Risk Of Prostate Cancer-specific Death Research Articles

Evaluating the impact of pre-diagnostic use of statins and testosterone replacement therapy on mortality outcomes in older men with hormone-related cancers: Surveillance, Epidemiology, and End Results-Medicare 2007-2015.

The link between the pre-diagnostic use of statins and testosterone replacement therapy and their impact on hormone-related cancers, prostate cancer, colorectal cancer, and male breast cancer survival remains a topic of controversy. Further, there is a knowledge gap concerning the joint effects of statins and testosterone replacement therapy on hormone-related cancer survival outcomes. To examine the independent and joint effects of pre-diagnostic use of statins and testosterone replacement therapy on the risk of all-cause and cause-specific mortality among older men diagnosed with hormone-related cancers, including prostate cancer, colorectal cancer, and male breast cancer. In 41,707 men (≥65 years) of Surveillance, Epidemiology, and End Results-Medicare 2007-2015, we identified 31,097 prostate cancer, 10,315 colorectal cancer, and 295 male breast cancer cases. Pre-diagnostic prescription of statins and testosterone replacement therapy was ascertained and categorized into four groups (Neither users, statins alone, testosterone replacement therapy alone, and Dual users). Multivariable-adjusted Cox proportional hazards and competing-risks (Fine-Gray subdistribution hazard) models were conducted. No significant associations were found in Cox-proportional hazard models for hormone-related cancers. However, in the Fine-Gray competing risk models among high-grade hormone-related cancers, statins alone had an 11% reduced risk of hormone-related cancer-specific death (hazard ratio: 0.89; 95% confidence interval: 0.81-0.99; p 0.0451). In the prostate cancer cohort with both statistical models, the use of testosterone replacement therapy alone had a 24% lower risk of all-cause death (hazard ratio: 0.76; 95% confidence interval: 0.59-0.97; p 0.0325) and a 57% lower risk of prostate cancer-specific death (hazard ratio: 0.43; 95% confidence interval: 0.24-0.75; p 0.0029). Similar inverse associations were found among aggressive prostate cancer cases with testosterone replacement therapy alone and statins alone. No significant associations were found in the colorectal cancer and male breast cancer sub-groups. Pre-diagnostic use of statins and testosterone replacement therapy showed a survival benefit with reduced mortality in high-grade hormone-related cancer patients (only statins) and aggressive prostate cancer patients in both statistical models. Findings of testosterone replacement therapy use in aggressive prostate cancer settings could facilitate clinical trials. Further studies with extended follow-up periods are needed to substantiate these findings.

Ten-years outcome analysis in patients with clinically localized prostate cancer treated by radical prostatectomy or external beam radiation therapy.

PurposeSince there was no consensus on treatment options for localized prostate cancer, we performed a retrospective study to compare the long-term survival benefit of radiotherapy (RT) versus laparoscopic radical prostatectomy (LRP) in Taiwan.Methods218 patients with clinically localized prostate cancer treated between 2008 and 2017 (64 with LRP and 154 with RT) were enrolled in this study. The outcomes of RT and LRP were assessed after patients were stratified according to Gleason score, stage, and risk group. Crude survival, prostate cancer-specific survival, and metastasis-free survival were evaluated using the log-rank test.ResultsThe 5-year crude survival rate was 93.3% in the LRP group and 59.3% in the RT group. A significant survival benefit was found in the LRP group compared with the RT group (p = 0.004). Furthermore, significant differences were found in disease-specific survival (93.3% vs. 64.7%, p = 0.022) and metastasis-free survival (48% vs. 40.2%, p = 0.045) between the LRP and RT groups.ConclusionsMen with localized prostate cancer treated initially with LRP had a lower risk of prostate cancer-specific death and metastases compared with those treated with RT.

Development and validation of a quantitative reactive stroma biomarker (qRS) for prostate cancer prognosis

To develop and validate a new tissue-based biomarker that improves prediction of outcomes in localized prostate cancer by quantifying the host response to tumor. We use digital image analysis and machine learning to develop a biomarker of the prostate stroma called quantitative reactive stroma (qRS). qRS is a measure of percentage tumor area with a distinct, reactive stromal architecture. Kaplan Meier analysis was used to determine survival in a large retrospective cohort of radical prostatectomy samples. qRS was validated in two additional, distinct cohorts that include international cases and tissue from both radical prostatectomy and biopsy specimens. In the developmental cohort (Baylor College of Medicine, n=482), patients whose tumor had qRS > 34% had increased risk of prostate cancer-specific death (HR 2.94; p=0.039). This result was replicated in two validation cohorts, where patients with qRS > 34% had increased risk of prostate cancer-specific death (MEDVAMC; n=332; HR 2.64; p=0.02) and also biochemical recurrence (Canary; n=988; HR 1.51; p=0.001). By multivariate analysis, these associations were shown to hold independent predictive value when compared to currently used clinicopathologic factors including Gleason score and PSA. qRS is a new, validated biomarker that predicts prostate cancer death and biochemical recurrence across three distinct cohorts. It measures host-response rather than tumor-based characteristics, and provides information not represented by standard prognostic measurements.

Self-reported Prostate Cancer Progression Status Is Accurate: A Validation Study.

Studies of prostate cancer progression are important for discovering risk factors that may increase the risk of prostate cancer-specific death; however, little is known about the validity of self-reported prostate cancer progression. We conducted a validation study of self-reported prostate cancer progression in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and in a prostate cancer cohort enrolled in a Fred Hutchinson Cancer Research Center (FHCRC)-based study. We calculated measures of validity for self-reported progression, including sensitivity, specificity, positive predictive value, and negative predictive value using medical records as the gold standard. Our results suggest that ascertaining prostate cancer progression-related events (i.e., prostate-specific antigen elevation, recurrence, metastasis, and use of secondary treatment) through self-report may be a viable option for identifying men whose disease has progressed after diagnosis or initial therapy, particularly when multiple questions related to progression are included in the assessment (aggregate cluster of questions: sensitivity = 0.76 [PLCO]; 0.93 [FHCRC], specificity = 0.80 [PLCO]; 0.97 [FHCRC]). With an aggregate positive predictive value of 0.50 (PLCO), however, our PLCO results suggest that additional medical record verification of self-reported progression events may be necessary to rule out false positives. Most individuals reporting no evidence of progression-related events, however, were true negatives (aggregate negative predictive value = 0.92 [PLCO]; 0.98 [FHCRC]). Thus, there may be limited utility to investing resources in chart review to confirm self-reported nonevents. Ascertaining prostate cancer progression through self-report provides an efficient and valid approach to enhancing existing cancer cohorts with updated data on progression status. See video abstract at, http://links.lww.com/EDE/B658.

Volume of Gleason pattern 4 stratifies risk of metastasis and death in patients with Gleason score 3+5=8/5+3=8 positive prostate core biopsies

Implementation of Grade Groups (GrGrs) has been widely accepted for reporting prostate cancer grade since the 2014 International Society of Urological Pathology consensus meeting. Despite their undisputed value for risk stratification, some GrGr are, a priori, quite heterogeneous in that they contain multiple Gleason patterns (GPs). In this regard, the prognostic significance of GP5 in biopsies with highest GrGr4 is uncertain and evaluated in this study. A search of all core biopsies positive for prostate cancer reviewed after 2005 was performed, and 71 cases with highest GrGr4 containing GP5 (i.e., 3+5=8 or 5+3=8; referred to as GrGr4/GP5pos) eligible for inclusion were identified. In addition, 95 core biopsy cases with highest GrGr4 and no GP5 (i.e, 4+4=8; referred to as GrGr4/GP5neg) were selected for comparison. Multiple pathologic parameters, including volume and amount of GP4, and clinical variables were collected to evaluate the influence of GP5 on disease recurrence, development of metastases, and disease-specific death. GrGr4/GP5pos cases did not show, as a group, statistically significant differences in prostatectomy findings, disease recurrence, metastases, and disease-specific mortality when compared with GrGr4/GP5neg cases. In addition, the risk of all outcomes evaluated in the study did not differ between the whole GrGr4/GP5pos and GrGr4/GP5neg groups. However, Kaplan-Meier analysis found that GrGr4/GP5pos cases with a significant amount of GP4 did show a higher risk of prostate cancer-specific death as well as bone and visceral metastases. Univariate Cox regression demonstrated that preoperative prostate specific antigen (PSA), total number of positive cores, and global GrGr5 were also associated with a higher chance of disease-specific death. In a multivariate model, only global GrGr5 and PSA >20ng/dL remained statistically significant. This study suggests that the mere presence of GP5 in core biopsies with highest GrGr4 disease may not portend a worse prognosis. In these cases, accounting for the case-wide volume of GP4 by reporting a global GrGr appears to be more relevant as it identifies a subset of GrGr4/GP5pos patients with global GrGr5 who have a higher risk of metastases and prostate cancer-specific mortality.

Taxane-based chemohormonal therapy for metastatic hormone-sensitive prostate cancer.

There has been considerable development in the treatment of advanced prostate cancer over the last decade. A number of agents, including docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and sipuleucel-T, have been reported to improve outcomes in men with castration-resistant disease and their use is being explored in hormone-sensitive prostate cancer. To assess the effects of early taxane-based chemohormonal therapy for newly diagnosed, metastatic, hormone-sensitive prostate cancer. We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, Google Scholar, and Web of Science), trials registries, other sources of grey literature, and conference proceedings, up to 10 August 2018. We applied no restrictions on publication language or status. We included randomized or quasi-randomized controlled trials in which participants were administered taxane-based chemotherapy with systemic androgen deprivation therapy (ADT) within 120 days of beginning ADT versus ADT alone at the time of diagnosis of metastatic disease. Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model. We rated the quality of evidence according to the GRADE approach. The search identified three studies in which 2,261 participants were randomized to receive either ADT alone, or taxane-based chemotherapy at a dose of 75mg per square meter of body surface area at three-weekly intervals for six or nine cycles in addition to ADT.Primary outcomesEarly treatment with taxane-based chemotherapy in addition to ADT probably reduces death from any cause compared to ADT alone (hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.68 to 0.87; moderate-certainty evidence); this would result in 94 fewer deaths per 1,000 men (95% CI 51 to 137 fewer deaths). We downgraded the certainty of evidence due to study limitations related to potential performance bias. Based on the results of one study with 375 participants, the addition of taxane-based chemotherapy to ADT may increase the incidence of Grade III to V adverse events compared to ADT alone (risk ratio (RR) 2.98, 95% CI 2.19 to 4.04; low-certainty evidence); this would result in 405 more Grade III to V adverse events per 1,000 men (95% CI 243 to 621 more events). We downgraded the certainty of evidence due to study limitations and imprecision.Secondary outcomesEarly taxane-based chemotherapy in addition to ADT probably reduces the risk of prostate cancer-specific death (RR 0.79, 95% CI 0.70 to 0.89; moderate-certainty evidence). We downgraded the certainty of evidence due to study limitations related to potential performance and detection bias. The addition of taxane-based chemotherapy also probably reduces disease progression compared to ADT alone (HR 0.63, 95% CI 0.56 to 0.71; moderate-certainty evidence). We downgraded the certainty of evidence because of study limitations related to potential performance bias. The addition of taxane-based chemotherapy to ADT may result in a large increase in the risk of treatment discontinuation due to adverse events (RR 79.41, 95% CI 4.92 to 1282.78; low-certainty evidence). We downgraded the certainty of evidence due to study limitations and imprecision. This estimate is derived from a single study with no events in the control arm but a discontinuation rate of 20% in the intervention arm. Taxane-based chemotherapy may increase the incidence of adverse events of any grade (RR 1.11, 95% CI 1.06 to 1.17; low-certainty evidence). We downgraded our assessment of the certainty of evidence due to very serious study limitations. There may be a small improvement, which may not be clinically important, in quality of life at 12 months with combination treatment (mean difference (MD) 2.85 on the Functional Assessment of Cancer Therapy-Prostate scale, 95% CI 0.13 higher to 5.57 higher; low-certainty evidence). We downgraded the certainty of evidence for study limitations related to potential performance, detection and attrition bias. Compared to ADT alone, the early (within 120 days of beginning ADT) addition of taxane-based chemotherapy to ADT for hormone-sensitive prostate cancer probably prolongs both overall and disease-specific survival and delays disease progression. There may be an increase in toxicity with taxane-based chemotherapy in combination with ADT. There may also be a small, clinically unimportant improvement in quality of life at 12 months with taxane-based chemotherapy and ADT treatment.

PD60-12 PROGNOSTIC VALUE OF COMBINED ANALYSIS OF PRO-NPY AND ERG PROTEIN EXPRESSION IN PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Markers III1 Apr 2018PD60-12 PROGNOSTIC VALUE OF COMBINED ANALYSIS OF PRO-NPY AND ERG PROTEIN EXPRESSION IN PROSTATE CANCER Gitte Kristensen, Martin Andreas Roeder, Kasper Drimer Berg, Johanna Elversang, Birgitte Groenkaer Toft, and Klaus Brasso Gitte KristensenGitte Kristensen More articles by this author , Martin Andreas RoederMartin Andreas Roeder More articles by this author , Kasper Drimer BergKasper Drimer Berg More articles by this author , Johanna ElversangJohanna Elversang More articles by this author , Birgitte Groenkaer ToftBirgitte Groenkaer Toft More articles by this author , and Klaus BrassoKlaus Brasso More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2824AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Apart from PSA, only few biomarkers reflecting prostate cancer (PCa) biology are introduced. Discovery of new biomarkers could refine prognostication for patients at risk of biochemical failure (BF) following radical prostatectomy (RP). Neuropeptide Y (NPY) and its precursor pro-NPY may be important factors for mitogenic and angiogenic activity. High expression of pro-NPY in ERG positive tumors has previously shown to be associated with increased risk of PCa specific death in men on watchful-waiting. This study aimed to investigate if combined analysis of pro-NPY and ERG protein expression in tumor tissue were associated with BF for men undergoing RP. METHODS The study included 311 consecutive patients, who underwent RP from Jan. 1st 2002 to Dec. 31st 2005 at the Department of Urology, Rigshospitalet, Copenhagen, Denmark. Pro-NPY and ERG protein expression were analyzed using immunohistochemistry (IHC; anti-pro-NPY: HPA044572; anti-ERG: EPR3864) on tissue arrays with tumor tissue from the RP specimens. pro-NPY immunoreactivity (IR) was scored semiquantitative as low (IR negative or weak) or high (IR moderate or strong). ERG IR was scored as negative or positive. Assessment of the IHC staining was done blinded. Clinicopathological information were collected from the medical records. Risk of BF was analyzed using multiple cause-specific Cox regression and stratified cumulative incidences (Aalen-Johansen method) using competing risk assessment. Death without BF was treated as a competing event. RESULTS After median 11.6 years follow-up, 147 men experienced BF. In total, 266 patients (85.5%) had high and 45 (14.5%) had low pro-NPY IR whereas 195 (62.7%) were ERG positive and 116 (37.3%) were ERG negative. The 10-year cumulative incidence of BF was 48.7% (95% CI: 33.7-63.7) in the pro-NPY low group compared with 44.1% (95% CI: 37.9-50.4) in the pro-NPY high group. In the multiple cause-specific Cox regression analysis pro-NPY high was not found associated with BF (HR: 0.82; 95% CI 0.5-1.4; p=0.49). The 10-year cumulative incidence for BF was 48.6% (95% CI: 33.2-64.0) in the ERG negative pro-NPY low group compared with 41.8% (95% CI: 34.6-49.0) in the ERG positive pro-NPY high group. The combination of ERG positive and pro-NPY high was not associated with a risk of BF in the multiple cause-specific Cox regression analysis (HR: 1.02; 95% CI 0.6-1.7; p=0.94). CONCLUSIONS pro-NPY expression alone or combined with ERG status was not found associated with risk of BF following RP. Analyses of association with time to initiation of secondary treatments and death are ongoing. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1151 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Gitte Kristensen More articles by this author Martin Andreas Roeder More articles by this author Kasper Drimer Berg More articles by this author Johanna Elversang More articles by this author Birgitte Groenkaer Toft More articles by this author Klaus Brasso More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract 1263: Dietary patterns after prostate cancer diagnosis in relation to disease-specific and total mortality

Abstract Objective: We investigated the relation of post-diagnostic dietary patterns with prostate cancer-specific and all-cause mortality. Methods: 926 men participating in the Physicians' Healthy Study diagnosed with non-metastatic prostate cancer completed a food frequency questionnaire (FFQ) a median of 5.1 years after diagnosis, and were followed thereafter to assess mortality for a median of 9.9 years. Two dietary patterns, a Prudent and a Western pattern, were identified using principal component analysis. Multivariate Cox proportional hazards regression was used to estimate the relative hazard of prostate cancer-specific and all-cause mortality in relation to post-diagnostic dietary pattern scores. Models were adjusted for age at diagnosis, time between diagnosis and FFQ completion, energy intake, vigorous exercise, BMI, smoking status, and a modified D'Amico risk score. Results: We identified 333 deaths, 56 due to prostate cancer, during 8,093 person-years of follow-up. The Prudent pattern was characterized by higher intake of vegetables, fruits, fish, legumes and whole grains, while the Western pattern was characterized by higher intake of processed and red meats, potatoes, high-fat dairy and refined grains. Men in the highest quartile (Q4) of the Western pattern had a higher risk of prostate cancer-specific death than men in the lowest quartile (Q1) (Hazard ratio [HR]: 2.39; 95% Confidence Interval [CI]: 0.95, 6.00; P for linear trend=0.03). The association between the Western pattern and prostate cancer-specific mortality appeared to be driven by intake of potatoes (HR[Q4 vs Q1]: 2.85; 95% CI: 1.06, 7.62; P for linear trend=0.01). In addition, the Western pattern was associated with higher all-cause mortality (HR[Q4 vs Q1]: 1.73; 95% CI: 1.20, 2.49; P for linear trend=0.005). A Prudent pattern after diagnosis was unrelated to prostate cancer-specific mortality but was associated with lower all-cause mortality (HR[Q4 vs Q1]: 0.60; 95% CI: 0.42, 0.88; P for linear trend=0.007). Conclusions: A Western dietary pattern may increase risk of prostate cancer-specific and all-cause mortality, whereas a Prudent dietary pattern may decrease the risk of all-cause mortality, all among men diagnosed with localized prostate cancer. Citation Format: Meng Yang, Stacey A. Kenfield, Erin L. Van Blarigan, Julie L. Kasperzyk, Howard D. Sesso, Jing Ma, Meir Stampfer, Jorge E. Chavarro. Dietary patterns after prostate cancer diagnosis in relation to disease-specific and total mortality. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1263. doi:10.1158/1538-7445.AM2014-1263

Screening for Prostate Cancer With the Prostate-Specific Antigen Test

Prostate cancer screening with the prostate-specific antigen (PSA) test remains controversial. To review evidence from randomized trials and related modeling studies examining the effect of PSA screening vs no screening on prostate cancer-specific mortality and to suggest an approach balancing potential benefits and harms. MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials were searched from January 1, 2010, to April 3, 2013, for PSA screening trials to update a previous systematic review. Another search was performed in EMBASE and MEDLINE to identify modeling studies extending the results of the 2 large randomized trials identified. The American Heart Association Evidence-Based Scoring System was used to rate level of evidence. Two trials-the Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC)-dominate the evidence regarding PSA screening. The former trial demonstrated an increase in cancer incidence in the screening group (relative risk [RR], 1.12; 95% CI, 1.07-1.17) but no cancer-specific mortality benefit to PSA screening after 13-year follow-up (RR, 1.09; 95% CI, 0.87-1.36). The ERSPC demonstrated an increase in cancer incidence with screening (RR, 1.63; 95% CI, 1.57-1.69) and an improvement in the risk of prostate cancer-specific death after 11 years (RR, 0.79; 95% CI, 0.68-0.91). The ERSPC documented that 37 additional men needed to receive a diagnosis through screening for every 1 fewer prostate cancer death after 11 years of follow-up among men aged 55 to 69 years (level B evidence for prostate cancer mortality reduction). Harms associated with screening include false-positive results and complications of biopsy and treatment. Modeling studies suggest that this high ratio of additional men receiving diagnoses to prostate cancer deaths prevented will decrease during a longer follow-up (level B evidence). Available evidence favors clinician discussion of the pros and cons of PSA screening with average-risk men aged 55 to 69 years. Only men who express a definite preference for screening should have PSA testing. Other strategies to mitigate the potential harms of screening include considering biennial screening, a higher PSA threshold for biopsy, and conservative therapy for men receiving a new diagnosis of prostate cancer.

Association of metabolic syndrome with poorer prostate cancer and overall survival in men receiving androgen deprivation therapy (ADT) for biochemical relapse.

4555 Background: The metabolic syndrome (MS) has been implicated in the development of prostate cancer (PC). In our previous study of a Veterans’ Administration (VA) cohort, MS was associated with a shorter duration of PC control with ADT. We report the impact of MS on overall survival (OS) and PC specific death for a cohort of patients with biochemical relapse. Methods: 273 pts (64 VA pts and 209 pts from Health Professionals Follow up Study) treated with ADT for biochemical recurrence post radiation or prostatectomy for PC were included. The modified Adult Treatment Panel III criteria for MS was used to identify patients with MS status prior to the commencement of ADT. Cox models tested for association of MS status with OS or time to PC specific death. With 42% overall death rate, 31% MS prevalence, there was 90% power to detect HR= 1.81 (type I error rate =0.05). Results: 31% pts (84/273) had MS and 15% pts (40/273) died of PC. Median follow-up was 9.5 years. The median OS with and without MS was 7.4 and 11.2 years respectively. Patients with hypertension, being African American, having diabetes and age were associated with increased risk of death from any causes, while hypertension and being African American were also associated with increased risk of PC specific death. A multivariate Cox regression model adjusted for age at diagnosis, race, definitive local therapy (RT vs. RP), PSA at diagnosis and Gleason score revealed MS was associated with a significantly increased risk of death from any cause and PC specific death (Table). Conclusions: In men receiving ADT for biochemically recurrent androgen dependent PC, the presence of MS at the commencement of ADT is associated with an increased risk of death from any cause as well as prostate cancer specifically. [Table: see text]

Association of metabolic syndrome with reduced survival among men receiving androgen deprivation therapy for nonmetastatic prostate cancer.

56 Background: The metabolic syndrome (MS) is a set of risk factors implicated in both the development of prostate cancer (PC) and as a recognized complication of androgen deprivation therapy (ADT). In our previous study of a Veterans’ Administration (VA) cohort of relapsed PC patients (pts) on ADT, MS was associated with a shorter duration of PC control. Methods: We studied 347 patients (72 from VA and 275 from Health Professionals Follow up Study) treated with ADT for non-metastatic PC. 88% for biochemical relapse post definitive local therapy and 12% treated with primary ADT. MS was assessed by the modified Adult Treatment Panel III criteria prior to the commencement of ADT. Cox models tested for association between MS status and time to overall survival (OS) or time to PC specific survival, stratified by cohorts (VA vs. HPFS). Cumulative incidence of PC specific death (accounting for competing risk of death from other causes and co-morbidities) by MS status was estimated. Results: 96 patients (28%) had MS. 62 patients (18%) died of PC during a median follow-up of 9.5 years. The median OS for patients with and without MS was 7.5 and 10.6 years respectively. A multivariate Cox model adjusted for age at start of ADT, diagnosis, stage, Gleason score and primary treatment showed MS was associated with a significant 53% increased risk of death from any cause (HR(95%CI) 1.53(1.05-2.22); p=0.03). MS patients tended to have increased risk of PC specific death (HR(95%CI) 1.6 (0.9-2.84); p=0.11). Individual MS components hypertension, dyslipidemia, obesity and diabetes were not associated with an increased risk of death from any cause or PC. The cumulative incidence of PC specific death did not differ by MS status. Conclusions In men receiving ADT for androgen dependent PC without metastases, the presence of MS at the commencement of ADT is associated with an increased risk of death compared to those pts without MS. The shorter time to death appears to be at least in part due to shorter time to dying from PC.

Active Surveillance Compared With Initial Treatment for Men With Low-Risk Prostate Cancer

In the United States, 192,000 men were diagnosed as having prostate cancer in 2009, the majority with low-risk, clinically localized disease. Treatment of these cancers is associated with substantial morbidity. Active surveillance is an alternative to initial treatment, but long-term outcomes and effect on quality of life have not been well characterized. To examine the quality-of-life benefits and risks of active surveillance compared with initial treatment for men with low-risk, clinically localized prostate cancer. Decision analysis using a simulation model was performed: men were treated at diagnosis with brachytherapy, intensity-modulated radiation therapy (IMRT), or radical prostatectomy or followed up by active surveillance (a strategy of close monitoring of newly diagnosed patients with serial prostate-specific antigen measurements, digital rectal examinations, and biopsies, with treatment at disease progression or patient choice). Probabilities and utilities were derived from previous studies and literature review. In the base case, the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was assumed to be 0.83. Men incurred short- and long-term adverse effects of treatment. Hypothetical cohorts of 65-year-old men newly diagnosed as having clinically localized, low-risk prostate cancer (prostate-specific antigen level <10 ng/mL, stage ≤T2a disease, and Gleason score ≤6). Quality-adjusted life expectancy (QALE). Active surveillance was associated with the greatest QALE (11.07 quality-adjusted life-years [QALYs]), followed by brachytherapy (10.57 QALYs), IMRT (10.51 QALYs), and radical prostatectomy (10.23 QALYs). Active surveillance remained associated with the highest QALE even if the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was as low as 0.6. However, the QALE gains and the optimal strategy were highly dependent on individual preferences for living under active surveillance and for having been treated. Under a wide range of assumptions, for a 65-year-old man, active surveillance is a reasonable approach to low-risk prostate cancer based on QALE compared with initial treatment. However, individual preferences play a central role in the decision whether to treat or to pursue active surveillance.

Genetic and plasma variation of insulin‐like growth factor binding proteins in relation to prostate cancer incidence and survival

Binding proteins regulate bioavailability of insulin-like growth factor-I (IGF-I) in the circulation and affect apoptosis of tumor cells in the prostate. We analyzed genetic variation within genes coding for IGF binding proteins in relation to prostate cancer incidence and survival. We also investigated if circulating IGFBP3 affects prostate cancer-specific survival. Eleven haplotype tagging SNPs and two single SNPs in the IGFBP1, IGFBP3, and IGFALS genes were genotyped within the CAncer Prostate in Sweden (CAPS) study including 2,774 cases and 1,736 controls. Plasma samples for analyses of total- and intact IGFBP3 levels were available for 1,521 cases and 909 controls. Complete follow-up of vital status was achieved by linkage to the Swedish Cause of Death Register. We found no clear association between the genetic variants and prostate cancer incidence or survival. The rare allele of the IGFBP3 SNP rs2854744 was associated with elevated plasma levels of total IGFBP3 (P(trend) = 9 x 10(-8)), but not intact IGFBP3 (P(trend) = 0.16). Elevated levels of total- (P(trend) = 0.03) and intact IGFBP3 (P(trend) = 6 x 10(-14)) were associated with increased risk of prostate cancer specific death. Treatment and tumor characteristics accounted for the association with total IGFBP3, whereas the association with intact IGFBP3 was attenuated, but still statistically significant in adjusted analysis (P(trend-adjusted) = 0.0004). Elevated intact IGFBP3 was also significantly associated with increased risk of prostate cancer-specific death among patients who were chemically or surgically castrated (P(trend-adjusted) = 0.0003), and among patients who had not been treated (P(trend-adjusted) = 0.02). Circulating levels of intact IGFBP3 measured after diagnosis is associated with increased risk of prostate cancer-specific death.

Genetic variation in the upstream region of ERG and prostate cancer

A considerable fraction of prostate cancers harbor a gene fusion between the androgen-regulated TMPRSS2 and ERG, one of the most frequently over-expressed proto-oncogenes in prostate cancer. Here, we investigated if inherited genetic variation upstream of ERG alters prostate cancer risk and survival. We genotyped 21 haplotype tagging SNPs (htSNPs) covering 123 kb of 5'UTR DNA including exon 3 of ERG in 2,760 incident prostate cancer cases and 1,647 controls from a population-based Swedish case-control study (CAPS). Individual SNPs and haplotypes were tested for association with prostate cancer risk and survival. One haplotype-'CTCGTATG' located 100 kb upstream of ERG-was associated with lethal prostate cancer (HR, 1.36; 95% CI, 1.2-1.9, p = 0.006). Carriers of the variant 'T' allele of rs2836626 were diagnosed with higher TNM-stage (p = 0.009) and had an increased risk of prostate cancer-specific death (HR = 1.3; 95% CI, 1.1-1.7, p = 0.009). However, this association did not remain statistically significant after adjusting for multiple testing. We found overall no association between ERG variation and prostate cancer risk. Genetic variation upstream of ERG may alter prostate cancer stage and ultimately prostate cancer-specific death but it is unlikely that it plays a role in prostate cancer development.

Central Abdominal Uptake of Indium-111 Capromab Pendetide (ProstaScint) Predicts for Poor Prognosis in Patients with Prostate Cancer

Central abdominal uptake (CAU) on immunoscintigraphy with capromab pendetide (CP) (ProstaScint) suggests the presence of metastases from prostate cancer, but tissue confirmation is difficult and invasive. We report the outcomes data from a cohort of patients with CAU on CP images obtained for staging. The records of 341 men with prostate cancer who underwent CP imaging at two institutions from 1994 to 1999 were reviewed. The patients were divided according to the presence or absence of CAU. Metastases were confirmed in 36 patients (52%) with CAU. The median follow-up was 4.1 years. Statistical analyses compared the differences in baseline characteristics, subsequent radiotherapy, intervention with androgen ablation, and survival. CAU was detected in 69 patients (20%). A total of 262 patients underwent pelvic radiotherapy after the scan, 57 (83%) with CAU and 205 (75%) without (P = 0.2). Of the 69 patients with positive CAU findings and the 272 patients with negative CAU findings, 10 (14.5%) and 14 (5.1%) had died during the follow-up period (P = 0.007). Prostate cancer-specific death occurred in 5 (7.2%) of 69 patients with CAU-positive findings versus 2 of 272 with CAU-negative findings, for a rate 10 times greater in the CAU-positive group (P = 0.02). The results were independent of either the use or timing of androgen blockade. The results of our study have shown that CAU on CP immunoscintigraphy is clinically important and correlates with a significantly greater risk of prostate cancer-specific death. These findings suggest that patients with CAU should be considered for earlier intervention with systemic therapy.

Racial Differences in Clinical Progression Among Medicare Recipients After Treatment for Localized Prostate Cancer (United States)

Prostate cancer recurrence impacts patient quality of life and risk of prostate-cancer specific death following definitive treatment. We investigate differences in disease-free survival among white, black, Hispanic, and Asian patients in a large, population-based database. Merged Surveillance, Epidemiology, and End Results Program (SEER) and Medicare files provided data on 23,353 white patients, 2,814 black patients, 480 Hispanic patients, and 566 Asian patients diagnosed at age 65-84 years with clinically localized prostate cancer between 1986 and 1996 in five SEER sites. Patients were followed through 1998. Racial differences in disease-free survival were assessed using Kaplan-Meier survival curves and Cox regression models. The 75th percentile disease-free survival time for black patients was 13 months less than that for white patients (95% confidence interval [CI]: 6.2-19.8 months), 29.7 months less than that for Hispanic patients (95% CI: 4.4-55.0 months), and 39.1 months less than that for Asian patients (95% CI: 12.1-66.1 months). In multivariate analysis, black race predicted shorter disease-free survival among surgery patients, but not among radiation patients. Black patients experienced shorter disease-free survival compared to white, Hispanic, and Asian patients, and the disease-free survival of white, Hispanic, and Asian patients were not statistically different. Earlier recurrence of prostate cancer may help explain black patients' increased risk of mortality from prostate cancer.

Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer

Objectives Controversy exists regarding the benefit of extended lymphadenectomy at radical prostatectomy for prostate cancer. We sought to determine whether more extended lymphadenectomy, along with radical prostatectomy, resulted in a decreased risk of prostate cancer-specific death at 10 years. Methods Data on all patients undergoing radical prostatectomy (with or without lymphadenectomy) for prostate cancer obtained from the Surveillance, Epidemiology, and End Results Program (1988 to 1991) were examined. All surviving patients had a minimal follow-up of 10 years. Multivariate Cox proportional hazards analysis was used to determine the independent effect of lymphadenectomy on the risk of prostate cancer-specific death. Results Patients undergoing excision of at least 4 lymph nodes (node-positive and node-negative patients) or more than 10 nodes (only node-negative patients) had a lower risk of prostate cancer-specific death at 10 years than did those who did not undergo lymphadenectomy. The removal of a greater number of nodes was associated with a greater likelihood of the presence of positive nodes. The presence of more than one positive node was associated with a greater risk of prostate cancer-related death. Conclusions Performing more extensive pelvic lymphadenectomy in patients undergoing radical prostatectomy could improve the accuracy of staging and reduce the risk of prostate cancer-specific death in the long term.