Adverse Prostate Cancer Outcomes Research Articles

An Inherited Allele Confers Prostate Cancer Progression and Drug Resistance via RFX6/HOXA10-Orchestrated TGFβ Signaling.

Genetic and epigenetic alterations are cancer hallmark characteristics. However, the role of inherited cancer predisposition alleles in co-opting lineage factor epigenetic reprogramming and tumor progression remains elusive. Here the FinnGen cohort phenome-wide analysis, along with multiple genome-wide association studies, has consistently identified the rs339331-RFX6/6q22 locus associated with prostate cancer (PCa) risk across diverse populations. It is uncovered that rs339331 resides in a reprogrammed androgen receptor (AR) binding site in PCa tumors, with the T risk allele enhancing AR chromatin occupancy. RFX6, an AR-regulated gene linked to rs339331, exhibits synergistic prognostic value for PCa recurrence and metastasis. This comprehensive in vitro and in vivo studies demonstrate the oncogenic functions of RFX6 in promoting PCa cell proliferation and metastasis. Mechanistically, RFX6 upregulates HOXA10 that profoundly correlates with adverse PCa outcomes and is pivotal in RFX6-mediated PCa progression, facilitating the epithelial-mesenchymal transition (EMT) and modulating the TGFβ/SMAD signaling axis. Clinically, HOXA10 elevation is associated with increased EMT scores, tumor advancement and PCa recurrence. Remarkably, reducing RFX6 expression restores enzalutamide sensitivity in resistant PCa cells and tumors. This findings reveal a complex interplay of genetic and epigenetic mechanisms in PCa pathogenesis and drug resistance, centered around disrupted prostate lineage AR signaling and abnormal RFX6 expression.

MP12-15 DISPARITIES IN PROSTATE CANCER SCREENING AND DIAGNOSIS AMONG PATIENTS WITH MEDICAID

You have accessJournal of UrologyCME1 Apr 2023MP12-15 DISPARITIES IN PROSTATE CANCER SCREENING AND DIAGNOSIS AMONG PATIENTS WITH MEDICAID Henry Gold, Andrew Stevens, Tasha Posid, Dairon Denis-Diaz, Hafsa Asif, Aliza Khuhro, and Shawn Dason Henry GoldHenry Gold More articles by this author , Andrew StevensAndrew Stevens More articles by this author , Tasha PosidTasha Posid More articles by this author , Dairon Denis-DiazDairon Denis-Diaz More articles by this author , Hafsa AsifHafsa Asif More articles by this author , Aliza KhuhroAliza Khuhro More articles by this author , and Shawn DasonShawn Dason More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003227.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Medicaid patients with prostate cancer are four times more likely to present with metastatic disease and twice as likely to die of their cancer compared to patients with private insurance. Medicaid participation is related to other factors that limit healthcare access, including socioeconomic status (18,000/year individual income limit in Ohio) and race (48% of Medicaid enrollees are black in our county vs. 24% of population). We hypothesize that adverse prostate cancer outcomes in the Medicaid population relate to limited access to both PSA screening and evaluation of abnormal results. We reviewed our institutional triage process for patients referred for an abnormal prostate cancer screen with the goal of ensuring equitable intake processes based on payor status. METHODS: This is a retrospective study of patients who presented to our institution with an elevated PSA or an abnormal prostate exam from 2012-2021. Initial data on demographics, payor status, time to first appointment, screening history, and diagnostic testing are reported. Statistical analysis was performed with SPSS (IBM Inc.). Means were compared with the student’s t-test and logistic regression was used for correlative analysis with two-tailed p values <0.05 considered significant. RESULTS: Our initial analysis cohort included 149 patients who were predominantly Caucasian (58.0%) and had a mean age of 67.5 years (SD=9.11). Mean income based on home address zip code was $83,726 (SD=$30,488) and patients had a mean of 2.91 (SD=1.2) prior PSAs. We had a much lower proportion of patients with Medicaid status (6.7%) than expected based on our overall departmental payor mix and the size of the Medicaid population in our catchment area. Patients with Medicaid were almost 10 times more likely to not show up to their first appointment than those with other insurance types (p=0.014). Medicaid patients were also less likely to receive a biopsy (p=0.07) and had a lower number of PSA tests prior to referral (p=0.08). A zip code with lower mean income negatively predicted receipt of MRI prior to a biopsy (p=0.02). Times between referral, scheduling, and appointment were not impacted by payor status or zip code. CONCLUSIONS: Our data confirm disparities in several factors in our prostate cancer screening referrals known to relate to prostate cancer outcomes. To address this, we are implementing a Medicaid-focused program at our institution to improve on “No-show” rates and optimize guideline concordant care. Outreach to primary care providers with a large Medicaid patient population is also critical in promoting equity in PSA screening. Source of Funding: Ohio State University Patient Care Innovation Award © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e139 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Henry Gold More articles by this author Andrew Stevens More articles by this author Tasha Posid More articles by this author Dairon Denis-Diaz More articles by this author Hafsa Asif More articles by this author Aliza Khuhro More articles by this author Shawn Dason More articles by this author Expand All Advertisement PDF downloadLoading ...

Efficacy and safety of relugolix in men with advanced prostate cancer based on baseline body mass index (BMI): A subgroup analysis from the randomized, phase 3 HERO study versus leuprolide (LEU).

5073 Background: BMI has been correlated with adverse prostate cancer outcomes, such as risk of biochemical failure, mortality and androgen deprivation therapy complications. Relugolix is a FDA-approved, once-daily oral GnRH receptor antagonist that has demonstrated superior continuous suppression of testosterone (T) to castrate levels through Week 48 compared to LEU (96.7% vs 88.8%, respectively; Shore N, NEJM 2020;382:2187) in men with advanced prostate cancer (APC). This HERO subgroup analysis looks at the impact of baseline BMI on efficacy and safety. Methods: HERO was a phase 3 randomized, open-label study to evaluate relugolix vs LEU in 930 men with APC. This analysis looked at all men enrolled and treated in the HERO study divided by baseline BMI (BMI subgroups: &lt;25.0 [underweight and healthy weight]; 25.0 – 29.9 [overweight]; and &gt;29.9 [obese]). Assessments included sustained T suppression to castrate levels (&lt;50 ng/dL) from Day 29 through 48 weeks, early T suppression to castrate levels (Day 4 and Day 15), prostate specific antigen (PSA) response (&gt;50% decrease from baseline) at Day 15 with confirmation at Day 29, and profound castration rate (&lt;20 ng/dL) at Day 15. T recovery subset analysis was not included due to low patient numbers. All analyses performed were descriptive. Results: Of the 930 men (relugolix:622; LEU:308) treated in HERO, 287 (30.9%) men had BMI &lt;25, 424 (45.6%) were 25 – 29.9, 219 (23.5%) were &gt;29.9. Sustained castration rates through 48 weeks were higher for the relugolix group than the LEU group and results for select key secondary endpoints were generally consistent across BMI categories, although PSA response proportions were lower in obese patients (table). No differences were noted in the incidence or types of adverse events within treatment groups in the subgroups analyzed. Conclusions: In this HERO study subgroup analysis, relugolix demonstrated greater continuous T suppression than LEU regardless of baseline BMI. Although higher BMI has been associated with poorer outcomes, we did not observe a similar trend with T responses. A numerically lower PSA response was seen in obese patients. Additional research with longer follow-up is warranted. Clinical trial information: NCT03085095. [Table: see text]

A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer.

Simple SummaryMen of African origin have a 2–3 times greater chance of developing prostate cancer than those of European origin, and of patients that are diagnosed with the disease, men of African descent are 2 times more likely to die compared to white men. Men of African origin are still greatly underrepresented in genetic studies and clinical trials. This, unfortunately, means that new discoveries in cancer treatment are missing key information on the group with a greater chance of mortality. The objective of this study was to increase our knowledge of prostate cancer in men undergoing a prostate biopsy. We carried out RNA sequencing of biopsy specimens and examined racial differences in prostate gene expression. A gene expression signature was uncovered which separated the men based on their race. Furthermore, within men of African descent this signature separated men with the most severe clinical characteristics.An emerging theory about racial differences in cancer risk and outcomes is that psychological and social stressors influence cellular stress responses; however, limited empirical data are available on racial differences in cellular stress responses among men who are at risk for adverse prostate cancer outcomes. In this study, we undertook a systems approach to examine molecular profiles and cellular stress responses in an important segment of African American (AA) and European American (EA) men: men undergoing prostate biopsy. We assessed the prostate transcriptome with a single biopsy core via high throughput RNA sequencing (RNA-Seq). Transcriptomic analyses uncovered impacted biological pathways including PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction pathway, and ECM-receptor interaction. Additionally, 187 genes mapping to the Gene Ontology (GO) terms RNA binding, structural constituent of ribosome, SRP-dependent co-translational protein targeting to membrane and the biological pathways, translation, L13a-mediated translational silencing of Ceruloplasmin expression were differentially expressed (DE) between EA and AA. This signature allowed separation of AA and EA patients, and AA patients with the most severe clinical characteristics. AA patients with elevated expression levels of this genomic signature presented with higher Gleason scores, a greater number of positive core biopsies, elevated dehydroepiandrosterone sulfate levels and serum vitamin D deficiency. Protein-protein interaction (PPI) network analysis revealed a high degree of connectivity between these 187 proteins.

Differential mast cell phenotypes in benign versus cancer tissues and prostate cancer oncologic outcomes

We reported previously that high numbers of mast cells in benign (extra-tumoral) regions of the prostate are associated with worse outcomes after radical prostatectomy including biochemical recurrence and the development of metastases. Herein, with a cohort of 384 men, we performed mast cell subtyping and report that higher minimum number of the tryptase-only (MCT ) subset of extra-tumoral mast cells is associated with increased risk of biochemical recurrence (comparing highest to lowest tertiles: HR 2.32, 95% CI 1.37-3.93; P-trend = 0.002), metastases (HR 3.62, 95% CI 1.75-7.47; P-trend 0.001), and death from prostate cancer (HR 2.87, 95% CI 1.19-6.95; P-trend = 0.02). Preliminary RNA sequencing and comparison of benign versus cancer tissue mast cells revealed differential expression of additional site-specific genes. We further demonstrate that the genes CXCR4 and TFE3 are more highly expressed in tumor-infiltrating mast cells as well as other tumor-infiltrating immune cells and in tumor cells, respectively, and represent an altered tumor microenvironment. KIT variants were also differentially expressed in benign versus cancer tissue mast cells, with KIT variant 1 (GNNK+ ) mast cells identified as more prevalent in extra-tumoral regions of the prostate. Finally, using an established mouse model, we found that mast cells do not infiltrate Hi-Myc tumors, providing a model to specifically examine the role of extra-tumoral mast cells in tumorigenesis. Hi-Myc mice crossed to mast cell knockout (Wsh) mice and aged to 1 year revealed a higher degree of pre-invasive lesions and invasive cancer in wild-type mice versus heterozygous and knockout mice. This suggests a dosage effect where higher numbers of extra-tumoral mast cells resulted in higher cancer invasion. Overall, our studies provide further evidence for a role of extra-tumoral mast cells in driving adverse prostate cancer outcomes. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Abstract C009: Post-diagnostic statin and metformin use and risk of biochemical recurrence risk among Black and White men diagnosed with prostate cancer at the Veterans Health Administration

Abstract BACKGROUND: Prostate cancer is the most common cancer among men in the United States. Black men represent a high-risk group that is more likely to be both diagnosed with and experience adverse prostate cancer outcomes. Both statins (to reduce cholesterol) and metformin (to treat diabetes) have been hypothesized to reduce the risk of biochemical recurrence (BCR), a clinically important outcome, among men with prostate cancer. However, few studies have examined this association specifically in Black men. Because Black men are at greater risk for adverse prostate cancer outcomes, the potential of commonly used medications, including metformin and statins, to reduce this increased risk needs to be investigated. Here, we have examined the potential of metformin and statins to reduce risk of prostate cancer recurrence in a racially-diverse cohort of men diagnosed with prostate cancer at the Veterans Health Administration (VHA). METHODS: Our cohort consisted of 20,359 Black and 52,004 White men that were diagnosed with prostate cancer between 1997-2009 at the VHA and received definitive treatment for prostate cancer (radical prostatectomy or radiation). Statin use and metformin use were defined as any statin or metformin prescription after prostate cancer diagnosis. BCR was defined using established definitions. (For men treated with radical prostatectomy, BCR was defined as a PSA of 0.2 ng/mL or higher for two consecutive assays without treatment. For men treated with radiation, BCR was defined as rise of 2 ng/ mL or more above the nadir achieved after radiation therapy.) Cox proportional hazard models adjusted for age at diagnosis, prostate cancer grade, prostate cancer stage, and locale (rural vs. urban) were used to assess the association between statin and metformin use. Statin and metformin use were analyzed in separate models, stratified by race. RESULTS: Statin use (69.9% of Black men; 75.4% of White men) and metformin use (29.4% of Black men; 24.3% of White men) were prevalent in our cohort. The mean BCR-free survival time was 5.7 years and 6.0 years in Black and White men, respectively, with 16.6% of Black men and 13.8% of White experiencing a BCR. Statin use was associated with a significantly reduced risk of BCR in the cohort as a whole (Hazard Ratio (HR): 0.87; 95% Confidence Interval (CI): 0.83, 0.91), Black men (HR: 0.84; 95% CI: 0.77, 0.90), and White men (HR:0.89; 95% CI: 0.84, 0.95). We observed no association between metformin use and risk of BCR [Overall (HR: 1.05; 95% CI: 1.00, 1.10), Black men (HR: 1.00; 95% CI: 0.93, 1.08), White men (HR: 1.05; 95% CI: 1.00. 1.11)]. CONCLUSION: Post-diagnostic statin use may reduce the risk of BCR in both Black and White men. This is one the few studies to examine statin use and metformin use specifically in Black men with prostate cancer. Importantly, because all patients treated at the VHA receive care regardless of insurance status, this study was able to control for socioeconomic status in ways other studies are unable. Citation Format: Saira Khan, Bettina Drake. Post-diagnostic statin and metformin use and risk of biochemical recurrence risk among Black and White men diagnosed with prostate cancer at the Veterans Health Administration [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C009.

Resiliency and Allostatic Load among Veterans at Risk for Adverse Prostate Cancer Outcomes.

To examine the relationships between resiliency, sociodemographic factors, and allostatic load among male Veterans. Cross-sectional study with minority (African American or Hispanic) and non-minority (White) male Veterans undergoing prostate biopsy. Veterans Affairs Medical Center located in Charleston, SC. Self-reported resilience measured using the two item sub-scale from the Connor-Davidson Resiliency Scale and allostatic load determined from biomarkers measured in blood. In this small sample, bounce-back resilience and allostatic load level had a significant negative correlation, while adaptation resilience and allostatic load were slightly correlated, but the association was not statistically significant. Sixty-six percent of participants reported that they were able to adapt and 40% reported they were able to bounce back. Higher income and lower PSA level were significantly correlated with greater adaptation resilience. Minority men were significantly more likely than non-minority men to report that they are able to bounce back. Married men were also significantly more likely than unmarried men to report that they were able to bounce back. It may be important to target resiliency training programs to Veterans based on their social determinants and to examine the effects of these programs on allostatic load.

High Extratumoral Mast Cell Counts Are Associated with a Higher Risk of Adverse Prostate Cancer Outcomes

Given our previous findings that low intratumoral and high extratumoral mast cell numbers are associated with higher risk of biochemical recurrence after radical prostatectomy, we now assessed this relationship with race and the development of metastases. We stained for mast cell tryptase via IHC and fluorescent immunolabeling in 885 men across multiple tissue microarray sets designed to assess biomarkers in association with race and prostate cancer outcomes (median follow-up, 7.0 years). Intratumoral and extratumoral mast cell counts were significantly lower in tissues from African-American compared with European-American men, but not within strata of cancer grade. There was no association between mast cell counts and ERG positivity, PTEN loss, or TP53 missense mutation. Higher minimum extratumoral mast cells were associated with an increased risk of biochemical recurrence [comparing highest with lowest tertiles: HR, 1.61; 95% confidence interval (CI), 1.12-2.29; P trend = 0.01]; this pattern was similar among European-American and African-American men and by grade of disease. There was no significant association between minimum intratumoral mast cell count and biochemical recurrence, overall or within strata of race and grade. Finally, high minimum number of extratumoral mast cells was associated with prostate cancer metastases (comparing highest with lowest tertiles: HR, 2.12; 95% CI, 1.24-3.63; P trend = 0.01). High extratumoral mast cell numbers are associated with biochemical recurrence and the development of metastases after radical prostatectomy. Higher numbers of benign tissue mast cells are associated with a higher risk of adverse outcomes after radical prostatectomy, including metastatic prostate cancer.

Kallikrein markers performance in pretreatment blood to predict early prostate cancer recurrence and metastasis after radical prostatectomy among very high‐risk men

To assess whether a prespecified statistical model based on the four kallikrein markers measured in blood-total, free, and intact prostate-specific antigen (PSA), together with human kallikrein-related peptidase 2 (hK2)-or any individual marker measured in pretreatment serum were associated with biochemical recurrence-free (BCR) or metastasis-free survival after radical prostatectomy (RP) in a subgroup of men with very high-risk disease. We identified 106 men treated at Mayo Clinic from 2004 to 2008 with pathological Gleason grade group 4 to 5 or seminal vesicle invasion at RP. Univariable and multivariable Cox models were used to test the association between standard predictors (Kattan nomogram and GPSM [Gleason, PSA, seminal vesicle and margin status] score), kallikrein panel, and individual kallikrein markers with the outcomes. BCR and metastasis occurred in 67 and 30 patients, respectively. The median follow-up for patients who did not develop a BCR was 10.3 years (interquartile range = 8.2-11.8). In this high-risk group, neither Kattan risk, GPSM score, or the kallikrein panel model was associated with either outcome. However, after adjusting for Kattan risk and GPSM score, separately, preoperative intact PSA was associated with both outcomes while hK2 was associated with metastasis-free survival. Conventional risk prediction tools were poor discriminators for risk of adverse outcomes after RP (Kattan risk and GPSM risk) in patients with very high-risk disease. Further studies are needed to define the role of individual kallikrein marker forms in the blood to predict adverse prostate cancer outcomes after RP in this high-risk setting.

Dysregulation of Sirtuin 2 (SIRT2) and histone H3K18 acetylation pathways associates with adverse prostate cancer outcomes

BackgroundHistones undergo extensive post-translational modifications and this epigenetic regulation plays an important role in modulating transcriptional programs capable of driving cancer progression. Acetylation of histone H3K18, associated with gene activation, is enhanced by P300 and opposed by the deacetylase Sirtuin2 (SIRT2). As these enzymes represent an important target for cancer therapy, we sought to determine whether the underlying genes are altered during prostate cancer (PCa) progression.MethodsTissue microarrays generated from 71 radical prostatectomy patients were initially immunostained for H3K18Ac, P300 and SIRT2. Protein levels were quantified using VECTRA automation and correlated with clinicopathologic parameters. The Cancer Genome Atlas (TGCA, n = 499) and Gene Expression Omnibus (n = 504) databases were queried for expression, genomic and clinical data. Statistics were performed using SPSSv23.ResultsNuclear histone H3K18Ac staining increases in primary cancer (p = 0.05) and further in metastases (p < 0.01) compared to benign on tissue arrays. P300 protein expression increases in cancer (p = 0.04) and metastases (p < 0.001). A progressive decrease in nuclear SIRT2 staining occurs comparing benign to cancer or metastases (p = 0.04 and p = 0.03 respectively). Decreased SIRT2 correlates with higher grade cancer (p = 0.02). Time to Prostate Specific Antigen (PSA) recurrence is shorter in patients exhibiting high compared to low H3K18Ac expression (350 vs. 1542 days respectively, P = 0.03). In GEO, SIRT2 mRNA levels are lower in primary and metastatic tumors (p = 0.01 and 0.001, respectively). TGCA analysis demonstrates SIRT2 deletion in 6% and increasing clinical stage, positive margins and lower PSA recurrence-free survival in patients with SIRT2 loss/deletion (p = 0.01, 0.04 and 0.04 respectively). In this dataset, a correlation between decreasing SIRT2 and increasing P300 mRNA expression occurs in tumor samples (R = −0.46).ConclusionsIn multiple datasets, decreases in SIRT2 expression portend worse clinicopathologic outcomes.Alterations in SIRT2-H3K18Ac suggest altered P300 activity and identify a subset of tumors that could benefit from histone deacetylation inhibition.

Prostate tumor DNA methylation is associated with cigarette smoking and adverse prostate cancer outcomes

DNA methylation has been hypothesized as a mechanism for explaining the association between smoking and adverse prostate cancer (PCa) outcomes. This study was aimed at assessing whether smoking is associated with prostate tumor DNA methylation and whether these alterations may explain in part the association of smoking with PCa recurrence and mortality. A total of 523 men had radical prostatectomy as their primary treatment, detailed smoking history data, long-term follow-up for PCa outcomes, and tumor tissue profiled for DNA methylation. Ninety percent of the men also had matched tumor gene expression data. A methylome-wide analysis was conducted to identify differentially methylated regions (DMRs) by smoking status. To select potential functionally relevant DMRs, their correlation with the messenger RNA (mRNA) expression of corresponding genes was evaluated. Finally, a smoking-related methylation score based on the top-ranked DMRs was created to assess its association with PCa outcomes. Forty DMRs were associated with smoking status, and 10 of these were strongly correlated with mRNA expression (aldehyde oxidase 1 [AOX1], claudin 5 [CLDN5], early B-cell factor 1 [EBF1], homeobox A7 [HOXA7], lectin galactoside-binding soluble 3 [LGALS3], microtubule-associated protein τ [MAPT], protocadherin γ A [PCDHGA]/protocadherin γ B [PCDHGB], paraoxonase 3 [PON3], synaptonemal complex protein 2 like [SYCP2L], and zinc finger and SCAN domain containing 12 [ZSCAN12]). Men who were in the highest tertile for the smoking-methylation score derived from these DMRs had a higher risk of recurrence (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.42-3.72) and lethal disease (OR, 4.21; 95% CI, 1.65-11.78) in comparison with men in the lower 2 tertiles. This integrative molecular epidemiology study supports the hypothesis that smoking-associated tumor DNA methylation changes may explain at least part of the association between smoking and adverse PCa outcomes. Future studies are warranted to confirm these findings and understand the implications for improving patient outcomes. Cancer 2016;122:2168-77. © 2016 American Cancer Society.

Racial disparities in prostate cancer care: Is adherence to National Comprehensive Cancer Network guidelines good enough for our patients?

Racial disparities in prostate cancer care: Is adherence to National Comprehensive Cancer Network guidelines good enough for our patients?

Association between Preoperative Erectile Dysfunction and Prostate Cancer Features—An Analysis from the Duke Prostate Center Database

Erectile dysfunction (ED) is related to several co-morbidities including obesity, metabolic syndrome, cigarette smoking, and low testosterone, all of which have been reported to be associated with adverse prostate cancer features. To examine whether preoperative ED has a relationship with adverse prostate cancer features in patients who underwent radical prostatectomy (RP). We analyzed data from our institution on 676 patients who underwent RP between 2001 and 2010. Crude and adjusted logistic regression models were used to investigate the association between preoperative ED and several pathological parameters. The log-rank test and multivariate proportional hazards model were conducted to determine the association of preoperative ED with biochemical recurrence (BCR). The expanded prostate cancer index composite (EPIC) instrument was used to evaluate preoperative erectile function (EF). Preoperative normal EF was defined as EPIC-SF ≥ 60 points while ED was defined as preoperative EPIC-SF lower than 60 points. Preoperatively, a total of 343 (50.7%) men had normal EF and 333 (49.3%) men had ED. After adjusting for covariates, preoperative ED was identified a risk factor for positive extracapsular extension (OR 1.57; P = 0.029) and high percentage of tumor involvement (OR 1.56; P = 0.047). In a Kaplan-Meier curve, a trend was identified that patients with ED had higher incidence of BCR than men with normal EF (P = 0.091). Moreover, using a multivariate Cox model, higher preoperative EF was negatively associated with BCR (HR 0.99; P = 0.014). These results suggest that the likelihood for adverse pathological outcomes as well as BCR following prostatectomy is higher among men with preoperative ED, though these results require validation in larger datasets. The present study indicates that preoperative ED might be a surrogate for adverse prostate cancer outcomes following RP.

Association of caveolin‐1 and ‐2 genetic variants and post‐treatment serum caveolin‐1 with prostate cancer risk and outcomes

Caveolin-1 (cav-1) is overexpressed by metastatic prostate cancer (PC) cells. Pre-operative serum cav-1 levels have been shown to be a prognostic marker for PC recurrence. This study evaluated the relationship between post-treatment serum cav-1 levels and single nucleotide polymorphisms (SNPs) in the cav-1 and -2 genes with risk of PC, aggressive PC, PC recurrence or death. Two case-control studies of PC among men in Washington State were combined for this analysis. Cases (n = 1,458) were diagnosed in 1993-1996 or 2002-2005 and identified via a SEER cancer registry. Age-matched controls (n = 1,351) were identified via random digit dialing. Logistic regression was used to assess the relationship between exposures (19 haplotype-tagging SNPs from all subjects and post-treatment serum cav-1 levels from a sample of 202 cases and 226 controls) and PC risk and aggressive PC. Cox proportional hazards regression was used to assess the relationship between exposures and PC recurrence and death. Rs9920 in cav-1 was associated with an increased relative risk of overall PC (OR(CT + CC) = 1.37, 95% CI = 1.12, 1.68) and aggressive PC (OR(CT + CC) = 1.57, 95% CI = 1.20, 2.06), but not with PC recurrence or death. High post-treatment serum cav-1 levels were not associated with PC risk, aggressive PC, or PC-specific death, but approached a significant inverse association with PC recurrence (hazard ratio = 0.69, 95% CI = 0.47, 1.00). We found modest evidence for an association with a variant in the cav-1 gene and risk of overall PC and aggressive PC, which merits further study. We found no evidence that higher post-treatment serum cav-1 is associated with risk of aggressive PC or adverse PC outcomes.