The impact of DNA methylation on the identification of recurrent prostate cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21086-21086
Author(s):  
J. J. Alumkal ◽  
Z. Zhang ◽  
E. B. Humphreys ◽  
C. Bennett ◽  
L. A. Mangold ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
Radical Prostatectomy ◽  
Biochemical Recurrence ◽  
Methylation Status ◽  
Surgical Margin ◽  
Multivariable Logistic Regression Analysis ◽  
Tissue Samples ◽  
Increased Risk ◽  
The Impact

21086 Purpose: Biochemical (PSA) recurrence of prostate cancer following radical prostatectomy remains a major problem. Better biomarkers are needed to identify high and low-risk patients. DNA methylation of promoter regions leads to gene silencing in many cancers. In this study, we assessed the impact of changes in DNA methylation on biochemical recurrence in men with prostate cancer. Methods: We examined the methylation status of fifteen genes using MSP (Methylation Specific PCR) on tissue samples from 151 patients with clinically localized prostate cancer for whom at least five years of follow-up after prostatectomy was available. Results: In a multivariable logistic regression analysis, extra capsular penetration, high Gleason score, and involvement of the lymph nodes, seminal vesicles, or surgical margin were associated with an increased risk of recurrence. In addition, samples with methylation of 2 specific genes involved in cell-cell adhesion and apoptosis were associated with biochemical recurrence with an odds ratio of 5.64 (95% CI=1.47–21.7, p=0.012) compared to samples without methylation of both of these genes. The methylation status of these 2 genes had a higher sensitivity (72.3%; 95% CI=57–84.4%) for detecting recurrences than all the clinico-pathological variables (p<0.02) except extra-capsular penetration (p=0.346). The methylation status of these 2 genes had a similar negative predictive value (79.0%; 95% CI=66.8–88.3%) as the individual clinico-pathological variables examined. Conclusion: DNA Methylation of specific genes is independently associated with an increased risk of biochemical recurrence after radical prostatectomy even one considers the prognostic clinico-pathologic variables used in the clinic today. Our findings should be validated on another larger group of patients with prostate cancer who have undergone radical prosatetectomies. No significant financial relationships to disclose.

scholarly journals The impact of prostate cancer upgrading and upstaging on biochemical recurrence and cancer-specific survival

2019 ◽  
Author(s):  
Arnas Bakavicius ◽  
Mingaile Drevinskaite ◽  
Kristina Daniunaite ◽  
Marija Barisiene ◽  
Sonata Jarmalaite ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Surgical Margin ◽  
Positive Surgical Margin ◽  
Cancer Specific Survival ◽  
Increased Risk ◽  
Definitive Therapy ◽  
Treatment Naïve ◽  
The Impact ◽  
Mean Time

Abstract Significant numbers of prostate cancer (PCa) patients experience tumour upgrading and upstaging between prostate biopsy and radical prostatectomy (RP) specimens. The aim of our study was to investigate the role of grade and stage increase on surgical and oncological outcomes.Methods Upgrading and upstaging rates were analysed in 676 treatment-naïve PCa patients who underwent RP with subsequent follow-up. Positive surgical margin (PSM), biochemical recurrence (BCR), overall (OS) and cancer specific survival (CSS) were analysed according to upgrading and upstaging.Results Upgrading was observed in 29% and upstaging in 22% of PCa patients. Patients undergoing upgrading or upstaging were 1.5-times more likely to have a PSM on RP pathology. Both upgrading and upstaging were associated with increased risk for BCR: 1.8 and 2.1-times, respectively. Mean time to BCR after RP was 2.1 years in upgraded cases and 2.7 years in patients with no upgrading (p < 0.001), while mean time to BCR was 1.9 years in upstaged and 2.8 years in non-upstaged cases (p < 0.001). Grade and stage increase after RP were associated with inferior ten-year CSS rates: 78% vs. 96% for upgrading (p = 0.002) and 77% vs. 95% for upstaging (p = 0.001).Conclusions Currently used risk stratification models are associated with a substantial number of misdiagnosis. Pathological upgrading and upstaging have been associated with inferior surgical results, substantial higher risk of BCR and inferior rates of important oncological outcomes, what should be considered when counselling PCa patients at the time of diagnosis or after definitive therapy.

scholarly journals The Impact of Prostate Cancer Upgrading and Upstaging on Biochemical Recurrence and Cancer-Specific Survival

Medicina ◽  
2020 ◽  
Vol 56 (2) ◽  
pp. 61
Author(s):  
Arnas Bakavičius ◽  
Mingailė Drevinskaitė ◽  
Kristina Daniūnaitė ◽  
Marija Barisienė ◽  
Sonata Jarmalaitė ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Surgical Margin ◽  
Positive Surgical Margin ◽  
Cancer Specific Survival ◽  
Oncological Outcomes ◽  
Increased Risk ◽  
Definitive Therapy ◽  
The Impact ◽  
Mean Time

Background and Objectives: Significant numbers of prostate cancer (PCa) patients experience tumour upgrading and upstaging between prostate biopsy and radical prostatectomy (RP) specimens. The aim of our study was to investigate the role of grade and stage increase on surgical and oncological outcomes. Materials and Methods: Upgrading and upstaging rates were analysed in 676 treatment-naïve PCa patients who underwent RP with subsequent follow-up. Positive surgical margin (PSM), biochemical recurrence (BCR), metastasis-free survival (MFS), overall (OS) and cancer specific survival (CSS) were analysed according to upgrading and upstaging. Results: Upgrading was observed in 29% and upstaging in 22% of PCa patients. Patients undergoing upgrading or upstaging were 1.5 times more likely to have a PSM on RP pathology. Both upgrading and upstaging were associated with increased risk for BCR: 1.8 and 2.1 times, respectively. Mean time to BCR after RP was 2.1 years in upgraded cases and 2.7 years in patients with no upgrading (p < 0.001), while mean time to BCR was 1.9 years in upstaged and 2.8 years in non-upstaged cases (p < 0.001). Grade and stage increase after RP were associated with inferior MFS rates and ten-year CSS: 89% vs. 98% for upgrading (p = 0.039) and 87% vs. 98% for upstaging (p = 0.008). Conclusions: Currently used risk stratification models are associated with substantial misdiagnosis. Pathological upgrading and upstaging have been associated with inferior surgical results, substantial higher risk of BCR and inferior rates of important oncological outcomes, which should be considered when counselling PCa patients at the time of diagnosis or after definitive therapy.

DNA Methylation Signatures for Prediction of Biochemical Recurrence After Radical Prostatectomy of Clinically Localized Prostate Cancer

2013 ◽  
Vol 31 (26) ◽  
pp. 3250-3258 ◽  
Author(s):  
Christa Haldrup ◽  
Kamilla Mundbjerg ◽  
Else Marie Vestergaard ◽  
Philippe Lamy ◽  
Peter Wild ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
Radical Prostatectomy ◽  
Biochemical Recurrence ◽  
Cox Regression ◽  
Area Under The Curve ◽  
Specific Area ◽  
Dna Hypermethylation ◽  
Tissue Samples ◽  
Delayed Treatment

PurposeDiagnostic and prognostic tools for prostate cancer (PC) are suboptimal, causing overtreatment of indolent PC and risk of delayed treatment of aggressive PC. Here, we identify six novel candidate DNA methylation markers for PC with promising diagnostic and prognostic potential.MethodsMicroarray-based screening and bisulfite sequencing of 20 nonmalignant and 29 PC tissue specimens were used to identify new candidate DNA hypermethylation markers for PC. Diagnostic and prognostic potential was evaluated in 35 nonmalignant prostate tissue samples, 293 radical prostatectomy (RP) samples (cohort 1, training), and 114 malignant RP samples (cohort 2, validation) collected in Denmark, Switzerland, Germany, and Finland. Sensitivity and specificity for PC were evaluated by receiver operating characteristic analyses. Correlations between DNA methylation levels and biochemical recurrence were assessed using log-rank tests and univariate and multivariate Cox regression analyses.ResultsHypermethylation of AOX1, C1orf114, GAS6, HAPLN3, KLF8, and MOB3B was highly cancer specific (area under the curve, 0.89 to 0.98). Furthermore, high C1orf114 methylation was significantly (P < .05) associated with biochemical recurrence in multivariate analysis in cohort 1 (hazard ratio [HR], 3.10; 95% CI, 1.89 to 5.09) and was successfully validated in cohort 2 (HR, 3.27; 95% CI, 1.17 to 9.12). Moreover, a significant (P < .05) three-gene prognostic methylation signature (AOX1/C1orf114/HAPLN3), classifying patients into low- and high-methylation subgroups, was trained in cohort 1 (HR, 1.91; 95% CI, 1.26 to 2.90) and validated in cohort 2 (HR, 2.33; 95% CI, 1.31 to 4.13).ConclusionWe identified six novel candidate DNA methylation markers for PC. C1orf114 hypermethylation and a three-gene methylation signature were independent predictors of time to biochemical recurrence after RP in two PC patient cohorts.

scholarly journals MP07-02 THE IMPACT OF QUANTITY AND TYPE OF GLEASON PATTERN 4 ON BIOCHEMICAL RECURRENCE FOLLOWING RADICAL PROSTATECTOMY FOR PROSTATE CANCER

2016 ◽  
Vol 195 (4S) ◽  
Author(s):  
Blake Anderson ◽  
Shane Pearce ◽  
Bonnie Choy ◽  
Gregory Zagaja ◽  
Gladell Paner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Biochemical Recurrence ◽  
Gleason Pattern ◽  
The Impact

scholarly journals The Metabolic Syndrome and Biochemical Recurrence following Radical Prostatectomy

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Jennifer M. Post ◽  
Jennifer L. Beebe-Dimmer ◽  
Hal Morgenstern ◽  
Christine Neslund-Dudas ◽  
Cathryn H. Bock ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metabolic Syndrome ◽  
Radical Prostatectomy ◽  
Racial Differences ◽  
Biochemical Recurrence ◽  
African American Men ◽  
Racially Diverse ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Reduce Risk

Metabolic syndrome refers to a set of conditions that increases the risk of cardiovascular disease and has been associated with an increased risk of prostate cancer, particularly among African American men. This study aimed to estimate the association of metabolic syndrome with biochemical recurrence (BCR) in a racially diverse population. Among 383 radical prostatectomy patients, 67 patients had documented biochemical recurrence. Hypertension was significantly, positively associated with the rate of BCR (hazard ratio (HR) = 2.1; 95%  CI = 1.1, 3.8). There were distinct racial differences in the prevalence of individual metabolic syndrome components; however, the observed associations with BCR did not differ appreciably by race. We conclude that hypertension may contribute to a poorer prognosis in surgically treated prostate cancer patients. Our findings suggest that targeting components of the metabolic syndrome which are potentially modifiable through lifestyle interventions may be a viable strategy to reduce risk of BCR in prostate cancer.

Obesity and metabolic syndrome correlate with a higher risk of biochemical recurrence in high risk and intermediate risk prostate cancer patients who underwent robotic-assisted laparoscopic prostatectomy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5580-5580
Author(s):  
Shifeng Mao ◽  
Ralph Miller ◽  
John Lyne ◽  
Jeffrey Cohen ◽  
Arash Samiei
Keyword(s):  
Prostate Cancer ◽  
Metabolic Syndrome ◽  
Biochemical Recurrence ◽  
Surgical Margin ◽  
Positive Surgical Margin ◽  
Obese Patients ◽  
Robotic Assisted ◽  
Laparoscopic Prostatectomy ◽  
Increased Risk ◽  
Significant Difference

5580 Background: Obesity and metabolic syndrome (MS) is prevalent in our society, and have been linked to a higher incidence of prostate cancer (PCa). The relationship of obesity or MS and cancer control has yielded mixed results in previous studies. We examined the correlation between the incidence of biochemical recurrence (BCR) with MS and BMI in a cohort of patients with PCa who underwent robotic-assisted laparoscopic prostatectomy (RALP). Methods: A retrospective study of patients who underwent RALP at a single center from 2007 to 2015 was conducted. Parameters including preoperative BMI, fasting glucose, lipid profile, blood pressure, PSA, Gleason score, pathologic stage, time to BCR, and surgical margin status were analyzed. Patients were categorized in high (HR), intermediate (IR), and low-risk (LR) groups based on the National Comprehensive Cancer Network (NCCN) guidelines. WHO classification was used for MS criteria, and BCR was defined as two consecutive postoperative PSA volume of ≥ 0.2 ng/mL. Obesity is defined as BMI ≥30 kg/m2. Results: A total of 726 patients with 189 in HR, 471 in IR and 66 patients in LR groups were included in this study with the median age of 59 (interquartile range [IQR] 55-64) years old. The median follow-up from surgery was 38 (IQR 22-46) months. More obese patients were found in the HR group compared to IR/LR group (46.5% vs. 33.1%, p<0.01). There were also more patients with MS in the HR group compared to IR/LR group (36.5% vs. 12.0%, p<0.01). Obese patients had a higher rate of BCR across risk groups in comparison to non-obese patients 32.1% vs. 15.4% (P<0.001), specifically 68% vs. 40%(p<0.01) in HR group and 21.3% vs. 12.7% (p=0.035) in the IR group. Similarly, patients with MS had a higher rate of BCR in HR and IR groups in comparison to the patients without MS, 39.1% vs. 18.7% (P<0.01); specifically, 67.7% vs. 42.2% (p<0.01) in HR and 29% vs. 11.6% (p<0.01) in the IR group. No correlation between MS or obesity and BCR was observed in LR group. There was no statistically significant difference in the positive surgical margin rate between obese and non-obese cohorts in each risk group. Conclusions: Among HR and IR-PCa patietns who underwent RALP, both obesity and MS correlate with increased risk of BCR. There were significantly more obesity and MS in HR-PCa patients, suggesting a potential pathophysiologic interplay between obesity or MS and cancer progression.

Role of Salvage Radical Prostatectomy for Recurrent Prostate Cancer After Radiation Therapy

2005 ◽  
Vol 23 (32) ◽  
pp. 8198-8203 ◽  
Author(s):  
Andrew J. Stephenson ◽  
James A. Eastham
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Radical Prostatectomy ◽  
Local Recurrence ◽  
Salvage Therapy ◽  
Biochemical Recurrence ◽  
Specific Antigen ◽  
Cancer Control ◽  
Increased Risk ◽  
Salvage Radical Prostatectomy

Patients with isolated local recurrence of prostate cancer after radiation therapy may potentially be cured of their disease by salvage radical prostatectomy (RP). The stage-specific 5-year cancer-control rates of salvage RP resemble those of standard RP. However, the ability to effectively administer salvage treatment to patients with radiorecurrent disease is compromised by the lack of diagnostic tests with sufficient sensitivity and specificity to detect local recurrence at an early stage while it is amenable to local salvage therapy. By the time biochemical recurrence is declared using the current American Society for Therapeutic Radiology and Oncology definition, the majority of patients have advanced local disease, precluding successful local salvage therapy. When salvage RP is performed at prostate-specific antigen levels of 10 ng/mL or less, an estimated 70% of patients are free of disease at 5 years. With better patient selection and technical modifications, the morbidity associated with salvage RP has improved substantially. Rates of urinary incontinence and anastomotic stricture are acceptable, although one third of patients will experience these complications. Salvage cryotherapy is a minimally invasive alternative to salvage RP, but cancer-control rates appear to be inferior and it does not provide a clear advantage over salvage RP in terms of reduced morbidity. Patients with local recurrence after radiation therapy are at increased risk of metastatic progression and cancer-specific mortality. Currently, salvage RP represents the only curative treatment option for these patients. Salvage RP may favorably alter the natural history of biochemical recurrence after radiation therapy, but it must be instituted early in the course of recurrent disease to be effective.

scholarly journals Evaluation of The Tumor Volume From Surgical Specimens After Radical Prostatectomy and Its Clinical Impact on The Prognosis of Patients With Localized Prostate Cancer

2021 ◽  
Author(s):  
Hyeong Dong Yuk ◽  
Seok-Soo Byun ◽  
Sung Kyu Hong ◽  
Hakmin Lee
Keyword(s):  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Biochemical Recurrence ◽  
Tumor Volume ◽  
Risk Group ◽  
Surgical Margin ◽  
Localized Prostate Cancer ◽  
Positive Surgical Margin ◽  
Continuous Variables ◽  
The Mean

Abstract We evaluated the contribution of tumor volume (TV) to localized prostate cancer (PCa) patients’ prognosis. We retrospectively analyzed the data of 2,394 patients who underwent radical prostatectomy (RP) for localized PCa. The effect of TV volume on prostate cancer patients' prognosis was analyzed through Kaplan-Meier and Cox-proportional analysis. The mean prostate volume for all patients was 36.5 ± 15.4 cc, and the mean TV was 5.9 ± 8.3 cc. A significant positive relationship was observed between the classification by risk group in D’ Amico risk classification and the National Comprehensive Cancer Network risk group. (P < 0.001). The high TV showed significantly worse pathologic outcomes than the low TV in terms of high rates of extra-capsular extension, seminal vesicle invasion, and positive surgical margin (P < 0.05). The patients with high TV had significantly shorter biochemical recurrence-free survivals than those with low TV (P < 0.001). Finally, based on multivariate Cox-proportional analyses, TV was revealed to be an independent predictor of postoperative biochemical recurrence as both categorical (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.13–1.78, P = 0.003] and continuous variables (HR: 1.04, 95% CI: 1.04–1.05, P < 0.001). TV was revealed to be an independent prognostic factor in the postoperative biochemical recurrence. Patients with a high number of positive core and longer tumor length were significantly related to higher TV.

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