Higher Biochemical Recurrence Rates Research Articles

Investigating racial differences in mortality and survival outcomes following radical prostatectomy: a systematic review and meta-analysis

BackgroundNotable variations in cancer rates, survival rates, mortality exist among certain populations in the US. We aim to examine how prostate cancer prognosis differs among black and white men from various ethnic backgrounds undergoing radical prostatectomy.MethodsWe performed a comprehensive search across MEDLINE and Google Scholar databases from inception to March 2023 for observational studies including black and white men undergoing radical prostatectomy. Outcomes of interest included either overall survival, prostate cancer survival, biochemical recurrence, or all-cause mortality. Studies were pooled using hazard ratios (HR) with 95% confidence intervals (CIs) using Review Manager (RevMan) version 5.4.1.ResultsIn patients undergoing radical prostatectomy, the risk of all-cause mortality was significantly greater in blacks in comparison to whites ([HR] 1.16, 95% CI 1.12–1.21; I2 = 51%; p < 0.00001). Pooled analysis shows higher rate of prostate-specific mortality in blacks treated compared to whites ([HR]: 1.08, 95% CI 0.86–1.37; I2 = 81%; p = 0.50). The risk of biochemical recurrence was significantly higher in blacks undergoing radical prostatectomy than in whites (HR: 1.27; 95% CI 1.11–1.45; I2 = 58%; p = 0.0007). On regional subgroup analysis, the mid-west and multi-institutional centers revealed a higher rate of biochemical recurrence in blacks than in whites. No significant difference was noted between blacks and whites for overall survival.ConclusionsOur research demonstrated elevated rates of all-cause mortality, prostate-specific mortality, and biochemical recurrence, with no significant differences in overall survival between blacks and whites. Further research is warranted to assess ethnic and geographic differences at a large scale.

The Association Between Lymphovascular or Perineural Invasion in Radical Prostatectomy Specimen and Biochemical Recurrence

Objective: The aim of this study was to test for the association between lymphovascular invasion or perineural invasion in radical prostatectomy (RP) specimens and biochemical recurrence (BCR). Methods: Relying on a tertiary-care database, we identified prostate cancer patients treated with RP between January 2014 and June 2023. Of these, the majority underwent robotic-assisted RP (81%). Kaplan–Meier survival analyses and Cox regression models addressed BCR according to either lymphovascular invasion or perineural invasion in RP specimens. Additionally, the linear trend test assessed the association between the Gleason Grade Group or pathologic tumor stage and lymphovascular or perineural invasion. Results: Of 822 patients, 78 (9%) exhibited lymphovascular invasion and 633 (77%) exhibited perineural invasion in RP specimens. In survival analyses, the five-year BCR-free survival rates were 62% in patients with lymphovascular invasion vs. 70% in patients without lymphovascular invasion (p = 0.04) and 64% in patients with perineural invasion vs. 82% in patients without perineural invasion (p = 0.01). In univariable Cox regression models, lymphovascular invasion (hazard ratio 1.58, 95% confidence interval 1.01–2.47; p = 0.045) and perineural invasion (hazard ratio 1.77, 95% confidence interval 1.13–2.77; p = 0.013) were both associated with a higher BCR rate. After accounting for age at surgery, PSA value, pathologic tumor stage, Gleason Grade Group, lymph node invasion, positive surgical margin, surgical approach, and adjuvant radiation therapy, lymphovascular (p = 0.740) or perineural invasion (p = 0.341) were not significantly associated with a higher BCR since the Gleason Grade Group and pathologic tumor stage highly correlated with lymphovascular as well as perineural invasion. Conclusions: In univariable models, lymphovascular or perineural invasion is associated with BCR. After adjustment for standard pathologic tumor characteristics, lymphovascular or perineural invasion is not an independent predictor for BCR.

Identification of a 9-gene signature to enhance biochemical recurrence prediction in primary prostate cancer: A benchmarking study using ten machine learning methods and twelve patient cohorts

Prostate cancer (PCa) is a prevalent malignancy among men worldwide, and biochemical recurrence (BCR) after radical prostatectomy (RP) is a critical turning point commonly used to guide the development of treatment strategies for primary PCa. However, the clinical parameters currently in use are inadequate for precise risk stratification and informing treatment choice. To address this issue, we conducted a study that collected transcriptomic data and clinical information from 1662 primary PCa patients across 12 multicenter cohorts globally. We leveraged 101 algorithm combinations that consisted of 10 machine learning methods to develop and validate a 9-gene signature, named BCR SCR, for predicting the risk of BCR after RP. Our results demonstrated that BCR SCR generally outperformed 102 published prognostic signatures. We further established the clinical significance of these nine genes in PCa progression at the protein level through immunohistochemistry on Tissue Microarray (TMA). Moreover, our data showed that patients with higher BCR SCR tended to have higher rates of BCR and distant metastasis after radical radiotherapy. Through drug target prediction analysis, we identified nine potential therapeutic agents for patients with high BCR SCR. In conclusion, the newly developed BCR SCR has significant translational potential in accurately stratifying the risk of patients who undergo RP, monitoring treatment courses, and developing new therapies for the disease.

Model risk scores may underestimate rate of biochemical recurrence in African American men with localized prostate cancer: a cohort analysis of over 3000 men.

This study aims to determine if there is a difference in prostate cancer nomogram-adjusted risk of biochemical recurrence (BCR) and/or adverse pathology (AP) between African American (AAM) and Caucasian men (CM) undergoing radical prostatectomy (RP). A retrospective review was performed of men undergoing RP in the Pennsylvania Urologic Regional Collaborative between 2015 and 2021. Cox proportional hazard regression models were used to compare the rate of BCR after RP, and logistic regression models were used to compare rates of AP after RP between CM and AAM, adjusting for the CAPRA, CAPRA-S, and MSKCC pre- and post-operative nomogram scores. Rates of BCR and AP after RP were analyzed from 3190 and 5029 men meeting inclusion criteria, respectively. The 2-year BCR-free survival was lower in AAM (72.5%) compared to CM (79.0%), with a hazard ratio (HR) of 1.38 (95% CI 1.16-1.63, p < 0.001). The rate of BCR was significantly greater in AAM compared to CM after adjustment for MSKCC pre-op (HR 1.29; 95% CI 1.08-1.53; p = 0.004), and post-op nomograms (HR 1.26; 95% CI 1.05-1.49; p < 0.001). There was a trend toward higher BCR rates among AAM after adjustment for CAPRA (HR 1.13; 95% CI 0.95-1.35; p = 0.17) and CAPRA-S nomograms (HR 1.11; 95% 0.93-1.32; p = 0.25), which did not reach statistical significance. The rate of AP was significantly greater in AAM compared to CM after adjusting for CAPRA (OR 1.28; 95% CI 1.10-1.50; p = 0.001) and MSKCC nomograms (OR 1.23; 95% CI 1.06-1.43; p = 0.007). This analysis of a large multicenter cohort provides further evidence that AAM may have higher rates of BCR and AP after RP than is predicted by CAPRA and MSKCC nomograms. Accordingly, AAM may benefit with closer post-operative surveillance and may be more likely to require salvage therapies.

Higher Preoperative Maximum Standardised Uptake Values (SUVmax) Are Associated with Higher Biochemical Recurrence Rates after Robot-Assisted Radical Prostatectomy for [68Ga]Ga-PSMA-11 and [18F]DCFPyL Positron Emission Tomography/Computed Tomography.

This study aimed to investigate the association between the 68Ga- or 18F-radiolabeled prostate-specific membrane antigen (PSMA) tracer expression, represented by the maximum standardised uptake value (SUVmax) of the dominant intraprostatic lesion, and biochemical recurrence (BCR) in primary prostate cancer (PCa) patients prior to robot-assisted radical prostatectomy (RARP). This was a retrospective, multi-centre cohort study of 446 patients who underwent [68Ga]Ga-PSMA-11 (n = 238) or [18F]DCFPyL (n = 206) Positron Emission Tomography/Computed Tomography (PET/CT) imaging prior to RARP. SUVmax was measured in the dominant intraprostatic PCa lesions. [18F]DCFPyL patients were scanned 60 ([18F]DCFPyL-60; n = 106) or 120 ([18F]DCFPyL-120; n = 120) minutes post-injection of a radiotracer and were analysed separately. To normalise the data, SUVmax was log transformed for further analyses. During a median follow-up of 24 months, 141 (30.4%) patients experienced BCR. Log2SUVmax was a significant predictor for BCR (p < 0.001). In the multivariable analysis accounting for these preoperative variables: initial prostate-specific antigen (PSA), radiologic tumour stage (mT), the biopsy International Society of Urological Pathology grade group (bISUP) and the prostate imaging and reporting data system (PI-RADS), Log2SUVmax was found to be an independent predictor for BCR in [68Ga]Ga-PSMA-11 (HR 1.32, p = 0.04) and [18F]DCFPyL-120 PET/CT scans (HR 1.55, p = 0.04), but not in [18F]DCFPyL-60 ones (HR 0.92, p = 0.72). The PSMA expression of the dominant intraprostatic lesion proved to be an independent predictor for BCR in patients with primary PCa who underwent [68Ga]Ga-PSMA-11 or [18F]DCFPyL-120 PET/CT scans, but not in those who underwent [18F]DCFPyL-60 PET/CT scans.

PD20-09 PROSTATE CANCER NOMOGRAMS MAY UNDERESTIMATE RATE OF BIOCHEMICAL RECURRENCE IN AFRICAN AMERICAN MEN: A COHORT ANALYSIS OF OVER 3000 MEN

You have accessJournal of UrologyCME1 Apr 2023PD20-09 PROSTATE CANCER NOMOGRAMS MAY UNDERESTIMATE RATE OF BIOCHEMICAL RECURRENCE IN AFRICAN AMERICAN MEN: A COHORT ANALYSIS OF OVER 3000 MEN Matthew Epstein and Adam Reese Matthew EpsteinMatthew Epstein More articles by this author and Adam ReeseAdam Reese More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003286.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: This study aims to determine if there is a difference in prostate cancer nomogram-adjusted risk of biochemical recurrence (BCR) and/or adverse pathology (AP) between African American (AAM) and Caucasian men (CM) undergoing radical prostatectomy (RP). METHODS: A retrospective review was performed of men undergoing RP in the Pennsylvania Urologic Regional Collaborative (PURC) between 2015-2021. Cox proportional hazards regression models were used to compare the rate of BCR after RP, and logistic regression models were used to compare rates of AP after RP between CM and AAM adjusting for the CAPRA, CAPRA-S, and MSKCC pre- and post-operative nomogram scores. RESULTS: Rates of BCR and AP after RP were analyzed from 3,190 and 5,029 men meeting inclusion criteria. The 2-year BCR free survival was lower in AAM (72.5%) compared to Caucasian men (CM) (79.0%), with a hazard ratio (HR) of 1.38 (95% CI 1.16-1.63, p<0.001), demonstrated in Figure 1. The rate of BCR was significantly greater in AAM compared to CM after adjustment for MSKCC pre-op (HR 1.29; 95% CI 1.08-1.53; p=0.004), and post-op nomograms (HR 1.26; 95% CI 1.05-1.49; p<0.001) (Table 1). There was a trend towards higher BCR rates among AAM after adjustment for CAPRA (HR 1.13; 95% CI 0.95-1.35; p=0.17) and CAPRA-S nomograms (HR 1.11; 95% 0.93-1.32; p=0.25), which did not reach statistical significance. The overall rate of AP was similar between AAM (38.4%) and CM (37.8%) (OR 1.02; 95% CI 0.89-1.17; p=0.72) but was significantly greater in AAM compared to CM after adjusting for CAPRA (OR 1.28; 95% CI 1.10-1.50; p=0.001) and MSKCC nomograms (OR 1.23; 95% CI 1.06-1.43; p=0.007). CONCLUSIONS: This analysis of a large multicenter cohort provides further evidence that AAM may have higher rates of BCR and AP after RP than is predicted by CAPRA and MSKCC nomograms. Accordingly, AAM may benefit with closer surveillance, and differently tailored thresholds in treatment protocols. Source of Funding: NA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e587 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Epstein More articles by this author Adam Reese More articles by this author Expand All Advertisement PDF downloadLoading ...

Survival Differences in High-Risk Prostate Cancer By Age.

Age is an established determining factor in survival in low-risk prostate cancer (PC), being this evidence weaker in high-risk tumors. Our aim is to evaluate the survival of patients with high-risk PC treated with curative intent and to identify differences across age at diagnosis. We did a retrospective analysis of patients with high-risk PC treated with surgery (RP) or radiotherapy (RDT) excluding N+ patients. We divided patients by age groups: <60, 60-70 and >70 years. We performed a comparative survival analysis.A multivariate analysis adjusted for clinically relevant variables and initial treatment received was performed. Of a total of 2383 patients, 378 met the selection criteria with a median follow-up of 8.9 years: 38 (10.1%) <60 years, 175 (46.3%) between 60-70 years, and 165 (43.6%) >70 years. Initial treatment with surgery was predominant in the younger group (RP:63.2%, RDT:36.8%), and with radiotherapy in the older group (RP:17%, RDT:83%) (p=0.001). In the survival analysis, significant differences were observed in overall survival, with better results for the younger group. However, these results were reversed in biochemical recurrence-free survival, with patients <60 years presenting a higher rate of biochemical recurrence at 10 years. In the multivariate analysis, age behaved as an independent risk variable only for overall survival, with a HR of 2.8 in the group >70 years (95%CI: 1.22-6.5; p=0.015). In our series, age appeared to be an independent prognostic factor for overall survival, with no differences in the rest of the survival rates.

Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape.

Background: Numerous studies have substantiated the association between aging and the progression of malignant tumors in humans, notably prostate cancer (PCa). Nevertheless, to the best of our knowledge, no studies have comprehensively elucidated the intricate characteristics of the aging microenvironment (AME) in PCa. Methods: AME regulatory patterns were determined using the NMF algorithm. Then an ageing microenvironment index (AMI) was constructed, with excellent prognostic and immunotherapy prediction ability, and its' clinical relevance was surveyed through spatial transcriptomics. Further, the drug response was analysed using the Genomics of Drug Sensitivity in Cancer (GDSC), the Connectivity Map (CMap) and CellMiner database for patients with PCa. Finally, the AME was studied using in vitro and vivo experiments. Results: Three different AME regulatory patterns were identified across 813 PCa patients, associated with distinct clinical prognosis and physiological pathways. Based on the AMI, patients with PCa were divided into the high-score and low-score subsets. Higher AMI score was significantly infiltrated with more immune cells, higher rate of biochemical recurrence (BCR) and worse response to immunotherapy, antiandrogen therapy and chemotherapy in PCa. In addition, we found that the combination of bicalutamide and embelin was capable of suppressing tumor growth of PCa. Besides, as the main components of AMI, COL1A1 and BGLAP act as oncogenes and were verified via in vivo and in vitro experiments. Conclusions: AME regulation is significantly associated with the diversity and complexity of TME. Quantitative evaluation of the AME regulatory patterns may provide promising novel molecular markers for individualised therapy in PCa.

May Outcomes of Robotic Radical Prostatectomy Performed After an Initial Surveillance Strategy Differ from Those from Immediate Surgery? A Propensity Score-Matched Analysis on 362 Patients Undergoing Surgery at a Referral Center.

Introduction: Active surveillance (AS) is a treatment strategy for low-risk prostate cancer (PCa) patients, with extended indication to some intermediate-risk PCa. However, active treatment is necessary in case of disease progression and robotic radical prostatectomy (RALP) is one of the treatment modalities. The aim of the study is to compare outcomes of a delayed RALP after an initial heterogeneous surveillance strategy with those of immediate RALP in a single referral center. Methods: Data from patients who underwent RALP after initial assumed "active surveillance" (referred from different institutions and backgrounds) were compared to those of patients who underwent an immediate RALP after propensity score (PS) matching. The PS analysis was performed matching ISUP score at the time of entering surveillance with ISUP at RALP for the control group; other matching covariates at the time of surgery were considered (including age, prostate-specific antigen, body mass index, prostate size, cT, pre-op Sexual Health Inventory for Men, etc.). Perioperative, functional, and oncological outcomes were compared between groups. Results: Three hundred sixty-two RALP patients were included (181 after surveillance and 181 immediate RALP). Patients after surveillance had a worse pT and ISUP score (p < 0.001); LVI and EPE were higher in the surveilled group (13% vs. 5%, p = 0.001; 38% vs. 22%, p = 0.001), without significant difference in positive surgical margin. At a median follow-up of 24 months, the risk of biochemical recurrence (BCR) was significantly higher for delayed RALP (hazard ratio: 4.0; 95% confidence interval: 1.4-12; p = 0.013), whereas potency and continence rate did not differ significantly. Conclusions: At a referral center receiving patients from diverse backgrounds, outcomes of RALP after heterogeneous surveillance strategies are variable and less predictable, maybe attributable to different protocols and surgical planning. The higher BCR rate in a high-risk surveilled cohort may suggest an increased burden of cancer-related care for RALP patients after surveillance.

Intraprostatic calcification and biochemical recurrence in men treated with cesium-131 prostate brachytherapy

Baseline intraprostatic calcification (IC) has been shown to be associated with a higher rate of biochemical recurrence (BCR) in men treated with iodine-125 prostate brachytherapy (PB). We evaluated this association in a cohort of men treated with cesium-131 PB. We retrospectively reviewed the charts of all low- and intermediate-risk prostate cancer patients treated with cesium-131 PB +/- external beam radiotherapy (EBRT) at our institution from 2/2011 to 7/2018. Patients with < 24 months of follow up or those who received androgen deprivation therapy were excluded. Baseline IC status (defined as one or more ICs ≥ 5 mm) was determined on post-PB CT scans. Cox analysis was used to assess predictors of BCR and Kaplan-Meier survival curves were calculated. Two hundred and sixteen low- and intermediate-risk prostate cancer patients treated with cesium-131 PB +/- EBRT were included. Median follow up was 56.9 months (range 24.1-111.4). Overall, 76 (35.2%) patients had baseline IC and 140 (64.8%) did not. Baseline disease characteristics did not differ significantly between groups. On univariate Cox analysis, only risk group (p = 0.047) and initial PSA (p = 0.016) were significant predictors of BCR, whereas baseline IC was not (p = 0.11). The 5-year BCR-free survival in patients with versus without baseline IC was 97.7% versus 93.8% (p = 0.405), respectively. In a cohort of low- and intermediate-risk prostate cancer patients treated with cesium-131 PB, the rate of BCR in men with baseline IC was low and baseline IC was not associated with a higher risk of BCR.

RNA-seq profile of African American men with a clinically localized prostate cancer.

BackgroundProstate cancer in African American (AA) men has a poor prognosis. This study aimed to identify potential genetic risk factors for prostate cancer in AA men.MethodsWe used prostate cancer tissue from 61 patients who underwent radical prostatectomy. We compared somatic gene expression in Caucasian (CA) and AA men using RNA sequencing.ResultsBy comparing the RNA-seq data obtained from prostate cancer tissue between AA and CA men, this study showed a significant difference in expression levels of 45 genes. Pathway analysis of 45 genes using Kyoto Encyclopedia of Genes and Genomesenrichment analysis revealed a neuroactive ligand–receptor interaction signal. In addition, the results of the Ingenuity Pathway Analysis showed pathways involved sphingosine-1-phosphate signaling. Furthermore, validating 45 genes in the The Cancer Genome Atlas (TCGA) Provisional cohort, cholinergic receptor muscarinic 3 expression level was significantly lower in AA than in CA men, and the results showed a significantly higher rate of biochemical recurrence in patients with low expression.ConclusionsWe identified genetic differences of clinically localized prostate cancer in AAs and CAs by RNA sequencing.

The significance of the visible tumor on preoperative magnetic resonance imaging in localized prostate cancer.

ObjectivesWe investigated the relationship between tumor characteristics and visible tumors on magnetic resonance imaging (MRI) and examined the prognosis of tumor detection on MRI compared with no tumor detection in localized prostate cancer.Materials and methodsWe reviewed 214 patients with pT2N0M0 prostate cancer who underwent radical prostatectomy between January 2009 and December 2016. All the patients underwent MRI preoperatively. The patients were divided into 2 groups postoperatively: no visible tumor on the MRI group (n = 96, 44.9%) and visible tumor on the MRI group (n = 118, 55.1%). The visible tumor was defined as Prostate Imaging Reporting and Data System, version 2 Grade ≥ 3 on MRI. Age, prostate-specific antigen, prostate volume, positive surgical margin (PSM), lymphovascular invasion, and biochemical recurrence (BCR) were compared between the 2 groups. We also assessed the relationship between visible tumors on MRI and oncologic characteristics.ResultsThe visible tumor on the MRI group showed a higher Gleason score ≥4 + 3 [45.8% versus (vs.) 17.7%], high frequency of postoperative PSMs (28.8% vs. 16.7%), and higher BCR rate (17.8% vs. 7.3%) than the no visible tumor on the MRI group. The Kaplan–Meier analysis for BCR-free survival also showed a significant difference (P = 0.006). In multivariate Cox regression analysis, the detection of tumors on MRI was associated with a higher BCR risk [hazard ratio: 3.35; 95% confidence interval (CI): 1.36-8.27; P = 0.009]. We found a positive association between visible tumors on MRI and primary Gleason pattern of ≥4 (odds ratio: 4.31; 95% CI: 2.21–8.40; P < 0.001).ConclusionsIn localized prostate cancer, BCR was significantly more frequent when the tumor was detected on MRI, and a visible tumor on MRI was associated with the Gleason score. Therefore, attention should be paid to the possibility of high-grade prostate cancer when a tumor is detected on MRI before radical prostatectomy, and active follow-up may be needed postoperatively.

Obesity and metabolic syndrome correlate with a higher risk of biochemical recurrence in high risk and intermediate risk prostate cancer patients who underwent robotic-assisted laparoscopic prostatectomy.

5580 Background: Obesity and metabolic syndrome (MS) is prevalent in our society, and have been linked to a higher incidence of prostate cancer (PCa). The relationship of obesity or MS and cancer control has yielded mixed results in previous studies. We examined the correlation between the incidence of biochemical recurrence (BCR) with MS and BMI in a cohort of patients with PCa who underwent robotic-assisted laparoscopic prostatectomy (RALP). Methods: A retrospective study of patients who underwent RALP at a single center from 2007 to 2015 was conducted. Parameters including preoperative BMI, fasting glucose, lipid profile, blood pressure, PSA, Gleason score, pathologic stage, time to BCR, and surgical margin status were analyzed. Patients were categorized in high (HR), intermediate (IR), and low-risk (LR) groups based on the National Comprehensive Cancer Network (NCCN) guidelines. WHO classification was used for MS criteria, and BCR was defined as two consecutive postoperative PSA volume of ≥ 0.2 ng/mL. Obesity is defined as BMI ≥30 kg/m2. Results: A total of 726 patients with 189 in HR, 471 in IR and 66 patients in LR groups were included in this study with the median age of 59 (interquartile range [IQR] 55-64) years old. The median follow-up from surgery was 38 (IQR 22-46) months. More obese patients were found in the HR group compared to IR/LR group (46.5% vs. 33.1%, p&lt;0.01). There were also more patients with MS in the HR group compared to IR/LR group (36.5% vs. 12.0%, p&lt;0.01). Obese patients had a higher rate of BCR across risk groups in comparison to non-obese patients 32.1% vs. 15.4% (P&lt;0.001), specifically 68% vs. 40%(p&lt;0.01) in HR group and 21.3% vs. 12.7% (p=0.035) in the IR group. Similarly, patients with MS had a higher rate of BCR in HR and IR groups in comparison to the patients without MS, 39.1% vs. 18.7% (P&lt;0.01); specifically, 67.7% vs. 42.2% (p&lt;0.01) in HR and 29% vs. 11.6% (p&lt;0.01) in the IR group. No correlation between MS or obesity and BCR was observed in LR group. There was no statistically significant difference in the positive surgical margin rate between obese and non-obese cohorts in each risk group. Conclusions: Among HR and IR-PCa patietns who underwent RALP, both obesity and MS correlate with increased risk of BCR. There were significantly more obesity and MS in HR-PCa patients, suggesting a potential pathophysiologic interplay between obesity or MS and cancer progression.

Molecular and Clinical Relevance of ZBTB38 Expression Levels in Prostate Cancer.

Prostate cancer is one of the most commonly diagnosed cancers in men. A number of genomic and clinical studies have led to a better understanding of prostate cancer biology. Still, the care of patients as well as the prediction of disease aggressiveness, recurrence and outcome remain challenging. Here, we showed that expression of the gene ZBTB38 is associated with poor prognosis in localised prostate cancer and could help discriminate aggressive localised prostate tumours from those who can benefit only from observation. Analysis of different prostate cancer cohorts indicates that low expression levels of ZBTB38 associate with increased levels of chromosomal abnormalities and more aggressive pathological features, including higher rate of biochemical recurrence of the disease. Importantly, gene expression profiling of these tumours, complemented with cellular assays on prostate cancer cell lines, unveiled that tumours with low levels of ZBTB38 expression might be targeted by doxorubicin, a compound generating reactive oxygen species. Our study shows that ZBTB38 is involved in prostate cancer pathogenesis and may represent a useful marker to identify high risk and highly rearranged localised prostate cancer susceptible to doxorubicin.

Neoadjuvant Therapy in High-Risk Prostate Cancer.

High-risk prostate cancer (PCa) is associated with higher rates of biochemical recurrence, clinical recurrence, metastasis, and PCa-specific death, compared to low-and intermediate-risk disease. Herein, we review the various definitions of high-risk PCa, describe the rationale for neoadjuvant therapy prior to radical prostatectomy, and summarize the contemporary data on neoadjuvant therapies. Since the 1990s, several randomized trials of neoadjuvant androgen deprivation therapy (ADT) have consistently demonstrated improved pathological parameters, specifically tumor downstaging and reduced extraprostatic extension, seminal vesicle invasion, and positive surgical margins without improvements in cancer-specific or overall survival. These studies, however, were not exclusive to high-risk patients and were limited by suboptimal follow-up periods. Newer studies of neoadjuvant ADT in high-risk PCa show promising pathological and oncological outcomes. Recent level 1 data suggests neoadjuvant chemohormonal therapy (CHT) may improve longer-term survival in high-risk PCa. Immunologic neoadjuvant trials are in their infancy, and further study is required. Neoadjuvant therapies may be promising additions to the multimodal therapeutic landscape of high-risk and locally advanced PCa in the near future.

Impact of time from biopsy to surgery on complications, functional and oncologic outcomes following radical prostatectomy.

ABSTRACTIntroduction:To determine the impact of time from biopsy to surgery on outcomes following radical prostatectomy (RP) as the optimal interval between prostate biopsy and RP is unknown.Material and methods:We identified 7, 350 men who underwent RP at our institution between 1994 and 2012 and had a prostate biopsy within one year of surgery. Patients were grouped into five time intervals for analysis: ≤ 3 weeks, 4-6 weeks, 7-12 weeks, 12-26 weeks, and > 26 weeks. Oncologic outcomes were stratified by NCCN disease risk for comparison. The associations of time interval with clinicopathologic features and survival were evaluated using multivariate logistic and Cox regression analyses.Results:Median time from biopsy to surgery was 61 days (IQR 37, 84). Median follow-up after RP was 7.1 years (IQR 4.2, 11.7) while the overall perioperative complication rate was 19.7% (1,448/7,350). Adjusting for pre-operative variables, men waiting 12-26 weeks until RP had the highest likelihood of nerve sparing (OR: 1.45, p = 0.02) while those in the 4-6 week group had higher overall complications (OR: 1.33, p = 0.01). High risk men waiting more than 6 months had higher rates of biochemical recurrence (HR: 3.38, p = 0.05). Limitations include the retrospective design.Conclusions:Surgery in the 4-6 week time period after biopsy is associated with higher complications. There appears to be increased biochemical recurrence rates in delaying RP after biopsy, for men with both low and high risk disease.

MP60-12 NOMOGRAM WITH PREDICTORS OF BIOCHEMICAL RECURRENCE IN MARGIN POSITIVE PROSTATE CANCER AFTER RADICAL PROSTATECTOMY WITHOUT ADJUVANT RADIOTHERAPY

INTRODUCTION AND OBJECTIVES:Men with positive surgical margin (PSM) at radical prostatectomy (RP) have higher rates of biochemical recurrence (BCR). The role of adjuvant radiotherapy (ART) for pati...

Focal Neuroendocrine Differentiation of Conventional Prostate Adenocarcinoma as a Prognostic Factor after Radical Prostatectomy: A Systematic Review and Meta-Analysis.

The biologic and prognostic value of focal neuroendocrine differentiation (NED) in conventional prostate adenocarcinoma (PC) patients who undergo radical prostatectomy (RP) remains controversial. In this systematic review and meta-analysis, we assessed the association of focal NED in conventional PC with oncological outcomes after RP. A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on December 2018 to find relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We used a fixed-effect model to analyze the impact of focal NED in RP specimen on progression-free survival defined by biochemical recurrence (BCR). A total of 16 studies with the outcomes of disease progression and survival were eligible. No patient in these studies received androgen deprivation therapy prior to RP. Eleven studies found no significant correlation between focal NED and outcomes of interest, while five studies reported a significant association of focal NED assessed by immunohistochemical chromogranin A or serotonin staining with BCR or survival. Focal NED was associated with higher BCR rates after RP with a pooled HR of 1.39 (95% CI 1.07‒1.81) in five studies. No heterogeneity was reported in this analysis (I2 = 21.7%, p = 0.276). In conclusion, focal NED in conventional PC is associated with worse prognosis after RP. Its presence should be reported in pathologic reports and its true clinical impact should be assessed in well-designed prospective controlled studies.

Prostate cancer in young men: Our experience.

133 Background: Prostate cancer (PCa) diagnosis is not uncommon in younger men. The three recognized risk factors for PCa are increasing age, african-american race and a family history (FH). Data about PCa treatment outcomes are controversial, younger men may have more aggressive disease and worse prognosis. On the other hand, more recent studies suggest higher rates of indolent PCa with more favorable outcomes in young men after radical prostatectomy (RP). We aimed to compare younger (G1, ≤ 55 yo) vs. older adults (G2, &gt; 56 yo) who underwent RP for PCa between 2010-2016 in terms of FH, race and tumor aggressiveness. Secondly, to determine if the PCa in G1 is more aggressive when there is a PCa familiar background. Methods: Between 2010-2016, 419 men underwent RP for clinically localized PCa at Central Lisbon Hospitals, of which 49 were aged ≤55 years at the time of RP. Clinical characteristics such as race, FH, PSA level, clinical stage, and biopsy Gleason score (BGS) were recorded before RP. Pathological parameters (pathological stage, GS and PSA) were collected after surgery. Results: In G1, 31% had PCa FH vs. 10% in G2 (p &lt; 0.001). Before RP, the average PSA in G1 was 7.47 vs. 8.08 in G2 (p = 0.371). In BGS, 44,3% had Gleason (G) 6, 37,4% G7, 6.9% G≥8, not significantly different between both groups (p = 0.651). Albeit, G1 had more aggressive tumors after RP: 27% G6, 45% G7 e 29% G≥8 vs. 37%, 53% e 11% respectively in G2 (p = 0.002). The pathological stage (pT) was not significantly different between groups (p = 0.243). Biochemical recurrence (BCR) was higher in G1 20% vs. 9% (p = 0.010). In a multivariate logistic regression model, the G1 had more BCR (p = 0.047) and higher PCa FH incidence (p = 0.002). When comparing african vs. caucasian men, the first group had more aggressive tumor histology (p = 0.021). Conclusions: Our study demonstrated that the youngest had superior pathological grades with higher BCR rates. Also, we found a strong relationship between G1 and FH of PCa. Data regarding pathological findings after RP in young men are still controversial. Recent studies confirm that pathological PCa characteristics in young men are not more aggressive than in older men. The present intends to add to the scientific debate around the impact of patients’ age in PCa aggressiveness and prognosis.

FGF-2 is a driving force for chromosomal instability and a stromal factor associated with adverse clinico-pathological features in prostate cancer

BackgroundThere is mounting evidence to suggest that stromal cells play an integral role in the progression of prostate cancer (PCa). One of the most frequently altered growth factors in PCa is fibroblast growth factor-2 (FGF-2). It has previously been proposed that early stages of PCa are characterized by a primarily exogenous, that is, stromal cell-derived FGF-2 production, whereas advanced tumors rely more on an autocrine FGF-2 production. Prostate cancer progression is characterized by an increase of genomic instability including aneuploidy and structural chromosomal alterations. Herein, we address 2 problems that have not been comprehensively answered. First, we ask whether exogenous FGF-2 can directly drive genomic instability to promote PCa progression. Second, we investigate whether and to what extent stromal FGF-2 expression is maintained in advanced PCa and whether this influences tumor progression and patient prognosis. MethodsIn vitro experiments to investigate the role of FGF-2 in numerical and structural chromosomal instability were performed using immunofluorescence microscopy, fluorescence in situ hybridization and single cell electrophoresis. A human patient-derived xenograft mouse model recapitulating osteoblastic PCa bone metastasis was used for in vivo validation experiments. The prognostic role of stromal FGF-2 expression was analyzed using immunohistochemical staining of a tissue microarray with primary tumor specimens from 162 predominantly high-risk patients with PCa. ResultsOur results show that FGF-2 not only rapidly induces mitotic defects and numerical chromosomal imbalances but also an enhanced DNA breakage to promote chromosomal instability. Using the patient-derived xenograft model, we show that a deregulation of the FGF axis results in an increase of mitotic aberrations as well as DNA damage checkpoint activation in vivo. The FGFR inhibitor dovitinib was found to reduce numerical chromosomal instability as well as DNA breakage, thus underscoring the relevance of the FGF axis in promoting genomic instability. An overexpression of tumor cell-associated FGF-2 was detected in 52 of 162 patients (32.1%), whereas a stromal overexpression was found in 27 of 165 patients (16%). Remarkably, a strong stromal FGF-2 expression was associated with a significantly higher clinical stage and higher biochemical recurrence rate. Patients with strong stromal FGF-2 expression also had a significantly worse biochemical recurrence-free survival. ConclusionsOur results underscore that exogenous FGF-2 can shape PCa cell genomes and that stromal FGF-2 expression is detectable in a sizeable proportion of advanced PCa where it is associated with adverse clinico-pathological features. Our results highlight the impact of the tumor stroma on malignant progression and provide a rationale for a further exploration of components of the tumor stroma as therapeutic targets in PCa.