scholarly journals A novel serum biomarker quintet reveals added prognostic value when combined with standard clinical parameters in prostate cancer patients by predicting biochemical recurrence and adverse pathology

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259093
Author(s):  
Alcibiade Athanasiou ◽  
Pierre Tennstedt ◽  
Anja Wittig ◽  
Ramy Huber ◽  
Oliver Straub ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Clinical Stage ◽  
Low Risk ◽  
Risk Patient ◽  
Clinical Grade ◽  
Grade Group ◽  
Kaplan Meier ◽  
Proposed Model ◽  
Prognostic Utility

The objective was to determine the prognostic utility of a new biomarker combination in prostate cancer (PCa) patients undergoing Radical Prostatectomy (RP). Serum samples and clinical data of 557 men who underwent RP for PCa with pathological stage (pT) <3 at Martini Clinic (Hamburg, Germany) were used for analysis. Clinical Grade Group and clinical stage was determined using biopsy samples while tumor marker concentrations were measured in serum using immunoassays. The prognostic utility of the proposed marker combination was assessed using Cox proportional hazard regression and Kaplan-Meier analysis. The performance was compared to the Cancer of the Prostate Risk Assessment (CAPRA) score in the overall cohort and in a low-risk patient subset. A multivariable model comprising fibronectin 1, galectin-3-binding protein, lumican, matrix metalloprotease 9, thrombospondin-1 and PSA together with clinical Grade Group (GG) and clinical stage (cT) was created. The proposed model was a significant predictor of biochemical recurrence (BCR) (HR 1.29 per 5 units score, 95%CI 1.20–1.38, p<0.001). The Kaplan-Meier analysis showed that the proposed model had a better prediction for low-risk disease after RP compared to CAPRA (respectively 5.0% vs. 9.1% chance of BCR). In a pre-defined low risk population subset, the risk of BCR using the proposed model was below 5.2% and thus lower when compared to CAPRA = 0–2 (9%), GG<2 (7%) and NCCN = low-risk (6%) subsets. Additionally, the proposed model could significantly (p<0.001) discriminate patients with adverse pathology (AP) events at RP from those without. In conclusion, the proposed model is superior to CAPRA for the prediction of BCR after RP in the overall cohort as well as a in a pre-defined low risk patient population subset. It is also significantly associated with AP at RP.

scholarly journals Pathologic and biochemical outcomes among African American and Caucasian men with low-risk prostate cancer in the search database: Implications for active surveillance candidacy.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 76-76
Author(s):  
Michael S. Leapman ◽  
Stephen J. Freedland ◽  
William J Aaronson ◽  
Christopher J. Kane ◽  
Martha K. Terris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Biochemical Recurrence ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Cox Proportional Hazards ◽  
Low Risk ◽  
Equal Access ◽  
Caucasian Race ◽  
Caucasian Men

76 Background: Racial disparities in the incidence and risk profile of prostate cancer (PCa) at diagnosis among African American (AA) men are well reported, however it remains unclear whether AA race is independently associated with adverse pathological findings among men with clinical low risk disease. Methods: We conducted a retrospective analysis among 895 men, with clinical low risk (Gleason 3+3, clinical stage ≤T2a, PSA≤10 ng/mL) treated with immediate radical prostatectomy within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. We evaluated clinical and demographic characteristics by AA or Caucasian race. Associations between AA versus Caucasian race with pathologic Gleason upgrade (≥3+4), major upgrade (≥4+3), upstage (pT3a or higher), margin status and biochemical recurrence (BCR) were examined using chi-square, logistic regression, log-rank, and Cox proportional hazards analyses. Results: We identified 355 AA and 540 Caucasian men with low-risk tumors within the SEARCH cohort followed for a median of 6.3 (IQR 3.8-8.9). AA men were younger (mean 59.5vs. 62.0 years), and had higher median PSA (5.5 vs. 5.1). Following adjustment for relevant covariates, AA race was not significantly associated with pathological upgrade (OR 1.335, 95% CI 0.936-1.905, p=0.111), major upgrade (OR 0.561, 95% CI 0.300-1.049, p=0.070), upstaging (OR 1.111, 95% CI 0.670-1.844, p=0.683), or positive surgical margins (OR 1.046, 95% CI 0.732-1.494, p=0.806). The 5-year recurrence-free survival rates were 73.4% and 78.4% for AA and Caucasian men, respectively (log-rank p=0.178). After adjustment for clinical and pathological characteristics, AA race was not significantly associated with BCR (HR 1.1.054, 95% CI 0.814-1.501, p=0.521). Conclusions: In a cohort of low-risk men treated with prostatectomy within an equal access health system with a high representation of AA men, no significant differences were observed in the rates of pathologic upgrading, upstaging or biochemical recurrence. These data support continued use of AS in AA. Upgrading and upstaging remain concerning possibilities for all men regardless of race.

25 The “low risk” patient with prostate cancer — Truth or myth?

2005 ◽  
Vol 4 (3) ◽  
pp. 9
Author(s):  
F. Burkhard ◽  
M. Schumacher ◽  
R. Markwalder ◽  
U.E. Studer
Keyword(s):  
Prostate Cancer ◽  
Low Risk ◽  
Risk Patient

scholarly journals An Eight-CircRNA Assessment Model for Predicting Biochemical Recurrence in Prostate Cancer

2020 ◽  
Vol 8 ◽  
Author(s):  
Shuo Wang ◽  
Wei Su ◽  
Chuanfan Zhong ◽  
Taowei Yang ◽  
Wenbin Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Score ◽  
Biochemical Recurrence ◽  
R Package ◽  
Low Risk ◽  
Assessment Model ◽  
High Morbidity ◽  
Sequencing Data ◽  
Go Analysis ◽  
Score Model

Prostate cancer (PCa) is a high morbidity malignancy in males, and biochemical recurrence (BCR) may appear after the surgery. Our study is designed to build up a risk score model using circular RNA sequencing data for PCa. The dataset is from the GEO database, using a cohort of 144 patients in Canada. We removed the low abundance circRNAs (FPKM &lt; 1) and obtained 546 circRNAs for the next step. BCR-related circRNAs were selected by Logistic regression using the “survival” and “survminer” R package. Least absolute shrinkage and selector operation (LASSO) regression with 10-fold cross-validation and penalty was used to construct a risk score model by “glmnet” R software package. In total, eight circRNAs (including circ_30029, circ_117300, circ_176436, circ_112897, circ_112897, circ_178252, circ_115617, circ_14736, and circ_17720) were involved in our risk score model. Further, we employed differentially expressed mRNAs between high and low risk score groups. The following Gene Ontology (GO) analysis were visualized by Omicshare Online tools. As per the GO analysis results, tumor immune microenvironment related pathways are significantly enriched. “CIBERSORT” and “ESTIMATE” R package were used to detect tumor-infiltrating immune cells and compare the level of microenvironment scores between high and low risk score groups. What’s more, we verified two of eight circRNA’s (circ_14736 and circ_17720) circular characteristics and tested their biological function with qPCR and CCK8 in vitro. circ_14736 and circ_17720 were detected in exosomes of PCa patients’ plasma. This is the first bioinformatics study to establish a prognosis model for prostate cancer using circRNA. These circRNAs were associated with CD8+ T cell activities and may serve as a circRNA-based liquid biopsy panel for disease prognosis.

Use of nuclear androgen receptor status to predict early biochemical recurrence of prostate cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21073-21073
Author(s):  
J. Diallo ◽  
A. Aldejmah ◽  
M. Alam Fahmy ◽  
I. Koumakpayi ◽  
A. Mes-Masson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Early Onset ◽  
Biochemical Recurrence ◽  
Normal Tissue ◽  
Cellular Localization ◽  
Nuclear Staining ◽  
Normal Prostate ◽  
Kaplan Meier ◽  
Hormone Sensitive

21073 Background: Prostate cancer (PCa) is a leading cause of cancer death in North American men. The androgen receptor (AR) has an established role in the progression of this disease; however, it is unclear at what stage it intervenes. It is also uncertain whether the AR can be a useful prognostic marker for PCa. In this study, we assessed AR expression and sub-cellular localization in normal prostate as well as in androgen sensitive and insensitive PCa (AIPCa) tissues, and evaluated the ability of the AR to predict biochemical recurrence (BCR). Methods: We used tissue micro-arrays containing prostate tissue cores obtained from cancer-free patients (n=43), AIPCa patients (n=36), and patients with hormone-sensitive cancers (n=64) from which were collected both cancerous and normal adjacent tissue. Using immmunohistochemistry, we stained the tissue micro-arrays with a monoclonal antibody recognizing the AR. Two observers assessed the frequency and intensity of both cytoplasmic and nuclear AR staining. AR cytoplasmic (Ci) and nuclear (Ni) indices were calculated by multiplying nuclear staining frequency and nuclear staining intensity. Kaplan Meier, and Cox multivariate analyses were done using SPSS. Results: We found that AR Ci increased significantly in AIPCa although a modest but significant increase in PCa Ci was observed compared to normal tissues. In contrast, AR Ni was significantly lower in cancer-free patients as opposed to that seen in normal tissue adjacent to cancer. Similarly, cancerous tissue exhibited higher AR Ni than its adjacent normal tissue (p<0.05, Kruskal-Wallis). Kaplan Meier analyses revealed that low AR Ni was predictive of an early onset of BCR (before 3-years) in the sub-cohort of hormone-sensitive patients (LR=6.51, p=0.011). Futhermore, low AR Ni remained an independent predictor of early BCR in a Cox multivariate model controlling for age, pre-operative PSA, lymph node invasion, Gleason score and surgical margin status (HR=2.28, 95% CI=1.04 - 5, p<0.05). Conclusions: We conclude that increased nuclear AR activity could be a pre-malignant step in PCa progression whereas its role within cancer cells may be more complex, as low AR nuclear activity was associated with early onset of BCR. No significant financial relationships to disclose.

Prostate brachytherapy implant quality on biochemical control.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 128-128
Author(s):  
Don Muller ◽  
Paul Monsour
Keyword(s):  
Prostate Cancer ◽  
Clinical Stage ◽  
Biochemical Failure ◽  
Low Risk ◽  
Prostate Brachytherapy ◽  
Gleason Grade ◽  
Intermediate Risk ◽  
Biochemical Control ◽  
Dosimetric Analysis

128 Background: prostate brachytherapy at our institution was analyzed for implant quality on biochemical control. Methods: We treated 368 patients with clinically localized prostate cancer. All patients underwent 1 month CT based dosimetric analysis. Follow up data was available on 289 patients with a minimum follow up of 5 years. Gleason score was 6 in 80% (n=233), and 7 in 20% (n=56). Clinical stage was T1c in 90% of cases (n=260), T2a was 8% (n=23), T2b was <1% (n=3), T2c was < 1% (n=2). The initial prostate-specific antigen was < 10 ng/ml in 95% (n=274), 10.1-20 ng/ml in 5% (15).Patients with low risk disease ( clinical stage T1c, Gleason score 6 with a PSA < 10 ng/ml) n=228. Patients with intermediate risk disease Gleason 7 adenocarcinoma or with a PSA> 10 ng/ml < 20 ng/ml )n= 61. All patients were treated with I (125). All patients underwent a 1-month CT-based dosimetric analysis. The implant dose was defined as the dose delivered to 90% of the prostate volume on post implant dosimetry (D(90)). Results: At minimum follow up of 5 years overall freedom from biochemical failure was 91.4%. For Gleason grade 6 freedom from biochemical failure was 95%. For Gleason grade 7 freedom from biochemical failure was 77%. Based on PSA freedom from biochemical failure for PSA <10 ng/ml at diagnosis was 92 % and for PSA >10 ng/ml and <20 ng/ml was 80%. In patients with low risk disease ( clinical stage T1c, Gleason 6 adenocarcinoma with a PSA < 10ng/ml) the freedom from biochemical failure was 94%. In patients with intermediate risk disease (Gleason 7 adenocarcinoma or with a PSA >10 ng/ml <20 ng/ml ) freedom from biochemical failure was 84%. Patients with optimal dose implants n=264 freedom from biochemical failure was 95%. Patients with suboptimal dose implants n=25 freedom from biochemical failure was 52% Conclusions: With a minimum follow up of 5 years our data support the use of implant alone in low risk prostate cancer patients with a freedom from biochemical failure of 94%. Our data also shows the importance of implant quality in achieving optimal out comes.

NRG Oncology RTOG 0415: A randomized phase III non-inferiority study comparing two fractionation schedules in patients with low-risk prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 1-1 ◽  
Author(s):  
W. Robert Lee ◽  
James J. Dignam ◽  
Mahul Amin ◽  
Deborah Bruner ◽  
Daniel Low ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Biochemical Recurrence ◽  
Disease Free Survival ◽  
Low Risk ◽  
Free Survival ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer ◽  
Grade 3 ◽  
Disease Free

1 Background: To determine whether the efficacy of a hypofractionated (H) schedule is no worse than a conventional (C) schedule in men with low-risk prostate cancer. Methods: From April 2006 to December 2009, one thousand one hundred fifteen men with low-risk prostate cancer (clinical stage T1-2a, Gleason ≤ 6, PSA < 10) were randomly assigned 1:1 to a conventional (C) schedule (73.8 Gy in 41 fractions over 8.2 weeks) or to a hypofractionated (H) schedule (70 Gy in 28 fractions over 5.6 weeks). The trial was designed to establish with 90% power and alpha = 0.05 that (H) results in 5-year disease-free survival (DFS) that is not lower than (C) by more than 7% (hazard ratio (HR) < 1.52). Secondary endpoints include freedom from biochemical recurrence (FFBR) and overall survival. At the third planned interim analysis (July 2015), the NRG Oncology Data Monitoring Committee recommended that the results of the trial be reported. Results: One thousand one hundred and one protocol eligible men were randomized: 547 to C and 554 to H. Median follow-up is 5.9 years. Baseline characteristics are not different according to treatment arm. At the time of analysis 185 DFS events have been observed; 99 in the C arm and 86 in the H arm. The estimated 7-year disease-free survival is 75.6% (95% CI 70.3, 80.1) in the C arm and 81.8% (77.5, 85.3) in the H arm. The DFS HR (C/H) is 0.85 (0.64, 1.14). Comparison of biochemical recurrence (HR = 0.77, (0.51, 1.17)) and overall survival (HR = 0.95, (0.65, 1.41)) also met protocol non-inferiority criteria. Grade ≥ 3 GI toxicity is 3.0% (C) vs. 4.6% (H), Relative risk (RR) for H vs. C 1.53, (95% CI 0.86, 2.83); grade ≥ 3 GU toxicity is 4.5% (C) vs. 6.4% (H), RR = 1.43 (0.86,2.37). Conclusions: In men with low-risk prostate cancer, 70 Gy in 28 fractions over 5.6 weeks is non-inferior to 73.8 Gy in 41 fractions over 8.2 weeks. Clinical trial information: NCT00331773.

scholarly journals Impact on Prostate Cancer Clinical Presentation After Non-Screening Policies at a Tertiary-Care Medical Center.

2020 ◽  
Author(s):  
Tarek Ajami ◽  
Jaime Durruty ◽  
Claudia Mercader ◽  
Leonardo Rodriguez ◽  
Maria Ribal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Task Force ◽  
Prostate Cancer Screening ◽  
Medical Center ◽  
Clinical Stage ◽  
Tertiary Care ◽  
Grade Group ◽  
Positive Biopsy ◽  
Tertiary Care Medical Center ◽  
Biopsy Rate

Abstract BACKGROUND:In May 2012 the US Preventive Task Force (USPTF) issued a ‘D’ recommendation for routine PSA-based prostate cancer early detection. This recommendation was implemented progressively in our health system. The aim of this study is to define its impact at a tertiary care institution. METHODS:A retrospective analysis was performed from 2012 till 2015 at a single center. We analyzed the total number of biopsies performed per year and the positive biopsy rate. For those patients with positive biopsies we recorded diagnostic PSA, clinical stage, ISUP grade group, nodal involvement and metastatic status at diagnosis. RESULTS:A total of 1686 biopsies were analyzed. The positive biopsy rate (PBR) increased from 25% in 2012 to 40% in 2015 (p<0.05). No change in median PSA was noticed (p=0.627). Biopsies detected higher ISUP grades (p=0.000). In addition, newly diagnosed prostate cancer presented higher clinical stage (p=0.005), higher metastatic rates (p=0.03) and a tendency to higher lymph node involvement although not statistically significant (p=0.09).CONCLUSION:After the 2012 recommendation, patients presented higher probability of diagnosing prostate cancer, with more adverse ISUP group, clinical stage and metastatic disease. These results should be considered to implement a risk adapted strategy for prostate cancer screening.

scholarly journals Immunophenotype Rearrangement in Response to Tumor Excision May Be Related to the Risk of Biochemical Recurrence in Prostate Cancer Patients

2021 ◽  
Vol 10 (16) ◽  
pp. 3709
Author(s):  
Paulius Bosas ◽  
Gintaras Zaleskis ◽  
Daiva Dabkevičiene ◽  
Neringa Dobrovolskiene ◽  
Agata Mlynska ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Biochemical Recurrence ◽  
Risk Group ◽  
Laparoscopic Approach ◽  
Low Risk ◽  
Tumor Excision

Background: Prostate cancer (PCa) is known to exhibit a wide spectrum of aggressiveness and relatively high immunogenicity. The aim of this study was to examine the effect of tumor excision on immunophenotype rearrangements in peripheral blood and to elucidate if it is associated with biochemical recurrence (BCR) in high risk (HR) and low risk (LR) patients. Methods: Radical prostatectomy (RP) was performed on 108 PCa stage pT2–pT3 patients. Preoperative vs. postoperative (one and three months) immunophenotype profile (T- and B-cell subsets, MDSC, NK, and T reg populations) was compared in peripheral blood of LR and HR groups. Results: The BCR-free survival difference was significant between the HR and LR groups. Postoperative PSA decay rate, defined as ePSA, was significantly slower in the HR group and predicted BCR at cut-off level ePSA = −2.0% d−1 (AUC = 0.85 (95% CI, 0.78–0.90). Three months following tumor excision, the LR group exhibited a recovery of natural killer CD3 − CD16+ CD56+ cells, from 232 cells/µL to 317 cells/µL (p < 0.05), which was not detectable in the HR group. Prostatectomy also resulted in an increased CD8+ population in the LR group, mostly due to CD8+ CD69+ compartment (from 186 cells/µL before surgery to 196 cells/µL three months after, p < 001). The CD8+ CD69+ subset increase without total T cell increase was present in the HR group (p < 0.001). Tumor excision resulted in a myeloid-derived suppressor cell (MDSC) number increase from 12.4 cells/µL to 16.2 cells/µL in the HR group, and no change was detectable in LR patients (p = 0.12). An immune signature of postoperative recovery was more likely to occur in patients undergoing laparoscopic radical prostatectomy (LRP). Open RP (ORP) was associated with increased MDSC numbers (p = 0.002), whereas LRP was characterized by an immunity sparing profile, with no change in MDSC subset (p = 0.16). Conclusion: Tumor excision in prostate cancer patients results in two distinct patterns of immunophenotype rearrangement. The low-risk group is highly responsive, revealing postoperative restoration of T cells, NK cells, and CD8+ CD69+ numbers and the absence of suppressor MDSC increase. The high-risk group presented a limited response, accompanied by a suppressor MDSC increase and CD8+ CD69+ increase. The laparoscopic approach, unlike ORP, did not result in an MDSC increase in the postoperative period.

Prostate cancer

2017 ◽  
Author(s):  
Matthew Cooperberg ◽  
Peter Carroll
Keyword(s):  
Prostate Cancer ◽  
Clinical Stage ◽  
Specific Antigen ◽  
Mortality Rates ◽  
Low Risk ◽  
Gleason Grade ◽  
Aggressive Treatment ◽  
Careful Monitoring ◽  
Biopsy Tissue

Management of prostate cancer remains controversial, in large part because of its wide heterogeneity in terms of aggressiveness and prognosis. Early detection efforts based on prostate specific antigen (PSA) and aggressive treatment of high-risk cancers have yielded major improvements in mortality rates, but overtreatment of low-risk cancers—those unlikely to cause symptoms or threaten life if they were never detected—is associated with high rates of avoidable toxicity and cost. Prostate cancer can be effectively risk-stratified based on tools (e.g. nomograms, CAPRA score) integrating the PSA level, Gleason grade, clinical stage, and extent of biopsy tissue involvement. Most men with low-risk tumours are eligible for active surveillance, a programme of careful monitoring based on PSA and follow-up biopsies. Men with higher-risk cancers are best served with radical prostatectomy or radiation therapy.

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