Application of histone modification in the risk prediction of the biochemical recurrence after radical prostatectomy

The role of histone modifications in the development and progression of cancer remains unclear. Here,we gave an investigation of the relationship between the various histone modifications and the risk prediction of the biochemical recurrence after radical prostatectomy （RP）. Histone 3 lysine 4 dimethylation （H3K4diMe）,trimethylation （H3K4triMe）,lysine 36 trimethylation （H3K36triMe）,histone 4 lysine 20 trimethylation （H4K20triMe）and acetylation of histome 3 lysine 9 （H3K9Ac） were evaluated using immnuohistochemistry coupled with the tissue microarray technique in 169 primary prostatectomy tissue samples. Recursive partitioning analysis （RPA） was used to analyze the data. Through global histone modification analysis in patients who underwent radical prostatectomy,we found that H3K4triMe can predict the risk of the biochemical recurrence for the low grade prostate cancer （Gleason score≤6） after RP. In the case of high grade prostate cancer （Gleason score≥7）,H4K20triMe and H3K9Ac accompanying with the pre-operation prostate-specific antigen （PSA） level could also predict the risk of the biochemical recurrence after RP. In combination with the Gieason score and pre-operation PSA level,the acetylation and methylation of histones H3 and H4 can predict the biochemical recurrence of the prostate cancer following RP.

The Impact of 18F-DCFPyL PSMA PET-CT in the Management of Prostate Cancer Biochemical Recurrence

Purpose: We evaluated the findings from 18F-DCFPyL PSMA PET-CTs performed on patients presenting biochemical recurrence (BCR) of prostate cancer (PCa) and assessed its impact on staging. Methods and materials: This was a multicenter retrospective analysis of patients with PCa and BCR who underwent 18F-DCFPyL PSMA PET-CT in 2020. The patients were stratified into two groups: BCR after prostatectomy (PSA ≥ 0.2 ng/mL) or BCR after radiotherapy (PSA ≥ 2 ng/mL + nadir). We analyzed the lesions according to number and location. The Shapiro-Wilk test was used to estimate the distribution of the variables. We calculated representative statistics for the quantitative variables including the mean, standard deviation, median, and interquartile range. The association between qualitative variables was examined using Chi-squared tests. Results: 40 patients with BCR were analyzed;67.5% presented disease progression, predominantly distant recurrence (42.5%), which was found exclusively in bone;55% presented ≤5 lesions and of these, 68.2% only presented 1 lesion. There was a change in staging in 66.7% of the cases;17.7% received ablative treatment with stereotactic radiotherapy (SABR). Conclusions: 18F-DCFPyL PSMA PET-CT represents a new way to manage patients with BCR that, in this study, resulted in a change in staging in 66.7% of cases and early identification of oligometastatic progressions in the subgroup of patients with PSA < 0.5 ng/mL.

Prognostic value of Controlling Nutritional Status score for postoperative complications and biochemical recurrence in prostate cancer patients undergoing laparoscopic radical prostatectomy

Background:Controlling Nutritional Status(CONUT)score was used for screening the preoperative nutritional status.The correlation between the CONUT score and the prognosis of patients with prostate cancer(PCa)has yet to be elucidated.Herein,we analyzed the prognostic value of CONUT scores in patients with PCa who underwent laparoscopic radical prostatectomy.Materials and methods:Data of 244 patients were retrospectively evaluated.Perioperative variables and follow-up data were analyzed.The patients were categorized into 2 groups according to their preoperative CONUT scores.Postoperative complication and incontinence rates were also compared.The Kaplan-Meier method was used to estimate the median biochemical recurrence-free survival(BCRFS)between the 2 groups.Univariate and multivariate Cox regression analyses were performed to identify the potential prognostic factors for BCRFS.Results:Patients were categorized into the low-CONUT group(CONUT score<3,n=207)and high-CONUT group(CONUT score≥3,n=37).The high-CONUT group had a higher overall complication rate(40.5%vs.19.3%,p=0.004),a higher major complication rate(10.8%vs.3.9%,p=0.013),and longer postoperative length of stay(8 days vs.7 days,p=0.017).More fever,urinary infection,abdominal infection,scrotal edema,rash,and hemorrhagic events(all p values<0.05)were observed in the high-CONUT group.A higher rate of urinary incontinence was observed in the high-CONUT group at 1(34.4%vs.13.2%,p=0.030)and 3 months(24.1%vs.8.2%,p=0.023)postoperatively.The high-CONUT group had shorter medium BCRFS(23.8 months vs.54.6 months,p=0.029),and a CONUT score≥3 was an independent risk factor for a shorter BCRFS(hazards ratio,1.842;p=0.026).Conclusions:The CONUT score is a useful predictive tool for higher postoperative complication rates and shorter BCRFS in patients with PCa who undergo laparoscopic radical prostatectomy.

An autophagy-related gene prognostic index predicting biochemical recurrence, metastasis, and drug resistance for prostate cancer

Given the dual role of autophagy presenting in tumorigenesis and inhibition,we established an autophagy-related gene prognostic index(ARGPI)with validation to well predict the biochemical recurrence(BCR),metastasis,as well as chemoresistance for patients with prostate cancer(PCa)who underwent radical radiotherapy or prostatectomy.Then,Lasso and COX regression was used to develop the ARGPI.We performed the whole analyses through R packages(version 3.6.3).Secreted phosphoprotein 1(SPP1),single-minded 2(SIM2),serine protease inhibitor b5(SERPINB5),aldehyde dehydrogenase 2(ALDH2),and acyl-CoA synthetase long-chain 3(ACSL3)were eventually used to establish the ARGPI score.Patients were divided into two different-risk groups based on the median ARGPI score,high-risk patients with a higher risk of BCR than low-risk patients(hazard ratio[HR]:5.46,95%confidence interval[CI]:3.23–9.24).The risk of metastasis of high-risk patients was higher than low-risk patients(HR:11.31,95%CI:4.89–26.12).In The Cancer Genome Atlas(TCGA)dataset,we observed similar prognostic value of ARGPI in terms of BCR-free survival(HR:1.79,95%CI:1.07–2.99)and metastasis-free survival(HR:1.80,95%CI:1.16–2.78).ARGPI score showed a diagnostic accuracy of 0.703 for drug resistance.Analysis of gene set enrichment analysis(GSEA)indicated that patients in the high-risk group were significantly positively related to interleukin(IL)-18 signaling pathway.Moreover,ARGPI score was significantly related to cancer-related fibroblasts(CAFs;r=0.36),macrophages(r=0.28),stromal score(r=0.38),immune score(r=0.35),estimate score(r=0.39),as well as tumor purity(r=−0.39;all P<0.05).Drug analysis showed that PI-103 was the common sensitive drug and cell line analysis indicated that PC3 was the common cell line of PI-103 and the definitive gene.In conclusion,we found that ARGPI could predict BCR,metastasis,and chemoresistance in PCa patients who underwent radical radiotherapy or prostatectomy.

Risk factors of positive surgical margin and biochemical recurrence of patients treated with radical prostatectomy： a single-center 10-year report

Background Many studies have shown that positive surgical margin and biochemical recurrence could impact the life of patients with prostate cancer treated with radical prostatectomy. With more and more patients with prostate cancer appeared in recent 20 years in China, it is necessary to investigate the risk of positive surgical margin and biochemical recurrence, and their possible impact on the prognosis of patients treated with radical prostatectomy. In this study, we analyzed the characteristics of patients with prostate cancer who had undergone radical prostatectomy in Macao area and tried to find any risk factor of positive surgical margin and biochemical recurrence and their relationship with the proanosis of these oatients.

National Comprehensive Cancer Network （NCCN） riSK classification in predicting biochemical recurrence after radical prostatectomy： a retrospective cohort study in Chinese prostate cancer patients

This study aimed to assess the role of the National Comprehensive Cancer Network （NCCN） risk classification in predicting biochemical recurrence （BCR） after radical prostatectomy （RP） in Chinese prostate cancer patients. We included a consecutive cohort of 385 patients with prostate cancer who underwent RP at Fudan University Shanghai Cancer Center （Shanghai, China） from March 2011 to December 2014. Gleason grade groups were applied at analysis according to the 2014 International Society of Urological Pathology Consensus. Risk groups were stratified according to the NCCN Clinical Practice Guidelines in Oncology： Prostate Cancer version 1, 2017. All 385 patients were divided into BCR and non-BCR groups. The clinicopathological characteristics were compared using an independent sample t-test, Chi-squared test, and Fisher＇s exact test. BCR-free survival was compared using the log-rank test and multivariable Cox proportional hazard analysis. During median follow-up of 48 months （range： 1-78 months）, 31 （8.05%） patients experienced BCR. The BCR group had higher prostate-specific antigen level at diagnosis （46.54 ± 39.58 ng m1-1 vs 21.02 ± 21.06 ng ml-1, P= 0.001）, more advanced pT stage （P= 0.002）, and higher pN1 rate （P〈 0.001）. NCCN risk classification was a significant predictor of BCR {P = 0.0006） and BCR-free survival （P = 0.003） after RP. As NCCN risk level increased, there was a significant decreasing trend in BCR-free survival rate （Ptrend = 0.0002）. This study confirmed and validated that NCCN risk classification was a significant predictor of BCR and BCR-free survival after RP.

Effect of serum testosterone and percent tumor volume on extra-prostatic extension and biochemical recurrence after laparoscopic radical prostatectomy

Several studies have revealed that the preoperative serum testosterone and percent tumor volume （PTV） predict extra-prostatic extension （EPE） and biochemical recurrence （BCR） after radical prostatectomy. This study investigated the prognostic significance of serum testosterone and PTV in relation to EPE and BCR after laparoscopic radical prostatectomy （LRP）. We reviewed 520 patients who underwent LRP between 2004 and 2012. PTV was determined as the sum of all visually estimated tumor foci in every section. BCR was defined as two consecutive increases in the postoperative prostate-specific antigen （PSA） 〉0.2 ng ml^-1. The threshold for serum total testosterone was 3.0 ng ml^-1, Multivariate logistic regression was used to define the effect of variables on the risk of EPE and BCR. A low serum testosterone （〈3.0 ng ml^-1） was associated with a high serum PSA, Gleason score, positive core percentage of the prostate biopsy, PTV, and all pathological variables. On multivariate analysis, similar to previous studies, the serum PSA, biopsy positive core percentage, Gleason score, and pathological variables predicted EPE and BCR. In addition, low serum testosterone （〈3.0 ng ml^-1, adjusted OR, 8.52; 95% CI, 5.04-14.4, P = 0.001） predicted EPE and PTV （adjusted OR, 1.02; 95% CI, 1.01-1.05, P = 0.046） predicted BCR. In addition to previous predictors of EPE and BCR, low serum testosterone and PTV are valuable predictors of EPE and BCR after LRP.

Factors influencing biochemical recurrence in patients who have received salvage radiotherapy after radical prostatectomy： a systematic review and meta-analysis

Several studies have evaluated the risk factors influencing biochemical recurrence （BCR） of prostate cancer in patients receiving salvage radiotherapy （SRT） for BCR after radical prostatectomy （RP）, but the results remain conflicting. In this study, we performed a meta-analysis to resolve this conflict. We searched the following databases： PubMed, Embase, and Web of Science using the following terms in ＂All fields＂： ＂salvage radiation therapy,＂ ＂salvage IMRT, S-IMRT, salvage radiotherapy, SRT, radical prostatectomy,＂ ＂RP, biochemical recurrence,＂ ＂BCR,＂ ＂biochemical relapse.＂ Eleven studies, with a total of 1383 patients, were included in our meta-analysis. Of all the variables, only Gleason score （GS） 〉7 （odds ratio [OR]： 3.82; 95% confidence interval [CI]： 2.60-5.64） and pathological tumor （pT） stage 〉3a （OR： 1.82; 95% Ch 1.36-2.42） were positively correlated with BCR. However, SRT combined with androgen deprivation therapy （ADT） （OR： 0.63; 95% CI： 0.44-0.90） and radiation therapy （RT） dose 〉64 Gy （OR： 0.35; 95% CI： 0.19-0.64） were negatively correlated with BCR. Perineural invasion （OR： 2.64; 95% CI： 1.11-6.26）, preoperative prostate-specific antigen （PSA） 〉10 ng m1-1 （OR： 1.36; 95% CI： 0.94-1.96）, positive surgical margin （OR： 0.92; 95% Ch 0.7-1.19）, and seminal vesicle involvement （SVI） （OR： 1.09; 95% Ch. 0.83-1.43） had no effect on BCR. Our meta-analysis indicated that pT stage, GS, RT dose, and SRT combined with ADT may influence BCR, while preoperative PSA, surgical margin, perineural invasion, and SVI have only a weak effect on BCR.

Prostate-specific antigen density predicts favorable pathology and biochemical recurrence in patients with intermediate-risk prostate cancer

This study was designed to identify clinical predictors of favorable pathology and biochemical recurrence （BCR） in patients with intermediate-risk prostate cancer （IRPCa）. Between 2006 and 2012, clinicopathological and oncological data from 203 consecutive men undergoing robot-assisted radical prostatectomy （RARP） for IRPCa were reviewed in a single-institutional retrospective study. Favorable pathology was defined as Gleason score 〈6 and organ-confined cancer as detected by surgical pathology. Logistic regression analysis was used to determine predictive variables of favorable pathology, and the Kaplan-Meier and multivariate Cox regression model were used to estimate BCR-free survival after RARP. Overall, 38 patients （18.7%） had favorable pathology after RARP. Lower quartile prostate-specific antigen density （PSAD） was associated with favorable pathology compared to the highest quartile PSAD after adjusting for preoperative PSA, clinical stage and biopsy Gleason score （odds ratio, 5.42; 95% confidence interval, 1.01-28.97; P = 0.048）. During a median 37.8 （interquartile range, 24.6-60.2） months of follow-up, 66 patients experienced BCR. There were significant differences with regard to BCR free survival by PSAD quartiles （log rank, P = 0.003）. Using a multivariable Cox proportion hazard model, PSAD was found to be an independent predictor of BCR in patients with IRPCa after RARP （hazard ratio, 4.641; 95% confidence interval, 1.109-19.417; P = 0.036）. The incorporation of the PSAD into risk assessments might provide additional prognostic information and identify some patients in whom active surveillance would be appropriate in patients with IRPCa.

A novel nomogram provides improved accuracy for predicting biochemical recurrence after radical prostatectomy

Background:Various prediction tools have been developed to predict biochemical recurrence(BCR)after radical prostatectomy(RP);however,few of the previous prediction tools used serum prostate-specific antigen(PSA)nadir after RP and maximum tumor diameter(MTD)at the same time.In this study,a nomogram incorporating MTD and PSA nadir was developed to predict BCR-free survival(BCRFS).Methods:A total of 337 patients who underwent RP between January 2010 and March 2017 were retrospectively enrolled in this study.The maximum diameter of the index lesion was measured on magnetic resonance imaging(MRI).Cox regression analysis was performed to evaluate independent predictors of BCR.A nomogram was subsequently developed for the prediction of BCRFS at 3 and 5 years after RP.Time-dependent receiver operating characteristic(ROC)curve and decision curve analyses were performed to identify the advantage of the new nomogram in comparison with the cancer of the prostate risk assessment post-surgical(CAPRA-S)score.Results:A novel nomogram was developed to predict BCR by including PSA nadir,MTD,Gleason score,surgical margin(SM),and seminal vesicle invasion(SVI),considering these variables were significantly associated with BCR in both univariate and multivariate analyses(P<0.05).In addition,a basic model including Gleason score,SM,and SVI was developed and used as a control to assess the incremental predictive power of the new model.The concordance index of our model was slightly higher than CAPRA-S model(0.76 vs.0.70,P=0.02)and it was significantly higher than that of the basic model(0.76 vs.0.66,P=0.001).Time-dependent ROC curve and decision curve analyses also demonstrated the advantages of the new nomogram.Conclusions:PSA nadir after RP and MTD based on MRI before surgery are independent predictors of BCR.By incorporating PSA nadir and MTD into the conventional predictive model,our newly developed nomogram significantly improved the accuracy in predicting BCRFS after RP.

MAPK9 as a therapeutic target:unveiling ferroptosis in localized prostate cancer progression

Background:Ferroptosis,a lipid peroxidation-mediated programmed cell death,is closely linked to tumor development,including prostate cancer(PCa).Despite established connections between ferroptosis and PCa,a comprehensive investigation is essential for understanding its impact on patient prognosis.Methods:A risk model incorporating four ferroptosis-related genes was developed and validated.Elevated risk scores correlated with an increased likelihood of biochemical recurrence(BCR),diminished immune infiltration,and adverse clinicopathological characteristics.To corroborate these results,we performed validation analyses utilizing datasets from both the Cancer Genome Atlas Cohort(TCGA)and the Gene Expression Synthesis Cohort(GEO).Moreover,we conducted further investigations into the pivotal gene identified in our model to explore its impact on tumor characteristics through cell proliferation and invasion assays,as well as animal studies conducted in vivo.Additionally,we conducted further experiments involving ferroptosis-related analysis to validate its association with ferroptosis.Results:The risk model demonstrated exceptional predictive capabilities for prognosis and therapeutic outcomes in PCa patients.Mitogen-activated protein kinase 9(MAPK9)emerged as a crucial gene within the model.In vivo and in vitro experiments explored MAPK9’s role in ferroptosis and its influence on tumor migration and proliferation.Conclusion:The findings provide a novel perspective for advancing ferroptosis exploration in PCa,bridging basic research and clinical applications.

Role of β-microseminoprotein from prostate cancer initiationto recurrence: A mini-review

Medline/Pubmed articles relevant to this topic were considered using the search terms ?-microseminoprotein, MSMB, prostate secretory protein of 94 amino acids and PSP94. Full articles were retrieved when the abstract was considered relevant. In addition, other data related to this topic including our own are discussed. Summary of fi ndings-?-microseminoprotein(MSMB) is increasingly being considered as a marker for prostatecancer, as reduced levels have been associated with the disease. Here we review various aspects of this protein including its biological and physiological variants, binding proteins and immune modulation; its importance as a marker for biochemical recurrence of prostate cancer; prostate cancer related splice variants and its therapeutic utility. Two of the most important properties of MSMB are related to anticancer functions and immune modulation. Predominant expression of two(short and full-length) splice variants of MSMB has been observed from normal prostate and several other tissues. In benign prostate hyperplasia the short isoform is dominant, constituting 98% of this isoform, whereas in prostate cancer 96% constitute the fulllength isoform. The MSMB promoter single nucleotide polymorphism rs10993994 with the C allele functions as an activated cyclic adenosine monophosphate response element binding protein binding site. This C variant of rs10993994 could be responsible for the production of splice variants under variable conditions. MSMB has binding motifs to a few known proteins including immunoglobulin G and several Cysteine-rich secretory proteins family proteins. MSMB bound to these proteins is considered as immune modulating. Use of MSMB as a urinary marker for detecting aggressive prostate cancers that could resist radiation and surgical treatments, seems possible, but needs further investigation. The ratio of MSMB splice variants could also be a possible approach in understanding prostate cancers, with higher ratios indicating severe disease.

Clinical outcomes for men with positive surgical margins after radical prostatectomy—results from the South Australian Prostate Cancer Clinical Outcomes Collaborative community-based registry

Objective Positive surgical margins(PSMs)after radical prostatectomy(RP)indicate failure of surgery to completely clear cancer.PSMs confer an increased risk of biochemical recurrence(BCR),but how more robust outcomes are affected is unclear.This study investigated factors associated with PSMs following RP and determined their impact on clinical outcomes(BCR,second treatment[radiotherapy and/or androgen deprivation therapy],and prostate cancer-specific mortality[PCSM]).Methods The study cohort included men diagnosed with prostate cancer(pT2-3b/N0/M0)between January 1998 and June 2016 who underwent RP from the South Australian Prostate Cancer Clinical Outcomes Collaborative database.Factors associated with risk of PSMs were identified using Poisson regression.The impact of PSMs on clinical outcomes(BCR,second treatment,and PCSM)was assessed using competing risk regression.Results Of the 2827 eligible participants,28%had PSMs—10%apical,6%bladder neck,17%posterolateral,and 5%at multiple locations.Median follow-up was 9.6 years with 81 deaths from prostate cancer recorded.Likelihood of PSM increased with higher pathological grade and pathological tumor stage,and greater tumour volume,but decreased with increasing surgeon volume(odds ratio[OR]:0.93;95%confidence interval[CI]:0.88-0.98,per 100 previous prostatectomies).PSMs were associated with increased risk of BCR(adjusted sub-distribution hazard ratio[sHR]2.5;95%CI 2.1-3.1)and second treatment(sHR 2.9;95%CI 2.4-3.5).Risk of BCR was increased similarly for each PSM location,but was higher for multiple margin sites.We found no association between PSMs and PCSM.Conclusion Our findings support previous research suggesting that PSMs are not independently associated with PCSM despite strong association with BCR.Reducing PSM rates remains an important objective,given the higher likelihood of secondary treatment with associated comorbidities.

syndecan-1和-2表达形式的变化可以预测前列腺癌生化复发

The clinical features of prostate cancer do not provide an accurate determination of patients undergoing biochemical relapse and are therefore not suitable as indicators of prognosis for recurrence. New molecular markers are needed for proper pre-treatment risk stratification of patients. Our aim was to assess the value of altered expression of syndecan-1 and -2 as a marker for predicting biochemical relapse in patients with clinically localized prostate cancer treated by radical prostatectomy. The expression of syndecan-1 and -2 was examined by immunohistochemical staining in a series of 60 paraffin-embedded tissue samples from patients with localized prostate cancer. Ten specimens from patients with benign prostatic hyperplasia were used as non-malignant controls. Semiquantitative analysis was performed to evaluate the staining patterns. To investigate the prognostic value, Kaplan-Meier survival curves were performed and compared by a log-rank test. In benign samples, syndecan-1 was expressed in basal and secretory epithelial cells with basolateral membrane Iocalisation, whereas syndecan-2 was expressed preferentially in basal cells. In prostate cancer samples, the expression patterns of both syndecans shifted to granular-cytoplasmic Iocalisation. Survival analysis showed a significant difference （P〈0.05） between normal and altered expression of syndecan-1 and -2 in free prostate-specific antigen recurrence survival curves. These data suggest that the expression of syndecan-1 and -2 can be used as a prognostic marker for patients with clinically localized orostate cancer, improving the larostate-specific antigen recurrence risk stratification.

Zoledronic acid combined with androgendeprivation therapy may prolong time to castration-resistant prostate cancer in hormone-naı¨ve metastatic prostate cancer patients e A propensity scoring approach

Objective:To clarify the oncological benefit of zoledronic acid for hormone-naive metastatic prostate cancer,patient outcome of androgen deprivation therapy with zoledronic acid(ADT+Z)and androgen deprivation therapy alone(ADT)was compared.Methods:Fifty-two patients with pathologically confirmed metastatic prostate cancer were prospectively enrolled and treated with combined androgen blockade(goserelin and bicalutamide)with zoledronic acid(4 mg every 4 weeks for 24 months).A propensity score-match with logistic regression analysis was applied to select 50 pair-matched cohorts(both from ADT+Z and from historical control cohorts who had undergone ADT alone),and patient outcomes were compared.Results:Patients with ADT+Z had significantly longer time to progression(TTP)than those with ADT(median TTP;24.2 vs.14.0 months,p=0.0092),while no significant difference of overall survival between two groups(p=0.1502).Multivariate analysis for biochemical recurrence revealed treatment with ADT was the sole independent prognostic factor(HR:1.724,95%CI:1.06-2.86,p=0.0297).Conclusion:Combination of zoledronic acid with ADT may prolong time to castration resistant prostate cancer.

转谷氨酰胺酶4在前列腺癌进展及预后中的作用

Transglutaminase 4 has been shown to enhance various biological properties of prostate cancer cells, e.g., cell-matrix adhesion, invasiveness and the epithelial-mesenchymal transition. The objectives of this study were to investigate the associations between transglutaminase 4 expression and the established features and biochemical recurrence of prostate cancer. Transglutaminase 4 immunostaining was performed on a tissue microarray. The expression of transglutaminase 4 was evaluated by a scoring method based on the intensity and extent of staining. The clinical and pathological information was obtained through a review of medical records. Follow-up data were obtained by consulting the hospital medical records and the prostate cancer database of our department and by contacting patients or family members. We then compared the transglutaminase 4 expression levels between the prostate cancer tissues and the paracarcinoma tissues and evaluated the correlation of transglutaminase 4 expression with the clinical parameters and biochemical recurrence of prostate cancer. Our results indicated that the transglutaminase 4 staining was significantly higher in tumour tissue than in paracarcinoma tissue （P^O.O01） and was positively associated with higher Gleason score （P^O.O01） and higher prostate-specific antigen level （P=0.005）. Patients with transglutaminase 4 overexpression experienced shorter biochemical recurrence-free survival after surgery （P=0.042） in the univariate analysis but not in the multivariate analysis （P=0. 139）, which indicated that transglutaminase 4 may serve as a potential predictor of biochemical recurrence of prostate cancer.

Treatment of Incidental Prostate Cancer Diagnosed during BPH Surgery with Radical Prostatectomy: Appropriate or over Treatment?

Objective: Prostate cancer is detected in pathology specimens in 3% - 16% of patients undergoing Benign Prostatic Hyperplasia (BPH) surgery. There is no consensus about the optimal treatment plan for these patients. In this study, T1a,b and T1c patients were compared oncologically and in terms of operative morbidity. Materials and Methods: This study included 54 patients (Group 1) undergoing RP based on the detection of incidental prostate cancer and 54 patients (Group 2) undergoing RP based on the diagnosis of carcinoma by biopsy in three different centers. The parameters that may affect the recurrence were investigated and compared between the two groups. Additionally, patient complaints after RP such as stress urinary incontinence, lower urinary tract symptoms and erectile dysfunction were evaluated according to questionnaires and were compared between the groups and within the group in which incidental carcinoma was identified. Data analysis was performed using SPSS version 15. Results: The mean age of the patients was 63.8 years (range 51 - 78 years) with a mean follow up of 60.4 months (range 12 - 82 months). There were statistical differences in age (p = 0.036), pre-RP PSA (p < 0.001) and pre-RP prostate volume (p < 0.001) between Group 1 and Group 2. Despite the absence of a statistically significant difference in PSM between the two groups (p = 0.09), ECE was more common in Group 2 patients (p = 0.014). None of the patients with T1a disease had biochemical recurrence which was observed in 9 patients (27.3%) with stage T1b disease (p = 0.007). There were significant differences in Gleason scores in BPH specimens and RP specimens, PSM, ECE and T stages between the two subgroups. The assessment of the morbidities that are likely to affect the quality of life by questionnaires revealed that there were no significant differences between Group 1 and Group 2 however significant differences were noted in the erection quality between the subgroups (p = 0.006). Conclusion: The course of the disease is determined by the stage of the disease (pT1a, pT1b) that indicates tumor burden in these patients. With regard to postoperative complications, the problems affecting the quality of life were not poorer in patients with T1a and T1b disease than that in patients with T1c disease, which is encouraging for radical surgery.

Role of co-expression of c-Myc, EZH2 and p27 in prognosis of prostate cancer patients after surgery

Background c-Myc, EZH2 and p27 were defined to modulate anti-tumoral effects and had ability in predicting prostate cancer value of prognosis is rarely. This study aimed to investigate the patients with intermediate-risk prostate cancer after surgery. the behavior of prostate cancer with pro-tumoral or progression, but the research of their co-expression prognostic value of combining tri-marker together in Methods Expression levels of c-Myc, EZH2 and p27 in 129 patients with intermediate-risk prostate cancer were assessed using immunohistochemistry in a semi-quantitative manner. The expression profiles of these three markers were analyzed and investigated for association with biochemical recurrence. Results In all, fifty of 129 cases experienced biochemical recurrence during a median follow-up time of 31 months （range, 6-60 months）. Of these relapse patients, one case without and 10 cases with any single positive marker were observed; 39 cases were detected with any two or all three positive markers （22 cases with any two and 17 cases with all three positive markers）. Survival analysis showed that patients with over-expression of c-Myc or EZH2, and lower expression of p27 manifested significantly higher biochemical recurrence rates. Subsequent multivariate analysis revealed that c-Myc, EZH2 and p27 expression statuses showed potential in predicting relapse, respectively. Notably, combining three markers together as a ＂composite index＂ （0 or 1, vs. 2 or 3 positive markers） provided powerful prognostic value （HR 6.57, 95% CI 3.02-14.31, P 〈0.001）. There was a significant difference between the patient subgroups with 0 or 1 and those with 2 or 3 positive markers expression statuses, and tri-marker composite index was an independent risk factor for predicting relapse in patients with intermediate-risk prostate cancer after surgery. Conclusion Composite index of c-Myc, EZH2, and p27 can be valued as powerful prognosis parameter for intermediate-risk prostate cancer patients after the surgery, and postoperative adjuvant therapy can be adopted accordingly.

Does intraoperative frozen section really predict significant positive surgical margins after robot-assisted laparoscopic prostatectomy?A retrospective study

We investigated the relationship between positive surgical margin(PSM)-related factors and biochemical recurrence(BCR)and the ability of intraoperative frozen sections to predict significant PSM in patients with prostate cancer.The study included 271 patients who underwent robot-assisted laparoscopic prostatectomy with bilateral nerve sparing and maximal urethral preservation.Intraoperative frozen sections of the periurethra,dorsal vein,and bladder neck were analyzed.The ability of PSM-related factors to predict BCR and significant PSM was assessed by logistic regression.Of 271 patients,108(39.9%)had PSM and 163(60.1%)had negative margins.Pathologic Gleason score^8(18.9%vs 7.5%,P=0.015)and T stage≥T3a(51.9%vs 24.6%,P<0.001)were significantly more frequent in the PSM group.Multivariate analysis showed that Gleason pattern≥4(vs<4;hazard ratio:4.386;P=0.0004)was the only significant predictor of BCR in the PSM cohort.Periurethral frozen sections had a sensitivity of 83.3%and a specificity of 84.2%in detecting PSM with Gleason pattern≥4.Multivariate analysis showed that membranous urethra length(odds ratio[OR]:0.79,P=0.0376)and extracapsular extension of the apex(OR:4.58,P=0.0226)on magnetic resonance imaging(MRI)and positive periurethral tissue(OR:17.85,P<0.0001)were associated with PSM of the apex.PSM with Gleason pattern≥4 is significantly predictive of BCR.Intraoperative frozen sections of periurethral tissue can independently predict PSM,whereas sections of the bladder neck and dorsal vein could not.Pathologic examination of these samples may help predict significant PSM in patients undergoing robot-assisted laparoscopic prostatectomy with preservation of functional outcomes.

Refining the American Urological Association and American Society for Radiation Oncology guideline for adjuvant radiotherapy after radical prostatectomy using the pathologic Gleason score

Recently, it has been suggested that the guideline for adjuvant radiotherapy （ART） following radical prostatectomy （RP） sponsored by the American Urological Association and American Society for Radiation Oncology （AUA/ASTRO） may result in a significant overtreatment. Thus, the objective of the present study was to refine the AUA/ASTRO guideline for ART in patients at risk for biochemical recurrence （BCR） after RP. To this end, we reviewed our prospectively maintained database and selected 193 patients who met the AUA/ASTRO ART criteria. With a median follow-up of 24.0 months, BCR rate was 17.6% （34/193）. When stratified by the Gleason score, BCR rate in men with Gleason score 6 was 6.8%. There was no significant association between BCR-free survival and surgical margin （P= 0.690） and pathologic stage （P= 0.353） in patients with the Gleason score 6. However, in patients with positive surgical margins （PSMs）/pathologic stage ≥T3, there was a significant difference in BCR-free survival according to Gleason score （≤7 vs8-10, P= 0.047）. Multivariate Cox regression analysis demonstrated that pathologic stage ≥T3 （HR = 2.106; P = 0.018）, PSMs （HR = 2.411; P = 0.003）, and pathologic Gleason score 8-10 （HR = 4.715; P 〈 0.001） were independent predictors of BCR after RP. Therefore, in addition to pathologic stage 〉T3 and PSMs, Gleason score 8-10 predicts 8CR after RP. In patients with Gleason score 6, observation rather than ART may be more appropriate regardless of stage and surgical margin status.