Preoperative PSA Research Articles

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.

Vesicourethral anastomosis including rhabdosphincter in retropubic radical prostatectomy: Technique and results

Retropubic radical prostatectomy (RRP) is still widely used in clinical practice in localized prostate cancer because of its high oncological success. The aim of this study was to define the continence status in patients where rhabdosphincter was included in the vesicourethral anastomosis. Between November 2004 and September 2010, 90 cases who underwent RRP by the same surgeon in our clinic were taken into the study. In all cases vesicourethral anastomosis was performed include the rhabdosphincter. The anastomosis was performed with mean 2.9 (0-7) interrupted no 2-0 vicryl sutures, depending on the angulation of symphysis pubis and pelvic cavity. Pad test was performed to all patients at 1, 3, 6 and 12 months postoperatively. We defined patients as 'continent' when they no need pad, as 'mild incontinence' when they use only one pad daily, as 'moderate incontinence' when they use two or three pads daily and as 'severe incontinence' when they use more than three pads daily. Preoperative total PSA value was 12.2 ng/ml (range: 2.7-84 ng/ml). Preoperative prostate biopsy results were found that Gleason scores were 5, 6, 7 and 8 in 7, 53, 21, 9 patients, respectively. Mean operation and urethral catheter removal time was 103 minutes (60-200) and 14,6 days (9-28), respectively. Mean hospital stay was 4.6 days (2-20). According to results of postoperative pad tests, 38 (42.2%), 48 (53.3%), 55 (61.1%) and 75 (83.3%) patients were defined as continent in first, third, sixth and twelfth months, respectively. We think that, our novel technique of vesicourethral anastomosis in standard RRP provides more optimal urethral position during fixation of pelvic floor and urethra, protect caudal retraction, preserve functional urethral length. Also strong full thickness stitch on urethra provides better urinary continence by hanging urethra in our patients. Although our early continence rate is better, our long term continence rate is similar to literature.

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.

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.

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

Prognostic value of unifocal and multifocal positive surgical margins in a large series of robot-assisted radical prostatectomy for prostate cancer

To evaluate the prognostic value of positive surgical margins (PSM) focality for the prediction of biochemical recurrence (BCR) in patients undergoing robotic-assisted radical prostatectomy (RARP) for prostate cancer. All men with clinically localized prostate cancer undergoing RARP in our tertiary referral centre between May 2005 and August 2016 were retrospectively identified. Patients with neoadjuvant therapy were excluded. Comparisons were made between cases with negative surgical margins (NSM), unifocal PSM (uPSM), and multifocal PSM (mPSM). From a total of 973 patients available for analysis, 315 (32%) had a PSM. In these patients, 190 had uPSM and 125 had mPSM. Focality of PSM was significantly associated with tumour stage and grade, preoperative PSA, and postoperative PSA persistence (all p < 0.001), but not with nerve sparing (NS) (p = 0.15). PSA persistence was found in 120 (12%) patients, resulting in 853 patients available for survival analyses with a median follow-up of 52months. Both uPSM and mPSM were found to be independent predictors of BCR, conferring a hazard ratio of 1.9 (95% CI 1.3-3.0; p = 0.002) and 3.4 (95% CI 2.1-5.6; p < 0.001), respectively, when compared to NSM. In subgroup analyses, PSM was particularly predictive for BCR when patients underwent unilateral or bilateral NS (p ≤ 0.003). Based on a large case series of RARP, we found PSM focality to be an independent predictor of BCR, with a 1.9- and 3.4-fold risk increase for BCR in case of uPSM and mPSM, respectively. PSM seems to be of particular prognostic relevance when NS has been performed.

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.

Tumor Gene Expression Profiling in Prostate Cancer (PCa) Identifies Molecular Taxonomies Associated with Node Positivity and Quantitative Imaging Features on Multiparametric MRI (mpMRI)

Genomic classifiers based on tumor gene expression add to the predictive power of clinicopathologic features in contemporary PCa risk stratification. Increasingly, mpMRI is utilized to identify occult high grade disease as well as to aid in pre-treatment staging of localized disease. We undertook a study to examine the association of tumor gene expression profiles following radical prostatectomy (RP) with radiographic features on pre-prostatectomy mpMRI. We queried an institutional review board-approved research registry of PCa patients who had preoperative 3T mpMRI followed by post-prostatectomy tumor molecular testing performed in the course of clinical care. Genomic testing was not geographically matched to mpMRI detected lesions. Our analysis focused on correlative findings between clinical information, a genomic classifier score, and MRI features. Statistical software was used for statistical modeling of associations between gene signatures, clinicopathologic variables and imaging characteristics. Forty-eight patients met criteria for this analysis. Median age was 67 years (range 45-78) and average pre-op PSA was 11.72. Pathologic findings after RP were: 28 (58%) Gleason Score (GS) 7 (17 were 3+4, 11 were 4+3), 5 (10%) GS 8, 15 (31%) GS 9, 42 (87.5%) had EPE, 15 (31.3%) had SVI, 30 (62.5%) had positive surgical margins (SM), and 13 (27%) were node positive. A majority of patients had pre-op PI-RADS 5 lesions (n=38) detected on mpMRI. No patients had clinically or radiographically suspicious lymph nodes prior to RP. The number of patients with Decipher low, intermediate, and high risk scores were 11 (23%), 11 (23%), and 26 (54%), respectively. Non-parametric testing demonstrated a significant association between Decipher score and PI-RADS score on mpMRI (Kruskal-Wallis Test, p<0.050). Similarly, mean apparent diffusion coefficients (ADC) were directly correlated with Decipher score (Kruskal-Wallis Test, p<0.05). mpMRI features alone did not correlate with positive SM and accounting for Decipher score in univariate or multivariate models did not improve the ability of mpMRI features to predict SM status. Higher post-operative decipher score was, however, associated with likelihood of pathologic node positivity (ANOVA p=0.009). A significant correlation was observed between Decipher scores and PI-RADS classification as well as mean tumor ADC values on mpMRI. A high risk Decipher score was associated with higher rates of pathologic LN positivity otherwise undetected on mpMRI. These data support further validation of genomic classifiers in combination with mpMRI for risk stratifying PCa patients.

Improvement of continence with preservation of pelvic stabilized structure in patients undergoing robot-assisted laparoscopic radical prostatectomy

Objective To investigate the effect of pelvic floor stabilized structure preservation (PPSS) during robot-assisted laparoscopic radical prostatectomy (RARP) on postoperative continence recovery. Methods From October 2017 to April 2018, 86 patients with prostatic cancer who underwent traditional RARP and RARP plus PPSS were included. There were 31 patients in non-PPSS group and 55 patients in PPSS group. In non-PPSS group, patients age was (68.48±7.79) years old, BMI was (24.79±3.05) kg/m2, median prostate volume was 63.54 (53.00-99.36)cm3, clinic T-stage T1-T2, T3, T4 accounted for 49.39%, 22.58%, 6.45% and ISUP grade 1, 2, 3, 4, 5 accounted for 22.58%, 22.81%, 12.90%, 12.90%, 19.35% respectively. In PPSS group, patients age was (69.53±6.81) years old, BMI was (23.95±3.03) kg/m2, median prostate volume was 73.39 (54.88-94.23)cm3, clinic T-stage T1-T2, T3, T4 accounted for 72.73%, 7.27%, 3.64% and ISUP grade 1, 2, 3, 4, 5 accounted for 21.82%, 18.18%, 23.64%, 18.18%, 10.91% respectively. The preoperative PSA, BMI, clinical T-stage, ISUP grade, and postoperative hospital days had no significant differences(P>0.05) between the two groups.Both groups were operated via transperitoneal approach. In the non PPSS group, endo-pelvic fascia and pubic prostate ligament was cut, and dorsal vessel complex was ligated. In PPSS group, the partial endo-pelvic fascia was bluntly pushed to the pelvic wall to preserve tendon arch, and pubic prostate ligament also was preserved without suturing and ligating dorsal vascular complex. The catheter was removed 7 d after RARP. The continence recovery were compared between the two groups, including pad number on the day of 1, 7, 14, 30, 90 and ICI-Q-SF scores on the day of 30 and 90 after catheter removal. Results There was no significant difference in pad numbers used between the two groups on the day of 1, 7, 14, 30 after catheter removal. On the 90th day, the proportions of using pad ≥4 in PPSS group were significantly lower than those in non-PPSS group (1.89% vs. 20.69%, P=0.004). No significant difference was found in ICI-Q-SF scores on the 30th and 90th day between the two groups. Univariate analysis showed that PPSS group used less pads than non-PPSS group on the 90th day [OR=0.07(95%CI 0.01-0.65), P=0.019]; T3 patients used more pads than T1-T2 patients [OR=9.19(95%CI 1.32-63.87), P=0.025]. After adjusting for age, ISUP grading, T staging, and PSA, multivariate regression analysis showed that the risk of using pad ≥4 in PPSS group compared with non-PPSS group was 0.46, 0.34, 0.27, 0.25, and 0.03 on the day of 1 , 7, 14 , 30 and 90 after catheter removal, respectively. The PPSS approach didn′t increase the risk of positive surgical margin. Conclusions Preservation of pelvic stabilized structure in RARP is very efficient in term of continence rate after RARP, and it does not increase the risk of positive surgical margin. Key words: Prostatic neoplasms; Robotic assisted laparoscopic radical prostatectomy; Pelvic stabilized structure; Continence

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

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.

Traitement focal par HIFU versus prostatectomie radicale robot-assistée pour cancer de la prostate localisé : résultats carcinologiques et fonctionnels à 1 an

To analyse the functional and oncologic outcomes at one year of focal therapy with HIFU compared with total prostatectomy in patients with localised prostate cancer (PCa). Retrospective and monocentric study from 2008 to 2014 comparing 2 cohorts of patients with localised PCa (T1/T2 clinical stage, Gleason score≤3+4=7 and PSA<15ng/mL), one treated by focal therapy (HIFU-F group), one by robot-assisted total prostatectomy (RATP group). Primary outcome was a trifecta defined as: absence of urinary incontinence, erectile function with sexual relations without treatment, negative PSA with negative surgical margins (RATP group) or negative biopsy cores (HIFU-F group). The 53 patients included in the "HIFU-F" group and the 66 patients in the "RATP" group were similar in terms of preoperative PSA, D'Amico risk group, erectile function but were different in terms of age, prostatic volume, length of cancer, Gleason score. Complication rate was not different. In multivariate analyse with propensity score, "HIFU-F" group achieved a better trifecta score than "RATP" group (OR=8,3, p=0,005). In case of low or intermediate risk localised PCa, "HIFU-F" group had better functional outcomes than initial learning curse "RATP" group, at one year. A long-term evaluation by a common endpoint is necessary to judge the oncological equivalence of both techniques. 3.

Predictors of early, intermediate and late biochemical recurrence after minimally invasive radical prostatectomy in a single-center cohort with a mean follow-up of 8 years

ObjectiveTo determine the predictors of early, intermediate and late biochemical recurrence (BR) following minimally invasive radical prostatectomy in patients with localized prostate cancer (PC). Material and methodsWe included 6195 patients with cT1-3N0M0 prostate cancer treated using radical laparoscopic prostatectomy (RLP) and radical robot-assisted prostatectomy at our institution between 2000 and 2016. None of the patients underwent adjuvant therapy. BR is defined as PSA levels ≥0.2ng/dL. The time to BR is divided into terciles to identify the variables associated with early (<12 months), intermediate (12–36 months) and late (>36 months) recurrence. We employed logistic regression models to determine the risk factors associated with each interval. ResultsWe identified 1148 (18.3%) patients with BR. The median time to BR was 24 months (IQR, 0.98–53.18). The multivariate analysis showed that preoperative PSA levels, lymph node invasion, positive margins and RLP are associated with early recurrence (p≤0.029 for all). Laparoscopic surgery was the only predictor of intermediate recurrence (p=0.001). The predictors of late recurrence included a pathological Gleason score ≥7, stage ≥pT3, positive margins and RLP (p≤0.02 for all). ConclusionsThe patients with high-risk prostate cancer can develop late recurrence and require long-term follow-up. Identifying patients with higher PSA levels and lymph node invasion has an important predictive role in the first year after surgery. The association between RLP and BR warrants further assessment.

PJY01 - Outcomes of robotic radical prostatectomy in patients with preoperative PSA levels less than 4 ng/mL

PJY01 - Outcomes of robotic radical prostatectomy in patients with preoperative PSA levels less than 4 ng/mL

Abstract A002: Comparison of circulating microRNAs in plasma before and after radical prostatectomy among men treated for prostate cancer

Abstract Introduction: MicroRNAs (miRNAs) have been linked to advanced prostate cancer; however, their role as circulating biomarkers of prostate cancer (PC) status has yet to be determined. We examined whether circulating miRNAs in plasma could be employed as biomarkers of disease among men treated for PC by radical prostatectomy (RP). Methods: Men with clinically localized PC scheduled for a RP were recruited. Demographics, medical history, clinical information, pre-RP blood, and post-RP blood within 1 year after RP were collected. Pre- and post-RP blood were processed into plasma and the expression of the 16 most statistically significant PC circulating miRNAs in plasma identified from our previous study (miR- 381, 34a, 523, 365, 122, 375, 1255b, 34b, 450b-5p, 639, 885-5p, 1260, 150, 378, 671-3p, 148a) were examined using real-time PCR. Wilcoxon signed ranked test was used to compare the median expression of these miRNAs between pre- and post-RP plasma. Results: There were 29 men, aged 43 to 77 years, included. Majority were white men (79.3%). The median preoperative serum PSA was 6.3 ng/mL. Majority had a pathologic Gleason score of 7 (3+4) (56%) and a pathologic tumor stage of T3 (60.7%). There was no statistically significant difference in miRNA expression between pre- and post-RP plasma. Conclusion: No difference in miRNA expression before and immediately after RP was observed, possibly due to the lack of impact of tumor removal on miRNA expression and the timing of plasma collections. Future studies that examine post-RP plasma miRNA expression over time with PC recurrence are warranted. Citation Format: Alicia C. McDonald, Jay D. Raman, Jing Shen, Jason Liao, Manish Vira. Comparison of circulating microRNAs in plasma before and after radical prostatectomy among men treated for prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A002.

Antidiabetic drugs influence molecular mechanisms in prostate cancer

ABSTRACT Background: We investigated the role of diabetes mellitus (DM) and the molecular mechanisms of antidiabetic drugs in prostate cancer (PCa). Patients and Methods: 167 patients with both DM and PCa underwent radical prostatectomy (RPE). We divided our patient collective into “metformin” users, “insulin” users, “other antidiabetic drug” users and those with “no antidiabetic drug/diet only” (control group) and analyzed differences in PCa aggressiveness and laboratory parameters among treatment groups. In addition, we generated a tissue-micro-array (TMA) from RPE specimens for the analysis of candidate target pathways of antidiabetic drugs by immunohistochemistry (IHC). Results: Gleason score of both biopsy and RPE, biopsy undergrading, tumor stage as well as positive resection margins did not significantly change among groups. Preoperative body mass-index, PSA, fPSA and prostate volume/weight did not change among the treatment groups. As well, CRP, GOT, GPT, yGT, LDH, amylase, hemoglobin, TSH, FT3 and FT4 did not differ. Metformin or insulin use was not associated with changes in biochemical tumor recurrence or PCa specific mortality rates. However, tissue TMA analyses by IHC showed decreased mTOR activation, as indicated by phospho-mTOR in cancer tissue of patients with metformin and also with insulin use compared to the control group. In addition, we were able to show that the androgen receptor and the epithelial-cell contact marker E-cadherin decreased upon metformin use compared to the control group. Conclusion: We did not find a connection between antidiabetic drugs and PCa aggressiveness or progression. However, tumor biology seems to be different among patients with and without antidiabetic drugs.

The Prognostic PDE4D7 Score in a Diagnostic Biopsy Prostate Cancer Patient Cohort with Longitudinal Biological Outcomes.

Purpose. To further validate the prognostic power of the biomarker PDE4D7, we investigated the correlation of PDE4D7 scores adjusted for presurgical clinical variables with longitudinal postsurgical biological outcomes. Methods. RNA was extracted from biopsy punches of resected tumors (550 patients; RP cohort) and diagnostic needle biopsies (168 patients; DB cohort). Cox regression and survival were applied to correlate PDE4D7 scores with patient outcomes. Logistic regression was used to combine the clinical CAPRA score with PDE4D7. Results. In univariate analysis, the PDE4D7 score was significantly associated with PSA recurrence after prostatectomy in both studied patient cohorts' analysis (HR 0.53; 95% CI 0.41-0.67; p<1.0E-04 and HR 0.47; 95% CI 0.33-0.65; p<1.0E-04, respectively). After adjustment for the presurgical clinical variables preoperative PSA, PSA density, biopsy Gleason, clinical stage, percentage tumor in the biopsy (data only available for RP cohort), and percentage of positive biopsies, the HR was 0.49 (95% CI 0.38-0.64; p<1.0E-04) and 0.43 (95% CI 0.29-0.63; p<1.0E-04), respectively. The addition of the PDE4D7 to the clinical CAPRA score increased the AUC by 5% over the CAPRA score alone (0.82 versus 0.77; p=0.004). This combination model stratified 14.6% patients of the DB cohort to no risk of biochemical relapse (NPV 100%) over a follow-up period of up to 15 years. Conclusions. The PDE4D7 score provides independent risk information for pretreatment risk stratification. Combining CAPRA with PDE4D7 scores significantly improved the clinical risk stratification before surgery.

The role of preoperative PSA level in prostate cancer

Background: PSA levels between 0-4 ng/ml is generally accepted as normal range, there is no world widely accepted cut-off value. PSA level is most commonly used for determining patients to whom needle biopsy should be performed. Authors aimed to investigate the relationship between preoperative PSA level and histopathological features.Methods: Ninety prostatic adenocarcinoma cases diagnosed between January 2013 and January 2018 and treated by RP were included. Patients had no measurement of PSA before the operation were excluded from the study. Patients were grouped according to preoperative PSA as low-risk (&lt;10 ng/ml), medium-risk (10-20 ng/ml) and high-risk (&gt;20 ng/ml). The relations between all of the histopathological parameters were analyzed in addition to the preoperative PSA levels.Results: The mean age and preoperative PSA level was found as 64.16, and 12.33, respectively. The presence of EPE and tumour positive base margin showed significant relation among PSA groups as well as the presence of lymphovascular invasion and the involvement of the seminal vesicles. Intracytoplasmic mucin and foamy cytoplasm was more common in low-risk PSA group and the difference was significant.Conclusions: PSA level is one of the most commonly used marker for predicting high risk patients before the operation however it may also show relation with various histopathological factors that have effect on the prognosis of prostatic adenocarcinoma.

The value of preoperative magnetic resonance imaging in detecting the distribution of neurovascular bundles before the nerve-sparing laproscopic radical prostatectomy

Objective To investigate the preoperative magnetic resonance imaging (MRI) examination of the distribution of neurovascular bundles (NVB) around the prostatic capsule, and its clinical value in the nerve-sparing laparoscopic radical prostatectomy (NS-LRP). Methods The clinical data of 42 patients with clinically localized prostate cancer who were admitted from January 2008 to January 2017 were retrospectively analyzed. Age ranged from 58 to 74 years, with an average of 68 years. Preoperative serum PSA range from 0.94 to 12.28 ng/dl, with an average of 7.01 ng/dl. Preoperative Gleason score range from 6 to 8, with an average of 6. Clinical stage: T1-T2 37 cases, T3 5 cases. The average preoperative International Erectile Function Index questionnaire-5 (IIEF-5) 21, of which 23 cases had normal erectile function (IIEF-5>22). All the 42 patients underwent MRI examination before operation. According to the distribution of NVB around the prostatic capsule, they were divided into 3 groups: 17 cases in group A, and no NVB was evident in all cases. In group B, 8 cases were visible but not obvious. In group C, 17 cases were evident NVB. There was no significant difference in age, preoperative serum PSA and Gleason score between the three groups (P>0.05). The preoperative IIEF-5 in group A, B, and C were 19.5, 22.8, and 21.5, respectively, with no statistically significant difference (P>0.05). All 42 cases received NS-LRP under general anesthesia. The differences in IIEF-5 before and after surgery were compared between the three groups. Results In this study, 42 cases were successfully completed. 42 patients were followed up for 12 to 36 months, with an average of 14.1 months. In group A, B, and C, postoperative IIEF-5 was 8.0, 14.1, and 15.5, respectively, which was statistically significant compared with preoperative values (P<0.05). The decrease of IIEF-5 afteroperation in group A was significantly different from that of group Band C (P<0.05). Conclusions Compared with patients with visible NVB on MRI examination, patients have no visible NVB observed on MRI with erectile function-related nerves around the prostatic capsule may be walking on both sides of the prostatic capsule and spreading over the entire anterior ventral surface of the prostate. To maxium-preserve NVB and postoperative erectile function to the utmost, NS-LRP surgery should be more accurately dissected on both sides and ventral side of the prostatic capsule. Key words: Neurovascular bundle; Distribution; Ventral; Magnetic resonance imaging; Erectile function; Nerve-sparing laparoscopic radical prostatectomy