Reduce Prostate Cancer-specific Mortality Research Articles

Navigating through the Controversies and Emerging Paradigms in Early Detection of Prostate Cancer: Bridging the Gap from Classic RCTs to Modern Population-Based Pilot Programs.

Over the last three decades, the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US-based Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening have steered the conversation around the early detection of prostate cancer. These two randomized trials assessed the effect of screening on prostate cancer disease-specific mortality. Elevated PSA levels were followed by a systematic sextant prostate biopsy. Standard repeat testing intervals were applied. After controversies from 2009 to 2016 due to contradicting results of the two trials, the results aligned in 2016 and showed that early PSA detection reduces prostate cancer-specific mortality. However, overdiagnosis rates of up to 50% were reported, and this sparked an intense debate on harms and benefits for almost 20 years. The balance between harms and benefits is highly debated and has initiated further research to investigate new ways of early detection. In the meantime, the knowledge and tools for the diagnostic algorithm improved. This is a continuously ongoing effort which focuses on individual risk-based screening algorithms that preserve the benefits of the purely PSA-based screening algorithms, while reducing the side effects. An important push towards investigating new techniques for early detection came from the European Commission on the 20th of September 2022. The European Commission published its updated recommendation to investigate prostate, lung, and gastric cancer early detection programs. This opened a new window of opportunity to move away from the trial setting to population-based early detection settings. With this review, we aim to review 30 years of historical evidence of prostate cancer screening, which led to the initiation of the 'The Prostate Cancer Awareness and Initiative for Screening in the European Union' (PRAISE-U) project, which aims to encourage the early detection and diagnosis of PCa through customized and risk-based screening programs.

Travel vaccines are strongly associated to reduced mortality in prostate cancer patients - a real effect or residual confounding?

Repurposing of existing drugs and vaccines for diseases that they were not originally intended for is a promising research field. Recently there has been evidence that oral cholera vaccine might be used in the treatment of inflammatory disease and some common cancers. Specifically, Ji et al showed that the administration of cholera vaccine after a prostate cancer diagnosis reduced prostate cancer specific mortality rates by almost 50%. In a cohort of men from Stockholm, Sweden, with more detailed cancer data and a higher coverage of exposure to vaccine, we replicated these findings using a marginal structural Cox model. We showed that administration of cholera vaccine after prostate cancer diagnosis is associated with a significant reduction in mortality (HR 0.46, 95% CI 0.31–0.69, p-value 0.0001) even after adjusting for all known confounders. However, the same effect (or even stronger) could be seen for several other traveling vaccines and malaria prophylaxis. Therefore, we conclude that this effect is most likely due to a healthy traveler bias and is an example of residual confounding.

Rethinking prostate cancer screening: could MRI be an alternative screening test?

In the past decade rigorous debate has taken place about population-based screening for prostate cancer. Although screening by serum PSA levels can reduce prostate cancer-specific mortality, it is unclear whether the benefits outweigh the risks of false-positive results and overdiagnosis of insignificant prostate cancer, and it is not recommended for population-based screening. MRI screening for prostate cancer has the potential to be analogous to mammography for breast cancer or low-dose CT for lung cancer. A number of potential barriers and technical challenges need to be overcome in order to implement such a programme. We discuss different approaches to MRI screening that could address these challenges, including abbreviated MRI protocols, targeted MRI screening, longer rescreening intervals and a multi-modal screening pathway. These approaches need further investigation, and we propose a phased stepwise research framework to ensure proper evaluation of the use of a fast MRI examination as a screening test for prostate cancer.

Central adiposity at diagnosis may reduce prostate cancer-specific mortality in African-Caribbean men with prostate cancer: 10-year follow-up of participants in a case-control study.

General and central adiposity are associated with the risk of developing prostate cancer (PCa), but the role of these exposures on PCa survival among men of African ancestry are less studied. This study aimed to investigate the association of anthropometry at diagnosis with all-cause and PCa-specific mortality and evaluate whether androgen deprivation therapy (ADT) modulated this risk. Associations between body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) at diagnosis and mortality were examined in 242 men with newly diagnosed PCa enrolled between 2005 and 2007 and re-evaluated 10.9years later. Multi-variable Cox proportional hazard models were used to examine associations of body size variables (using standard WHO cut-points and as continuous variables) with mortality, adjusted for sociodemographic characteristics, Gleason score, smoking, diabetes, primary treatment, and ADT therapy. A total of 139 deaths (all-cause mortality 6.98/100 person-years) occurred (PCa-specific deaths, 56; other causes, 66; causes unknown, 17). In multi-variable analysis BMI, WC and WHR categories at diagnosis were not associated with all-cause mortality even after adjusting for ADT. While WHR (but not BMI or WC) when included as a continuous variable predicted lower PCa-specific mortality (multi-variable adjusted WHR per 0.1 difference: HR, 0.50; 95%CI 0.28, 0.93), the effect disappeared with ADT covariance and excluding deaths within the first 2years. Our study suggests that central adiposity as measured by WHR may improve long-term survival among men of African ancestry. Metabolic studies to understand the mechanism for this association are needed.

Associations among statins, preventive care, and prostate cancer mortality

Increasing evidence indicates an association between statins and reduced prostate cancer-specific mortality (PCSM). However, significant bias may exist in these studies. One particularly challenging bias to assess is the healthy user effect, which may be quantified by screening patterns. We aimed to evaluate the association between statin use, screening, and PCSM in a dataset with detailed longitudinal information. We used the Veterans Affairs Informatics and Computing Infrastructure to assemble a cohort of patients diagnosed with prostate cancer (PC) between 2000 and 2015. We collected patient-level demographic, comorbidity, and tumor data. We also assessed markers of preventive care utilization including cholesterol and prostate specific antigen (PSA) screening rates. Patients were considered prediagnosis statin users if they had at least one prescription one or more years prior to PC diagnosis. We evaluated PCSM using hierarchical Fine-Gray regression models and all-cause mortality (ACM) using a cox regression model. The final cohort contained 68,432 men including 40,772 (59.6%) prediagnosis statin users and 27,660 (40.4%) nonusers. Prediagnosis statin users had higher screening rates than nonusers for cholesterol (90 vs. 69%, p < 0.001) and PSA (76 vs. 67%, p < 0.001). In the model which excluded screening, prediagnosis statin users had improved PCSM (SHR 0.90, 95% CI 0.84-0.97; p = 0.004) and ACM (HR 0.96, 95% CI 0.93-0.99; p = 0.02). However, after including cholesterol and PSA screening rates, prediagnosis statin users and nonusers showed no differences in PCSM (SHR 0.98, 95% CI 0.91-1.06; p = 0.59) or ACM (HR 1.02, 95% CI 0.98-1.05; p = 0.25). We found that statin users tend to have more screening than nonusers. When we considered screening utilization, we observed no relationship between statin use before a prostate cancer diagnosis and prostate cancer mortality.

Statin use, high cholesterol and prostate cancer progression; results from HCaP-NC.

Statin use is associated with lower advanced prostate cancer risk and reduced prostate cancer-specific mortality, but prior studies were conducted mainly in white men. We examined the effect of statin use on risk of prostate cancer progression in a population-based, minority-enriched cohort. We used data from prostate cancer cases (45% African American) diagnosed between 2004 and 2007 who participated in the Health Care Access and Prostate Cancer Treatment in North Carolina cohort (HCaP-NC). We abstracted statin use at diagnosis. Men reported if they had ever been diagnosed with high cholesterol. Multivariable Cox proportional hazards analysis was used to examine associations between statin use and risk of prostate cancer progression (biochemical recurrence or secondary treatment), overall and by race. In secondary analysis, we examined the association between high cholesterol and risk of progression, overall, and by statin use. Of 669 men, 244 (36%) were statin users at diagnosis. During 3.8 years median follow-up, 138 men experienced prostate cancer progression. There was no association between statin use and risk of progression, either overall (HR 1.03; 95%CI 0.72-1.46) or stratified by race. High cholesterol was inversely associated with risk of progression, particularly among statin users (HR 0.43; 95%CI 0.20-0.94; p-interaction = 0.22) and in men with higher perceived access to care (HR 0.57; 95%CI 0.36-0.90; p-interaction = 0.03). Study limitations included a relatively small sample size, short follow-up, and lack of data regarding post diagnosis statin use. Statin use at diagnosis was not associated with prostate cancer progression in the population-based, minority-enriched HCaP-NC. Greater healthcare engagement, including actively controlling serum cholesterol, may be linked to better prostate cancer-specific outcomes.

MP11-20 OTHER MALIGNANCIES PRIOR PROSTATE CANCER DIAGNOSIS – CLINICAL OUTCOME AFTER RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy II1 Apr 2018MP11-20 OTHER MALIGNANCIES PRIOR PROSTATE CANCER DIAGNOSIS – CLINICAL OUTCOME AFTER RADICAL PROSTATECTOMY Pierre Tennstedt, Peter Klippenstein, Thorsten Schlomm, Burkhard Beyer, Raisa S. Pompe, Uwe Michl, Georg Salomon, Alexander Haese, Budäus Lars, Hans Heinzer, Hendrik Isbarn, Thomas Steuber, Hartwig Huland, Derya Tilki, and Markus Graefen Pierre TennstedtPierre Tennstedt More articles by this author , Peter KlippensteinPeter Klippenstein More articles by this author , Thorsten SchlommThorsten Schlomm More articles by this author , Burkhard BeyerBurkhard Beyer More articles by this author , Raisa S. PompeRaisa S. Pompe More articles by this author , Uwe MichlUwe Michl More articles by this author , Georg SalomonGeorg Salomon More articles by this author , Alexander HaeseAlexander Haese More articles by this author , Budäus LarsBudäus Lars More articles by this author , Hans HeinzerHans Heinzer More articles by this author , Hendrik IsbarnHendrik Isbarn More articles by this author , Thomas SteuberThomas Steuber More articles by this author , Hartwig HulandHartwig Huland More articles by this author , Derya TilkiDerya Tilki More articles by this author , and Markus GraefenMarkus Graefen More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.386AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prior cancer is not a rarity in men diagnosed with prostate cancer. We examined oncological outcomes in these men. METHODS We retrospectively analyzed 24,814 who underwent radical prostatectomy (RP) between 1992 and 2016. Patients with another malignancy prior prostate cancer diagnosis were identified using patient information from medical records and self-administrated questionnaires. Statistical analysis was performed using R. Biochemical recurrence-free survival, metastasis-free survival, overall survival and prostate cancer-specific survival were analyzed using multivariable Cox proportional hazard, propensity score matching, competing risk and Kaplan Meier analyses. RESULTS Of all patients, 7% were diagnosed with other malignancy prior to prostate cancer (PCa) diagnosis. Patients with other malignancy prior PCa were older than patients without (median: 66yrs. vs. 64 yrs.), but showed no differences in the distribution of D'Amico risk groups, pT-stage and pathological Gleason score. The risk of biochemical recurrence (HR 1.01; 95%CI 0.91-1.13) and metastasis development (HR 0.9; 95%CI 0.7-1.1) after RP was similar. The risk to die by all-cause mortality was significantly increased (HR 1.7; 95%CI 1.4-2.0), while prostate cancer-specific survival was significantly lower (HR 0.4; 95%CI 0.2-0.7) in patients with additional malignancy. Cumulative risk of prostate cancerspecific mortality and other-cause mortality at 180 months was 2.5% vs. 5.4% and 31.6% vs. 6.6% for patient with other malignancy or without, respectively. CONCLUSIONS Patients with malignancies prior to prostate cancer have comparable tumor characteristics as patients without. Malignancies other than prostate cancer led to a higher other-cause mortality but a reduced prostate cancer-specific mortality. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e134 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Pierre Tennstedt More articles by this author Peter Klippenstein More articles by this author Thorsten Schlomm More articles by this author Burkhard Beyer More articles by this author Raisa S. Pompe More articles by this author Uwe Michl More articles by this author Georg Salomon More articles by this author Alexander Haese More articles by this author Budäus Lars More articles by this author Hans Heinzer More articles by this author Hendrik Isbarn More articles by this author Thomas Steuber More articles by this author Hartwig Huland More articles by this author Derya Tilki More articles by this author Markus Graefen More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Significant association of brachytherapy boost with reduced prostate cancer-specific mortality in contemporary patients with localized, unfavorable-risk prostate cancer.

A randomized trial recently found that adding brachytherapy (BT) boost to external beam radiation therapy (EBRT) improves biochemical recurrence-free survival but not prostate cancer-specific mortality (PCSM). We investigated the relationship between BT boost and PCSM in a modern cohort from a large population-based database. We conducted an analysis of patients in Surveillance, Epidemiology, and End Results diagnosed with intermediate- or high-risk prostate cancer in 2004-2011, treated with EBRT only or EBRT + BT. The cumulative incidence of PCSM was evaluated in the presence of other-cause mortality as a competing risk. Propensity score matching and multivariable Fine and Gray proportional hazard models were used to evaluate the association of combined modality RT on PCSM. A total of 52,535 patients were identified, of which 19.6% were treated with EBRT + BT. One-third of cases were high-risk. On multivariable analysis, the adjusted hazard ratio (AHR) of PCSM for EBRT + BT vs. EBRT alone was 0.69 (95% confidence interval [CI], 0.55-0.87, p = 0.002), and the adjusted incidence of PCSM was 1.8% vs. 2.7% at 8 years, respectively. In subgroup analyses, the AHR for PCSM was also significantly reduced with EBRT + BT for high-risk disease (AHR 0.70; 95% CI, 0.52-0.94, p = 0.02; adjusted incidence of PCSM at 8 years, 5.4% vs. 7.6%), but not for intermediate-risk disease. BT boost was associated with a moderate reduction to PCSM in men with localized unfavorable-risk prostate cancer. Those most likely to benefit are younger patients with high-risk disease.

Impact of beta-blockers on prostate cancer mortality: a meta-analysis of 16,825 patients.

IntroductionIncreasing evidence suggests that beta-blocker use might be associated with reduced mortality in prostate cancer patients. To provide a quantitative assessment of this association, we pooled data available to examine the association between beta-blocker use and mortality of prostate cancer.MethodsWe identified studies by a literature search of MEDLINE (from 1 January 1966) and EMBASE (from 1 January 1974), through 10 September 2014, and by searching the reference lists of pertinent articles. Two authors independently screened and reviewed the eligibility of each study. The primary outcomes were prostate cancer-specific mortality and all-cause mortality.ResultsA total of four studies including 16,825 patients were included in this meta-analysis. Analysis of all studies showed that beta-blocker use was associated with reduced prostate cancer-specific mortality (hazard ratio =0.85, 95% confidence interval =0.77–0.94), without any heterogeneity between studies (Q=3.59, I 2=16.5%, P=0.309). However, we observed no association with all-cause mortality (hazard ratio =0.97, 95% confidence interval =0.90–1.04). There was also no evidence of the presence of significant heterogeneity between the four studies (Q=2.48, I 2=0.0%, P=0.480).ConclusionThese findings indicate that beta-blocker use was associated with reduced cancer-specific mortality among prostate cancer patients taking beta-blockers.

Can pelvic lymph node dissection be omitted in intermediate-risk prostate cancer patients? A SEER-based comparative study using inverse-probability-of-treatment weighting.

95 Background: To investigate whether pelvic lymph node dissection (PLND) reduces prostate cancer specific mortality (PCSM) in surgically-treated men with intermediate-risk prostate cancer (Pca). Methods: We identified 44,112 men diagnosed with intermediate-risk Pca from 2004-2009 in Surveillance, Epidemiology and End Results Program (SEER). We used inverse-probability-of-treatment weighting (IPTW) to adjust for baseline characteristics between PLND + radical prostatectomy (RP, N=26,571), versus RP alone (N=17,541) groups; Cox competing-risk model and propensity score-adjusted analyses were used for validation. Gleason scores were based on prostatectomy since biopsy scores were not available for RP-treated patients in SEER from 2004-2009. Results: After a median follow-up of 54 months, there was no survival benefit associated with PLND + RP compared to RP alone (Gray's test, P=0.30). After IPTW adjustment for baseline characteristics, PLND was still not associated with PCSM (AHR: 0.93, 95% CI: 0.65-1.33). This result was consistent with propensity score-adjusted model (AHR=1.05, 95% CI: 0.71-1.55) and the Cox competing-risk model (AHR=1.06, 95% CI: 0.71-1.57). Of men who received RP with PLND, 502 men (1.9%) had pathologically positive lymph nodes, which were associated with a higher risk for PCSM (AHR: 4.02, 95%CI: 1.83-8.84). Conclusions: PLND with RP was not associated with reduced PCSM compared with RP alone in men with intermediate-risk disease, suggesting that PLND is diagnostic but not therapeutic in this patient population. However, a caveat of this study is that risk group was defined by pathologic Gleason score; the 5% of clinically intermediate risk patients who are typically found to have Gleason 8-10 disease at prostatectomy could not be included in this analysis. [Table: see text]

β-Adrenergic Receptor Signaling in Prostate Cancer

Enhanced sympathetic signaling, often associated with obesity and chronic stress, is increasingly acknowledged as a contributor to cancer aggressiveness. In prostate cancer, intact sympathetic nerves are critical for tumor formation, and sympathectomy induces apoptosis and blocks tumor growth. Perineural invasion, involving enrichment of intra-prostatic nerves, is frequently observed in prostate cancer and is associated with poor prognosis. β2-adrenergic receptor (ADRB2), the most abundant receptor for sympathetic signals in prostate luminal cells, has been shown to regulate trans-differentiation of cancer cells to neuroendocrine-like cells and to affect apoptosis, angiogenesis, epithelial–mesenchymal transition, migration, and metastasis. Epidemiologic studies have shown that use of β-blockers, inhibiting β-adrenergic receptor activity, is associated with reduced prostate cancer-specific mortality. In this review, we aim to present an overview on how β-adrenergic receptor and its downstream signaling cascade influence the development of aggressive prostate cancer, primarily through regulating neuroendocrine differentiation.

Maintenance Therapy Containing Metformin and/or Zyflamend for Advanced Prostate Cancer: A Case Series.

Metformin is derived from galegine, a natural ingredient, and recent studies have suggested that metformin could enhance the antitumor effects of hormone ablative therapy or chemotherapy and reduce prostate cancer-specific mortality. Zyflamend is a combination of herbal extracts that reduces inflammation and comprises turmeric, holy basil, green tea, oregano, ginger, rosemary, Chinese goldthread, hu zhang, barberry, and basil skullcap. We propose a maintenance regimen with metformin and/or Zyflamend that targets cancer stem cells and the tumor microenvironment to keep the cancer dormant and prevent it from activation from dormancy. Herein, we report the clinical course of four patients who experienced a clinical response after treatment with metformin and/or Zyflamend.

Validation of proposed prostate cancer biomarkers with gene expression data: a long road to travel

Biomarkers are important for early detection of cancer, prognosis, response prediction, and detection of residual or relapsing disease. Special attention has been given to diagnostic markers for prostate cancer since it is thought that early detection and surgery might reduce prostate cancer-specific mortality. The use of prostate-specific antigen, PSA (KLK3), has been debated on the base of cohort studies that show that its use in preventive screenings only marginally influences mortality from prostate cancer. Many groups have identified alternative or additional markers, among which PCA3, in order to detect early prostate cancer through screening, to distinguish potentially lethal from indolent prostate cancers, and to guide the treatment decision. The large number of markers proposed has led us to the present study in which we analyze these indicators for their diagnostic and prognostic potential using publicly available genomic data. We identified 380 markers from literature analysis on 20,000 articles on prostate cancer markers. The most interesting ones appeared to be claudin 3 (CLDN3) and alpha-methysacyl-CoA racemase highly expressed in prostate cancer and filamin C (FLNC) and keratin 5 with highest expression in normal prostate tissue. None of the markers proposed can compete with PSA for tissue specificity. The indicators proposed generally show a great variability of expression in normal and tumor tissue or are expressed at similar levels in other tissues. Those proposed as prognostic markers distinguish cases with marginally different risk of progression and appear to have a clinically limited use. We used data sets sampling 152 prostate tissues, data sets with 281 prostate cancers analyzed by microarray analysis and a study of integrated genomics on 218 cases to develop a multigene score. A multivariate model that combines several indicators increases the discrimination power but does not add impressively to the information obtained from Gleason scoring. This analysis of 10 years of marker research suggests that diagnostic and prognostic testing is more difficult in prostate cancer than in other neoplasms and that we must continue to search for better candidates.Electronic supplementary materialThe online version of this article (doi:10.1007/s10555-013-9470-4) contains supplementary material, which is available to authorized users.

Low-dose aspirin and survival in men with prostate cancer: a study using the UK Clinical Practice Research Datalink

Aspirin use is associated with reduced risk of, and death from, prostate cancer. Our aim was to determine whether low-dose aspirin use after a prostate cancer diagnosis was associated with reduced prostate cancer-specific mortality. A cohort of newly diagnosed prostate cancer patients (1998-2006) was identified in the UK Clinical Practice Research Datalink (confirmed by cancer registry linkage). A nested case-control analysis was conducted using conditional logistic regression to compare aspirin usage in cases (prostate cancer deaths) with up to three controls (matched by age and year of diagnosis). Post-diagnostic low-dose aspirin use was identified in 52% of 1,184 prostate cancer-specific deaths and 39% of 3,531 matched controls (unadjusted OR 1.51, 95% CI 1.19, 1.90; p<0.001). After adjustment for confounders including treatment and comorbidities, this association was attenuated (adjusted OR 1.02 95% CI 0.78, 1.34; p=0.86). Adjustment for estrogen therapy accounted for the majority of this attenuation. There was also no evidence of dose-response association after adjustments. Compared with no use, patients with 1-11 prescriptions and 12 or more prescriptions had adjusted ORs of 1.07 (95% CI 0.78, 1.47; p=0.66) and 0.97 (95% CI 0.69, 1.37; p=0.88), respectively. There was no evidence of a protective association between low-dose aspirin use in the year prior to diagnosis and prostate cancer-specific mortality (adjusted OR1.04 95% CI 0.89, 1.22; p=0.60). We found no evidence of an association between low-dose aspirin use before or after diagnosis and risk of prostate cancer-specific mortality, after potential confounders were accounted for, in UK prostate cancer patients.

Radical prostatectomy does not improve survival compared to observation for localised prostate cancer in a prospective randomised trial

Commentary on: Wilt TJ, Brawer MK, Jones KM, et al. Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J...

RETRACTED: High-Dose Conformal Radiotherapy Reduces Prostate Cancer–Specific Mortality: Results of a Meta-analysis

To determine in a meta-analysis whether prostate cancer-specific mortality (PCSM), biochemical or clinical failure (BCF), and overall mortality (OM) in men with localized prostate cancer treated with conformal high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT). The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing conformal HDRT with CDRT for localized prostate cancer. Five randomized, controlled trials (2508 patients) that met the study criteria were identified. Pooled results from these randomized, controlled trials showed a significant reduction in the incidence of PCSM and BCF rates at 5 years in patients treated with HDRT (p = 0.04 and p < 0.0001, respectively), with an absolute risk reduction (ARR) of PCSM and BCF at 5 years of 1.7% and 12.6%, respectively. Two trials evaluated PCSM with 10 years of follow up. The pooled results from these trials showed a statistical benefit for HDRT in terms of PCSM (p = 0.03). In the subgroup analysis, trials that used androgen deprivation therapy (ADT) showed an ARR for BCF of 12.9% (number needed to treat = 7.7, p < 0.00001), whereas trials without ADT had an ARR of 13.6% (number needed to treat = 7, p < 0.00001). There was no difference in the OM rate at 5 and 10 years (p = 0.99 and p = 0.11, respectively) between the groups receiving HDRT and CDRT. This meta-analysis is the first study to show that HDRT is superior to CDRT in preventing disease progression and prostate cancer-specific death in trials that used conformational technique to increase the total dose. Despite the limitations of our study in evaluating the role of ADT and HDRT, our data show no benefit for HDRT arms in terms of BCF in trials with or without ADT.

The confusion surrounding prostate cancer screening faced by family physicians

Primary care physicians, in the forefront of prostate cancer screening, are challenged with confusing and often conflicting guidelines. The lack of uniformity on the optimal prostate cancer screening recommendations stems from conflicting interpretations of the results of recent screening studies. Unfortunately, two large trials, initially planned to define the usefulness of screening, were both significantly flawed and provided conflicting results and further fueled the debate.1,2 Not surprisingly, these results have led to a lack of consensus on the best screening practices among various medical associations and guideline committees. The limitations of prostate-specific antigen (PSA) itself as a screening tool have precluded standardized and widely adopted guidelines from being developed to date.3 Several guidelines have been established; the American Urological Association and Canadian Urological Association favour the inclusion of PSA testing as a tool for prostate cancer screening,4,5 while the Canadian Task Force on Preventative Health Care and the U.S Preventative Services Task Force (USPSTF) recommend against screening.6,7 These are in addition to provincial and advocacy organizations’ recommendations – it is no wonder physicians and patients are confused. Controversy surrounding optimal prostate cancer screening for primary care physicians was renewed with the recent publication of the USPSTF statement, which attracted considerable media attention. Their recommendations were against PSA-based screening for prostate cancer in all men. PSA screening was labelled a “Grade D” recommendation, which states that there is moderate or high certainty that PSA screening has no benefit, or that the harms outweigh any benefits.7 It is important to stress the results of the European Randomized Study of Screening for Prostate Cancer, considered the best PSA screening study to date. It was demonstrated that screening reduced the rate of prostate cancer death by 20%, with additional two-year follow-up consolidating these findings.2,8 Being the largest trial to date and suffering fewer methodological limitations than its U.S. counterpart, this European study represents “level one” evidence that screening does reduce prostate cancer-specific mortality. It was proposed that the modest benefit conveyed should support a “grade C” recommendation; this leaves the decision regarding PSA screening to the patient and primary care physician.9 The results of the survey in this issue of CUAJ provide evidence to suggest that Ontario family physicians use their own management strategies in deciding whether to offer prostate cancer screening to their patients.10 As well, there is apparent heterogeneity in the use of screening, as well as in the attitudes concerning its value. Interestingly, although almost 80% screen for prostate cancer, a considerably lower percentage of family physicians believe that the benefits of screening outweigh its risks, which suggests that other patient factors prompt the decision to screen. Obviously, a primary weakness of the paper is the poor response rate. The results do, however, provide a glimpse into the practice patterns of physicians directly involved in screening. It is likely that the results can be extrapolated to the rest of the country, as these findings have been corroborated by other papers addressing the same question in Newfoundland and British Columbia.11,12 Most importantly, the survey shows the need not only to provide clear and evidence-based guidelines, but also for better education on prostate cancer screening for family physicians. A significant onus of responsibility for this lies with our own association and members. It highlights the importance of relaying our own CUA guidelines to family physicians, and educating them regarding the evidence and considerations surrounding prostate cancer screening.

The importance of combined radiation and endocrine therapy in locally advanced prostate cancer

The importance of combined radiation and endocrine therapy in locally advanced 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.

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.