Preoperative PSA Level Research Articles

Establishment and validation of nomogram for positive surgical margin of prostate cancer

Objective To establish a nomogram model for predicting positive resection margins after prostate cancer surgery, and to perform the corresponding verification, in order to predict the risk of positive resection margins after surgery. Methods A total of 2 215 prostate cancer patients from The First Affiliated Hospital of Naval Medical University, Hospital, Peking University First Hospital, Peking University Third Hospital, Peking University, and First Affiliated Hospital of Xi′an Jiaotong University were included in the PC-follow database from 2015 to 2018, and a simple random sampling method was used. They were divided into 1 770 patients in the modeling group and 445 patients in the verification group. In the modeling group, the age ( 70 years), PSA ( 20 ng/ml), pelvic MRI (negative, suspicious, positive), clinical stage of the tumor (T1-T2, ≥T3), percentage of positive needles (≤33%, 34%-66%, >66%), Gleason score of biopsy pathology (≤6 points, 7 points, ≥8 points). Univariate and multivariate logistic analysis were performed to screen meaningful indicators to construct a nomogram model. The model was used for validation in the validation group. Results The results of multivariate analysis showed that preoperative PSA level (OR=2.046, 95%CI 1.022 to 4.251, P=0.009), percentage of puncture positive needles (OR=1.502, 95%CI 1.136 to 1.978, P=0.002), Gleason score of puncture pathology (OR=1.568, 95%CI 1.063 to 2.313, P=0.028), pelvic MRI were correlated (OR=1.525, 95%CI 1.160 to 2.005, P=0.033). Establish a nomogram model for independent predictors of positive margin of prostate cancer. The area under the receiver operating characteristic (ROC) curve of the validation group is 0.776. The area under the ROC curve of the preoperative PSA level, percentage of puncture positive needles, puncture pathology Gleason score, pelvic MRI, postoperative pathology Gleason score were 0.554, 0.615, 0.556, 0.522, and 0.560, respectively. The difference between the nomogram model and other indicators was statistically significant (P<0.05). Conclusions The constructed nomogram model has higher diagnostic value than the preoperative PSA level, percentage of puncture positive needles, Gleason score of puncturing pathology, pelvic MRI, and postoperative pathological Gleason score in predicting positive margin. Key words: Prostatic neoplasms; Prostate cancer; Positive surgical margin; Models statistical

Incidence, predictive factors and survival outcomes of incidental prostate cancer in patients who underwent radical cystectomy for bladder cancer

BACKGROUND The aim of this study was to analyze the incidence, preoperative findings, pathological features and prognosis in patients with incidental prostate cancer (iPCa) detected at radical cystectomy (RC) for bladder cancer (BCa). METHODS We retrospectively reviewed data of patients who underwent RC for BCa at our Institution between January 2005 and March 2018. Data regarding patient's history, preoperative digital rectal examination (DRE), total serum PSA level were collected from the chart review. Univariable and multivariable Cox regression models addressed the association of iPCa with recurrence-free survival (RFS) and overall survival (OS). RESULTS We obtained a final study cohort of 177 patients. Median age was 69 years (IQR 42-89) and 80(45.2%) patients had iPCa. Patients with iPCa had higher age, preoperative PSA levels and a significant rate of suspicious DRE (all P<0.05). Four patients had BCR during a median follow-up of 28 months (IQR 6-159) and none died for prostate cancer. In multivariable analyses adjusted for age, bladder cancer BCa pT and pN stage and LVI the ten-years RFS and OS rates were not impacted by iPCa regardless of whether it is a clinically significant cancer or not (HR=1.25, 95% CI: 0.65-2.38, P=0.51 vs. HR=1.37, 95% CI: 0.71-2.64, P=0.35) (HR=1.04, 95% CI: 0.53-1.86, P=0.89 vs. HR=1.20, 95% CI: 0.22-6.72, P=0.83). CONCLUSIONS iPCa is quite common in our study group and most of cases are organ-confined and well differentiated. Regardless of clinical relevance, iPCa does not have an impact on survival outcomes as BCa is driving the prognosis of these patients.

The impact of very high initial PSA on oncological outcomes after radical prostatectomy for clinically localized prostate cancer

BackgroundTo analyze oncological outcomes of very high-risk patients with initial PSA 50-99.9 and ≥100 ng/ml who underwent radical prostatectomy (RP) for clinically localized prostate cancer. MethodsOverall, 2,811 RP patients (1992-2018) with negative preoperative CT-scan and bone scintigraphy were included. The impact of preoperative PSA level, categorized as 20-49.9 (n = 2,195) vs. 50-99.9 (n = 454) vs. ≥100 ng/ml (n = 162) on biochemical recurrence (BCR)-free survival, metastasis-free survival (MFS) and cancer-specific survival (CSS) was assessed using Kaplan-Meier and multivariable Cox regression models. ResultsMedian follow-up was 47.5 months. Ten-year BCR-free survival rates were 46.9 vs. 32.1 vs. 29.0% within PSA-categories 20-49.9 vs. 50-99.9 vs. ≥100 ng/ml, respectively (P < 0.001). Ten-year MFS rates were 78.4 vs. 67.2 vs. 37.3% within PSA-categories 20-49.9 vs. 50-99.9 vs. ≥100 ng/ml (P < 0.001). 10-year CSS rates were 93.7 vs. 85.5 vs. 66.7% within PSA-categories 20-49.9 vs. 50-99.9 vs. ≥100 ng/ml (P < 0.001). In multivariable analyses, PSA-categories 50-99.9 ng/ml and ≥100 ng/ml were independently predicting higher risk of BCR (hazard ratio [HR]: 1.3 and 1.4), metastatic progression (HR: 1.4 and 2.3), and cancer-specific mortality (CSM, HR: 1.9 and 3.4) compared with PSA-category 20-49.9 ng/ml. ConclusionInitial PSA levels ≥50 ng/ml are associated with higher risk of BCR, metastatic progression, and CSM compared with high-risk patients with PSA of 20-49.9 ng/ml. In consequence, these patients may be counseled about a potentially increased risk of undetected metastases prior to RP possibly necessitating intensified multimodal treatments in the future.

Loss of cytoplasmic survivin expression is an independent predictor of poor prognosis in radically operated prostate cancer patients.

Survivin is an inhibitor of apoptosis. Aberrant survivin expression occurs in malignant tumors and has often been linked to unfavorable patient outcome. Here we analyzed 12 432 prostate cancers by immunohistochemistry. Survivin immunostaining was regularly expressed at high levels in normal prostate epithelium but expression was often reduced in prostate cancers. Among 9492 evaluable prostate cancers, 9% expressed survivin strongly, 19% moderately, 28% weakly, and 44% lacked it. Loss of cytoplasmic survivin was seen in advanced tumor stage, higher Gleason score, preoperative PSA levels, and Ki‐67 labeling index, and associated with earlier PSA recurrence (P < .0001). Survivin loss was significantly more common in cancers carrying TMPRSS2:ERG fusions (61% survivin negative) than in ERG wild‐type cancers (32% survivin negative; P < .0001). Multivariate analysis revealed that reduced cytoplasmic survivin expression predicted poor prognosis independent from Gleason score, pT, pN, and serum PSA level. This was valid for ERG‐positive and ERG‐negative cancers. Survivin expression loss even retained its prognostic impact in 1020 PTEN deleted cancers, a group that is already characterized by dismal patient prognosis. In conclusion, reduced survivin expression is associated with more aggressive tumors and inferior prognosis in prostate cancer.

Androgen deprivation therapy in men with node-positive prostate cancer treated with postoperative radiotherapy

BackgroundIn men with node-positive prostate cancer after radical prostatectomy there are limited data on the value of adding androgen deprivation therapy (ADT) to postoperative radiotherapy. ObjectiveTo determine whether there is a clear oncologic benefit to ADT in the setting of node-positive prostate cancer treated with postoperative radiotherapy. MethodsWe analyzed data for 372 prostate cancer patients treated at San Raffaele Hospital with postoperative radiotherapy for node-positive disease after radical prostatectomy, 272 received both ADT and radiotherapy. Eighty-six men were followed without an event for more than 10 years. ResultsPatients who received postoperative radiotherapy + ADT had more aggressive disease, with higher preoperative PSA level, higher rate of ISUP grade 5, pT3b-T4 tumors and ≥3 positive nodes. At multivariable Cox regression, the comparison between men treated by postoperative radiotherapy + ADT vs. radiotherapy alone did not show a significant difference for overall (hazards ratio: 0.91; 95% confidence interval: 0.45, 1.84; P = 0.8) and cancer-specific survival (hazards ratio: 5.39; 95% confidence intervalI: 0.70, 41.39; P = 0.11). These results remained consistent in a number of sensitivity analyses, including propensity score matching. Consideration of 95% CIs suggests that a clinically significant benefit of ADT in node-positive patients receiving radiotherapy after surgery is unlikely. ConclusionsWe can exclude the sort of large survival benefit that would be required to justify the risks and toxicities of ADT in men with node-positive disease receiving postoperative radiotherapy. Awaiting larger and more powered studies on this topic, men with pN+ prostate cancer treated with postoperative radiotherapy should not receive ADT outside well-controlled clinical trials.

Nomograms to Predict the Probabilities of Adverse Features Indicated for Adjuvant Radiotherapy for Patients with Prostate Cancer That May Help to Individualize Initial Treatment Options

It is recommended that prostate cancer patients with positive margin(s)(PM) or extra-prostatic extension(EPE) after radical prostatectomy (RP) underwent adjuvant radiotherapy(RT). There is high level evidence supporting definitive RT as the primary treatment regimen as it was shown to be equivalent with RP. Predicting adverse features after surgery may help to individualize initial treatment options. The purpose of this study is to develop nomograms through the correlation of pretreatment PSA, clinical T stage and biopsy Gleason Score(GS) with adverse features such as EPE or PM that are commonly indicated for adjuvant RT. We analyzed 1921 RP patients between January, 2007 and December, 2019 at our hospital. Patients who had a history of neoadjuvant hormonal therapy, or transurethral resection of the prostate were excluded. All patients had a preoperative PSA level, biopsy GS, pelvic MRI and other examinations for staging. PSAmax level, clinical T stage (T2a/b, T2c, T3a, T3b), and biopsy GS (5 to 6, 3+4 = 7, 4 + 3 = 7, 8, 9 to 10) were recorded as preoperative predictors. These predictors were used in multivariable logistic regression analysis based nomograms to estimate the probabilities of EPE and PM after RP, respectively. The predictive accuracy and discriminative ability were determined by concordance index (C-index) and calibration curve. Analyses were performed with statistical software. A total of 1060 patients were eligible. Median age was 66(33-82) years.10.9% of the patients underwent open RP, 89.1% received laparoscopic RP, including 18 patients who received robot-assisted laparoscopic surgery. Preoperatively, 62.6% of patients had a PSA higher than 20 ng/mL; 83.1% were organ confined disease; and 76.6% had biopsy GS≤7. Postoperatively, 30.1% had PM, 54.3% had EPE. In addition, 48.7% (429/881) of patients who were clinically diagnosed with organ-confined disease(≤T2) were found to have EPE (≥T3) after surgery. As for the Gleason Score, 11.7%(95/812) of the patients who had biopsy GS< 8 had upgraded to 8 to 10 after surgery. Nomograms were developed for the predicted probabilities of having the indications of adjuvant radiation therapy (pathologically EPE disease or PM, respectively). The calibration curve for probabilities showed good agreement between prediction by nomogram and actual observation. The C-index of the nomograms for predicting for EPE disease, or PM were 0.70 and 0.76, respectively. The risk of having one of the indications of adjuvant radiation therapy increased with increases in predictors. Using clinic-pathological information, we produced nomograms which may accurately predict the probabilities of having indications for adjuvant radiation therapy after RP. Based on these nomograms, patients at high risk of having an indication of adjuvant RT may choose to receive definitive RT to avoid toxicities and therefore improve cost-effectiveness without compromising efficacy.

Nuclear ELAC2 overexpression is associated with increased hazard for relapse after radical prostatectomy.

ELAC2 is a ubiquitously expressed enzyme potentially involved in tRNA processing and cell signaling pathways. Mutations of the ELAC2 gene have been found to confer increased prostate cancer susceptibility in families. ELAC2 protein expression was analyzed by immunohistochemistry in 9,262 patients and Kaplan-Meier curves of PSA recurrence-free survival were calculated in 8,513 patients treated with radical prostatectomy. Nuclear ELAC2 staining was observed in 60.8% of prostate cancers. It was weak in 26.3%, moderate in 26.6% and strong in 7.9%. Strong nuclear ELAC2 expression was associated with advanced tumor stage, nodal metastasis, higher Gleason grade, presence of TMPRSS2:ERG fusion, higher Ki67-labeling index and PTEN deletion. The difference in 1-, 5- and 10-year recurrence-free survival between strong and weak nuclear ELAC2 intensity is 7.2/13.8/17.6% in all cancers, 7.4/16.1/26.5% in the ERG negative subset, and 3.1/5.7/9.8% in the ERG positive subset. Regarding the univariate hazard ratio, PSA recurrence-free survival after prostatectomy for strong nuclear ELAC2 expression is 1.89 (1.64–2.10, p < 0.0001). It is independent of preoperative PSA-level, Gleason grade, pathological stage, surgical margin stage, and lymph node stage (multivariate hazard ratio 1.29 (1.11–1.49, p = 0.001). We conclude that nuclear ELAC2 expression is an independent prognostic marker for PSA recurrence-free survival after radical prostatectomy with a weak to moderate increase of the hazard ratio for biochemical relapse.

Assessment of 5-year overall survival in bladder cancer patients with incidental prostate cancer identified at radical cystoprostatectomy.

To investigate the oncological impact of incidental prostate cancer (iPCa) found during radical cystoprostatectomy (RCP) on overall survival (OS) prognosis of urothelial carcinoma of the bladder (BCa). A total of 122 RCP cases resected between 2002 and 2012 at our center were included for study. Survival of BCa patient was compared using the Kaplan-Meier method and the log-rank test. Cox proportional hazards regression models were used to analyze the impact of iPCa on the 5-year overall mortality of BCa patients after RCP. Among the 122 BCa cases that underwent RCP, 38 cases (31.1%) had iPCa, in which, 17 cases (44.7%) were identified as clinically significant iPCa (csPCa). BCa patients with iPCa were older (71 vs 64years, p = 0.004) and had higher preoperative PSA level (3.1ng/mL vs 1.4ng/mL, p = 0.017) when compared to those without iPCa. Cases with iPCa showed a more favorable 5-year OS than cases without iPCa, although this difference did not reach statistical significance (p = 0.219). When excluding the higher risk cases with Gleason score (GS) ≥ 4 + 3 and/or preoperative PSA > 10ng/mL, BCa patients with iPCa showed a significantly longer OS than cases without iPCa on univariate analysis (p = 0.044), but not on multivariate analysis (p = 0.125). Our results demonstrated that the frequent findings of low-risk iPCa in BCa patients could indicate the potential possibility of shared pathogenesis pathways between iPCa and BCa. Future study with a larger cohort is warranted to validate this result.

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.

Elective pelvic irradiation in prostate cancer patients with biochemical failure following radical prostatectomy: A propensity score matching analysis.

PurposeTo investigate whether whole pelvic radiotherapy (WPRT) improves biochemical relapse-free survival (bRFS) vs. prostate bed radiotherapy (PBRT) in prostate cancer patients receiving salvage radiotherapy (SRT) after radical prostatectomy.MethodsData from patients with prostate cancer who underwent SRT for biochemical recurrence between 2005 and 2012 in two academic institutions were retrospectively reviewed. Patients treated with WPRT in one hospital were compared with patients treated with PBRT in the other. Propensity scoring was performed to balance the characteristics of the different treatment groups, and bRFS was compared.ResultsData from a total of 191 patients were included in the analysis (WPRT, n = 108; PBRT, n = 83). The median follow-up period was 66 months. Prior to matching, patients who received WPRT had higher pathologic Gleason scores as well as a higher incidence of pre-SRT PSA levels >0.5 ng/mL and lower rates of concurrent androgen-deprivation therapy. Propensity score matching balanced these characteristics and generated a cohort comprising 56 patients from each group. In the matched cohort, the 5 year bRFS of the WPRT group was significantly higher than that of the PBRT group (65.9 vs. 42.2%, p = 0.017). Multivariate analysis revealed that WPRT was an independent prognostic factor for bRFS (hazard ratio: 0.45, 95% confidence interval: 0.26–0.75, p = 0.002). This benefit of WPRT on bRFS was maintained in subgroup analyses, especially in patients with preoperative PSA level ≤20 ng/mL or pre-SRT PSA level ≥0.4 ng/mL.ConclusionsThese data suggest that, following radical prostatectomy, elective WPRT during SRT may improve bRFS compared with PBRT in selected patients. Patients with preoperative PSA level ≤20 ng/mL or pre-SRT PSA level ≥0.4 ng/mL represent a potential subgroup who benefit most from receiving WPRT. Results of prospective randomized trials are awaited to confirm this finding.

The prognosis value of EphA3 and the androgen receptor in prostate cancer treated with radical prostatectomy.

BackgroundThis study aimed to preliminarily assess the relationship between erythropoietin‐producing hepatocellular carcinoma receptor A3 (EphA3) and androgen receptor (AR) protein expression levels and prognosis in prostate cancer (PCa) to better understand the role of EphA3 in the prognosis and progression of PCa.MaterialsWe investigated the expression of EphA3 and AR in human PCa by immunohistochemistry.ResultsEphA3 and AR were both significantly upregulated in PCa, with expression mainly localized to the nucleus. A high level of AR expression was found in 48.4% of 64 tumor samples, which was significantly more than in the adjacent tissue samples (15.6%) (P < 0.01). The percentage of samples expressing a high level of EphA3 was significantly greater in the PCa samples (54.7%) than in the adjacent tissue samples (20.3%) for the 64 tumors (P < 0.01). The high levels of EphA3 and AR expression in the PCa tissue samples were both correlated with the pathological stage, bladder and rectal invasion, distant metastasis, and preoperative PSA level (both P < 0.05). The survival time was significantly shorter in high levels of AR expression of patients. (P < 0.01). A high level of EphA3 in PCa patients suggests a poor prognosis (P < 0.05). Biochemical recurrence, distant metastasis, and the final scores of EphA3 and AR expression were significantly correlated with the prognosis of PCa (P < 0.05).ConclusionsIncreased EphA3 expression is an independent prognostic factor for a poor outcome and decreased survival in PCa.

MP09-03 COULD A SPECIFIC PORTION OF D'AMICO INTERMEDIATE GROUP BE RECLASSIFIED AS A LOW RISK GROUP ACCORDING TO MULIPARAMETRIC MAGNETIC RESONANCE IMAGING?

INTRODUCTION AND OBJECTIVES:Various recent literature suggests that a negative multiparametric MRI (mpMRI) allows to rule out significant prostate cancer. The objective of our study was to investigate whether a specific portion of D'Amico intermediate risk group could be reclassified as low risk if the mpMRI is negative. We evaluated the histopathological results after radical prostatectomy (RP) in preoperative D'Amico intermediate risk patients that had a negative preoperative mpMRI.METHODS:We retrospectively identified 604 D'Amico intermediate risk patients and 355 low risk patients among 1,347 who underwent a preoperative mpMRI and radical prostatectomy in a single institution. Intermediate risk patients were sub-classified according to Gleason score, clinical stage and preoperative PSA level and the positivity of mpMRI. The final pathology from each RP specimen of each sub-classified group was compared with that of D'Amico low risk group. The MRIs were considered negative when no suspicious lesion was...

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

The Clinicopathologic and Prognostic Significance of Programmed Cell Death Ligand 1 (PD-L1) Expression in Patients With Prostate Cancer: A Systematic Review and Meta-Analysis.

Background: Programmed cell death ligand 1 (PD-L1) expression has been shown to correlate with poor prognosis in diverse human cancers. However, limited data exist on the prognostic and clinicopathologic significance of PD-L1 expression in prostate cancers (PCa), and the curative effect of anti-PD-1/PD-L1 therapy remains controversial. In this systematic review and meta-analysis, we aimed to evaluate the prognostic and clinicopathologic value of PD-L1 in PCa.Methods: We performed a systematic literature search in the PubMed, Cochrane Library, EMBASE, Web of Science, and SCOPUS databases up to July 21st, 2018. Pooled prevalence of PD-L1 in PCa was calculated using Freeman-Tukey double arcsine transformation by R software version 3.5.0. The data from the studies were examined by a meta-analysis using Review Manager software 5.3 to calculate pooled hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) to estimate the prognostic and clinicopathologic value of PD-L1 in PCa. Heterogeneity was tested by the Chi-squared test and I2 statistic.Results: Five studies with 2,272 patients were included in this meta-analysis. The pooled prevalence of PD-L1 in PCa was 35% (95% CI 0.32 to 0.37). Both PD-L1 expression (HR = 1.78; 95% CI 1.39 to 2.27; p < 0.00001) and PD-L1 DNA methylation (HR = 2.23; 95% CI 1.51 to 3.29; p < 0.0001) were significantly associated with poor biochemical recurrence-free survival (BCR-FS). PD-L1 tended to have high expression levels in high Gleason score cases (OR = 1.54; 95% CI, 1.17 to 2.03; P = 0.002) and androgen receptor-positive cases (OR = 2.42, 95% CI 1.31 to 4.50; P = 0.005). However, PD-L1 had relatively weak correlation with age, pathologic stage, lymph node metastasis and preoperative PSA level.Conclusions: This meta-analysis confirms the negative prognostic significance of PD-L1 expression and mPD-L1 in PCa patients. Additionally, PD-L1 has a statistically significant correlation with Gleason score and androgen receptor status, while the correlations with age, pathologic stage, lymph node metastasis, and preoperative PSA level were not statistically significant. However, the number of included studies is too small to make the conclusions more convincing, so more retrospective large-cohort studies are expected for the further confirmation of these findings.

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.

High FOXM1 expression is a prognostic marker for poor clinical outcomes in prostate cancer.

Purpose: We aimed to investigate the expression of FOXM1 and to determine the relationships between FOXM1 expression and clinicopathologic characteristics in patients with PCa. Furthermore, we reconfirmed the prognostic impact of FOXM1 in different cohorts using already published data.Patients and Methods: Formalin-fixed, paraffin-embedded tissues were collected from patients with low- (n=17), intermediate- (n=36), and high-risk (n=29) disease, from patients with CRPC (n=2) and from patients with BPH (n=28). To analyze FOXM1 expression, we performed IHC analyses. Also, we analyzed gene expression data from cBioPortal to evaluate the associations between FOXM1 alteration and prognosis of PCa.Results: FOXM1 expression measured using Allred score differed between patients with BPH, and low-, intermediate-, and high-risk PCa (0.3, 1.5, 4.8, and 6.2, respectively; p<0.001). Patients with high FOXM1 expression had higher preoperative PSA levels (p=0.023), more advanced tumor stages (p=0.047), and higher pathologic Gleason score (p<0.001) than those with low FOXM1 expression. ROC curve analysis indicated that FOXM1 expression was a useful marker for discriminating PCa from BPH (AUC 0.851, 95% CI 0.783-0.920) and for discriminating high-risk PCa from low- and intermediate-risk PCa (AUC 0.807, 95% CI 0.719-0.894). In multivariate analyses, high FOXM1 expression was an independent predictor of BCR. Finally, in the TCGA dataset, FOXM1 alteration was associated with poor overall (p=4.521e-4) and disease-free survival (p=0.0108).Conclusions: In patients with PCa, high FOXM1 expression was associated with advanced tumor stages, high Gleason score, and poor prognosis. These data suggest a role of FOXM1 in biologically and clinically aggressive PCa.

Patient-derived, three-dimensional spheroid cultures provide a versatile translational model for the study of organ-confined prostate cancer.

To generate and characterize 3D spheroid suspension cultures from radical prostatectomy (RP) specimens as a versatile model system for organ-confined prostate cancer (PCa). Cancerous tissue samples from RP specimens were excised by a uropathologist. Preparation of 3D spheroids was done by mechanical disintegration and limited enzymatic digestion followed by serial filtration through 100μm- and 40μm-cell strainers. Thereafter, spheroids were cultured in a modified stem cell medium and characterized by a live/dead assay, whole-spheroid immunohistochemistry (IHC; CK5, CK8, AMACR, PSA, Ki67, AR, αSMA, Vimentin, E-Cadherin) and PSA-measurements in culture medium. Furthermore, their response to pharmaceutical treatment with docetaxel, bicalutamide, enzalutamide and abiraterone was tested. 173 RP cases were included. The median preoperative PSA-level was 16.12ng/ml [range 0.99;345], the median Gleason score was 7b [6;10]. 64 cases were excluded due to low tumor content in frozen sections (43) or to insufficient spheroid formation (21). In the remaining 109 cases, spheroids formed successfully and stayed viable for up to several months. IHC analysis revealed AR-, CK8-, and AMACR-positivity in nearly all cases, while CK5-positive cells were detectable only occasionally as were α-SMA and Vimentin. E-Cadherin was positive in most cases. Furthermore, spheroids proved to be amenable to cryopreservation. While abiraterone had no effect and docetaxel only a moderate effect, spheroid viability was markedly reduced upon bicalutamide and enzalutamide treatment. Multicellular 3D spheroids can be generated from patient-derived RP tissue samples and serve as an innovative in vitro model of organ-confined PCa.

Clinical value of cholinesterase in the prediction of biochemical recurrence after radical prostatectomy

PurposeTo evaluate the predictive and prognostic role as well as the clinical impact on decision-making of serum cholinesterase (ChoE) levels in patients treated with radical prostatectomy for clinically nonmetastatic prostate cancer. Materials and methodsWe conducted a retrospective analysis of our multi institutional database. Preoperative ChoE was evaluated as continuous and dichotomized variable using a visual assessment of the functional form of the association of ChoE with biochemical recurrence (BCR)-free survival. We assessed its association with perioperative clinicopathologic characteristics and outcomes. Multivariable models established its independent prognostic value for BCR. Cox proportional hazard coefficients were used to build nomograms for the prediction of early and late BCR. Decision curve analysis was used to assess the clinical impact on decision making of preoperative ChoE. ResultsIn all, 6,041 patients were available for the analysis. Decreased ChoE was associated with higher biopsy Gleason score, preoperative PSA levels, pathologic Gleason score, pathological stage, lymph node metastasis, positive surgical margin, and lymphovascular invasion at radical prostatectomy (all P < 0.01). Preoperative ChoE ≤ 6.52 U/ml was associated with higher probability of BCR (HR 1.72, 95% CI 1.48–1.99, P < 0.001). Preoperative and postoperative multivariable models that adjusted for the effects of established clinicopathologic features confirmed its independent association with BCR. In decision curve analysis inclusion of preoperative ChoE did not improve the net benefit of preoperative and postoperative models for the prediction of BCR. ConclusionsDespite independent association with clinicopathologic features and BCR, preoperative serum ChoE has no impact on clinical decision making. Future studies should investigate the possible relationship between ChoE activity and neoplastic cell transformation with a rational for targeting.

Clinicopathologic analysis of prostatic cancer with single positive core biopsy after radical prostatectomy

Objective To evaluate the clinical and pathological features of patients with prostate cancer who were diagnosed by single positive core biopsy and treated by radical prostatectomy (RP). Methods Between July 2012 and June 2016, 164 patients with prostate cancer diagnosed by single positive core biopsy underwent RP.The mean age was 66.3 years old (ranged 41-82 years old), and the mean PSA level was 12.3 ng/ml (ranged 0.6-59.5 ng/ml). The biopsy Gleason score showed 6 scores in 113 cases, 3+ 4=7 scores in 21 cases, 4+ 3=7 scores in 18 cases, ≥8 scores in 12 cases.Clinical stage was cT1 in 71 cases, cT2 in 92 cases, and cT3 in 1 case. The patients were divided into subgroups according to age, preoperative PSA level, biopsy Gleason score and clinical stage, and the pathological results were compared among these subgroups. Results Of the 164 patients, 67 cases had Gleason score ≤6, 52 cases Gleason score 3+ 4=7, 24 case Gleason score 4+ 3=7, and 11 cases Gleason score ≥8. Ten patients had pT0 disease according to the RP specimen, 3 had extraprostatic extensions, 5 had seminal vesicle invasions, and 24 had positive surgical margins. Compared to the biopsy, the Gleason score of RP specimens was higher in 53 cases, concordant in 77 cases, and lower in 24 cases. There was no significant difference in the postoperative pathological features between the age group 7 was significantly increased in PSA ≥10 ng/ml group [41.4%(36/87) vs. 66.2%(51/77), P<0.05]. When the biopsy Gleason score was divided into four groups (6, 3+ 4=7, 4+ 3=7, ≥8), there were significant differences in postoperative pathological stages among the four groups (P<0.05), and the patients with biopsy Gleason score 6 were more likely to have no residual cancer (stage T0) when compared with other Gleason scores [8.8%(10/113) vs. 0, P=0.09]. The probability of no residual cancer in clinical T1 stage patients was significantly higher than that in T2 stage [11.3%(8/71) vs. 2.8%(2/92), P=0.02], while the probability of Gleason score upgrading was significantly lower [23.9%(17/71) vs. 39.1%(36/92), P<0.05]. Conclusions Most single core prostate cancer have clinically significant disease. The treatment plan must be evaluated individually for patients with single core prostate cancer. Key words: Prostatic neoplasms; Biopsy; Single positive core; Pathological stage