scholarly journals 5hmC Level Predicts Biochemical Failure Following Radical Prostatectomy in Prostate Cancer Patients with ERG Negative Tumors

2019 ◽  
Vol 20 (5) ◽  
pp. 1025 ◽  
Author(s):  
Gitte Kristensen ◽  
Siri Strand ◽  
Martin Røder ◽  
Kasper Berg ◽  
Birgitte Toft ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Assessment ◽  
Radical Prostatectomy ◽  
Cox Regression ◽  
Predictive Biomarker ◽  
Biochemical Failure ◽  
Regression Analyses ◽  
5Hmc Level ◽  
Increased Risk

This study aimed to validate whether 5-hydroxymethylcytosine (5hmC) level in combination with ERG expression is a predictive biomarker for biochemical failure (BF) in men undergoing radical prostatectomy (RP) for prostate cancer (PCa). The study included 592 PCa patients from two consecutive Danish RP cohorts. 5hmC level and ERG expression were analyzed using immunohistochemistry in RP specimens. 5hmC was scored as low or high and ERG was scored as negative or positive. Risk of BF was analyzed using stratified cumulative incidences and multiple cause-specific Cox regression using competing risk assessment. Median follow-up was 10 years (95% CI: 9.5–10.2). In total, 246 patients (41.6%) had low and 346 patients (58.4%) had high 5hmC level. No significant association was found between 5hmC level or ERG expression and time to BF (p = 0.2 and p = 1.0, respectively). However, for men with ERG negative tumors, high 5hmC level was associated with increased risk of BF following RP (p = 0.01). In multiple cause-specific Cox regression analyses of ERG negative patients, high 5hmC expression was associated with time to BF (HR: 1.8; 95% CI: 1.2–2.7; p = 0.003). In conclusion, high 5hmC level was correlated with time to BF in men with ERG negative PCa, which is in accordance with previous results.

Predictive value of AZGP1 following radical prostatectomy for prostate cancer: a cohort study and meta-analysis

2019 ◽  
Vol 72 (10) ◽  
pp. 696-704 ◽  
Author(s):  
Gitte Kristensen ◽  
Kasper Drimer Berg ◽  
Birgitte Grønkær Toft ◽  
Hein Vincent Stroomberg ◽  
Rosalie Nolley ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Cox Regression ◽  
Meta Analysis ◽  
Model Performance ◽  
Biochemical Failure ◽  
Castration Resistant ◽  
Specific Mortality ◽  
Tissue Biomarker

AimsZinc-alpha 2-glycoprotein (AZGP1) is a promising tissue biomarker to predict outcomes in men undergoing treatment for localised prostate cancer (PCa). We aimed to examine the association between AZGP1 expression and the endpoints: risk of biochemical failure (BF), initiating castration-based treatment, developing castration-resistant PCa (CRPC) and PCa-specific mortality following radical prostatectomy (RP).MethodsThe study included a prospective cohort of 302 patients who underwent RP for PCa from 2002 to 2005. AZGP1 expression was analysed using immunohistochemistry on tissue microarray RP specimens and was scored semiquantitively as low or high expression. Risk of all endpoints was analysed using stratified cumulative incidences and cause-specific Cox regression, and validated with receiver operating curves, calibration and discrimination in competing-risk analyses. A meta-analysis was performed including previous studies investigating AZGP1 expression and risk of BF following RP.ResultsMedian time of follow-up was 14.0 years. The cumulative incidence of all endpoints was significantly higher in patients with low AZGP1 expression compared with patients with high AZGP1 expression (p<0.001). In a multivariate analysis, low AZGP1 expression increases the risk of BF (HR 2.7; 95% CI 1.9 to 3.8; p<0.0001), castration-based treatment (HR 2.2; 95% CI 1.2 to 4.2; p=0.01) and CRPC (HR 2.3; 95% CI 1.1 to 5.0; p=0.03). Validation showed a low risk of prediction error and a high model performance for all endpoints. In a meta-analysis, low AZGP1 was associated with BF (HR 1.7; 95% CI 1.2 to 2.5).ConclusionsLow AZGP1 expression is associated with the risk of aggressive time-dependent outcomes in men undergoing RP for localised PCa.

scholarly journals Observation with or without late radiotherapy is equivalent to early radiotherapy in high-risk prostate cancer after radical prostatectomy: A SEER-Medicare analysis on trends, survival outcomes and complications

2019 ◽  
Author(s):  
Young Suk Suk Kwon ◽  
Wei Wang ◽  
Arnav Srivast ◽  
Thomas L Jang ◽  
Singer A Eric ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Cox Regression ◽  
Survival Outcomes ◽  
Study Cohort ◽  
High Risk Prostate Cancer ◽  
Pathologic Features ◽  
Risk Prostate Cancer

Abstract Introduction: While early radiotherapy (eRT) after radical prostatectomy (RP) has shown to improve oncologic outcomes in patients with high-risk prostate cancer (PCa) in a recent clinical trial, controversy remains regarding its benefit. We aimed to illustrate national trends of post-RP radiotherapy and compare outcomes and toxicities in patients receiving eRT vs. observation with or without late radiotherapy (lRT). Methods: Utilizing the Surveillance, Epidemiology and End Results (SEER)-Medicare data from 2001 to 2011, we identified 7557 patients with high-risk pathologic features after RP (≥ pT3N0 and/or positive surgical margins). Our study cohort was consisted of patients receiving RT within 6 months of surgery (eRT), those receiving RT after 6 months (IRT), and those never receiving RT (observation). Another subcohort, delayed RT (dRT), encompassed both IRT and observation. Trends of post-RP radiotherapy were compared using the Cochran-Armitage trend test. Cox regression models identified factors predictive of worse survival outcomes. Kaplan-Meier analyses compared the eRT and the dRT groups. Results: Among those with pathologically confirmed high-risk PCa after RP, 12.7% (n=959), 13.2% (n=1710), and 74.1% (n=4888) underwent eRT, lRT, and observation without RT, respectively. Of these strategies, the proportion of men on observation without RT increased significantly over time (p=0.004). Multivariable Cox regression model demonstrated similar outcomes between the eRT and the dRT groups. At a median follow up of 5.9 years, five-year overall and cancer-specific survival outcomes were more favorable in the dRT group, when compared to the eRT group. Radiation related toxicities, including urinary incontinence, erectile dysfunction, and urethral stricture, were higher in the eRT group when compared to the lRT group. Conclusions: Our results suggest that a blanket adoption of the eRT in high-risk PCa based on clinical trials with limited follow up may result in overtreatment of a significant number of men and expose them to unnecessary radiation toxicity.

Association of SPARC expression with metastatic progression and prostate cancer-specific mortality after radical prostatectomy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5071-5071
Author(s):  
Claudio Jeldres ◽  
Richard Bruce Johnston ◽  
Christopher R. Porter ◽  
Peter Nelson
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Cox Regression ◽  
Metastatic Progression ◽  
Rank Tests ◽  
Cancer Specific Survival ◽  
Cytoplasmic Staining ◽  
Sparc Expression ◽  
Log Rank Tests

5071 Background: We assessed the expression of the glycoprotein SPARC (secreted protein, acidic, rich in cysteine) in patients with prostate cancer (PCa) treated with radical prostatectomy (RP) and studied its association with adverse clinico-pathological features at RP and long-term clinical outcomes, such as metastatic progression after surgery and cancer-specific death. Methods: Tissues from 78 patients with PCa were used to quantify SPARC expression using tissue microarray (TMA) and immunohistochemistry techniques (IHC). Anti-SPARC mouse monoclonal antibody were use to target the protein and for each patients 4 samples of tissue were used for cytoplasmic staining. Staining of each core was reviewed by an uropathologist who assigned a score (score 0-3) to each core and a global score also assigned to each patient (score 0-3). Analyses of the data relied in cross tables, T-test analyses, survival plots and Cox regression models. Results: Higher expression of SPARC protein was recorded in patients who develop metastases during follow-up after RP (p=0.025) and in patients who died of PCa after RP (p=0.002). Median follow-up of the cohort was 9.3 years after RP. At 5 years, 95.5%, 92.0% and 89.3% of patients were metastases-free for SPARC expression score 1, 2 and 3 respectively. For the same categories, 10 years after RP, 82.2%, 77.0% and 69.9% were metastases-free (Log-rank tests all p≤0.05). Similarly, patients with high SPARC expression had worse cancer-specific survival at 5 and 10 years after RP compared to those with low SPARC expression (Log-rank tests all p≤0.01 when score 1 was compared to score 2 or score 3). Finally, advanced stage at RP (T3-T4) [p=0.04] and high Gleason sum (8-10) [p=0.02] were also associated with higher expression of SPARC. Conclusions: High SPARC expression was associated with worse outcomes in men with prostate cancer treated with radical prostatectomy. Men who developed metastatic disease and men who succumbed to prostate cancer had higher levels of SPARC at radical prostatectomy than their counterpart. SPARC may have an important role in the progression of the disease and may eventually help clinician to better ascertain the risk of progression of the disease.

The effect of the timing of biochemical failure after external beam radiotherapy or low-dose-rate brachytherapy for definitive prostate cancer treatment.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 28-28
Author(s):  
Jay P. Ciezki ◽  
Chandana A. Reddy ◽  
Omar Y. Mian ◽  
Rahul D. Tendulkar ◽  
James Ulchaker ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dose Rate ◽  
Low Dose ◽  
Cox Regression ◽  
Biochemical Failure ◽  
External Beam ◽  
Low Dose Rate ◽  
Post Therapy ◽  
Low Dose Rate Brachytherapy

28 Background: To assess the effect of the timing of biochemical failure (bF) after definitive radiotherapy with external beam (EBRT) or low dose-rate brachytherapy (LDR) on clinical failure (cF) and prostate cancer-specific mortality (PCSM). Methods: From 1996 to 2009, 4478 patients were treated and by 2010, 456 patients were noted to have a bF. They were categorized as early (< 5 years post-therapy) or late (≥ 5 years post-therapy) failures. Factors thought to influence cF and PCSM were scored. Cox regression was used to assess the timing of bF on cF and Fine and Gray regression was used to assess the timing of bF on PCSM. Results: There were 330 (72.4 %) patients categorized as early and 126 (27.6 %) as late failures. The median PSA follow-up post-radiotherapy for the early bF group is 82 months vs. 155 months for the late bF group, and the median PSA follow-up post-bF is 54 months for the early bF group vs. 69 months for the late bF group. The early failures were more likely to be high-risk (p = 0.0080), have a higher Gleason score (p = 0.0008), and use ADT (p = 0.0325). The five-year rate of cF post early bF is 61% vs 43% post late bF (p <0.0001). The five-year rate of PCSM post early bF is 27% vs 9% post late bF (p <0.0001). The multivariable analyses assessing the cF and PCSM are shown in Table. Conclusions: Early bF is associated with higher rates of cF and PCSM. Patients treated with LDR have a lower risk of PCSM. [Table: see text]

scholarly journals Clinical Significance of Multiparametric Magnetic Resonance Imaging as a Preoperative Predictor of Oncologic Outcome in Very Low‐Risk Prostate Cancer

2019 ◽  
Vol 8 (4) ◽  
pp. 542
Author(s):  
Doo Yong Chung ◽  
Min Seok Kim ◽  
Jong Soo Lee ◽  
Hyeok Jun Goh ◽  
Dong Hoon Koh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Cox Regression ◽  
Low Risk ◽  
P Value ◽  
Resonance Imaging ◽  
Multiparametric Magnetic Resonance Imaging ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer

Currently, multiparametric magnetic resonance imaging (mpMRI) is not an indication for patients with very low-risk prostate cancer. In this study, we aimed to evaluate the usefulness of mpMRI as a diagnostic tool in these patients. We retrospectively analyzed the clinical and pathological data of individuals with very low-risk prostate cancer, according to the NCCN guidelines, who underwent mpMRI before radical prostatectomy at our institution between 2010 and 2016. Patients who did not undergo pre-evaluation with mpMRI were excluded. We analyzed the factors associated with biochemical recurrence (BCR) using Cox regression model, logistic regression analysis, and Kaplan–Meier curve. Of 253 very low-risk prostate cancer patients, we observed 26 (10.3%) with BCR during the follow-up period in this study. The median follow-up from radical prostatectomy was 53 months (IQR 33–74). The multivariate Cox regression analyses demonstrated that the only factor associated with BCR in very low-risk patients was increase in the pathologic Gleason score (GS) (HR: 2.185, p-value 0.048). In addition, multivariate logistic analyses identified prostate specific antigen (PSA) (OR: 1.353, p-value 0.010), PSA density (OR: 1.160, p-value 0.013), and suspicious lesion on mpMRI (OR: 1.995, p-value 0.019) as the independent preoperative predictors associated with the pathologic GS upgrade. In our study, the pathologic GS upgrade after radical prostatectomy in very low-risk prostate cancer patients demonstrated a negative impact on BCR and mpMRI is a good prognostic tool to predict the pathologic GS upgrade. We believe that the implementation of mpMRI would be beneficial to determine the treatment strategy for these patients.

Positive surgical margins and biochemical recurrence in obese patients with intermediate- and high-grade prostate cancer with radical prostatectomy.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 50-50
Author(s):  
Emma Holliday Ramahi ◽  
Katherine Cox Ansley ◽  
Matthew W. Jackson ◽  
Joseph W. Basler ◽  
Fei Du ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Technical Difficulty ◽  
Biochemical Failure ◽  
Study Cohort ◽  
High Grade ◽  
Positive Margins ◽  
Primary Endpoints ◽  
Increased Risk ◽  
Pre Treatment

50 Background: The relationship between obesity and prostate cancer outcomes is unclear. We performed a retrospective cohort study to determine the effect of body mass index (BMI) on a cohort of patients with intermediate to high grade prostate cancer treated with radical prostatectomy (RP). Methods: Our retrospective study cohort included 582 men diagnosed with Gleason 7-10 prostate cancer between 1998 and 2008 and treated with RP at a single institution. Patients were stratified into four groups on the basis of their BMI at the time of prostate cancer diagnosis (<25, 25-30, 30-35 or >35). The primary endpoints for comparison were biochemical failure free survival (BFFS) and the incidence of positive margins. PSA >0.2 ng/dl was used to define biochemical failure. Results: After adjusting for age, Gleason score, pre-treatment PSA and the presence of diabetes, we found patients with increasing BMI had an increased frequency of biochemical failure after RP. Compared to patients with a normal BMI (<25), patients with BMI 25-30, 30-35, and >35 had 1.82 (1.12, 2.97; p = 0.02), 2.14 (1.33, 3.45; p = 0.002) and 2.29 (1.1, 4.78; p = 0.03) times higher rates of biochemical failure, respectively. We additionally found increased positive margins after RP in patients with a BMI 30-35 and >35 (41.4% and 45.5%, respectively) when compared to patients with a BMI of <25 and 25-30 (33.3% and 28.9%, respectively); p = 0.02. Conclusions: Patients with increasing BMI seem to be at significantly increased risk for biochemical failure following RP potentially due to the increased technical difficulty of the surgery and increased incidence of positive margins. [Table: see text]

Insomnia among elderly men and risk of prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 78-78 ◽  
Author(s):  
Lara Sigurdardottir ◽  
Unnur Anna Valdimarsdottir ◽  
Lorelei Mucci ◽  
Katja Fall ◽  
Jennifer R. Rider ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Sleep Disturbances ◽  
Potential Role ◽  
Cox Regression ◽  
Positive Association ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Biological Explanation ◽  
Underlying Mechanisms

78 Background: While a large number of studies have reported a positive association between sleep disruption and breast cancer, little is known about its potential role in prostate cancer. Methods: Within the prospective AGES-Reykjavik cohort study, we followed 2102 men from 2002-2006 until the end of 2009. The men answered questions on sleep disturbances, which were combined in various ways to reflect onset and/or maintenance insomnia. Information on the occurrence of prostate cancer was obtained through record-linkages across the Icelandic Cancer and Causes of Death Registers. We used Cox regression models with 95% confidence intervals [CIs] to estimate age- and multivariable adjusted hazard ratios [HR] of prostate cancer by symptoms of insomnia. Results: During follow-up, 135 men (6,4%) were diagnosed with prostate cancer. Compared to men without insomnia, men with severe onset and maintenance insomnia and very severe insomnia were at increased risk of total prostate cancer with HR 1.9 (CI 1.2, 3.0) and 2.2 (CI 1.3, 3.8), respectively. For advanced prostate cancer, the corresponding HRs were 2.3 (CI 0.9-6.2) and 3.7 (CI 1.4-9.9), respectively. Conclusions: These data suggest that insomnia may confer an increased risk of prostate cancer. Reduced melatonin levels represent a plausible biological explanation, although additional studies using biomarkers and longer follow-up times are needed to further clarify the underlying mechanisms.

Real-world cardiovascular outcomes with novel anti-androgen agents in prostate cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16510-e16510
Author(s):  
Amit Kulkarni ◽  
Nathan Rubin ◽  
Tony Tholkes ◽  
Anna Prizment ◽  
Charles J. Ryan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Real World ◽  
Cox Regression ◽  
Primary Outcome Measure ◽  
Real World Data ◽  
Claims Database ◽  
Increased Risk ◽  
Time Dependent Covariates ◽  
Medical Claims Database

e16510 Background: Abiraterone use is associated with significant cardiovascular (CV) morbidity in clinical trials, but the magnitude of this morbidity in contemporary US prostate cancer (PC) population remains unknown. We examined a large medical claims database to answer this important question. Methods: We retrospectively reviewed Marketscan claims database (1/1/2013 to 9/30/2015) to identify adults with diagnosis of localized PC, recurrent localized PC, biochemically recurrent non-metastatic PC and metastatic PC who received treatment with androgen deprivation therapy (ADT) alone or ADT with novel antiandrogen agents (abiraterone or enzalutamide). The primary outcome measure was composite severe CV outcome of acute myocardial infarction (MI), stroke or heart failure (HF). We used Cox regression model with time dependent covariates to estimate the CV risk of various therapies. Results: A total of 7030 patients of PC were identified- 1285 received ADT for localized PC, 424 received ADT for recurrent localized PC, 554 received ADT for biochemically recurrent non-metastatic PC, 256 received ADT alone for metastatic PC and 1366 received abiraterone or enzalutamide with ADT for metastatic PC. During the study period, 143 severe CV events occurred, resulting in an incidence rate of 0.74 per 100 patient-years. In multivariate analysis, abiraterone use was associated with a trend towards increased risk of severe CV compared to non-abiraterone users (HR = 1.58; 95% CI: 0.98-2.59, p= 0.06). No such increased risk was detected for ADT (HR = 1.35; 95% CI: 0.92-2.00, p= 0.12) or enzalutamide (HR = 0.84 95% CI: 0.34-2.11, p= 0.71). Conclusions: To our knowledge, this is the first study to present real-world data on CV outcomes of PC patients receiving novel anti-androgens. Our findings support the trend towards increased severe CV risk seen in abiraterone trials. No such association was seen for enzalutamide. Additional analyses with a longer follow-up duration are planned.

scholarly journals PUMA and NOXA Expression in Tumor-Associated Benign Prostatic Epithelial Cells Are Predictive of Prostate Cancer Biochemical Recurrence

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3187
Author(s):  
Sylvie Clairefond ◽  
Benjamin Péant ◽  
Véronique Ouellet ◽  
Véronique Barrès ◽  
Zhe Tian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Epithelial Cells ◽  
Biochemical Recurrence ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Tissue Microarrays ◽  
Regression Analyses ◽  
Kaplan Meier ◽  
Puma Expression

Background: Given that treatment decisions in prostate cancer (PC) are often based on risk, there remains a need to find clinically relevant prognostic biomarkers to stratify PC patients. We evaluated PUMA and NOXA expression in benign and tumor regions of the prostate using immunofluorescence techniques and determined their prognostic significance in PC. Methods: PUMA and NOXA expression levels were quantified on six tissue microarrays (TMAs) generated from radical prostatectomy samples (n = 285). TMAs were constructed using two cores of benign tissue and two cores of tumor tissue from each patient. Association between biomarker expression and biochemical recurrence (BCR) at 3 years was established using log-rank (LR) and multivariate Cox regression analyses. Results: Kaplan–Meier analysis showed a significant association between BCR and extreme levels (low or high) of PUMA expression in benign epithelial cells (LR = 8.831, p = 0.003). Further analysis revealed a significant association between high NOXA expression in benign epithelial cells and BCR (LR = 14.854, p < 0.001). The combination of extreme PUMA and high NOXA expression identified patients with the highest risk of BCR (LR = 16.778, p < 0.001) in Kaplan–Meier and in a multivariate Cox regression analyses (HR: 2.935 (1.645–5.236), p < 0.001). Conclusions: The combination of PUMA and NOXA protein expression in benign epithelial cells was predictive of recurrence following radical prostatectomy and was independent of PSA at diagnosis, Gleason score and pathologic stage.

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