Higher Preoperative PSA Research Articles

Preoperative Factors for Lymphovascular Invasion in Prostate Cancer: A Systematic Review and Meta-Analysis.

Lymphovascular invasion (LVI) is one of the most important prognostic factors in prostate cancer (PCa) and is correlated with worse survival rates, biochemical recurrence (BCR), and lymph node metastasis (LNM). The ability to predict LVI preoperatively in PCa may be useful for proposing variations in the diagnosis and management strategies. We performed a systematic review and meta-analysis to identify preoperative clinicopathological factors that correlate with LVI in final histopathological specimens in PCa patients. Systematic literature searches of PubMed, Embase, and Web of Science were performed up to 31 January 2023. A total of thirty-nine studies including 389,918 patients were included, most of which were retrospective and single-center. PSA level, clinical T stage, and biopsy Gleason score were significantly correlated with LVI in PCa specimens. Meta-analyses revealed that these factors were the strongest predictors of LVI in PCa patients. Prostate volume, BMI, and age were not significant predictors of LVI. A multitude of preoperative factors correlate with LVI in final histopathology. Meta-analyses confirmed correlation of LVI in final histopathology with higher preoperative PSA, clinical T stage, and biopsy Gleason score. This study implies advancements in risk stratification and enhanced clinical decision-making, and it underscores the importance of future research dedicated to validation and exploration of contemporary risk factors in PCa.

Diagnostic Role and Prognostic Impact of PSAP Immunohistochemistry: A Tissue Microarray Study on 31,358 Cancer Tissues.

Prostate-specific acid phosphatase (PSAP) is a marker for prostate cancer. To assess the specificity and prognostic impact of PSAP, 14,137 samples from 127 different tumor (sub)types, 17,747 prostate cancers, and 76 different normal tissue types were analyzed via immunohistochemistry in a tissue microarray format. In normal tissues, PSAP staining was limited to the prostate epithelial cells. In prostate cancers, PSAP was seen in 100% of Gleason 3 + 3, 95.5% of Gleason 4 + 4, 93.8% of recurrent cancer under androgen deprivation therapy, 91.0% of Gleason 5 + 5, and 31.2% of small cell neuroendocrine cancer. In non-prostatic tumors, PSAP immunostaining was only found in 3.2% of pancreatic neuroendocrine tumors and in 0.8% of diffuse-type gastric adenocarcinomas. In prostate cancer, reduced PSAP staining was strongly linked to an advanced pT stage, a high classical and quantitative Gleason score, lymph node metastasis, high pre-operative PSA levels, early PSA recurrence (p < 0.0001 each), high androgen receptor expression, and TMPRSS2:ERG fusions. A low level of PSAP expression was linked to PSA recurrence independent of pre- and postoperative prognostic markers in ERG-negative cancers. Positive PSAP immunostaining is highly specific for prostate cancer. Reduced PSAP expression is associated with aggressive prostate cancers. These findings make PSAP a candidate marker for prognostic multiparameter panels in ERG-negative prostate cancers.

Focal nodular enhancement on DCE MRI of the prostatectomy bed: radiologic-pathologic correlations and prognostic value.

To determine the concordance of dynamic contrast-enhanced (DCE) imaging findings with clinico-pathologic characteristics and their prognostic impact for predicting biochemical recurrence (BCR) in patients who underwent radical prostatectomy (RP) for prostate cancer. This retrospective study included patients who underwent MRI within 1 year after RP between November 2019 and October 2020. DCE findings and their concordance with the presence and location of positive surgical margin (PSM) were assessed using RP specimens. Kaplan-Meier and logistic regression analyses were used to evaluate the prognostic impact of DCE findings for BCR. Among the 272 men (mean age ± standard deviation, 66.6 ± 7.4 years), focal nodular enhancement was more frequently observed in those with PSM compared to those with negative margin (85.4% versus 14.6%; p < 0.001). The sites of focal nodular enhancement were 72.9% (35/48) concordant with the PSM locations. Focal nodular enhancement was associated with a higher Gleason score, higher preoperative PSA (≥ 10 ng/mL), higher Gleason grade at the surgical margin, and non-limited margin involvement (p = 0.002, 0.006, 0.032, and 0.001, respectively). In patients without BCR at the time of MRI, focal nodular enhancement was associated with a shorter time to BCR (p < 0.001) and a significant factor predicting 1-year BCR in both univariate (odds ratio = 8.4 [95% CI: 2.5-28.3]; p = 0.001) and multivariate (odds ratio = 5.49 [1.56-19.3]; p = 0.008) analyses. Focal nodular enhancement on post-prostatectomy MRI was associated with adverse clinico-pathologic characteristics of high risk for recurrence and can be a predictor for 1-year BCR in patients undergoing RP. • Focal nodular enhancement (PI-RR DCE score ≥ 4) was 72.9% (35/48) concordant with the site of positive resection margin by radiologic-histologic correlation. • Focal nodular enhancement (PI-RR DCE score ≥ 4) was associated with higher Gleason score ( ≥ 8), preoperative PSA ( > 10 ng/mL), and Gleason grade 4 or 5 at the surgical margin and non-limited margin involvement (p ≤ 0.032). • In patients without BCR at the time of MRI, focal nodular enhancement was a significant factor predicting 1-year BCR (odds ratio = 5.49; 95% CI: 1.56-19.3; p = 0.008).

Cohort study of patients with oligorecurrent prostate cancer: Oncological outcomes of patients treated with salvage lymph node dissection via PSMA radioguided surgery.

5009 Background: Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) allows detection of small and/or atypically localized metastatic prostate cancer (PCa) lesions. In a subset of patients with recurrent oligometastatic PCa salvage surgery with PSMA-targeted radioguidance (PSMA-RGS) may be of value. We aimed to evaluate the oncological outcomes of salvage PSMA-RGS for oligo-recurrent PCa and determine predictive preoperative factors of improved outcomes. Methods: In this cohort study within two tertiary care centers, patients with biochemical recurrence (BCR) after radical prostatectomy (RP) and imaging with PSMA PET receiving salvage PSMA-RGS between 2014 and 2020 were analyzed. Kaplan-Meier and multivariable Cox regression models adjusted for various parameters were used to test for BCR-free survival (BFS) and therapy-free survival (TFS) differences. Postoperative complications were classified according to Clavien-Dindo. Results: Overall, 364 patients were assessed. At PSMA-RGS, median (IQR) age and preoperative PSA was 67 (61-71) years and 1.0 (0.5-1.9) ng/ml. Metastatic soft-tissue lesions from PCa metastases could be removed in 343 (94.2%) patients. Within three months from surgery, 24 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. During follow-up, 225 patients experienced BCR and 121 patients received further therapy. Median follow-up for patients who did not experience BCR and who did not receive further therapy was 10.8 months and 10.3 months, respectively. Median (IQR) BFS and TFS was 7.8 (5.4-10.5) and 35.5 months (25.9-45.9 months). At two years of follow-up, BFS rate was 31.9% and TFS rate was 58.0%. In multivariable analyses, higher preoperative PSA (HR: 1.1), higher number of PSMA-avid lesions on preoperative imaging (HR: 1.2) and multiple (pelvic plus retroperitoneal) localizations (HR: 1.9), as well as retroperitoneal localization (HR: 2.0) of lesions in PSMA PET imaging were independent predictors of BCR after PSMA-RGS. Limitations are the retrospective design and lack of a control group. Conclusions: As salvage surgery in oligo-recurrent PCa currently constitutes an experimental treatment approach careful patient selection is mandatory based on life expectancy, low PSA values and low number of PSMA PET avid lesions located in the pelvis. Further studies are needed to confirm our findings and define the oncological value of salvage surgical procedures in oligo-recurrent PCa.

Cohort study of oligorecurrent prostate cancer patients: Oncological outcomes of patients treated with salvage lymph node dissection via PSMA radioguided surgery.

106 Background: Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET) allows detection of small and/or atypically localized metastatic prostate cancer (PCa) lesions. In a subset of patients with recurrent oligometastatic PCa salvage surgery with PSMA-targeted radioguidance (PSMA-RGS) may be of value. We aimed to evaluate the oncological outcomes of salvage PSMA-RGS for oligorecurrent PCa and determine predictive preoperative factors of improved outcomes. Methods: In this cohort study within two tertiary care centers, patients with biochemical recurrence (BCR) after radical prostatectomy (RP) and imaging with PSMA PET receiving salvage PSMA-RGS between 2014 and 2020 were analyzed. Kaplan-Meier and multivariable Cox regression models adjusted for various parameters were used to test for BCR-free survival (BFS) and therapy-free survival (TFS) differences. Postoperative complications were classified according to Clavien-Dindo. Results: Overall, 364 patients were assessed. At PSMA-RGS, median (IQR) age and preoperative PSA was 67 (61-71) years and 1.0 (0.5-1.9) ng/ml. Metastatic soft-tissue lesions were removed in 356 (94.4%) patients. Within three months from surgery, 25 (6.6%) patients suffered from Clavien-Dindo complications grade III-IV. During follow-up, 235 patients experienced BCR and 129 patients received further therapy. Median follow-up for patients who did not experience BCR and who did not receive further therapy was 11.1 months and 10.5 months, respectively. Median (IQR) BFS and TFS was 7.8 (5.4-10.9) and 34.9 (24.7-43.5) months. At two years of follow-up, BFS rate was 31.9% and TFS rate was 56.6%. In multivariable analyses, higher preoperative PSA (HR: 1.06), higher number of PSMA-avid lesions on preoperative imaging (HR: 1.2) and multiple (pelvic plus retroperitoneal) localizations (HR: 1.7), as well as retroperitoneal localization (HR: 2.0) of lesions in PSMA PET imaging were independent predictors of BCR after PSMA-RGS. Limitations are the retrospective design and lack of a control group. Conclusions: As salvage surgery in oligorecurrent PCa currently constitutes an experimental treatment approach careful patient selection is mandatory based on life expectancy, low PSA values and low number of PSMA PET avid lesions located in the pelvis. Further studies are needed to confirm our findings and define the oncological value of salvage surgical procedures in oligorecurrent PCa.

PD19-07 RISK FACTORS AND IMPACTS OF POSITIVE SURGICAL MARGIN IN AFRICAN AMERICAN UNDERGOING ROBOTIC-ASSISTED RADICAL PROSTATECTOMY

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy II (PD19)1 Sep 2021PD19-07 RISK FACTORS AND IMPACTS OF POSITIVE SURGICAL MARGIN IN AFRICAN AMERICAN UNDERGOING ROBOTIC-ASSISTED RADICAL PROSTATECTOMY Shuo Liu, Bridget Krol, Justin Refugia, Adam Cohen, Ram Pathak, and Ashok Hemal Shuo LiuShuo Liu More articles by this author , Bridget KrolBridget Krol More articles by this author , Justin RefugiaJustin Refugia More articles by this author , Adam CohenAdam Cohen More articles by this author , Ram PathakRam Pathak More articles by this author , and Ashok HemalAshok Hemal More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002008.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer disproportionately impacts African American (AA) males. Margin status remains an important measure of the quality of disease clearance by radical prostatectomy. Unfortunately, historical series have shown that AA men tend to fare worse in this metric comparing to other ethnicities. Furthermore, recent studies have reported positive surgical margin (PSM) rates of up to 34.7% in AA men undergoing robot-assisted radical prostatectomy (RARP). Our study aims to investigate the potential risk factors for PSM in this patient group and its impact on biochemical recurrence-free survival (BCRFS). METHODS: 246 AA men underwent RARP between 2009 and 2019 at our institution. Preoperative patient and disease characteristics, perioperative variables, postoperative and pathological outcomes were recorded and compared according to final margin status. Favorable PSM was defined as PSM noted on pathology with additional margins as negative or with a sub-millimeter unifocal margin. Unfavorable PSM was defined as any PSM not favorable. RESULTS: Adverse pathology (pathological stage >T3, pathological ISUP >3, or positive nodal disease) was seen in 45.1% (111). Favorable PSM status was observed in 52 (21.1%) and unfavorable PSM in 28 (11.4%). PSM was associated with reduction in BCRFS (log-rank p<0.001). Margin multifocality did not further increase disease recurrence. Patients with PSM had higher preoperative PSA (p<0.001), higher clinical risk category (p=0.007), higher pathological grade (p=0.002) and incidences of perineural invasion (PNI) (p<0.001), as well as higher percentages of clinical and pathological T3 disease. Furthermore, patients with PSM were more likely to clinically understaged on final pathological analysis (p<0.001). CONCLUSIONS: PSM rate in AA men remained high in the era of robot-assisted surgery and significantly affected BCRFS. These patients were also more likely to have other adverse pathological features. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e364-e364 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shuo Liu More articles by this author Bridget Krol More articles by this author Justin Refugia More articles by this author Adam Cohen More articles by this author Ram Pathak More articles by this author Ashok Hemal More articles by this author Expand All Advertisement Loading ...

The significance of a high preoperative PSA level for the detection of incidental prostate cancer in LUTS patients with large prostates.

To evaluate the diagnostic value of a high preoperative PSA level for the detection of incidental prostate cancer (iPCa) in LUTS patients with very large prostates (> 100cc). We conducted a retrospective analysis of 1125 men treated for LUTS with holmium laser enucleation of the prostate (HoLEP). Patients were stratified according to a preoperative PSA level higher (high PSA; n = 365) or lower than 10ng/ml (low PSA; n = 760). Preoperative and histopathological parameters were compared between both cohorts. Logistic regression models were used to identify independent predictors of iPCa. Demographic parameters were similar between both cohorts. The median PSA levels were 14.2ng/ml (11.5-19.9) and 4ng/ml (2.4-6.0). The prostate volume was significantly higher in the high PSA group (105cc vs. 75cc; p < 0.001). Correspondingly, the PSA density was significantly increased in the high PSA cohort compared to the low PSA cohort (0.14 vs. 0.05; p < 0.001). The overall detection rate of iPCa showed no difference between groups (9.5% vs. 9.9%). More preoperative prostate biopsies were performed in the high PSA group compared to the low PSA group (46.8% vs. 17.6%; p < 0.001). However, the rate of false negative results was comparable between groups (12.7% vs. 11.1%; p = 0.726). In logistic regression models all PSA-related parameters failed to predict iPCa. PSA-guided approaches to predict iPCa in LUTS patients with very large prostates are not accurate. This finding is useful in clinical practice for counselling our patients and to prevent unwarranted diagnostic procedures.

Down-Regulation of S100A8 is an Independent Predictor of PSA Recurrence in Prostate Cancer Treated by Radical Prostatectomy

Dysregulation of S100A8 is described in many different human tumor types, but its role in prostate cancer is unknown. To evaluate the clinical relevance of S100A8 expression in prostate cancer, a tissue microarray containing 13,665 tumors was analyzed by immunohistochemistry. Cytoplasmic S100A8 staining was compared to prostate cancer phenotype, patient prognosis and molecular features including TMPRSS2:ERG fusion status and deletions of PTEN, 3p, 5q and 6q. S100A8 immunostaining was typically seen in normal prostate tissue but lost in 60% of 9786 interpretable prostate cancers. In the remaining tumors, S100A8 was considered weak in 17.9%, moderate in 17.8% and strong in 5.4% of cases. Loss of S100A8 expression was linked to advanced tumor stage, high Gleason grade, positive nodal status, positive surgical margin and high preoperative PSA (P < .0001 each). In addition, loss of S100A8 expression was associated with TMPRSS2:ERG fusions (P < .0001), deletions of PTEN, 3p, and 6q (P < .005), and a high number of genomic deletions per tumor (P = .0009). Absence of S100A8 immunostaining was also linked to an elevated risk for early PSA recurrence (P < .0001). In a multivariate analysis limited to features that are preoperatively available, the prognostic impact of S100A8 expression (P < .0001) was independent of clinical stage, Gleason grade, and serum PSA level (P < .0001). Taken together, the results of our study demonstrate that complete loss of S100A8 expression is linked to adverse tumor features and predicts early biochemical recurrence in prostate cancer. S100A8 measurement, either alone or in combination might be of clinical utility in prostate cancers.

Accuracy of the preoperative PSA level for predicting clinically significant incidental transitional zone-prostate cancer before endoscopic enucleation of very large adenoma.

To analyse the accuracy of high preoperative PSA levels for predicting transitional zone incidental PCa (TZ-PCa) in men with very large prostates. Perioperative data from 375 consecutive patients who underwent endoscopic enucleation of the prostate (EEP) for benign prostatic obstruction between July 2013 and December 2018 were retrospectively reviewed. Patients were stratified into three groups according to the preoperative PSA level: low-PSA (< 4ng/mL), intermediate-PSA (4 ≤ PSA < 10ng/mL) and high-PSA (≥ 10ng/mL). Men in each group were propensity score matched by age, 5α-reductase inhibitor (5-ARI) use, prostate volume and mpMRI. The TZ-PCa incidence rate was retrospectively compared by preoperative PSA level in a propensity score model including all predetermined variables. Age, prostate volume, 5-ARI use were similar between patient groups. The median PSA levels in the low-, intermediate- and high-PSA groups were 3 [2.3; 3.4], 6.6 [5.3; 8.1] and 12.7 [11; 16.7] ng/mL, respectively. The median prostate volume was > 100 grams in all groups (108, 105 and 120cc, respectively). The T1a-Gleason 6 incidental TZ-PCa rate was statistically comparable between the three groups (3.4, 5.1 and 8.6% in the low-, intermediate- and high-PSA groups, respectively). The detection rate of clinically significant TZ-PCa was low for preoperative PSA levels > 4ng/mL (1.7%); with no difference between the intermediate- and high-PSA groups. In men with large glands, the clinically significant incidental TZ-PCa detection rate was similar regardless of the preoperative PSA level stratum. Such details may help with patient counselling during BPH surgical management.

MP01-13 A HIGH PREOPERATIVE PSA LEVEL IS NOT ACCURATE TO PREDICT INCIDENTAL PROSTATE CANCER DETECTION IN PATIENT UNDERWENT ENDOSCOPIC ENUCLEATION OF THE PROSTATE FOR LARGE GLANDS.

INTRODUCTION AND OBJECTIVES:Incidental prostate cancer (IPCa) detection is estimated between 6 and 12% on open prostatectomy or morcellation sample chips analysis. High preoperative PSA level has b...

PT171 - A high preoperative PSA level is not accurate to predict incidental prostate cancer detection in patient underwent endoscopic enucleation of the prostate for large glands

PT171 - A high preoperative PSA level is not accurate to predict incidental prostate cancer detection in patient underwent endoscopic enucleation of the prostate for large glands

Free testosterone value before radical prostatectomy is related to oncologic outcomes and post-operative erectile function

PurposeTo investigate whether free testosterone (FT) prior to radical prostatectomy was related to post-operative oncologic outcomes, erectile function and continence.MethodsThe data of 586 patients with available information underwent treatment in our center was retrospectively reviewed. Total testosterone (TT) was tested by chemiluminescence immunoassay, and FT value was calculated using Vermeulen’s formula. Post-operative continence and erectile function were evaluated by the requirement of pad and the IIEF-5 score at 12 months.ResultsThe median TT and FT value was 344 ng/dL (interquartile, IQR 314–374) and 6.9 ng/dL (IQR 6.4–7.3), and 106 patients (18.1%) and 152 patients (25.9%) were evaluated as having low TT and low FT based on current guidelines. Low TT and FT value were both related to older age (both p < 0.001), concomitant diabetes (p = 0.018 & 0.049), higher possibility of pre-operative erectile dysfunction (ED, both p < 0.001), higher pre-operative PSA value (both p < 0.001), higher clinical stage (both p < 0.001) and higher Gleason score in biopsy (both p < 0.001). Low FT was related to higher risk for pT3 (p = 0.020) and high Gleason score (p = 0.011) in logistic regression. The median follow-up duration was 52 moths (IQR 29–67) and FT was found to be an independent risk factor for biochemical recurrence (p = 0.005). In logistic regression TT was related to pre-operative ED (p = 0.010) and FT was related to post-operative ED (p = 0.001).ConclusionLow FT value before radical prostatectomy was related to adverse pathological outcomes, biochemical recurrence and post-operative ED.

The impact of single positive surgical margin features on biochemical recurrence after robotic radical prostatectomy.

ABSTRACTObjective:Parameters predictive of biochemical or clinical recurrence after Radical Prostatectomy (RP) were determined as pre-treatment PSA value, pathologic tumor stage, tumor grade and presence of Positive Surgical Margin (PSM), extracapsular extension and seminal vesicle invasion and the status of pelvic lymph nodes. The aim of our study is to evaluate the effect of additional features in patients undergoing RP in our clinic.Materials and Methods:We studied 556 RP operations performed between 2009 and 2016 for prostate cancer at this clinic. Preoperative and postoperative data of the patients were retrospectively reviewed. RP specimens were examined by two pathologists specialized in this subject. Of these patients, 78 (14.02%) patients with PSM were included in the study. The pathology slides of these patients were reassessed. The length of PSM (mm), localization (apex, basis and posterolateral) and Gleason pattern at this margin was determined and statistical correlations with BCR were calculated.Results:The mean follow-up after the RP of 41 patients included in the study was 37.4 ± 13.2 months. During the follow-up period of the patients, BCR was observed in 16 patients (39.02%). No statistically significant difference was observed in age and prostate volume between the groups with and without BCR development (p > 0.05). Preoperative PSA level was found to be statistically significantly higher in the group with BCR development compared to the group without recurrence (p = 0.004). In-group comparisons in each aforementioned Gleason score groups were performed in terms of BCR development and the preoperative Gleason score in the group with development of recurrence was found to be statistically significantly higher compared to the group without recurrence (p = 0.007). The length of the surgical margin was measured as 7.4 ± 4.4 mm in the BCR-developing group and 4.7 ± 3.8 mm in the no-BCR- developing group; it was statistically significantly higher in the group with development of recurrence (p = 0.03).Conclusion:Length and location of the PSM and the Gleason score detected in the PSM region could not predict biochemical recurrence according to the results of this present study. However high preoperative PSA value is an independent prognostic factor for biochemical recurrence.

The correlation analysis of positive surgical margin and biochemical recurrence after robot-assisted laparoscopic radical prostatectomy

Objective To explore the influencing factors and correlation of positive surgical margin (PSM) and biochemical recurrence (BCR) in men after robot-assisted radical prostatectomy (RALP). Methods The clinical data of 190 patients with local or locally advanced prostate cancer who underwent RALP by single surgeon in the Department of Urology of Changhai Hospital from January 2016 to September 2017 were collected. Age was (67.5±6.9) years old; median body mass index (BMI), preoperative PSA, prostate weight were 24.2 kg/m2 (16.6-34.2 kg/m2), 15.0 ng/ml (1.41-393.94 ng/ml) and 36.9 g (8.65-207.58 g) respectively. The group of surgical margin was divided into negative surgical margin, apex-only PSM, base-only PSM as well as apex and base PSM. Characteristics between patients stratified by surgical margin or BCR were compared using χ2 test. The influencing factors of PSM were analyzed by logistic regression. Cox regression was used for the analysis of predictive factors of BCR. Log-rank test and Kaplan-Meier curves were used for comparing the BCR rate between the groups of surgical margin. Results Of all the 190 enrolled patients, total PSM rate was 24.7% (47/190), apex-only PSM rate was 13.2 % (25/190), base-only PSM rate was 5.8% (11/190), apex and base PSM rate was 5.8 % (11/190). Multivariate analysis showed the independent predictive factors influencing PSM were preoperative PSA (P=0.048) and pathological stage (P=0.004 ). The median follow-up period was 7.3 months (0.9-26.6 months) and BCR happened in 19.5% (37/190) patients. The rates of BCR were 15.4% (22/143), 16.0% (4/25), 27.3% (3/11) and 72.7% (8/11) in the patients with negative surgical margin, apex-only PSM, base-only PSM and both apex and base PSM respectively. Log-rank test revealed that the rate of BCR in patients with apex and base PSM was higher than that in patients with negative surgical margin (P<0.001) or patients with apex-only PSM(P=0.002). Cox analysis indicated that higher preoperative PSA (P=0.040), higher pathological stage (P=0.041) and higher pathological Gleason score (P=0.004) were the independent predictors of BCR. PSM was not a predictive factor of BCR (P=0.257). Conclusions Preoperative PSA and pathological stage are the influencing factors of PSM. Higher preoperative PSA, higher pathological stage and higher pathological Gleason Score are the predictive factors of BCR. PSM may not be a predictive factor of BCR. The relationship between PSM and BCR needs further study. Key words: Prostatic neoplasms; Radical prostatectomy; Robot; Positive surgical margin; Biochemical recurrence

Expression of LMO2 in Prostate Carcinoma and Adjacent Prostatic Parenchyma.

LMO2 (LIM domain only) is a member of transcription factor family of proteins characterized by their cysteine-rich, zinc-binding LIM domains. Its expression in prostate cancer cells, as well as in adjacent stroma, is described in a study in a cohort of 83 patients treated with radical prostatectomy for clinically localized prostate adenocarcinoma. Authors found that LMO2 overexpression in prostate cancer was strongly associated with features indicative of worse prognosis (higher preoperative PSA, higher Gleason score, positive surgical margins, and extraprostatic extension of disease). Expression of LMO2 was also associated with biochemical disease progression. We analysed immunohistochemical expression of LMO2 in prostate cancer epithelial and stromal cells, as well as in adjacent parenchyma. Significant negative correlation between glandular expression of LMO2 in carcinoma and stromal expression in BPH (ρ = -0.238, P = 0.033) was found, but also be-tween stromal expression in carcinomas and glandular expression in BPH (ρ = -0.255, P = 0.021). Positive correlation was found between stromal expression in BPH and stromal expression in carci-nomas (ρ = 0.306, P = 0.005). Study results support the potential role of LMO2 in prostatic carcino-genesis and cancer progression.

MP82-14 SINGLE NUCLEOTIDE POLYMORPHISMS AND RISK OF PROSTATE CANCER: DEVELOPMENT AND VALIDATION OF A NOVEL GENETIC RISK SCORE FOR INDIVIDUALIZED SCREENING AND DIAGNOSTIC PROGRAMMES

You have accessJournal of UrologyProstate Cancer: Detection & Screening VII1 Apr 2018MP82-14 SINGLE NUCLEOTIDE POLYMORPHISMS AND RISK OF PROSTATE CANCER: DEVELOPMENT AND VALIDATION OF A NOVEL GENETIC RISK SCORE FOR INDIVIDUALIZED SCREENING AND DIAGNOSTIC PROGRAMMES Vito Cucchiara, Vincenzo Mirone, Dejan Lazarevic, Davide Cittaro, Giovanni Tonon, Matteo Zoccolillo, Marco Emilio Bianchi, Giorgio Gandaglia, Nicola Fossati, Shahrokh F Shariat, Francesco Montorsi, and Alberto Briganti Vito CucchiaraVito Cucchiara More articles by this author , Vincenzo MironeVincenzo Mirone More articles by this author , Dejan LazarevicDejan Lazarevic More articles by this author , Davide CittaroDavide Cittaro More articles by this author , Giovanni TononGiovanni Tonon More articles by this author , Matteo ZoccolilloMatteo Zoccolillo More articles by this author , Marco Emilio BianchiMarco Emilio Bianchi More articles by this author , Giorgio GandagliaGiorgio Gandaglia More articles by this author , Nicola FossatiNicola Fossati More articles by this author , Shahrokh F ShariatShahrokh F Shariat More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Alberto BrigantiAlberto Briganti More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2742AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Genome-wide association studies have characterized more than 100 common SNPs associated with prostate cancer (PCa) that can explain approximately one third of the genetic susceptibility. We aimed at discovering and validating a SNPs signature able to identify individuals at higher risk of PCa in an unscreened patient population METHODS After IRB approval, whole blood genomic DNA (gDNA) was extracted from 354 PCa patients with localized PCa treated with radical prostatectomy (cases) and from 267 healthy individuals with no family history of PCa (controls). Haloplex custom designed-gene panels covering the exons of 78 genes and 128 SNPs identified population-specific PCa risk polymorphisms in 98 cases and 91 controls. Of more than 2,000 variants evaluated, 26 SNPs (p<0.05) were investigated in a validation cohort of 256 PCa patients and 176 controls. In the validation study, gene enriched library was prepared by using Fluidigm Access Array System and loaded on Illumina MiSeq. Genotype frequencies were tested by using Cochran-Armitage test. Wilcoxon-Mann-Whitney test and logistic regressions analyzed the association of SNPs sets with PCa (p<0.05). Individual weighted genetic risk scores (wGRSs) were calculated based on the natural logarithm of the OR of the selected polymorphisms. The AUC was assessed whether the wGRS in addition to pre-diagnostic PSA improved PCa prediction RESULTS Of the 26 genotyped SNPs evaluated in the validation study, we identified 7 variants (rs7141529, rs117879878, rs34764062, rs1419133, rs2227983, rs5919432, and rs6152) more frequent in cases versus controls (all p<0.001) with ORs ranging from 1.51 to 3.08 per risk allele. The wGRS was higher in patients as compared to controls, even after age-matching (p<0.001). The addition of cumulative risk alleles to the model containing PSA levels improved (p=0.004) the predictive value in discriminating individuals with PCa and without cancer (AUC from 0.584 to 0.711; p<0.001). When considering disease characteristics, variant rs5919432 (locus Xq12, androgen receptor-gene) was associated with a higher preoperative PSA with a mean difference between patients and controls of 1.3±0.22 ng/mL (p=0.005) CONCLUSIONS Our study defines a population-specific set of SNPs associated with PCa. Genetic markers might provide an opportunity to identify men at highest risk of PCa. Incorporation of a genetic signature of PCa risk into clinical practice may offer improvements in patient selection for PCa screening and decision making. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1111-e1112 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Vito Cucchiara More articles by this author Vincenzo Mirone More articles by this author Dejan Lazarevic More articles by this author Davide Cittaro More articles by this author Giovanni Tonon More articles by this author Matteo Zoccolillo More articles by this author Marco Emilio Bianchi More articles by this author Giorgio Gandaglia More articles by this author Nicola Fossati More articles by this author Shahrokh F Shariat More articles by this author Francesco Montorsi More articles by this author Alberto Briganti More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Immunohistochemically detected IDH1R132H mutation is rare and mostly heterogeneous in prostate cancer

IDH1 mutations are oncogenic through induction of DNA damage and genome instability. They are of therapeutic interest because they confer increased sensitivity to radiation and cytotoxic therapy and hold potential for vaccination therapy. In this study, we analyzed more than 17,000 primary prostate cancer tissues with a mutation-specific antibody for the IDH1R132H mutation. IDH1 mutation-specific staining was found in 42 of 15,531 (0.3%) interpretable cancers. IDH1 mutation was associated with higher preoperative PSA and Gleason grade (p<0.05, each) but was unrelated to PSA recurrence. A comparison with other molecular tumor features available from earlier studies revealed that TMPRSS2-ERG fusion as well as deletion of PTEN, 5q21, 6q15, and 3p13 was less frequent in IDH1-mutated than in non-mutated cancer. Increased lethality of genetically instable, "aberration-rich" cancer cells in the presence of IDH1 mutations could possibly explain this observation. Heterogeneity analysis revealed a homogeneous mutation in only 1 of 16 IDH1-mutated cancers. This high degree of heterogeneity may profoundly limit therapeutic targeting of IDH1 mutations in prostate cancer. The data show that 0.3% of prostate cancers have an IDH1R132H mutation and that these are mostly heterogeneous. Once specific anti-IDH1 therapy becomes reality, only a very small group of prostate cancer patients may benefit from such a treatment.

Genomic Gain of 16p13.3 in Prostate Cancer Predicts Poor Clinical Outcome after Surgical Intervention

Identifying tumors with high metastatic potential is key to improving the clinical management of prostate cancer. Recently, we characterized a chromosome 16p13.3 gain frequently observed in prostate cancer metastases and now demonstrate the prognostic value of this genomic alteration in surgically treated prostate cancer. Dual-color FISH was used to detect 16p13.3 gain on a human tissue microarray representing 304 primary radical prostatectomy (RP) cases with clinical follow-up data. The results were validated in an external dataset. The 16p13.3 gain was detected in 42% (113/267) of the specimens scorable by FISH and was significantly associated with clinicopathologic features of aggressive prostate cancer, including high preoperative PSA (P = 0.03) levels, high Gleason score (GS, P < 0.0001), advanced pathologic tumor stage (P < 0.0001), and positive surgical margins (P = 0.009). The 16p13.3 gain predicted biochemical recurrence (BCR) in the overall cohort (log-rank P = 0.0005), and in subsets of patients with PSA ≤10 or GS ≤7 (log-rank P = 0.02 and P = 0.006, respectively). Moreover, combining the 16p13.3 gain status with standard prognostic markers improved BCR risk stratification and identified a subgroup of patients with high probability of recurrence. The 16p13.3 gain status was also associated with an increased risk of developing distant metastases (log-rank P = 0.03) further substantiating its role in prostate cancer progression.Implications: This study demonstrates the prognostic significance of the 16p13.3 genomic gain in primary prostate tumors, suggesting potential utility in the clinical management of the disease by identifying patients at high risk of recurrence who may benefit from adjuvant therapies. Mol Cancer Res; 16(1); 115-23. ©2017 AACR.

Positive surgical margins and biochemical recurrence following minimally-invasive radical prostatectomy \u2013 An analysis of outcomes from a UK tertiary referral centre

BackgroundPositive surgical margins are a strong prognostic marker of disease outcome following radical prostatectomy, though prior evidence is largely from a PSA-screened population. We therefore aim to evaluate the biochemical recurrence in men with positive surgical margins (PSM) after minimally-invasive radical prostatectomy (MIRP) in a UK tertiary centre.MethodsRetrospective study of men undergoing laparoscopic or robotic-assisted radical prostatectomy between 2002 and 2014. Men with positive surgical margins (PSM) were identified and their biochemical recurrence (BCR) rate compared with men without PSM. The primary outcome measures were BCR rates and time to BCR. Cox regression was used to estimate adjusted hazard ratios for biochemical recurrence rate (BCR), accounting for potential confounders.ResultsFive hundred ninety-two men were included for analysis. Pre-operative D’Amico risk stratification showed 37.5%, 53.3% and 9.3% of patients in the low, intermediate and high-risk groups, respectively. On final pathological analysis, the proportion of patients with local staging pT2, pT3a and pT3b was 68.8%, 25.2% and 6.1% respectively. Overall positive margin rate was 30.6%. On multivariate analysis, the only pre-operative factor associated with PSM was age >65years. Patients with PSM were more likely to have higher tumour volume and more advanced pathological local stage. The BCR rate was 10.7% in margin-positive patients and 5.1% in margin-negative patients, at median 4.4-year follow-up. Upon multivariate analysis, high pre-operative PSA and high Gleason group were the only significant predictors of BCR (P<0.05).ConclusionsIn comparison to patients with negative surgical margins, those with PSM do not translate into worse medium-term oncological outcomes in the majority of cases amongst our cohort. We found that high pre-operative PSA and high Gleason group were the only significant predictors of BCR.

Clinical Variables That Predict for Adverse Pathological Features in Intermediate Risk Prostate Cancer

Significant clinical heterogeneity exists in man with intermediate risk prostate cancer (IRP). Precise risk stratification may aid optimal management recommendation. The present study was conducted to evaluate risk of up-grading and adverse pathological features with a larger cohort of patients. Patients with IRP, as defined by NCCN guideline, were included in this study. Men with unfavorable IRP included any IRP with a primary Gleason score (GS) of 4, percentage of positive biopsy cores >=50%, or multiple intermediate risk factors. Clinical and pathological reports from 1560 patients with IRP who underwent radical prostatectomy (RP) at our institution were reviewed and analyzed. The rates of pathologic Gleason upgrade (GU), and adverse pathological features (defined as extracapsular extension, seminal vesicle invasion, positive surgical margins, or positive lymph node involvement) were reported. Chi-square tests were used to assess differences in categorical variables and t-tests for continuous variables between groups. Multivariable logistic regression analysis was used to determine clinical factors that significantly predicted for adverse pathological outcomes. A total of 329 (21.1%) and 650 (41.7%) of patients had GU or adverse pathologic features at the time of RP, respectively. Patients with GU were older (p<0.001), had a higher preoperative PSA (p<0.001), and lower GS on biopsy (p<0.001). Patients with adverse pathologic features were older (p<0.001), had a higher preoperative PSA (p<0.001), higher GS on biopsy (p<0.001), higher clinical T stage (p<0.001), higher percent positive cores on biopsy (38.2% vs. 29.6%, p<0.001), higher percent positive perineural invasion on biopsy (17.9% vs. 9.1%, p<0.001), and a higher incidence of unfavorable IRP (66.3% vs. 48.8%, p<0.001). Race was not a significant risk factor for any of these adverse pathological outcomes. On multivariable analysis, increasing PSA level, older age, biopsy GS, and unfavorable intermediate risk category were statistically significantly associated with GU and adverse pathologic features. An increased percent positivity of cancer on core was associated with adverse pathologic features. Based on our single institution experience, we have identified key clinical variables that are associated with GU and adverse pathological features in patients with IRP. These are important considerations when planning for optimal treatment for this cohort of patients.