scholarly journals Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer

2013 ◽  
Vol 31 (14) ◽  
pp. 1748-1757 ◽  
Author(s):  
Elena Castro ◽  
Chee Goh ◽  
David Olmos ◽  
Ed Saunders ◽  
Daniel Leongamornlert ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Survival Outcomes ◽  
Nodal Involvement ◽  
Poor Survival ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Clinicopathologic Characteristics ◽  
Cox Regression Analysis

Purpose To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. Patients and Methods This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1). Results PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. Conclusion Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients.

Percentage of positive biopsy cores to predict distant metastasis of prostate cancer after definitive radiation therapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 80-80
Author(s):  
J. Huang ◽  
L. L. Kestin ◽  
F. A. Vicini ◽  
S. G. Williams ◽  
H. Ye ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Distant Metastasis ◽  
Prognostic Value ◽  
Cox Regression ◽  
Androgen Deprivation ◽  
Biochemical Failure ◽  
Clinical Failure ◽  
Cox Regression Analysis ◽  
Positive Biopsy

80 Background: To assess the prognostic value of percentage of positive biopsy cores (PPC) and perineural invasion (PNI) in predicting clinical outcome following radiotherapy (RT) for prostate cancer. Methods: One thousand and fifty-six patients with clinical stage T1-T3 N0 M0 prostate cancer, who had ≥ 4 biopsy cores sampled and complete biopsy core data available, were treated with either adaptive image-guided RT (median 75.6 Gy, n=387), low-dose EBRT (median 66.6 Gy, n=393), or EBRT and high-dose rate brachytherapy boost (n=276) at William Beaumont Hospital (1993-2004). Neoadjuvant and/or adjuvant androgen deprivation (AD) were given to 253 patients (24%). Multivariate cox regression analysis included PPC, gleason score, PSA, T stage, PNI, RT dose, androgen deprivation, and age. Biochemical failure (BF) was scored according to the Phoenix definition. Clinical failure (CF) was defined as any locoregional recurrence (LRR) or distant metastasis (DM). Median follow-up was 7.6 years. Results: Median cores sampled was 7, median PPC was 33%, and 18% had PNI. On univariate Cox regression, both PPC and PNI were predicators of biochemical failure and clinical failure (all P<0.05). On multivariate Cox regression, PPC, either as continuous or categorical variable, remained an independent predicator of BF, CF, DM, cause-specific survival, and overall survival (all P<0.05). PPC of >50% was associated with significantly higher DM (HR 4.01, 95% CI 1.86-8.61), and its independent predicative value remained significant whether AD was given or not (all P<0.05). Combining ≤50% vs ≥50% PPC with NCCN risk group stratification demonstrated added prognostic value of DM for intermediate-risk (HR 5.44, 95% CI 1.78-16.6) and high-risk groups (HR 4.39, 95% CI 1.70-2.84), with or without AD (all P<0.05). On multivariate Cox regression, PNI was an independent predicator of LRR only (HR 2.51, 95% CI 1.18-5.33). Conclusions: PPC is an independent and powerful predicator of DM for intermediate- and high-risk prostate cancer, regardless the use of AD. It should be considered for risk stratification and when designing for future trials testing adjuvant treatment after definitive RT for prostate cancer. No significant financial relationships to disclose.

Impact of metformin on prostate cancer (PC) outcomes in the E3805 CHAARTED trial.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 181-181 ◽  
Author(s):  
David Frazier Jarrard ◽  
Yu-Hui Chen ◽  
Glenn Liu ◽  
Michael Anthony Carducci ◽  
Mario A. Eisenberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Local Therapy ◽  
Cox Proportional Hazards ◽  
Clinicopathologic Characteristics ◽  
Cox Regression Analysis ◽  
Anticancer Properties ◽  
Cox Proportional Hazards Models

181 Background: To evaluate whether metformin (Met) a widely-used, nontoxic oral antidiabetic drug with putative anticancer properties leads to improvements in prostate cancer (PC) outcomes in the CHAARTED trial. Methods: In the CHAARTED database where metformin use at baseline was recorded prospectively, we identified patients with metastatic PC who underwent either ADT alone or ADT and docetaxel (D) chemotherapy. Cox proportional hazards models were used to determine the effect of Metformin on outcomes. Results: A total of 788 patients (median age, 63 y) had complete data after randomization. Comparison of ADT+D+Met (n = 39) to ADT+D (n = 357) and ADT+Met (n = 29) to ADT alone (n = 363) revealed similar clinicopathologic characteristics. Cause of death was PC in 13(81%) of ADT+D+Met, 72(85%) ADT+D, 9(82%) ADT+Met and 105(84%) ADT alone groups. See table for PC outcomes and overall survival by metformin use. Cox regression analysis for overall survival stratified by stratification factors at randomization demonstrates Met use was associated with a trend for worse overall survival (HR 1.47 95%CI: [0.95,2.26], p = 0.08) with adjustment for treatment arm and prior local therapy. In contrast, ADT+D use (HR 0.62; 95%CI: [0.47,0.81]) and prior local therapy with surgery or radiation (HR 0.56; 95% CI: [0.38, 0.82]) were associated with improved survival. Conclusions: In this study, baseline metformin did not improve PC outcomes. Partial support and drug supply by Sanofi. Clinical trial information: NCT00309985. [Table: see text]

scholarly journals Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2844
Author(s):  
Christopher J. D. Wallis ◽  
Bobby Shayegan ◽  
Scott C. Morgan ◽  
Robert J. Hamilton ◽  
Ilias Cagiannos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Clinical Decision Making ◽  
Cox Regression ◽  
De Novo ◽  
Population Based ◽  
Population Based Study ◽  
Cox Regression Analysis ◽  
Lymphocyte Ratio ◽  
Laboratory Markers

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan–Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71–83). The median survival was 18 months (IQR: 10–31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

Perioperative Activation of Disseminated Tumor Cells in Bone Marrow of Patients With Prostate Cancer

2009 ◽  
Vol 27 (10) ◽  
pp. 1549-1556 ◽  
Author(s):  
Dorothea Weckermann ◽  
Bernhard Polzer ◽  
Thomas Ragg ◽  
Andreas Blana ◽  
Günter Schlimok ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Tumor Cells ◽  
Cox Regression ◽  
Systemic Disease ◽  
Disseminated Tumor Cells ◽  
Comparative Genomic ◽  
Prognostic Impact ◽  
Primary Tumors ◽  
Cox Regression Analysis

Purpose The outcome of prostate cancer is highly unpredictable. To assess the dynamics of systemic disease and to identify patients at high risk for early relapse we followed the fate of disseminated tumor cells in bone marrow for up to 10 years and genetically analyzed such cells isolated at various stages of disease. Patients and Methods Nine hundred bone marrow aspirates from 384 patients were stained using the monoclonal antibody A45-B/B3 directed against cytokeratins 8, 18, and 19. Log-rank statistics and Cox regression analysis were applied to determine the prognostic impact of positive cells detected before surgery (244 patients) and postoperatively (214 patients). Samples from primary tumors (n = 55) and single disseminated tumor cells (n = 100) were analyzed by comparative genomic hybridization. Results Detection of cytokeratin-positive cells before surgery was the strongest independent risk factor for metastasis within 48 months (P < .001; relative risk [RR], 5.5; 95% CI, 2.4 to 12.9). In contrast, cytokeratin-positive cells detected 6 months to 10 years after radical prostatectomy were consistently present in bone marrow with a prevalence of approximately 20% but had no influence on disease outcome. Characteristic genotypes of cytokeratin-positive cells were selected at manifestation of metastasis. Conclusion Cytokeratin-positive cells in the bone marrow of prostate cancer patients are only prognostically relevant when detected before surgery. Because we could not identify significant genetic differences between pre- and postoperatively isolated tumor cells before manifestation of metastasis, we postulate the existence of perioperative stimuli that activate disseminated tumor cells. Patients with cytokeratin-positive cells in bone marrow before surgery may therefore benefit from adjuvant therapies.

Factors Predictive of Distant Metastases in Patients With Breast Cancer Who Have a Pathologic Complete Response After Neoadjuvant Chemotherapy

2005 ◽  
Vol 23 (28) ◽  
pp. 7098-7104 ◽  
Author(s):  
Ana M. Gonzalez-Angulo ◽  
Sean E. McGuire ◽  
Thomas A. Buchholz ◽  
Susan L. Tucker ◽  
Henry M. Kuerer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Distant Metastases ◽  
Complete Response ◽  
Cox Regression Analysis

Purpose To identify clinicopathological factors predictive of distant metastasis in patients who had a pathologic complete response (pCR) after neoadjuvant chemotherapy (NC). Methods Retrospective review of 226 patients at our institution identified as having a pCR was performed. Clinical stage at diagnosis was I (2%), II (36%), IIIA (27%), IIIB (23%), and IIIC (12%). Eleven percent of all patients were inflammatory breast cancers (IBC). Ninety-five percent received anthracycline-based chemotherapy; 42% also received taxane-based therapy. The relationship of distant metastasis with clinicopathologic factors was evaluated, and Cox regression analysis was performed to identify independent predictors of development of distant metastasis. Results Median follow-up was 63 months. There were 31 distant metastases. Ten-year distant metastasis-free rate was 82%. Multivariate Cox regression analysis using combined stage revealed that clinical stages IIIB, IIIC, and IBC (hazard ratio [HR], 4.24; 95% CI, 1.96 to 9.18; P < .0001), identification of ≤ 10 lymph nodes (HR, 2.94; 95% CI, 1.40 to 6.15; P = .004), and premenopausal status (HR, 3.08; 95% CI, 1.25 to 7.59; P = .015) predicted for distant metastasis. Freedom from distant metastasis at 10 years was 97% for no factors, 88% for one factor, 77% for two factors, and 31% for three factors (P < .0001). Conclusion A small percentage of breast cancer patients with pCR experience recurrence. We identified factors that independently predicted for distant metastasis development. Our data suggest that premenopausal patients with advanced local disease and suboptimal axillary node evaluation may be candidates for clinical trials to determine whether more aggressive or investigational adjuvant therapy will be of benefit.

scholarly journals Tertiary Gleason Pattern 5 is An Independent Risk Factor for Prostate Cancer with GS 7: A Retrospective Study from China.

2021 ◽  
Author(s):  
Desheng Cai ◽  
Zixin Wang ◽  
Yu Fan ◽  
Lin Cai ◽  
Kan Gong
Keyword(s):  
Prostate Cancer ◽  
Risk Factor ◽  
Independent Risk Factor ◽  
Cox Regression ◽  
Prostate Volume ◽  
Surgical Margin ◽  
Rank Test ◽  
Positive Surgical Margin ◽  
Cox Regression Analysis ◽  
Gleason Pattern

Abstract Background: Tertiary Gleason pattern 5 (TGP5) was found to be prognostic in prostate cancer (PCa) after radical prostatectomy (RP), but related data from China was rare. Our study was aimed at finding out the effect of TGP5 on PCa with Gleason score (GS) 7 and supplementing data from China in this field.Methods: A total of 229 cases met with inclusion criteria during Jan. 2014 to Dec. 2018 were reviewed. Cases were divided into GS 7 without TGP5 and GS 7 with TGP5. We compared age at diagnosis, preoperative PSA level, prostate volume, PSA density (PSAD), GS variation, clinical T staging, pathological T staging, T staging variation, extra-prostatic extension (EPE), positive surgical margin (PSM) and seminal vesicle invasion (SVI) between the groups. Effects of TGP5 on prognosis of PCa with GS 7 were evaluated using biochemical recurrence (BCR) as the primary end point.Results: TGP5 was related to higher PSM rate (P=0.001) and BCR rate (P=0.009) but not related to higher preoperative PSA level, larger prostate volume, higher PSAD, GS upgrade, poorer clinical/pathological T staging, T upstaging, EPE and SVI (all P>0.05). The median follow-up time was 24 months (interquartile range 17.5-45.5). TGP5 was an independent risk factor to PCa with GS 7 after RP using Kaplan-Meier log-rank test (P=0.018). Both univariable and multivariable cox-regression analysis pointed out that TGP5 increased the incidence of BCR in PCa with GS 7 (P<0.05). Stratified analyses were also done.Conclusion: TGP5 is an independent risk factor predicting of BCR after RP in PCa with GS 7 from China. TGP5 is related to higher PSM rate and BCR incidence. It is time to renew the contemporary Grading Group system with the consideration of TGP.

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.

scholarly journals Identification and Validation of a Prognostic 5-Protein Signature for Biochemical Recurrence Following Radical Prostatectomy for Prostate Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Daojun Lv ◽  
Zanfeng Cao ◽  
Wenjie Li ◽  
Haige Zheng ◽  
Xiangkun Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Analysis ◽  
Biochemical Recurrence ◽  
Cox Regression ◽  
Characteristic Curve ◽  
The Cancer Genome Atlas ◽  
Medical Decision ◽  
Regression Analyses ◽  
Cox Regression Analysis ◽  
Protein Signature

Background: Biochemical recurrence (BCR) is an indicator of prostate cancer (PCa)-specific recurrence and mortality. However, there is a lack of an effective prediction model that can be used to predict prognosis and to determine the optimal method of treatment for patients with BCR. Hence, the aim of this study was to construct a protein-based nomogram that could predict BCR in PCa.Methods: Protein expression data of PCa patients was obtained from The Cancer Proteome Atlas (TCPA) database. Clinical data on the patients was downloaded from The Cancer Genome Atlas (TCGA) database. Lasso and Cox regression analyses were conducted to select the most significant prognostic proteins and formulate a protein signature that could predict BCR. Subsequently, Kaplan–Meier survival analysis and Cox regression analyses were conducted to evaluate the performance of the prognostic protein-based signature. Additionally, a nomogram was constructed using multivariate Cox regression analysis.Results: We constructed a 5-protein-based prognostic prediction signature that could be used to identify high-risk and low-risk groups of PCa patients. The survival analysis demonstrated that patients with a higher BCR showed significantly worse survival than those with a lower BCR (p &lt; 0.0001). The time-dependent receiver operating characteristic curve showed that the signature had an excellent prognostic efficiency for 1, 3, and 5-year BCR (area under curve in training set: 0.691, 0.797, 0.808 and 0.74, 0.739, 0.82 in the test set). Univariate and multivariate analyses indicated that this 5-protein signature could be used as independent prognosis marker for PCa patients. Moreover, the concordance index (C-index) confirmed the predictive value of this 5-protein signature in 3, 5, and 10-year BCR overall survival (C-index: 0.764, 95% confidence interval: 0.701–0.827). Finally, we constructed a nomogram to predict BCR of PCa.Conclusions: Our study identified a 5-protein-based signature and constructed a nomogram that could reliably predict BCR. The findings might be of paramount importance for the prediction of PCa prognosis and medical decision-making.Subjects: Bioinformatics, oncology, urology.

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