Active Surveillance in Younger Men With Prostate Cancer

Purpose The suitability of younger patients with prostate cancer (PCa) for initial active surveillance (AS) has been questioned on the basis of eventual treatment necessity and concerns of safety; however, the role of age on surveillance outcomes has not been well defined. Patients and Methods We identified men managed with AS at our institution with a minimum follow-up of 6 months. The primary study objective was to examine the association of age with risk of biopsy-based Gleason score upgrade during AS. We also examined the association of age with related end points, including overall biopsy-determined progression, definitive treatment, and pathologic and biochemical outcomes after delayed radical prostatectomy (RP), using descriptive statistics, the Kaplan-Meier method, and multivariable Cox proportional hazards regression. Results A total of 1,433 patients were followed for a median of 49 months; 74% underwent initial biopsy at a referring institution. Median age at diagnosis was 63 years, including 599 patients (42%) ≤ 60 years old and 834 (58%) > 60 years old. The 3- and 5-year biopsy-based Gleason score upgrade-free rates were 73% and 55%, respectively, for men ≤ 60 years old compared with 64% and 48%, respectively, for men older than 60 years ( P < .01). On Cox regression analysis, younger age was independently associated with lower risk of biopsy-based Gleason score upgrade (hazard ratio per 1-year decrease, 0.969 [95% CI, 0.956 to 0.983]; P < .01), and persisted upon restriction to men meeting strict AS inclusion criteria. There was no significant association between younger age and risk of definitive treatment or risk of biochemical recurrence after delayed RP. Conclusion Younger patient age was associated with decreased risk of biopsy-based Gleason score upgrade during AS but not with risk of definitive treatment in the intermediate term. AS represents a strategy to mitigate overtreatment in young patients with low-risk PCa in the early term.

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Differences among Men on Active Surveillance for Very Low-Risk Prostate Cancer Detected Through Population-Based versus Opportunistic Prostate-Specific Antigen-Screening

Urologia Internationalis ◽

10.1159/000368417 ◽

2015 ◽

Vol 94 (3) ◽

pp. 330-336

Author(s):

Marco Randazzo ◽

Josef Beatrice ◽

Andreas Huber ◽

Rainer Grobholz ◽

Lukas Manka ◽

...

Keyword(s):

Prostate Cancer ◽

Active Surveillance ◽

Cox Regression ◽

Screening Program ◽

Specific Antigen ◽

Population Based ◽

Low Risk ◽

Cox Regression Analysis ◽

Risk Prostate Cancer ◽

Low Risk Prostate Cancer

Introduction: Very low-risk prostate cancer (PCa) is being increasingly managed by active surveillance (AS). Our aim was to assess the influence of the origin of diagnosis on PCa characteristics and treatment rates among men with very low-risk PCa in our prospective AS cohort. Methods: Overall, 191 men with very low-risk PCa fulfilling Epstein-criteria underwent protocol-based AS. These men originated either from the prospective population-based screening program (P-AS) or were diagnosed by opportunistic screening (O-AS). Results: Overall, n = 86 (45.0%) originated from the P-AS group, whereas n = 105 (55.0%) from the O-AS group. On univariate Cox regression analysis, age (HR 0.96, 95% CI 0.92-1.00; p = 0.05), origin of diagnosis (HR 0.72, 95% CI 0.41-1.28; p = 0.001), number of positive cores (HR 2.15, 95% CI 1.18-3.90; p = 0.01) and maximum core involvement (HR 1.03, 95% CI 0.99-1.05; p = 0.05) were predictors for treatment necessity. On multivariate analysis, age (HR 0.95, 95% CI 0.89-0.99; p = 0.05), number of positive cores (HR 2.07, 95% CI 1.10-3.88; p = 0.02), maximum core involvement (HR 1.03, 95% CI 1.00-1.06; p = 0.04) but not origin of diagnosis were independent predictors for treatment necessity. Four men developed biochemical recurrence (all from O-AS group [p = 0.05]). Conclusion: The origin of PCa diagnosis in men undergoing AS had no influence on disease progression and treatment necessity.

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Chromogranine A and neuron-specific enolase as the main predictors of survival for hormone-refractory prostate cancer (HRPC) patients

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15594 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15594-15594

Author(s):

A. Banu ◽

E. Banu ◽

D. Dionysopoulos ◽

J. Medioni ◽

F. Scotte ◽

...

Keyword(s):

Prostate Cancer ◽

Regression Analysis ◽

Gleason Score ◽

Cox Regression ◽

Neuron Specific Enolase ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Metastatic Sites ◽

Ecog Ps ◽

The Impact

15594 Background: Clinical studies suggested that the extent of neuro-endocrine differentiation in prostate cancer increases with tumor progression and the development of androgen refractory status. Chromogranine (CgA) and neuron-specific enolase (NSE) are currently explored as surrogate markers. Methods: Eligible chemonaive HRPC patients (pts) were required to have an ECOG performance status (PS) ≤ 2. Before chemotherapy initiation, we quantified NSE, CgA and PSA in the venous blood using commercial kits. We evaluated the impact of baseline NSE, CgA and PSA on overall survival (OS) using multivariate Cox regression analysis, stratified by chemotherapy regimen. Secondary, we studied the correlation between NSE, CgA, PSA and other important variables as age, Gleason score, hemoglobin, number of metastatic sites and ECOG PS. Results: Data of 39 consecutive HRPC pts treated between December 01–06 in a single French center were analyzed. Chemotherapy was docetaxel-based in 92% of pts. Median age was 71 years (range 51–86) and 79% of pts had bone metastases. Elevated NSE, CgA and PSA were observed in 6, 9 and 30% of pts and median levels were 10.8, 67 and 23.3 ng/mL, respectively. Gleason 8–10 was present in 49% of pts. Significant correlations were observed between NSE and the number of metastatic sites and between CgA and age, hemoglobin and ECOG PS. The baseline PSA was only correlated with Gleason score. Median OS for the entire cohort was 24.4 months (95% CI, 18.8–29.9). Two-year OS was 15% and only 19% of patients are dead. Univariate Cox regression analysis showed only a significant relationship between OS and baseline NSE: hazard ratio= 1.09 (95% CI, 1.03–1.16), P=0.006. No other known prognostic factors are related to outcome. A multivariate model including baseline NSE, CgA, ECOG PS and Gleason score showed a 15% rise of the risk of death related to NSE (borderline P value). Conclusions: NSE was the most powerful predictor of survival for HRPC pts. Our results emphasize the theory that cells secreting NSE are chemoresistant, with a negative impact on OS. No significant financial relationships to disclose.

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Loss of miR-378 in prostate cancer, a common regulator of KLK2 and KLK4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients

Biological Chemistry ◽

10.1515/hsz-2014-0150 ◽

2014 ◽

Vol 395 (9) ◽

pp. 1095-1104 ◽

Cited By ~ 19

Author(s):

Margaritis Avgeris ◽

Konstantinos Stravodimos ◽

Andreas Scorilas

Keyword(s):

Prostate Cancer ◽

Gleason Score ◽

Cox Regression ◽

Elevated Serum ◽

Recurrence Risk ◽

Tumor Stage ◽

Short Term ◽

Prostate Hyperplasia ◽

Cox Regression Analysis ◽

Improve Risk Stratification

Abstract A large number of prostate cancer (PCa) patients receive treatment without significant benefits, strengthening the need for accurate prognosis, which can be supported by the study of miRNAs. In silico specificity analysis was performed for the identification of miRNAs able to regulate KLK2 and KLK4 expression. Total RNA was extracted from prostate tissues obtained from PCa and benign prostate hyperplasia patients. Thereafter, RNA was polyadenylated and reverse transcribed to cDNA, which was used for qPCR analysis. miR-378 was predicted to target both KLK2 and KLK4 and downregulated levels detected in PCa patients (p=0.050). The reduction of miR-378 was correlated with higher Gleason score (p=0.018), larger diameter tumors (p=0.034), and elevated serum PSA (p=0.006). Regarding prognosis, miR-378 was able to improve risk stratification according to Gleason score or tumor stage, while higher risk to recur highlighted for the patients expressing lower miR-378 levels. Finally, the loss of miR-378 was able to predict the short-term relapse of ‘high’- and ‘very high’-recurrence-risk patients, independent of Gleason score, tumor stage, PSA, and age as indicated by Kaplan-Meier survival curves (p=0.030) and multivariate Cox regression analysis (p=0.018). In conclusion, loss of miR-378 expression increases the risk for PCa progression and relapse, despite active treatment.

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Does perineural invasion in a radical prostatectomy specimen predict biochemical recurrence in men with prostate cancer?

Canadian Urological Association Journal ◽

10.5489/cuaj.2619 ◽

2015 ◽

Vol 9 (5-6) ◽

pp. 252 ◽

Cited By ~ 12

Author(s):

Fairleigh Reeves ◽

Christopher M. Hovens ◽

Laurence Harewood ◽

Shayne Battye ◽

Justin S. Peters ◽

...

Keyword(s):

Prostate Cancer ◽

Regression Analysis ◽

Radical Prostatectomy ◽

Gleason Score ◽

Biochemical Recurrence ◽

Perineural Invasion ◽

Cox Regression ◽

Clinicopathological Parameters ◽

Positive Surgical Margin ◽

Cox Regression Analysis

Introduction: The ability of perineural invasion (PNI) in radical prostatectomy (RP) specimens to predict biochemical recurrence (BCR) is unclear. This study investigates this controversial question in a large cohort.Methods: A retrospective analysis was undertaken of prospectively collected data from 1497 men who underwent RP (no neoadjuvant therapy) for clinically localized prostate cancer. The association of PNI at RP with other clinicopathological parameters was evaluated. The correlation of clinicopathological factors and BCR (defined as prostate-specific antigen [PSA] >0.2 ng/mL) was investigated with univariable and multivariable Cox regression analysis in 1159 men.Results: PNI-positive patients were significantly more likely to have a higher RP Gleason score, pT3 disease, positive surgical margins, and greater cancer volume (p < 0.0005). The presence of PNI significantly correlated with BCR on univariable (hazard ratio 2.30, 95% confidence interval 1.50–3.55, p < 0.0005), but not multivariable analysis (p = 0.602). On multivariable Cox regression analysis the only independent prognostic factors were preoperative PSA, RP Gleason score, pT-stage, and positive surgical margin status. These findings are limited by a relatively short follow-up time and retrospective study design.Conclusions: PNI at RP is not an independent predictor of BCR. Therefore, routine reporting of PNI is not indicated. Future research should be targeted at the biology of PNI to increase the understanding of its role in prostate cancer progression.

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PVT1 Expression Is a Predictor for Poor Survival of Prostate Cancer Patients

Technology in Cancer Research & Treatment ◽

10.1177/1533033820971610 ◽

2021 ◽

Vol 20 ◽

pp. 153303382097161

Author(s):

Jianhua Liu ◽

Yanqing Li ◽

Qiqi Zhang ◽

Chaoxiang Lv ◽

Mingwei Wang ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Gleason Score ◽

Roc Curve ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Cox Regression ◽

Molecular Therapy ◽

Vital Status ◽

Cox Regression Analysis

Objective: Dysregulation of long noncoding RNA is associated with a variety of cancers and LncRNA has anticancer or carcinogenic activities. PVT1, as a long noncoding RNA, plays an important role in the development of cancer. Methods: We use R to download and analyze the data in TCGA database. ROC curve is generated to evaluate the significance of PVT1 expression for the diagnosis of prostate cancer. Chi-square test is used to test correlation between PVT1 expression and clinical pathological features. Survival curve and univariate and multivariate cox regression analysis is performed to compare differences in the effect on the survival rate between PVT1 high expression and low expression. Results: The expression of PTV1 in tumor tissues was significantly higher than that in normal tissues(P<2.2e-16). The difference of PTV1 expression was observed according to vital status (P = 0.0051) and Gleason score (P = 0.0012). The expression of PTV1 is significantly associated with T classification (P < 0.0001), N classification (P = 0.0499), PSA (P = 0.0001), Gleason Score (P < 0.0001), targeted molecular therapy (P = 0.0264) and vital status(P = 0.0036). The area under the ROC curve (AUC) was 0.860, which revealed PTV1 expression has excellent diagnostic value in prostate cancer. Patients with high PVT1 expression had a worse prognosis. Conclusions: PVT1 expression may be a biomarker for the diagnosis and prognosis of prostate cancer.

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Prognostic Models for Patients With Gleason Score 9 Prostate Cancer: A Population-Based Study

Frontiers in Oncology ◽

10.3389/fonc.2021.633312 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jianhui Qiu ◽

Desheng Cai ◽

Zixin Wang ◽

Jingcheng Zhou ◽

Yanqing Gong ◽

...

Keyword(s):

Prostate Cancer ◽

Marital Status ◽

Gleason Score ◽

Cox Regression ◽

Population Based ◽

Competing Risk ◽

Age At Diagnosis ◽

Population Based Study ◽

Cox Regression Analysis ◽

Gleason Pattern

Purpose: Gleason score (GS) system is one of the most widely used histological grading methods for prostate cancer (PCa) all over the world. GS can be obtained by adding the primary Gleason pattern (GP) and secondary GP. Different proportions of GP 4 and GP 5 in prostate specimens can both lead to GS 9. In this study, we explored whether GP 5 + 4 or GP 4 + 5 was associated with different prognoses among patients with GS 9 PCa.Materials and methods: A retrospective population-based study was conducted on 10,124 subjects diagnosed with GS 9 PCa between 2004 and 2009 from the Surveillance, Epidemiology, and End Results program. A 1:1 propensity-score matching (PSM) was performed to balance the baseline characteristics between the GP 4 + 5 and 5 + 4 groups and to compare the prognoses between the two groups. Cox regression analysis and Fine-Gray competing risk regression models were adopted to screen the covariates significantly associated with all-cause mortality (ACM) and cancer-specific mortality (CAM).Results: GP 5 + 4 was associated with higher risks of ACM and CSM before or after PSM than GP 4 + 5. In the original cohort, there were eight independent predictors for ACM, which were age at diagnosis, race, AJCC NM stage, PSA levels, treatments, GP, and marital status, confirmed by the Cox analysis; and nine independent predictors for CSM, which were age at diagnosis, race, AJCC TNM stage, PSA levels, treatments, GP, and marital status, confirmed by the competing-risk model.Conclusion: GP 5 + 4 was associated with a poorer overall survival and cancer-specific survival compared with GP 4 + 5.

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Five-year follow-up of active surveillance for prostate cancer: A Canadian community-based urological experience

Canadian Urological Association Journal ◽

10.5489/cuaj.2186 ◽

2014 ◽

Vol 8 (11-12) ◽

pp. 768 ◽

Cited By ~ 5

Author(s):

J. Matthew J. Andrews ◽

James E. Ashfield ◽

Michael Morse ◽

Thomas F. Whelan

Keyword(s):

Prostate Cancer ◽

Median Time ◽

Active Surveillance ◽

Cox Regression ◽

Specific Antigen ◽

Cox Regression Analysis ◽

Factors Associated ◽

Psa Density ◽

Prostate Biopsies

Introduction: We assessed oncological outcomes of active surveillance (AS) using a community database and identified factors associated with disease reclassification on surveillance biopsy.Methods: A retrospective review was performed on 200 men on AS. Prostate-specific antigen (PSA) was measured every 3 to 6 months. Prostate biopsies were performed every 1 to 4 years, and at the individual physician’s discretion. Disease reclassification was defined as clinical T1 to cT2 progression, or histologically as >2 cores positive, Gleason score >6, or >50% core involvement on surveillance biopsy. Multivariate Cox regression analysis evaluated factors associated with disease reclassification. Kaplan-Meier survival curves were plotted.Results: We assessed a heterogeneous cohort of 86 patients, with a median age 67.2 years, who received ≥1 surveillance biopsies. The median follow-up was 5.2 years. The median times to first and second surveillance biopsies were 730 and 763 days, respectively. Overall, 47% of patients were reclassified on surveillance biopsy after a median 2.1 years. Factors associated with disease reclassification were PSA density >0.20 (p < 0.0001, hazard ratio [HR] 4.55, 95% confidence interval [CI] 2.116–9.782) and ≥3 positive cores (p = 0.0152, HR 3.956, 95% CI 1.304–12.003) at diagnosis, and number of positive cores on surveillance biopsy. In total, 25 (29%) patients received delayed intervention, with a median time to intervention of 2.6 years. The median time on AS was 4.4 years, with an overall survival of 95% and prostate-specific survival of 100%.Conclusions: Our community study supports AS to reduce over treatmentof prostate cancer. PSA density >0.20 and ≥3 cores positive are associated with disease reclassification on surveillance biopsy.

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5 Gleason score-associated gene signatures serve as novel biomarkers for identifying early recurring events and contributing to early diagnosis for Prostate Adenocarcinoma

10.21203/rs.3.rs-41108/v1 ◽

2020 ◽

Author(s):

Lingyu Zhang ◽

Yu Li ◽

Weiwei Liu ◽

Xuchu Wang ◽

Ying Ping ◽

...

Keyword(s):

Prostate Cancer ◽

Gleason Score ◽

Cox Regression ◽

Tnm Classification ◽

Cox Proportional Hazards ◽

The Cancer Genome Atlas ◽

Prognostic Models ◽

Diagnostic Efficiency ◽

Cox Regression Analysis ◽

Gene Signatures

Abstract Background: Prostate cancer (PCa) recurrence leads to much higher mortality than those without recurring events. Early and accurate laboratory diagnosis is particularly important for early identification of patients at high risk of recurrence and to benefit from additional systemic intervention. This study aimed to develop efficient and accurate Prostate Cancer diagnostic and prognostic biomarkers for the identification of initial tumor new events. Methods: Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) data portal were utilized to obtain differentially expressed genes (DEGs) and clinical trait information in PCa. WGCNA analysis obtained the most relevant clinical traits and genes enriched in several modules. Univariate Cox regression analysis and multivariate Cox proportional hazards (Cox-PH) model was employed to candidate gene signatures related to Disease-Free Interval (DFI). Internal and external cohort was utilized to test and validate the validity, accuracy, and clinical utility of prognostic models.Results: We constructed and optimized a valid and credible model for predicting patient outcomes, based on 5 Gleason score-associated gene signatures (ZNF695, CENPA, TROAP, BIRC5, KIF20A). Furthermore, ROC and Kaplan-Meier analysis revealed higher diagnostic efficiency for PCa and predictive effectiveness in tumor recurrence and metastasis. Calibration curve also revealed high prediction accuracy in internal TCGA cohort and external GEO cohort. The model was prognostically significant in the stratified cohort, including TNM classification and Gleason score, and was deemed to be an independent PCa prognostic factor, and superioring to other clinicopathological characteristics. On the other hand, we also measured the correlation between gene signatures’ expression and inflammation landscape. 5 gene signatures were significantly positively correlated with tumor purity and negatively correlated with the immersion levels of CD8+ T cells. Conclusions: Our study identified and validated 5 gene signatures as biomarkers for prostate cancer diagnosis, providing an assessment of DFI while predicting tumor progression, possibly providing novel theories for the treatment of prostate cancer.

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