scholarly journals High expression of Sterol-O-Acyl transferase 1 (SOAT1), an enzyme involved in cholesterol metabolism, is associated with earlier biochemical recurrence in high risk prostate cancer

2021 ◽  
Author(s):  
Carolin Eckhardt ◽  
Iuliu Sbiera ◽  
Markus Krebs ◽  
Silviu Sbiera ◽  
Martin Spahn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Biochemical Recurrence ◽  
Proportional Hazards ◽  
Cholesterol Metabolism ◽  
Cox Proportional Hazards ◽  
Clinical Recurrence ◽  
Free Survival ◽  
Kaplan Meier ◽  
Cancer Aggressiveness

Abstract Background Prostate cancer (PCa) is the most frequent cancer in men. The prognosis of PCa is heterogeneous with many clinically indolent tumors and rare highly aggressive cases. Reliable tissue markers of prognosis are lacking. Active cholesteryl ester synthesis has been associated with prostate cancer aggressiveness. Sterol-O-Acyl transferases (SOAT) 1 and 2 catalyze cholesterol esterification in humans. Objective To investigate the value of SOAT1 and SOAT2 tissue expression as prognostic markers in high risk PCa. Patients and methods Formalin-fixed paraffin-embedded tissue samples from 305 high risk PCa cases treated with radical prostatectomy were analyzed for SOAT1 and SOAT2 protein expression by semi-quantitative immunohistochemistry. The Kaplan–Meier method and Cox proportional hazards modeling were used to compare outcome. Main outcome measure Biochemical recurrence (BCR) free survival. Results SOAT1 expression was high in 73 (25%) and low in 219 (75%; not evaluable: 13) tumors. SOAT2 was highly expressed in 40 (14%) and at low levels in 249 (86%) samples (not evaluable: 16). By Kaplan–Meier analysis, we found significantly shorter median BCR free survival of 93 months (95% confidence interval 23.6–123.1) in patients with high SOAT1 vs. 134 months (112.6–220.2, Log-rank p < 0.001) with low SOAT1. SOAT2 expression was not significantly associated with BCR. After adjustment for age, preoperative PSA, tumor stage, Gleason score, resection status, lymph node involvement and year of surgery, high SOAT1 but not SOAT2 expression was associated with shorter BCR free survival with a hazard ratio of 2.40 (95% CI 1.57–3.68, p < 0.001). Time to clinical recurrence and overall survival were not significantly associated with SOAT1 and SOAT2 expression Conclusions SOAT1 expression is strongly associated with BCR free survival alone and after multivariable adjustment in high risk PCa. SOAT1 may serve as a histologic marker of prognosis and holds promise as a future treatment target.

Is expanded radiographic criteria for clinically positive lymph nodes associated with outcome in pathologically node positive prostate cancer?

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 126-126
Author(s):  
Chad A. Reichard ◽  
Justin Gregg ◽  
Tharakeswara Bathala ◽  
Mary F. Achim ◽  
John W. Davis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Nodes ◽  
Gleason Score ◽  
Biochemical Recurrence ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Free Survival ◽  
Outcome Differences ◽  
Baseline Psa ◽  
Positive Lymph Nodes

126 Background: Patients with pN1 prostate cancer (PCa) have heterogeneous outcomes largely dependent on variables only known post-treatment. Traditionally, the size criteria for clinically positive pelvic adenopathy is axial diameter of 10mm. We employed expanded radiographic criteria (ERC) to evaluate for association with differences in outcome differences. Methods: 187 men treated with RP BPLND for PCa from 2001-2013 were identified as pN1. Imaging studies were re-reviewed by a single radiologist (TB) for nodes that were considered positive if they were 8mm or greater in size OR if they were 6mm or greater in size AND either rounded, asymmetrical OR heterogeneously enhancing. This yielded a group of 34 cN1 patients by ERC. Time to biochemical recurrence (BCR) was compared between cN0 and cN1 patients by K-M method. Cox proportional hazards modeling was used to determine association of baseline PSA, node status, adjuvant therapy, Gleason score, positive margins, and ECR with time to BCR and overall survival (OS). Results: Median age (61 v 59 p = 0.3), baseline PSA (8.7 v 11.1 p = 0.2), and positive margin rate (33% vs 32% p = 0.9) did not differ between cN0 and cN1 patients. Median number of positive LNs was higher in the cN1 group (2.7 v 1.8) p = 0.03. Median biochemical recurrence free survival did not differ between groups (3.3 vs 1.8 years p = 0.3) (Fig1). Only Gleason score was associated with shorter BCR free survival HR 1.3 (95%CI 1.0-1.62, p = 0.047). cN1 disease with expanded radiographic criteria did not predict BCR (HR 1.03, 95CI 0.62-171, p = 0.9) or ACM (HR 0.46, 95CI, 0.1-2.12, p = 0.3). Conclusions: Expanded radiographic criteria for clinically positive lymph nodes was not associated with BCR-free survival or OS in a group of pN1 PCa patients. Further study is required to determine if cN1 status based on expanded clinical criteria or more sensitive imaging methods is associated with outcome differences.

scholarly journals Event-Free Survival after 68Ga-PSMA-11 PET/CT in recurrent Hormone-Sensitive Prostate Cancer (HSPC) patients eligible for Salvage Therapy.

2021 ◽  
Author(s):  
Francesco Ceci ◽  
Guido Rovera ◽  
Giuseppe Carlo Iorio ◽  
Alessia Guarneri ◽  
Valeria Chiofalo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Salvage Therapy ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Event Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Psma Pet ◽  
Hormone Sensitive

Abstract Background/AimProstate-Specific-Membrane-Antigen/Positron Emission Tomography (PSMA-PET) detects with high accuracy disease-recurrence, leading to changes in the management of biochemically-recurrent (BCR) prostate cancer (PCa). However, data regarding the oncological outcomes of patients who performed PSMA-PET are needed. The aim of this study was to evaluate the incidence of clinically-relevant events during follow-up in patients who performed PSMA-PET for BCR after radical treatment. Materials and Methodsthis analysis included consecutive, hormone-sensitive, hormone-free, recurrent PCa patients (HSPC) enrolled through a prospective study. All patients were eligible for salvage therapy, having at least 24 months of follow-up after PSMA-PET. The primary endpoint was the Event-Free Survival (EFS), defined as the time between the PSMA-PET and the date of event/last follow-up. The Kaplan-Meier method was used to estimate the EFS curves. EFS was also investigated by Cox proportional hazards regression. Events were defined as: death, radiological progression or PSA recurrence after therapy. ResultsOne-hundred and seventy-six (n=176) patients were analyzed (median PSA 0.62 [IQR:0.43–1.00] ng/mL; median follow-up of 35.4 [IQR:26.5-40.3] months). The EFS was 78.8% at one year, 65.2% (2-years), and 52.2% (3-years). Patients with clinically relevant events had a significantly higher median PSA (0.81 [IQR:0.53-1.28] vs 0.51 [IQR:0.36-0.80] ng/mL) and a lower PSAdt (5.4 [IQR:3.7-11.6] vs 12.7 [IQR:6.6-24.3] months) (p<0,001) compared to event-free patients. The Kaplan-Meier curves showed that PSA>0.5 ng/mL, PSAdt≤6 months and a positive PSMA-PET result were associated with a higher event rate (p<0.01). No significant differences of event rates were observed in patients who received changes in therapy management after PSMA-PET vs. patients who did not receive therapy changes. Finally, PSA> 0.5 ng/mL and PSAdt≤ 6months were statistically significant event-predictors in multi-variate model (p<0.001). ConclusionIn this cohort of HSPC patients prospectively enrolled, low PSA and long PSAdt were significant predictors of event. Furthermore, a lower incidence of events was observed also in patients having negative PSMA-PET, since longer EFS was significantly more probable in case of a negative scan.

Characterization of circulating tumor cells in patients with localized high risk prostate cancer, post-prostatectomy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23055-e23055
Author(s):  
Archana Anantharaman ◽  
Terence W. Friedlander ◽  
Christopher J. Welty ◽  
Kreshnik Zejnullahu ◽  
Jeffrey Hough ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Biochemical Recurrence ◽  
Copy Number ◽  
Large Scale ◽  
Proportional Hazards ◽  
Predictive Biomarkers ◽  
Cox Proportional Hazards

e23055 Background: Approximately 15% of men with newly diagnosed prostate cancer (PCa) have high-risk features, which increase the risk of recurrence. Better predictive biomarkers, such as circulating tumor cells (CTCs), could allow for earlier detection of biochemical recurrence. Here, we aim to evaluate the ability to detect CTCs using an enrichment free, unbiased CTC identification technology from men with high risk, localized PCa after radical prostatectomy (RP) and correlate their presence with prospective clinical data. Methods: Blood samples of 31 patients with high risk, localized PCa obtained 2-4 months post RP were shipped to Epic Sciences on an IRB approved protocol. All nucleated cells were subjected to immunofluorescent (IF) staining for cytokeratin (CK), CD45, and AR N terminus. CTCs were identified by fluorescent scanners using algorithmic analysis. CK expressing (CK+) CTCs were enumerated and analyzed for AR expression and individually sequenced for copy number variation (CNV) and large scale transition (LST, a surrogate of genomic instability). Patients were followed prospectively for biochemical recurrence, defined as detectable PSA. Progression free survival was calculated using Kaplan-Meier and Cox proportional hazards. Results: CTCs were detected in 87.1% (27/31) samples with an average of 5.6 CTCs/ml (range: 0 – 22.87) detected per patient. AR expression was detected in 12.9% (4/31) of patients. Ninety-nine CTCs from 14 patients were amenable to LST and CNV sequencing and analyses. 10.1% (10/99) CTCs from 7 patients exhibited higher ( > = 6) LSTs than control WBCs (95% WBCs had LST < 6). Copy number alterations were identified in CTCs in commonly mutated genes in PCa, including AR, MYC, and TP53 amplification and deletions in PTEN and RB1. Patients with higher CTC burdens exhibited a trend toward shorter PFS (hazard ratio: 1.65; 95% CI: 0.7-3.86; p: 0.13). Conclusions: There was a high incidence of CTC detection after RP in patients with high risk, localized PCa. We observed a trend toward shorter PFS in those with higher CTC burden and genomic alterations detectable in CTCs are consistent with established CNAs in PCa. Tissue genomic correlatives are under analysis.

scholarly journals Single High Intensity Focused Ultrasound Session as a Whole Gland Primary Treatment for Clinically Localized Prostate Cancer: 10-Year Outcomes

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ksenija Limani ◽  
Fouad Aoun ◽  
Serge Holz ◽  
Marianne Paesmans ◽  
Alexandre Peltier ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Rate ◽  
High Risk ◽  
High Intensity ◽  
Biochemical Recurrence ◽  
Focused Ultrasound ◽  
High Intensity Focused Ultrasound ◽  
Localized Prostate Cancer ◽  
Single Session ◽  
Free Survival

Objectives. To assess the treatment outcomes of a single session of whole gland high intensity focused ultrasound (HIFU) for patients with localized prostate cancer (PCa).Methods. Response rates were defined using the Stuttgart and Phoenix criteria. Complications were graded according to the Clavien score.Results. At a median follow-up of 94months, 48 (44.4%) and 50 (46.3%) patients experienced biochemical recurrence for Phoenix and Stuttgart definition, respectively. The 5- and 10-year actuarial biochemical recurrence free survival rates were 57% and 40%, respectively. The 10-year overall survival rate, cancer specific survival rate, and metastasis free survival rate were 72%, 90%, and 70%, respectively. Preoperative high risk category, Gleason score, preoperative PSA, and postoperative nadir PSA were independent predictors of oncological failure. 24.5% of patients had self-resolving LUTS, 18.2% had urinary tract infection, and 18.2% had acute urinary retention. A grade 3b complication occurred in 27 patients. Pad-free continence rate was 87.9% and the erectile dysfunction rate was 30.8%.Conclusion. Single session HIFU can be alternative therapy for patients with low risk PCa. Patients with intermediate risk should be informed about the need of multiple sessions of HIFU and/or adjuvant treatments and HIFU performed very poorly in high risk patients.

Association between radiographic response and overall survival in men with metastatic castration-resistant prostate cancer receiving chemotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 118-118
Author(s):  
G. Sonpavde ◽  
G. R. Pond ◽  
W. R. Berry ◽  
R. De Wit ◽  
M. A. Eisenberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Objective Assessment ◽  
Objective Response ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier

118 Background: In men with metastatic castration resistant prostate cancer (CRPC),the association of measurable tumor responses with overall survival (OS) is unknown. We retrospectively evaluated the TAX327 phase III trial to study this relationship. Methods: Eligible patients for this analysis included those with WHO-defined measurable metastatic disease randomized to receive either docetaxel or mitoxantrone. OS was estimated using the Kaplan-Meier method and the prognostic relationship of WHO-defined radiologic response with OS was performed using Cox proportional hazards regression. Landmark analyses evaluated survival from baseline and 2, 3, 4 and 6 months after baseline. Results: Four hundred and twelve patients enrolled on the TAX327 trial had measurable tumors. Thirty-seven patients exhibited a complete or partial objective response (CR/PR, 9.0%), 116 had stable disease (SD, 28.2%), 99 had progressive disease (PD,24%) and 160 (38.8%) did not have a post-baseline objective assessment. Partial responders demonstrated longer median OS (29.0 months) than patients with SD (22.1 months), or those with PD (10.8 months) or those who were not assessed (12.7 months). These results remained after landmark analysis. We found a significant association between ≥30% PSA declines and radiologic response, with ≥30% PSA declines occurring in all patients with CR/PR, 79.8% of patients with SD and 34.4% with PD. Radiologic response remained a significant but modest post-treatment prognostic factor for OS after adjusting for treatment, pain-response and ≥30% PSA-decline (p=0.009). Conclusions: In men with metastatic CRPC and measurable disease receiving chemotherapy, objective tumor response was prognostic for OS, and appears to complement PSA assessment. [Table: see text]

Evidence for a field effect in early prostate cancer (PCa): Gene expression profiles in normal-appearing prostate tissue (NT) adjacent to tumor (T) as predictors of clinical outcome.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5029-5029 ◽  
Author(s):  
Eric A. Klein ◽  
Sara Moscovita Falzarano ◽  
Nan Zhang ◽  
Dejan Knezevic ◽  
Tara Maddala ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Field Effect ◽  
Proportional Hazards ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cox Proportional Hazards ◽  
Clinical Recurrence ◽  
Molecular Alterations ◽  
Cox Proportional Hazards Models

5029 Background: We previously identified genes whose expression predicts aggressive PCa (clinical recurrence (cR), prostate cancer death (PCD), adverse pathology) when assessed in histologically heterogeneous tumor foci and in biopsies (Klein ASCO 2012). These results enabled the definition of a multi-gene Genomic Prostate Score (GPS), which has been clinically validated (Cooperberg AUA 2013). There is interest regarding a possible field effect in PCa, i.e. molecular alterations throughout the gland that may influence PCa development. We conducted exploratory analyses to evaluate gene expression, including GPS, in adjacent normal-appearing tissue (NT) for prediction of cR and PCD. Methods: Cohort sampling was used to select 127 patients with and 374 without cR from 2,641 patients treated with RP for T1/T2 PCa. Expression of 732 genes was measured by qRT-PCR separately in T and NT (defined as > 3 mm from T) specimens. GPS (0-100 units) was determined using the genes and algorithm from the validation study. Analysis used Cox proportional hazards models and Storey’s false discovery rate (FDR) control. Results: 410 evaluable patients had paired T and NT. Of the 405 genes which were predictive of outcome in T (FDR < 20%), 289 (71%) showed similar but weaker effects in NT. 47 genes were associated with cR in NT (FDR < 20%), of which 34 also concordantly predicted cR in T (FDR < 20%). GPS assessed in NT significantly predicted time to cR (HR/20 units = 1.8; 95% CI: 1.3-2.4; p< 0.001) and PCD (HR/20 units = 1.9; 95% CI: 1.2-3.0; p = 0.005) but was less predictive than GPS in T (HR/20 units = 4.8 for cR; 95% CI: 3.7-6.2; p < 0.001 and HR/20 units = 6.9 for PCD; 95% CI: 4.4-10.7; p < 0.001). The strongest components of GPS in predicting cR and PCD in NT were stromal response and androgen signaling genes (p < 0.05); proliferation and cellular organization genes did not consistently provide a significant contribution in NT. Conclusions: These data indicate that gene expression profiles, including GPS, can predict outcome in NT, albeit more weakly than in tumor. These findings suggest that there is an underlying field effect associated with the development of aggressive PCa.

The importance of surgical margins for biochemical recurrence in high-risk prostate cancer patients.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 75-75
Author(s):  
Victor Srougi ◽  
Rafael Sanchez-Salas ◽  
Fernando P. Secin ◽  
Igor Nunes-Silva ◽  
Mohammed Baghdadi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Gleason Score ◽  
Biochemical Recurrence ◽  
Surgical Margins ◽  
Pathological Stage ◽  
Free Survival ◽  
Positive Surgical Margins ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

75 Background: High-risk prostate cancer (PCa) is associated with greater risk of biochemical recurrence and cancer specific lethality. A multi-modal treatment is required for this group of patients, comprising surgery as part of it. However, the role of surgery as monotherapy is still under investigation. The purpose of this study is to analyze the influence of surgical margins on biochemical recurrence (BCR) among patients with high-risk prostate cancer (PCa) treated with robot assisted radical prostatectomy (RARP) since the start of our robotic program. Methods: We retrospectively analyzed our prospectively collected database of 5695 minimally invasive prostatectomies performed between 2000 and 2015. Clinical, pathological and oncological outcomes were evaluated in patients fulfilling Damico´s high risk characteristics. Primary endpoint was BCR, defined as post-operative PSA ≥ 0,2. Patients with neoadjuvant or adjuvant therapy were excluded. BCR was estimated with Kaplan-Meier curves. Cox proportional hazards regression was used to estimate variables associated with BCR. Results: We identified 199 high-risk PCa patients treated with RARP during the study period. Gleason score ≥ 8, PSA ≥ 20 and clinical stage ≥ T2c were present in 44%, 35% and 11% of the patients, respectively. The rate of positive surgical margins was 25%. With a median follow-up of 23 months (interquartile 12 – 34 months), 31% of the patients had BCR. Five-year BCR-free survival was 34,5%. Gleason score ≥ 8, PSA ≥ 20 and positive surgical margins were not predictors of BCR. A positive correlation of pathological stage ≥ T3 and BCR was found with (HR = 2.9; 95% CI = 1.2-6.9). Conclusions: The 5-years BCR-free survival was poor despite a low rate of positive surgical margins, when compared to historical series. We found that pathological stage ≥ T3 has a significant correlation with the BCR and that negative surgical margins do not assure good prognosis for high-risk patients.

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