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, but clinical data have been limited. We investigated whether use of ACs was associated with the risk of death from prostate cancer. This study comprised 5,955 men in the Cancer of the Prostate Strategic Urologic Research Endeavor database with localized adenocarcinoma of the prostate treated with radical prostatectomy (RP) or radiotherapy (RT). Of them, 2,175 (37%) were receiving ACs (warfarin, clopidogrel, enoxaparin, and/or aspirin). The risk of prostate cancer-specific mortality (PCSM) was compared between the AC and non-AC groups. After a median follow-up of 70 months, risk of PCSM was significantly lower in the AC group compared with the non-AC group (3% v 8% at 10 years; P < .01). The risks of disease recurrence and bone metastasis were also significantly lower. In a subgroup analysis by clinical risk category, the reduction in PCSM was most prominent in patients with high-risk disease (4% v 19% at 10 years; P < .01). The benefit from AC was present across treatment modalities (RT or RP). Analysis by type of AC medication suggested that the PCSM reduction was primarily associated with aspirin. Multivariable analysis indicated that aspirin use was independently associated with a lower risk of PCSM (adjusted hazard ratio, 0.43; 95% CI, 0.21 to 0.87; P = .02). AC therapy, particularly aspirin, was associated with a reduced risk of PCSM in men treated with RT or RP for prostate cancer. The association was most prominent in patients with high-risk disease.

Prostate cancer–specific mortality and competing causes of mortality among elderly men after local therapy for prostate cancer.

103 Background: The benefit of definitive local therapy among elderly patients (&gt; 65 years) with localized prostate cancer (PC) is uncertain, particularly for those with comorbid illness. Despite this uncertainty, the majority of these men currently receive local therapy. We analyzed the risk of prostate cancer-specific mortality (PCSM) relative to competing causes of mortality (CCM), stratified by disease severity and comorbidity, among contemporary men treated at two high-volume hospitals Methods: Between 1995-2005, 4237 consecutive men aged 65 years or older were managed by radical prostatectomy (N = 1634), external-beam radiotherapy (N = 1570), or brachytherapy (N = 1033) at Cleveland Clinic or Barnes-Jewish Hospital. Clinical information was obtained from prospective data bases. Comorbidity was assessed using ACE-27 and Charlson Comorbidity indices. PC risk was classified according to D’Amico criteria. Fine and Gray competing risk analysis was used to assess PCSM and CCM at 10 years. Results: Over a median follow-up of 72 months (IQR: 46-97), 88 and 748 PCSM and CCM events were observed. Among healthy men with low risk PC, 10 year PCSM was 2% and CCM was 19%. Among healthy men with high risk PC, PCSM was 11% and CCM was 27%. In the group with moderate-to-severe comorbidities, CCM was 49, 59%, and 58% and PCSM was 1%, 3%, and 21% among those with low-, intermediate- and high-risk PC, respectively. Among these unhealthy men, 26% were treated by radical prostatectomy, of whom 45% had low-risk PC and 16% had high-risk PC. Among healthy men, 41% were treated by radical prostatectomy, of whom 54% and 9% had low- and high-risk PC, respectively. Conclusions: The risk of PCSM vs. CCM for older men is low, particularly for those with moderate-to-severe comorbidity; 49-59% had died from CCM within 10 years. Current evidence suggests that local therapy for PC is associated with a 25% reduction in PCSM, at best. Thus, with active surveillance, it is unlikely that PCSM would exceed 5-7% in those with low- and intermediate-risk PC. These results should inform elderly men and physicians about the risk of PCSM and CCM when deciding upon treatment for localized PC.

The Impact of Brachytherapy on Prostate Cancer–Specific Mortality for Definitive Radiation Therapy of High-Grade Prostate Cancer: A Population-Based Analysis

This population-based analysis compared prostate cancer-specific mortality (PCSM) in a cohort of patients with high-risk prostate cancer after nonsurgical treatment with external beam radiation therapy (EBRT), brachytherapy (BT), or combination (BT + EBRT). We identified from the Surveillance, Epidemiology and End Results database patients diagnosed from 1988 through 2002 with T1-T3N0M0 prostate adenocarcinoma of poorly differentiated grade and treated with BT, EBRT, or BT + EBRT. During this time frame, the database defined high grade as prostate cancers with Gleason score 8-10, or Gleason grade 4-5 if the score was not recorded. This corresponds to a cohort primarily with high-risk prostate cancer, although some cases where only Gleason grade was recorded may have included intermediate-risk cancer. We used multivariate models to examine patient and tumor characteristics associated with the likelihood of treatment with each radiation modality and the effect of radiation modality on PCSM. There were 12,745 patients treated with EBRT (73.5%), BT (7.1%), or BT + EBRT (19.4%) included in the analysis. The median follow-up time for all patients was 6.4 years. The use of BT or BT + EBRT increased from 5.1% in 1988-1992 to 31.4% in 1998-2002. Significant predictors of use of BT or BT + EBRT were younger age, later year of diagnosis, urban residence, and earlier T-stage. On multivariate analysis, treatment with either BT (hazard ratio, 0.66; 95% confidence interval, 0.49-0.86) or BT + EBRT (hazard ratio, 0.77; 95% confidence ratio, 0.66-0.90) was associated with significant reduction in PCSM compared with EBRT alone. In patients with high-grade prostate cancer, treatment with brachytherapy is associated with reduced PCSM compared with EBRT alone. Our results suggest that brachytherapy should be investigated as a component of definitive treatment strategies for patients with high-risk prostate cancer.

Screening for Prostate Cancer: A Review of the Evidence for the U.S. Preventive Services Task Force

Screening can detect prostate cancer at earlier, asymptomatic stages, when treatments might be more effective. To update the 2002 and 2008 U.S. Preventive Services Task Force evidence reviews on screening and treatments for prostate cancer. MEDLINE (2002 to July 2011) and the Cochrane Library Database (through second quarter of 2011). Randomized trials of prostate-specific antigen-based screening, randomized trials and cohort studies of prostatectomy or radiation therapy versus watchful waiting, and large observational studies of perioperative harms. Investigators abstracted and checked study details and quality using predefined criteria. Of 5 screening trials, the 2 largest and highest-quality studies reported conflicting results. One found that screening was associated with reduced prostate cancer-specific mortality compared with no screening in a subgroup of men aged 55 to 69 years after 9 years (relative risk, 0.80 [95% CI, 0.65 to 0.98]; absolute risk reduction, 0.07 percentage point). The other found no statistically significant effect after 10 years (relative risk, 1.1 [CI, 0.80 to 1.5]). After 3 or 4 screening rounds, 12% to 13% of screened men had false-positive results. Serious infections or urine retention occurred after 0.5% to 1.0% of prostate biopsies. There were 3 randomized trials and 23 cohort studies of treatments. One good-quality trial found that prostatectomy for localized prostate cancer decreased risk for prostate cancer-specific mortality compared with watchful waiting through 13 years of follow-up (relative risk, 0.62 [CI, 0.44 to 0.87]; absolute risk reduction, 6.1%). Benefits seemed to be limited to men younger than 65 years. Treating approximately 3 men with prostatectomy or 7 men with radiation therapy instead of watchful waiting would each result in 1 additional case of erectile dysfunction. Treating approximately 5 men with prostatectomy would result in 1 additional case of urinary incontinence. Prostatectomy was associated with perioperative death (about 0.5%) and cardiovascular events (0.6% to 3%), and radiation therapy was associated with bowel dysfunction. Only English-language articles were included. Few studies evaluated newer therapies. Prostate-specific antigen-based screening results in small or no reduction in prostate cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary. Agency for Healthcare Research and Quality.

Integrating Evidence and Individual Preferences Using a Web-Based Multi-Criteria Decision Analytic Tool

Annalisa© (AL) is a web-based decision-support template grounded in multi-criteria decision analysis (MCDA). It uses a simple expected value algorithm to calculate a score for each option by taking into account the individual's preferences for different criteria (as importance weights) and the evidence of the performance of each option on each criterion. Given the uncertainty surrounding the trade offs between benefits and harms for prostate cancer screening, this topic was chosen as the vehicle to introduce this new decision-support template. The aim of the study was to introduce a new decision-support template, AL, and to develop and pilot a decision-support tool for prostate cancer screening using it. A decision-support tool for prostate cancer screening (ALProst) was implemented in the AL template. ALProst incorporated evidence on both the benefits and the potential harms of prostate cancer screening (the 'attributes') from published randomized controlled trials (RCTs). Individual weights for each attribute were elicited during interviews. By combining the individual's preferences and the evidence, the best option for the user was identified on the basis of quantified scores. A convenience sample of computer-proficient primary-care physicians (general practitioners [GPs] in Australia) from the Sydney Metropolitan area (Australia) were invited to complete a face-to-face interview involving the decision-support tool. Preference for undergoing prostate-specific antigen testing for prostate cancer, both personally and for their patients, was sought prior to seeing the tool. After gaining hands-on experience with using the tool, GPs were asked to comment on the merits of the template and the tool. Preference for presenting the benefits of prostate cancer screening as the relative or absolute risk reduction in prostate cancer-specific mortality was also sought. Of 60 GPs approached, ten (six men and four women) completed an interview (16.7% response rate). Most GPs agreed/strongly agreed with positive statements about the ease with which they could use AL (seven GPs), and understand the information in, and format of, AL (nine and eight, respectively). Eight agreed/strongly agreed that ALProst would be a useful tool for discussing prostate cancer screening with their patients. GPs were also asked to nominate difficult clinical decisions that they, and their patients, have had to make; responses included cancer screening (including prostate cancer); treating patients with multiple illnesses/diseases; managing multiple cardiovascular disease risk factors; and managing patients who are receiving multiple medications. The common element was the need to consider multiple factors in making these complex decisions. AL is distinguishable from most other decision-support templates available today by its underlying conceptual framework, MCDA, and its power to combine individual preferences with evidence to derive the best option for the user quantitatively. It therefore becomes potentially useful for all decisions at all levels in the healthcare system. Moreover, it will provide a universal graphic 'language' that can overcome the burden to patients of encountering a plethora of widely varying decision aids for different conditions during their lifetime.

Screening for prostate cancer: an updated Cochrane systematic review

•To determine whether screening for prostate cancer reduces prostate cancer-specific mortality, impact on all-cause mortality and patient health-related quality of life. •An update to our 2006 Cochrane systematic review was performed by re-running an updated search of several databases, including MEDLINE and the Cochrane CENTRAL Register of Controlled Trials. • Articles were included if they were a randomized controlled trial (RCT) examining screening vs no screening for prostate cancer. Data was collected and analysed according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. •Five RCTs with a total of 341,351 participants were included in this updated Cochrane systematic review. All involved PSA testing, although the interval and threshold for further evaluation varied across trials. The age of participants was 50-74 years, with durations of patient follow-up of 7-15 years. •The methodological quality of three of the studies was assessed as posing a high risk of bias. •Meta-analysis of the five included studies indicated no statistically significant difference in prostate cancer-specific mortality between men randomized to screening and control [relative risk (RR) 0.95, 95% CI 0.85-1.07]. Sub-group analyses indicated that prostate cancer-specific mortality was not affected by age at which participants were screened. A pre-planned analysis of a 'core' age group of men aged 55-69 years from the largest RCT (European Randomised Study of Screening for Prostate Cancer) reported a significant 20% relative reduction in prostate cancer-specific mortality; (95% CI 0.65-0.98; absolute risk 0.71 per 1000 men). The number of men diagnosed with prostate cancer was significantly greater in men randomized to screening, compared with those randomized to control (RR 1.35, 95% CI 1.06-1.72). •Harms of screening included high rates of false-positive results for the PSA test, over-diagnosis and adverse events associated with transrectal ultrasonography guided biopsies such as infection, bleeding and pain. •Prostate cancer screening did not significantly decrease all-cause or prostate cancer-specific mortality in a combined meta-analysis of five RCTs. •Any benefits from prostate cancer screening may take > 10 years to accrue; therefore, men who have a life expectancy of < 10-15 years should be informed that screening for prostate cancer is not beneficial and has harms.

Fish consumption and prostate cancer risk: a review and meta-analysis

Prostate cancer incidence varies 60-fold globally, which suggests the roles of lifestyle and dietary factors in its cause. To our knowledge, a comprehensive assessment of the association between fish consumption and prostate cancer incidence and mortality has not been reported. We conducted a meta-analysis of fish intake and prostate cancer by focusing on the incidence of prostate cancer and prostate cancer-specific mortality and included subgroup analyses based on race, fish type, method of fish preparation, and high-grade and high-stage cancer. We searched MEDLINE and EMBASE databases (May 2009) for case-control and cohort studies that assessed fish intake and prostate cancer risk. Two authors independently assessed eligibility and extracted data. There was no association between fish consumption and a significant reduction in prostate cancer incidence [12 case-control studies (n = 5777 cases and 9805 control subjects), odds ratio (OR): 0.85; 95% CI: 0.72, 1.00; and 12 cohort studies (n = 445,820), relative risk (RR): 1.01; 95% CI: 0.90, 1.14]. It was not possible to perform a meta-analysis for high-grade disease (one case-control study, OR: 1.44; 95% CI: 0.58, 3.03), locally advanced disease (one cohort study, RR: 0.80; 95% CI: 0.61, 1.13), or metastatic disease (one cohort study, RR: 0.56; 95% CI: 0.37, 0.86). There was an association between fish consumption and a significant 63% reduction in prostate cancer-specific mortality [4 cohort studies (n = 49,661), RR: 0.37; 95% CI: 0.18, 0.74]. Our analyses provide no strong evidence of a protective association of fish consumption with prostate cancer incidence but showed a significant 63% reduction in prostate cancer-specific mortality.

Latest results from the UK trials evaluating prostate cancer screening and treatment: The CAP and ProtecT studies

The European Randomised Study of Screening for Prostate Cancer (ERSPC) demonstrated a significant reduction in prostate cancer-specific mortality. The ongoing Comparison Arm for ProtecT (CAP) cluster randomised controlled trial (RCT) evaluates prostate cancer screening effectiveness by comparing primary care centres allocated to a round of prostate specific antigen (PSA) testing (intervention) or standard clinical care. Over 550 centres (around 450,000 men) were randomised in eight United Kingdom areas (2002–2008). Intervention group participants were also eligible for the ProtecT (Prostate testing for cancer and Treatment) RCT evaluating active monitoring, radiotherapy and radical prostatectomy treatments for localised prostate cancer. In ProtecT, over 1500 of around 3000 men with prostate cancer were randomised from over 10,000 with an elevated PSA in around 111,000 attendees at clinics. Investigation of the psychological impact of screening in a sub-sample showed that 10% of men still experienced high distress up to 3 months following prostate biopsies (22/227), although most were relatively unaffected. The risk of prostate cancer with a raised PSA was lower if urinary symptoms were present (frequent nocturia odds ratio (OR) 0.44, 95% confidence interval (CI) 0.22–0.83) or if a repeat PSA decreased by ⩾20% prior to biopsy (OR 0.43, 95% CI 0.35–0.52). Men aged 45–49 years attended PSA clinics less frequently (442/1299, 34%) in a nested cohort with a cancer detection rate of 2.3% (10/442). The CAP and ProtecT trials (ISRCTN92187251 and ISRCTN20141217) will help resolve the prostate cancer screening debate, define the optimum treatment for localised disease and generate evidence to improve men’s health.

Prostate-Specific Antigen Screening and Prostate Cancer Mortality: Implications of a Randomized European Study

Evaluation of: Schroder FH, Hugosson J, Roobol MJ et al.: Screening and prostate-cancer mortality in a randomized European study. N. Engl. J. Med. 360, 1320–1328 (2009). Over the past two decades, prostate-specific antigen has become the primary modality for prostate cancer screening and has led to earlier detection. However, the question remains as to whether earlier detection actually leads to reductions in prostate cancer-specific mortality, especially since prostate cancer treatment can be associated with significant quality-of-life issues, including impotence and incontinence. Recently, long-term studies from Europe and the USA have demonstrated conflicting results with regard to this question. The European study demonstrated a 20% reduction in prostate cancer-specific mortality in men receiving routine screening, but concluded that 1410 men would need screening and 48 men would need treatment for prostate cancer in order to prevent one death. These findings demonstrated that prostate-specific antigen screening reduces prostate cancer-specific mortality, but reconfirmed the association of screening with a significant rate of overdiagnosis.

Prostate cancer mortality in relation to screening by prostate-specific antigen testing and digital rectal examination: a population-based study in middle-aged men

Although prostate cancer screening by measurement of serum prostate-specific antigen (PSA) and digital rectal examination (DRE) is common in clinical practice, the impact of such screening on prostate cancer-specific mortality remains uncertain. Data from a population-based case-control study in King County, Washington, among men aged 50-64 years (706 cases, 645 controls) were used to examine the relationships between PSA and DRE screening and fatal prostate cancer and other-cause mortality. Incident cases were diagnosed in 1993-1996, identified via the Seattle-Puget Sound SEER cancer registry and followed for vital status through 1 June 2007. Controls were ascertained by random digit dialing and frequency age-matched to cases. The screening variable used in this analysis was self-reported receipt of one or more PSA and/or DRE tests performed as part of a routine checkup in the five-year period before diagnosis or reference date. A smaller proportion of men with fatal prostate cancer had one or more PSA and/or DRE screening tests compared to controls, resulting in an adjusted odds ratios (OR) of 0.38 (95% CI 0.19-0.77). There was no association, however, between PSA and/or DRE screening and other-cause mortality (OR = 1.02; 95% CI 0.51-2.02). Results of this study suggest a reduction in prostate cancer-specific mortality associated with PSA and/or DRE screening in middle-aged men. Findings should be interpreted cautiously, however, as results are based on observational data. Further, the study was not able to separate the relative efficacy of PSA versus DRE screening.

The effect of androgen deprivation therapy (ADT) on lipid and HbA1C parameters

4562 Background: Studies suggest a reduction in prostate cancer-specific mortality with early versus delayed ADT. However, these same studies show no effect on overall mortality, raising the possibility of competing risk factors. Patients receiving ADT are known to be at increased risk for weight gain and truncal obesity, risk factors for insulin resistance and cardiovascular disease. In current practice, ADT is often administered prior to the development of clinical metastases and patients are treated for longer periods of time. Thus it is important to determine if ADT has an effect on lipid parameters. Methods: We analyzed a database collected during studies of Plenaxis compared to Lupron or to Lupron + Casodex. Patients were randomized in a 2:1 fashion to Plenaxis vs Lupron-based therapy. Fasting lipid profiles, glucose measurements, HbA1C levels and body weights were measured at baseline and on treatment days 85, 169. Fewer patients were available for analysis on days 253 and 336. 1,099 patients enrolled in the trial and 226 patients were on lipid lowering agents (statins) at the time of enrollment. One-sample t-tests were used to determine changes between baseline pretreatment values and each subsequent measurement for each treatment group and within each population (statins and no statins) using Bonferri-adjusted p-values of 0.01. Results: In all three treatment groups, there were significant increases in triglycerides, cholesterol and LDL between baseline and day 85 and baseline and day 169. There were also significant increases in HDL. All patients had increases in HbA1C from baseline to day 85. Only patients not on statins demonstrated statistically significant weight gain. No significant changes were observed in fasting glucose levels. Conclusions: ADT may affect both serum lipid values and HbA1C independent of statin therapy or the type of ADT. ADT may also result in increased HDL levels, thus the overall effect of ADT on serum lipids and cardiovascular risk is not certain. Although it is not possible to determine from this study whether these trends persist beyond 6 months, these data suggest that ADT therapy may be associated with risk factors for cardiovascular disease. Larger studies to investigate these parameters are warranted. No significant financial relationships to disclose.