Predictor Of Biochemical Recurrence-free Survival Research Articles

Distinct Adverse Clinical Outcomes of Small and Large Cribriform Patterns on Gleason 7 Prostate Cancer: A Preliminary Study.

We aimed to evaluate the effect of large and small cribriform morphology on survival following radical prostatectomy. We included 30 patients who underwent radical prostatectomy with curative intent between 2015 and 2022. Patients with the final pathology of Gleason 7 were included. Patients' radical prostatectomy specimens were reviewed by an experienced genitourinary pathologist. The diverse growth patterns of Gleason grade 4 were specified as poorly formed/fused glands, cribriform glands, and glomeruloid glands. The cribriform morphology was subdivided into small and large cribriform. Large cribriform growth morphology was defined by its size, which was double that of benign prostate glands. Small and large cribriform glands' percentages were indicated semiquantitatively. The cribriform morphology subtype present at 50% and higher was defined as the dominant pattern. The effect of histopathological patterns on biochemical recurrence and clinical progression was analyzed. Thirteen patients were small cribriform pattern dominant (group 1), whereas 14 of the patients were large cribriform pattern dominant (group 2). Pathological T, N stages, and surgical margin positivity were similar between groups. Biochemical recurrence and clinical progression rates were significantly higher in group 2. The large cribriform dominant patients had worse 2-year biochemical recurrence-free survival than small cribriform dominant patients (45.5% vs. 66.7%). In the univariate analysis, International Society of Urological Pathology grade, Gleason pattern 4 percentage, large cribriform pattern dominancy, and pT stage were predictors for biochemical recurrence-free survival. International Society of Urological Pathology grade was the only independent predictor for biochemical recurrence-free survival. Large cribriform pattern dominancy is associated with worse biochemical recurrence-free survival in Gleason 7 prostate cancer.

Adjusting the duration of androgen deprivation therapy (ADT) based on nadir PSA for high risk localized prostate cancer patients treated with definitive external beam radiation therapy and ADT

BackgroundA nadir Prostate-Specific Antigen (nPSA) of 0.06 ng/mL has been shown to be a strong independent predictor of biochemical recurrence-free survival (bRFS) in patients with intermediate or high-risk (HR) prostate cancer treated with definitive external beam radiation therapy (RT) and androgen deprivation therapy (ADT). We aimed to examine the association between the duration of ADT and bRFS in HR localized prostate cancer, based on nPSA.MethodsBetween 1998 and 2015, 204 patients with HR localized prostate cancer were identified. Of them, 157 patients (77.0%) reached the desired nPSA of < 0.06 ng/mL (favorable group), while 47 (23.0%) did not (unfavorable group). Duration of ADT varied among patients depending on physician preference, patient tolerance, and/or compliance. Survival outcomes were calculated using Kaplan–Meier methods and predictors of outcomes using multi-variable cox regression model.ResultsIn the favorable group, ADT for at least 12 months lead to superior bRFS compared to ≤ 9 months of ADT (P = 0.036). However, no significant difference was seen when examining the value of receiving ADT beyond 12, 18, or 24 months, respectively. On univariate analysis for bRFS, the use of ADT for at least 12 months was significant (P = 0.012) as well as time to nadir PSA (tnPSA), (≤ 6 vs > 6 months); (P = 0.043). The presenting T stage was borderline significant (HR 3.074; 95% CI 0.972–9.719; P = 0.056), while PSA at presentation, Gleason Score and age were not. On multivariate analysis, the use of ADT for 12 months (P = 0.012) and tnPSA (P = 0.037) remained significant. In the unfavorable group, receiving ADT beyond 9 and 12 months was associated with improved bRFS (P = 0.044 and 0.019, respectively). However, beyond 18 months, there was no significant difference.ConclusionIn HR localized prostate cancer patients treated with definitive RT and ADT, the total duration of ADT may be adjusted according to treatment response using nPSA. In patients reaching a nPSA below 0.06 ng/mL, a total of 12 months of ADT may be sufficient, while in those not reaching a nPSA below 0.06 ng/mL, a total duration of 18 months is required.

Preoperative Predictors of Biochemical Recurrence-Free Survival in High-Risk Prostate Cancer Following Radical Prostatectomy.

Background: D'Amico high-risk prostate cancer (Pca) patients experience poor and heterogeneous oncological outcomes. This heterogeneity highlights a need to extensively explore factors associated with poor outcomes to guide decision-making.Objective: To assess predictors of biochemical recurrence (BCR)-free survival in high-risk patients following radical prostatectomy (RP), and subsequently establish a model predicting outcomes.Methods: We retrospectively identified D'Amico high-risk non-metastatic Pca patients who underwent RP between 2013 and 2019 in our hospital. We collected data including PSA level, clinical stage, biopsy Gleason score (GS), number of D'Amico high-risk factors (RF), the inflammatory status (Neutrophil-to-lymphocyte ratio [NLR], derived NLR [dNLR], platelet-to-lymphocyte ratio [PLR] and LDH). Kaplan–Meier methods were used to analyze BCR-free survival. Univariate and multivariate analyses were performed using Cox proportional hazards model to evaluate the association between clinicopathological parameters and BCR-free survival.Results: The median follow-up time for the 101 patients' cohort was 26 months (range: 3–81 months). The number of RF (1RF vs. ≥2RF), biopsy GS (<8 vs. ≥8), clinical stage (≤cT2c vs. >cT2c), pathological stage, and the presence of adverse pathological features were significant predictors of BCR (P < 0.05). Other parameters including inflammatory status (dNLR, NLR, PLR, and LDH) were not of predictive value. On multivariable analysis, biopsy GS (<8 vs. ≥8; HR 2.439) and clinical stage (≤cT2c vs. >cT2c; HR 3.271) were the independent predictors of BCR. Based on these two independent predictors, patients were stratified into three risk subgroups: favorable (0 risk factor; 47% of patients), intermediate (1 risk factor; 42 %), unfavorable (2 risk factors; 11%). The intermediate and unfavorable subgroups have a significantly shorter median BCR-free survival compared to the favorable subgroup (P < 0.001).Conclusion: Several factors are associated with BCR. Clinical stage (≤cT2c vs. >cT2c) and biopsy GS (<8 vs. ≥8) are the independent predictors of BCR. The stratification of high-risk patients into risk subgroups based on these two predictors shows that the intermediate and unfavorable subgroups have a significantly shorter median BCR-free survival compared to the favorable subgroup. The preoperative stratification model may help urologists and patients during decision-making. In non-metastatic high-risk patients, preoperative inflammatory markers (NLR, dNLR, PLR, and LDH) are not of prognostic value.

Predicting biochemical recurrence after radical prostatectomy: the role of prognostic grade group and index tumor nodule

The aim of the current study was to test whether the grade group assessed in the index tumor nodule predicts biochemical recurrence after surgery. The study cohort series included 144 consecutive patients treated by laparoscopic radical prostatectomy. The following parameters were evaluated in each case: type of radical prostatectomy (with/without lymphadenectomy), pT and pN status, histologic type of prostate carcinoma (acinar versus mixed histology), surgical margin resection status, perineural invasion, lymphovascular invasion, biochemical recurrence status, presence of tertiary Gleason 5 pattern, and grade group that was assessed both in overall prostate cancer and in index (dominant) tumor nodule. Twenty patients (13.9%) experienced postoperative biochemical recurrence at a mean follow-up time of 12.2 months. The univariate survival analysis selected type of radical prostatectomy, histological subtype, lymphovascular invasion, American Joint Committee on Cancer pT and pN classification, tertiary Gleason 5 pattern, preoperative serum prostate specific antigen level, and the grade group assessed in both the overall prostate and index tumor nodule as significant for biochemical recurrence-free survival. Type of radical prostatectomy (P = .020), histological subtype (P = .002), lymphovascular invasion (P = .023), tertiary Gleason pattern 5 (P = .016), and grade group classification in index tumor nodule (P ≤ .0001) were selected as independent predictors of biochemical recurrence-free survival. In conclusion, our results validate grade group in the index tumor nodule as an independent predictor of biochemical recurrence-free survival, thus emphasizing the value of reporting grade group in index tumor nodule. The main limitation of our study is the relatively low number of cases in the current series, suggesting the need of large confirmatory studies.

Decreased expression of TCF12 contributes to progression and predicts biochemical recurrence in patients with prostate cancer.

As a member of helix-loop-helix protein family, transcription factor 12 functions as either an oncogene or a tumor suppressor in various human cancers. However, there are no reports on its involvement in prostate cancer. To investigate clinical relevance of transcription factor 12 in prostate cancer and to evaluate its roles in malignant phenotypes of this cancer in vitro and in vivo, we here examined expression patterns of transcription factor 12 protein in 50 prostate cancer tissue specimens by immunohistochemistry. Then, associations of transcription factor 12 expression with various clinicopathological characteristics and patients' prognosis of prostate cancer were evaluated. Its involvements in cancer cell proliferation, migration, invasion, and tumor growth were determined by in vitro and in vivo experiments. As a result, the positive immunostaining of transcription factor 12 protein was localized in cytoplasm and/or nucleus of prostate cancer cells. Its expression levels were decreased with prostate cancer Gleason score increased. Statistically, the decreased expression of transcription factor 12 protein more frequently occurred in prostate cancer patients with high Gleason score, positive metastasis, prostate-specific antigen failure, and short biochemical recurrence-free survival (all p < 0.05). Importantly, multivariate analysis showed that the status of transcription factor 12 expression was an independent predictor of biochemical recurrence-free survival in prostate cancer. Functionally, enforced expression of transcription factor 12 suppressed cell proliferation, migration, and invasion in vitro and inhibited tumor growth in vivo. In conclusion, transcription factor 12 protein may be a novel molecule which plays a critical role in prostate cancer progression and patients' prognosis, suggesting it might be a promising therapeutic target for prostate cancer therapy.

Long noncoding RNA LINC01296 is associated with poor prognosis in prostate cancer and promotes cancer-cell proliferation and metastasis.

Background/purposeLong noncoding RNAs (lncRNAs) have emerged as important regulators and biomarkers of tumor development and progression. This study investigated the clinical significance, biological functions, and underlying mechanisms of long intergenic non-protein-coding RNA 1296 (LINC01296) in prostate cancer.Materials and methodsLINC01296 expression in prostate cancer tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between LINC01296 expression and clinicopathologic characteristics of prostate cancer was analyzed using Kaplan–Meier analysis and the Cox proportional-hazard model. Small interfering RNA was used to suppress LINC01296, and knockdown efficiency was examined by qRT-PCR. Cell Counting Kit 8 assay, colony-formation assay, migration and invasion assays, and Western blot assay were used to explore the role of LINC01296 in tumor progression further.ResultsLINC01296-expression level was higher in prostate cancer tissues and prostate cancer cells than in adjacent nontumor tissues and immortalized normal prostate stromal WPMY1 cells. LINC01296 expression was correlated with preoperative prostate specific antigen (P=0.002), lymph-node metastasis (P=0.035), Gleason score (P<0.001), and tumor stage (P=0.036). Patients with higher LINC01296 expression displayed advanced clinical features and shorter biochemical recurrence-free survival time than those with lower LINC01296 expression. Multivariate analysis showed that LINC01296 expression was an independent predictor of biochemical recurrence-free survival in prostate cancer. Additionally, LINC01296 knockdown inhibited prostate cancer-cell proliferation, migration, and invasion, demonstrated in an in vitro study involving regulation of PI3K–Akt–mTOR signaling and epithelial–mesenchymal transition.ConclusionThe results demonstrated that LINC01296 is a novel molecule involved in prostate cancer development and progression, and thus is a potential biomarker of prognosis.

Positive expression of NR6A1/CT150 as a predictor of biochemical recurrence-free survival in prostate cancer patients.

NR6A1/CT150, as an orphan receptor, is a novel member of the cancer-testis (CT) antigen family. Here, we investigated the expression and function of NR6A1 and its underlying mechanisms in prostate cancer (PCa) patients who underwent radical prostatectomy. A total of 303 cases of prostate cancer after radical prostatectomy were analysed in a tissue microarray (TMA) for NR6A1 immunohistochemistry-based protein expression. Kaplan–Meier/log-rank analysis and Cox regression analysis were used to investigate the relationship between NR6A1 expression and clinicopathological factors in PCa. NR6A1 mRNA expression was examined by reversing transcriptase-polymerase chain reaction (RT-PCR). Knockdown of NR6A1 by small interfering RNA mediated gene silencing and overexpression of NR6A1 through lentivirus were utilized to investigate its potential role in prostate cancer cells. NR6A1 protein expression was 29.7% (90/303) and mRNA expression was 28.1%(9/32) in PCa patients. NR6A1 expression was significantly associated with Gleason score (GS) (P=0.003) and tumor stage (P=0.042). The patients with positive NR6A1 expression have a shorter biochemical recurrence-free survival. NR6A1 predicted biochemical recurrence in univariate (P=0.0159) and multivariate models (P=0.0317). In addition, gene silencing of NR6A1 resulted in G0/G1 phase cell cycle arrest, and decreased metastatic and invasive potential of prostate cancer cells DU145 and PC3. In contrast, overexpression of NR6A1 reduced G0/G1 phase cell cycle arrest, and promoted metastatic and invasive potential of prostate cancer cells 22RV1. And overexpression of NR6A1 significantly promoted tumor growth in vivo. What's more, down regulation of NR6A1 could reverse epithelial-to-mesenchymal transition (EMT) process in DU145 and PC3 cell lines, and the overexpression could enhance EMT process in 22RV1 cell line. NR6A1 played a prominent role in migration and invasion of PCa cells, and it is indicated that NR6A1 may act as a novel marker for biochemical recurrence after radical prostatectomy.

Pathological, Oncologic and Functional Outcomes of a Prospective Registry of Salvage High Intensity Focused Ultrasound Ablation for Radiorecurrent Prostate Cancer

In this prospective registry we prospectively assessed the oncologic, functional and safety outcomes of salvage high intensity focused ultrasound for radiorecurrent prostate cancer. A total of 81 men were prospectively recruited and evaluated at regular scheduled study visits to 6 months after high intensity focused ultrasound and thereafter as per standard of care. Transrectal ultrasound guided biopsy was performed at 6 months. The primary end point was absence or histological persistence of disease at 6-month biopsy. Secondary end points included quality of life, biochemical recurrence-free survival, overall survival, cancer specific survival and progression to androgen deprivation therapy. Survival analysis was performed according to the Kaplan-Meier method and multivariate analysis was performed using the log rank (Mantel-Cox) test. Mean ± SD prostate specific antigen before high intensity focused ultrasound was 4.06 ± 2.88 ng/ml. At 6 months 63 men underwent biopsy, of whom 22 (35%) had residual disease. At a mean followup of 53.5 ± 31.6 months median biochemical recurrence-free survival was 63 months. The 5-year overall and cancer specific survival rates were 88% and 94.4%, respectively. Nadir prostate specific antigen less than 0.5 ng/ml was a significant predictor of biochemical recurrence-free survival (p=0.014, 95% CI 1.22-5.87). I-PSS significantly increased (p <0.001) while IIEF-5 scores decreased and the SF-36 score did not change significantly. The rate of rectal fistulization and severe incontinence was 3.7% each. A total of 223 complications were recorded in the 180 days after high intensity focused ultrasound (Clavien-Dindo grade 1-195, grade II-20, grade III-7, grade IVa-1). Salvage high intensity focused ultrasound appears to be a viable treatment option for radiorecurrent prostate cancer, with acceptable morbidity.

Does bilateral seminal vesicle invasion at radical prostatectomy predict worse prognosis than unilateral invasion among patients with pT3b prostate cancers?

To determine whether bilateral seminal vesicle invasion is associated with worse biochemical recurrence-free survival than unilateral seminal vesicle invasion after radical prostatectomy. We reviewed the clinicopathological data of 598 men who underwent radical prostatectomy between 2008 and 2015. Among them, 107 (17.9%) had seminal vesicle invasion. After excluding cases with neo-/adjuvant hormone treatment or radiotherapy, 93 were included in the analysis. We compared biochemical recurrence-free survival rates in subgroups with or without bilateral seminal vesicle invasion using Kaplan-Meier estimates. Cox proportional hazard regression models were used to determine the predictors of biochemical recurrence-free survival. Bilateral prostatic lobes and bilateral seminal vesicles were involved by prostate cancers in 85 (91.4%) and 35 patients (37.6%), respectively. Actuarial 3-year and 5-year biochemical recurrence-free survival rates in patients with pT3b tumors with/without bilateral seminal vesicle invasion were 13.0%/34.3%, and 4.3%/19.8%, respectively. On multivariable analysis, preoperative prostate-specific antigen (hazard ratio 1.01, 95% confidence interval 1.00-1.02, P = 0.034), lymph node metastasis (hazard ratio 2.88, 95% confidence interval 1.43-5.81, P = 0.003) and bilateral seminal vesicle invasion (hazard ratio 1.75, 95% confidence interval 1.01-3.05, P = 0.047) were independent predictors of biochemical recurrence-free survival. After excluding cases with lymph node metastasis, preoperative prostate-specific antigen, surgical margin status and bilateral seminal vesicle invasion were independent predictors of biochemical recurrence-free survival. Although most men with seminal vesicle invasion experience biochemical recurrences after radical prostatectomy, their survival outcome is not uniform. Bilateral seminal vesicle invasion seems to represent an independent prognostic factor for pT3b patients, together with the preoperative prostate-specific antigen and lymph node status.

Modification of the pT2 substage classification in prostate adenocarcinoma

The current substage classification of pT2 prostate cancer (AJCC, 7th edition, 2010) into pT2a (unilateral tumors <1/2 of lobe), pT2b (unilateral tumors ≥1/2 of lobe), and pT2c (bilateral tumors) is of questionable relevance. Many studies show no difference in prognosis between substages, and incidence of pT2b prostate cancer is low. Other classification systems have been proposed based on tumor volume, as measured by dominant nodule size or tumor percentage. We characterized pT2b tumors and assessed the utility of current pT2 substaging in predicting biochemical recurrence-free survival after radical prostatectomy and compared them with different substaging methods based on tumor volume. Patients with pT2 tumors were selected among patients who underwent radical prostatectomy from 1998 to 2008. Dominant nodule size was dichotomized as <1.6 cm versus ≥1.6 cm. Tumor percentage was dichotomized as ≤25% versus >25%. Kaplan-Meier analysis and multivariate Cox proportional hazard regression models were used to evaluate pathological parameters predictive of biochemical recurrence-free survival. Of 785 patients who met criteria, 145 (18.5%) were pT2a, 15 (1.9%) were pT2b, and 625 (79.6%) were pT2c. The pT2 substages were not significant predictors of biochemical recurrence-free survival on univariate or multivariate analysis. In a multivariate model, tumor percentage >25% (P=.002) was associated with decreased biochemical recurrence-free survival. In patients with stage pT2 prostate cancer, the current substaging method lacks predictive value for biochemical recurrence-free survival after accounting for other pathologic and clinical predictors. However, tumor percentage (≤25% versus >25%) is a promising approach to substaging of pT2 prostate cancer based on its prognostic significance.

Single Positive Lymph Node Prostate Cancer Can Be Treated Surgically without Recurrence

Purpose/ObjectivesTo investigate pN1 prostate cancer (PCa) patients treated surgically without immediate adjuvant treatment.Materials and MethodsWe analyzed the database of 2316 patients at our institution who underwent robot-assisted radical prostatectomy (RARP)/radical prostatectomy (RP) between July 2005 and November 2012. 87 patients with pN1 PCa and received no neoadjuvant and immediate adjuvant therapy were included in the study. Included pN1 PCa patients were followed up for median of 60 months. Biochemical recurrence (BCR)-free survival, metastasis-free survival (MFS), cancer specific survival (CSS), and overall survival (OS) rates were determined by using Kaplan-Meier analysis. Cox regression analysis was performed to investigate the impact of prostate-specific antigen (PSA) level, Gleason score, extraprostatic extension, seminal vesicle invasion, perineural invasion, lymphovascular invasion, positive surgical margin, tumor volume, early post-operative PSA(6 weeks), PSA nadir, lymph node yield, and number of pathologically positive lymph nodes on survival.ResultsThe 5-year OS rate of patients was 86.1%, while the CSS rate was 89.6%. The metastasis-free and BCR-free survival rates were 71% and 19.1%, respectively, and each was significantly correlated with the number of positive lymph nodes on log rank tests (p = 0.004 and p = 0.039, respectively). The presence of 2 or more pathologically positive LNs (HR:2.20; 95% CI 1.30–3.72; p = 0.003) and a Gleason score ≥8 (HR: 2.40;95% CI: 1.32–4.38; p = 0.04) were significant negative predictors of BCR free survival on multivariable regression analysis. Furthermore, the presence of 2 or more positive lymph nodes (HR: 1.06; 95% CI 1.01–1.11; p = 0.029) were significant negative predictors of metastasis-free survival on multivariable regression analysis. Additionally, in the patients who had no BCR without adjuvant treatment 9 patients out of 10 (90%) had single positive LN and 5 patients out of 10 (50%) had Gleason score 7. Therefore, single positive LN, and Gleason scores ≤7 have significantly low risk of disease progression.ConclusionspN1 PCa patients have heterogenous clinical courses. Patients with single positive LN, and Gleason scores ≤7 have low risk of recurrence. Close observation with delayed adjuvant hormone therapy can be considered in these patients.

MP69-04 SINGLE POSITIVE LYMPH NODE PROSTATE CANCER CAN BE SURGICALLY CURED IN SELECTIVE CASES

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy V1 Apr 2016MP69-04 SINGLE POSITIVE LYMPH NODE PROSTATE CANCER CAN BE SURGICALLY CURED IN SELECTIVE CASES Dae Keun Kim, Kyo Chul Koo, Ki Hong Kim, Ali Abdel Raheem, Byung Ha Chung, Young Deuk Choi, and Koon Ho Rha Dae Keun KimDae Keun Kim More articles by this author , Kyo Chul KooKyo Chul Koo More articles by this author , Ki Hong KimKi Hong Kim More articles by this author , Ali Abdel RaheemAli Abdel Raheem More articles by this author , Byung Ha ChungByung Ha Chung More articles by this author , Young Deuk ChoiYoung Deuk Choi More articles by this author , and Koon Ho RhaKoon Ho Rha More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1382AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To investigate the curability of pN1 prostate cancer (PCa) patients treated surgically without immediate adjuvant treatment. METHODS We analyzed the database of 2316 patients at our institution who underwent robot-assisted radical prostatectomy (RARP) /radical prostatectomy (RP) between July 2005 and November 2012. 87 patients with pN1 PCa and received no neoadjuvant and immediate adjuvant therapy were included in the study. Included pN1 PCa patients were followed up for median of 60 months. Biochemical recurrence (BCR)- free survival, metastasis-free survival, cancer specific survival (CSS), and overall survival (OS) rates are determined by using Kaplan-Meier analysis. Cox regression analysis was performed to investigate the impact of prostate-specific antigen (PSA) level, Gleason score, extraprostatic extension, seminal vesicle invasion, perineural invasion, lymphovascular invasion, positive surgical margin, tumor volume, early post-operative PSA (6 weeks), PSA nadir, lymph node yield, and number of pathologically positive lymph nodes on survival. RESULTS The 5-year OS rate of patients was 86.1%, while the CSS rate was 89.6%. The metastasis-free and BCR-free rates were 71% and 19.1%, respectively, and each was significantly correlated with the number of positive lymph nodes on log rank tests (p = 0.004 and p = 0.039, respectively). The presence of 2 or more pathologically positive LNs (HR: 2.20; 95% CI 1.30-3.72; p = 0.003) and a Gleason score more than or equal 8 (HR: 2.40; 95% CI: 1.32–4.38; p = 0.04) were significant negative predictors of BCR free survival on multivariable regression analysis. Furthermore, the presence of 2 or more positive lymph nodes (HR: 1.06; 95% CI 1.01-1.11; p = 0.029) were significant negative predictors of metastasis-free survival on multivariable regression analysis. Additionally, in the patients who had no BCR without adjuvant treatment 9 patients out of 10 (90%) had single positive LN and 5 patients out of 10 (50%) had Gleason score 7. Therefore, single positive LN, and Gleason scores less than or equal 7 have significantly low risk of disease progression. CONCLUSIONS pN1 PCa patients have heterogenous clinical courses. Patients with single positive LN, and Gleason scores less than or equal 7 have chance of surgical curability. Close observation with delayed adjuvant hormone therapy can be considered in these patients. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e899 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Dae Keun Kim More articles by this author Kyo Chul Koo More articles by this author Ki Hong Kim More articles by this author Ali Abdel Raheem More articles by this author Byung Ha Chung More articles by this author Young Deuk Choi More articles by this author Koon Ho Rha More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Overexpression of long non-coding RNA LOC400891 promotes tumor progression and poor prognosis in prostate cancer.

Tumor recurrence and metastasis remain the major obstacles for the successful treatment of patients diagnosed with prostate cancer (PCa). In recent years, long non-coding RNAs (lncRNAs) have been considered as key regulators of tumor behavior. In this study, we investigated the biological role and clinical relevance of the lncRNA LOC400891 in prostate cancer. Using of lncRNAs expression chips screening and the biological analysis, we found the target lncRNA (LOC400891). Moreover, the expression levels of lncRNA LOC400891 in PCa tissues and cell lines were evaluated by quantitative real-time PCR (qRT-PCR), and its association with biochemical recurrence-free survival of patients was analyzed by statistical analysis. Furthermore, the effect of LOC400891 on proliferation, migration, and invasion was studied in PCa cells. We found that the expression level of LOC400891 was higher in PCa tissues and cells compared to adjacent non-tumor tissues and normal prostate stromal immortalized cells WPMY-1. The patients with higher LOC400891 expression had an advanced clinical features and a shorter biochemical recurrence-free survival time than those with lower LOC400891 expression. Furthermore, multivariate analysis showed that the status of LOC400891 expression was an independent predictor of biochemical recurrence-free survival in PCa. We also found that knockdown of LOC400891 could inhibit cell proliferation, migration, and invasion in vitro study. Our data suggested that lncRNA LOC400891 was a novel molecule involved in PCa progression, which provided a potential prognostic biomarker and therapeutic target.

Association of BCL9 expression with prostate cancer clinicopathological features and survival

B-cell lymphoma 9 (BCL9) as a co-activator for β-catenin-mediated transcription is highly expressed in tumors. The aim of our study is to investigate the expression of BCL9, and its clinicopathological significance in prostate cancer (PCa). Immunohistochemistry was conducted to analyze the expression of BCL9 in 98 PCa samples and 20 benign prostate hyperplasia (BPH) samples. The associations of BCL9 expression with clinicopathological features and prognosis in PCa patients were analyzed with various statistical methods, such as chi-square test, Kaplan-Meier method and log-rank test. The positive rate of BCL9 was 53.1% (52/98) in prostate cancer group, and 25.0% (5/20) in benign group (P=0.022). In addition, BCL9 expression in PCa tissues was significantly associated with Gleason score (P=0.016), and biochemical recurrence (P=0.020). Moreover, Kaplan-Meier survival analysis showed that the higher expression of BCL9 was correlated with shorter biochemical recurrence-free survival (P=0.037). However, BCL9 was not an independent prognostic predictor for biochemical recurrence-free survival in patients with PCa after the multivariate analysis was conducted (Hazard ratio =1.73, P=0.384). Our study demonstrates the up-regulation of BCL9 is associated with PCa's early diagnosis and malignant degree.

Significance of preoperative butyrylcholinesterase as an independent predictor of biochemical recurrence-free survival in patients with prostate cancer treated with radical prostatectomy.

Butyrylcholinesterase (BChE) is an alpha-glycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, inflammation, injury, infection, malnutrition, and malignant disease. In this study, we analyzed the potential prognostic significance of preoperative BChE levels in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP). We retrospectively evaluated 535 patients with PCa who underwent RP from 1996-2014 at a single institution. Serum BChE was routinely measured in all patients before operation. Covariates included age, preoperative laboratory data [prostate-specific antigen (PSA), hemoglobin, total protein, albumin, BChE, lactate dehydrogenase, C-reactive protein], clinical T, biopsy Gleason score, D'Amico risk classification, and RP with/without neoadjuvant therapy. Univariate and multivariate analyses were performed to identify clinical factors associated with biochemical recurrence-free survival (BRFS). Univariate analyses were performed using the Kaplan-Meier and log-rank methods, and multivariate analysis was performed using a Cox proportional hazard model. The median BChE level was 255 U/L (normal range 168-470 U/L). The median age of the enrolled patients was 68 years, and the median PSA level at diagnosis of PCa was 8.39 ng/mL. The median follow-up period was 65 months. The 5-year BRFS rate was 72.9 %. The 5-year BRFS rates in the BChE ≥ 168 and ≤ 167 U/L groups were 77.7 and 55.0 %, respectively (P < 0.001). In univariate analysis, BChE, cT, biopsy Gleason score, and D'Amico risk classification were significantly associated with BRFS. Multivariate analysis revealed that BChE was significantly associated with BRFS. This study validated preoperative serum BChE levels as an independent prognostic factor for PCa after RP.

MP62-13 PRIOR BLADDER OUTFLOW SURGERY OR LARGE PROSTATE VOLUME DOES NOT ADVERSELY AFFECT BIOCHEMICAL RECURRENCE-FREE SURVIVAL IN LOW DOSE RATE PROSTATE BRACHYTHERAPY: AN INTERMEDIATE TERM ANALYSIS

You have accessJournal of UrologyProstate Cancer: Localized V1 Apr 2015MP62-13 PRIOR BLADDER OUTFLOW SURGERY OR LARGE PROSTATE VOLUME DOES NOT ADVERSELY AFFECT BIOCHEMICAL RECURRENCE-FREE SURVIVAL IN LOW DOSE RATE PROSTATE BRACHYTHERAPY: AN INTERMEDIATE TERM ANALYSIS Áine Goggins, Hidekazu Yamamoto, Peter Acher, Stephen Morris, Ronald Beaney, Ben Challacombe, and Rick Popert Áine GogginsÁine Goggins More articles by this author , Hidekazu YamamotoHidekazu Yamamoto More articles by this author , Peter AcherPeter Acher More articles by this author , Stephen MorrisStephen Morris More articles by this author , Ronald BeaneyRonald Beaney More articles by this author , Ben ChallacombeBen Challacombe More articles by this author , and Rick PopertRick Popert More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2387AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The oncological outcomes of prostate brachytherapy remain uncertain in patients with large prostate volumes or previous bladder outflow obstruction surgery (PBOS). Here, the impact of PBOS and prostate size on intermediate term biochemical recurrence-free survival (BRFS) was investigated. METHODS Inclusion criteria were patients undergoing low dose rate prostate brachytherapy (LDRB) as monotherapy for localized prostate cancer between 2003-13, with or without PBOS. Data collected included PSA kinetics before and after LDRB, Gleason score, prostate volume, age, race, clinical and MRI stage, Charlson co-morbidity index, social deprivation status, & dosimetric parameters (D90 & V100). Primary outcome was biochemical recurrence-free survival, defined by a rise in PSA >2ng/ml above nadir. Secondary outcomes were the incidence of toxicity according to the Radiation Therapy Oncology Group toxicity grading, salvage therapy, PSA nadir, and time to nadir. Univariate Kaplan-Meier, and multivariate cox proportional hazards and logistic regression analyses were conducted. RESULTS A total of 407 patients with a median follow up of 43 months were included. 78 (19%) had PBOS, which consisted of TURP (n=72), HoLEP (n=4), HoLAP (n=1) and Millin's prostatectomy (n=1). Pathological grades were Gleason 6 or 7 for all cases. PBOS group contained a higher proportion Gleason 7 case (51%) compared to the Non-PBOS group (37%). Mean D90 and V100 were 171(±13)Gy and 96(±5%), respectively. Biochemical relapse occurred in 3/78 (4%) of PBOS and 20/329 (6%) of non-PBOS. By logrank analysis PBOS did not affect BRFS (p=0.52) however, a trend for favourable BRFS was observed in larger prostate volumes when analysed by size quartiles (p=0.02). Multivariate analysis of pre-treatment variables showed large prostate volume to be the only predictor of BRFS (HR=0.60 per 10mls increase in size, p=0.026). With the inclusion of post-treatment data (ie. PSA nadir, time to PSA, D90 and V100), independent predictors of BRFS were prostate volume (HR=0.50, p=0.024), PSA nadir (p=0.003) and time to nadir (p<0.001). History of bladder outflow surgery did not predict BRFS. A high pre-treatment PSA was the only pre-operative and post-operative predictor of grade III toxicity (HR=1.26, p=0.01). CONCLUSIONS Large prostate size is an independent predictor of favourable biochemical outcome after LDRB. PBOS did not affect BRFS nor increase the incidence of grade III toxicity and hence is not a reason to deny LDRB. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e785-e786 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Áine Goggins More articles by this author Hidekazu Yamamoto More articles by this author Peter Acher More articles by this author Stephen Morris More articles by this author Ronald Beaney More articles by this author Ben Challacombe More articles by this author Rick Popert More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

TWIST overexpression predicts biochemical recurrence-free survival in prostate cancer patients treated with radical prostatectomy

Objective. The aim of this study was to determine whether TWIST and androgen receptor (AR) expression can predict the outcome in radical prostatectomy (RP) patients. Material and methods. Samples from different tumour areas of 181 prostate cancer patients were analysed for TWIST and AR expression, and the results were correlated with known clinicopathological data and biochemical recurrence-free survival (BFS). Results. TWIST overexpression in the margin area of the tumour (M-TWIST) was related to positive surgical margin (p = 0.047), capsule invasion (p = 0.006) and biochemical recurrence (BCR) (p = 0.004). AR expression in the margin area of the tumour (M-AR) was associated with high Gleason score (p = 0.004), positive surgical margin (p = 0.004) and BCR (p = 0.05). M-TWIST overexpression was clearly associated with M-AR expression (p < 0.0001). Four parameters, i.e. M-TWIST overexpression (p < 0.0001), positive surgical margin (p = 0.003), high Gleason score (p < 0.0001) and M-AR expression (p = 0.008), predicted BFS. In the multivariate analysis, M-TWIST overexpression (p = 0.011) and Gleason score (p = 0.002) were the only independent predictors of BFS. Conclusions. M-TWIST overexpression is associated with clinicopathological prognosis factors and M-AR overexpression and is a powerful independent predictor of BFS in conjunction with the Gleason score in prostate cancer patients treated with RP.

Obesity and Long-Term Survival after Radical Prostatectomy

Obesity is a modifiable risk factor associated with worse outcomes for many cancers, yet implications for prostate cancer are not well understood. Notably the impact of body mass index on long-term survival after treatment is unclear. We performed a retrospective cohort study on a large series of men who underwent radical prostatectomy to assess the impact of obesity on long-term biochemical recurrence-free survival, prostate cancer specific survival and overall survival. Between 1982 and 2012, 11,152 men underwent radical prostatectomy at a single tertiary referral center. Patients were stratified according to body mass index as normal weight (body mass index less than 25kg/m(2)), overweight (body mass index 25 to less than 30 kg/m(2)), mild obesity (body mass index 30 to less than 35 kg/m(2)) and moderate/severe obesity (body mass index 35kg/m(2) or greater), comprising 27.6%, 56.0%, 14.1% and 2.3% of thecohort, respectively. Covariates included age, preoperative prostate specific antigen, surgery year, Gleason score, pathological stage, surgical margin and race. Predictors of biochemical recurrence-free survival, prostate cancer specific survival and overall survival were identified using Cox proportional hazard models. Median followup was 5 years (range 1 to 27). Actuarial 20-year biochemical recurrence-free survival for mild and moderate/severe obesity was 65% and 51%, respectively, compared to 76% for normal weight men (p ≤0.001). In a multivariate model obesity was a significant predictor of biochemical recurrence-free survival (mild HR 1.30, p = 0.002; moderate/severe HR 1.45, p=0.028) and overall survival (mild HR 1.41, p = 0.003; moderate/severe HR 1.81, p = 0.033). However, only mild obesity was significantly associated with prostate cancer specific survival (HR 1.51, p = 0.040), whereas moderate/severe obesity was not (HR 1.58, p = 0.356). Obese men have higher rates of biochemical recurrence than normal weight patients during long-term followup. Obesity at the time of surgery independently predicts overall survival and biochemical recurrence-free survival but not prostate cancer specific survival.

MicroRNA-30c serves as an independent biochemical recurrence predictor and potential tumor suppressor for prostate cancer

MicroRNA-30c (miR-30c) acts as a tumor suppressor or a tumor promoter in various human malignancies. However, the involvement of miR-30c in prostate cancer (PCa) is still unclear. The aim of this study was to investigate the molecular function and the clinical significance of miR-30c in PCa. Expression levels of miR-30c in PCa tissues and cells were detected by quantitative real-time-PCR (qRT-PCR). Additionally, the associations of miR-30c expression with clinicopathological features and prognosis in PCa patients were analyzed. The potential role of miR-30c in tumorigenesis of PCa cells was further evaluated by in vitro cell assays. MiR-30c was significantly down-regulated in PCa tissues and cells compared with the corresponding controls (P<0.05). In addition, the downregulation of miR-30c in PCa tissues was significantly associated with higher Gleason score (P=0.009), advanced pathological stage (P=0.016) and biochemical recurrence (P=0.034). Moreover, Kaplan-Meier survival analysis showed that the reduced expression of miR-30c was correlated with shorter biochemical recurrence-free survival (P=0.023). The multivariate analysis also identified miR-30c as an independent prognostic predictor for biochemical recurrence-free survival in patients with PCa. Furthermore, the enforced expression of miR-30c suppressed proliferation, migration and invasion of PCa cells in vitro. Our data indicated the involvement of miR-30c in PCa progression and suggested its potential role as an independent predictor of biochemical recurrence in PCa. On cellular level, miR-30c may function as a tumor suppressor for PCa cells by inhibiting tumor cell proliferation, migration and invasion.

Promoter methylation of protocadherin8 is an independent prognostic factor for biochemical recurrence of early-stage prostate cancer.

BackgroundProtocadherin8 has been demonstrated to play critical roles in initiation and progression of several human cancers. It is frequently inactivated by promoter methylation in cancers and may be used as a potential biomarker. However, the methylation status of protocadherin8 and its clinical significance in prostate cancer remains largely unknown. The purpose of this study was to evaluate the clinical significance of protocadherin8 methylation in early-stage prostate cancer.Material/MethodsThe promoter methylation status of protocadherin8 in 162 prostate cancer tissues and 47 normal prostate tissues was examined using methylation-specific PCR (MSP). Subsequently, the relationships between protocadherin8 methylation and clinicopathological features of prostate cancer patients and biochemical recurrence-free survival of patients were analyzed.ResultsWe found that protocadherin8 methylation occurred frequently in prostate cancer tissues but not in normal prostate tissues. Moreover, protocadherin8 methylation was significantly associated with advanced pathologic stage, higher level of preoperative prostate specific antigen (PSA), higher Gleason score, positive lymph node metastasis, and biochemical recurrence. In addition, patients with protocadherin8 methylated have shorter biochemical recurrence-free survival time than patients without. Multivariate Cox regression analysis revealed that protocadherin8 methylation was an independent predictor of biochemical recurrence-free survival in prostate cancer patients.ConclusionsPromoter methylation of protocadherin8 is a frequent event in prostate cancer, and might be used as an independent prognostic factor for biochemical recurrence-free survival in patients with prostate cancer.