Independent Predictor Of Biochemical Recurrence Research Articles

Circulating Vitamin D and Selenium Levels and Outcome in Prostate Cancer Patients: Lessons from the MARTINI-Lifestyle Cohort

BackgroundDietary agents, in particular vitamin D (Vit D) and selenium, are widely used by prostate cancer (PCa) patients to improve cancer outcomes. ObjectiveTo investigate whether plasma Vit D and selenium levels prior to radical prostatectomy (RP) are associated with worse pathologic tumor characteristics and increased risk of disease recurrence. Design, setting, and participantsA total of 3849 men with PCa scheduled for RP in the Martini-Klinik at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, between January 2014 and December 2018 were included in this study. Outcome measurements and statistical analysisAge, and clinical and laboratory values were collected prior to RP. Biochemical recurrence (BCR) was defined as prostate-specific antigen (PSA) ≥0.2 μg/l and rising after RP. Kaplan-Meier plots depicted BCR-free survival. Cox regression models (adjusted for age, preoperative PSA, pT stage, pN stage, pGG, surgical margin status, and year of surgery) tested the relationship between oncologic outcomes and Vit D and selenium levels. Results and limitationsMedian plasma Vit D and selenium levels were 19.3 and 71 μg/l, respectively. Circulating Vit D and selenium levels correlated inversely with PSA values. Histologic grade, pT stage, and pN stage were not associated with Vit D and selenium levels at the time of RP. In the overall cohort, BCR-free survival at 3 yr of follow-up was 82.9%. When stratified according to median Vit D levels, BCR-free survival at 3 yr of follow-up was 82.7% and 83.0% (p ≤ 0.59). Upon stratification according to median selenium levels, BCR-free survival was 82.2% and 83.7% (p = 0.19). In a multivariable Cox regression model predicting BCR, lower Vit D and selenium levels were not independent predictors of BCR. ConclusionsPlasma Vit D and selenium levels prior to RP were not associated with BCR-free survival. Patient summaryThe results of the MARTINI-Lifestyle cohort could not show a correlation between the occurrence of biochemical recurrence of prostate cancer after radical prostatectomy and the serum levels of vitamin D and selenium. A recommendation should therefore be made to compensate for a potential deficiency and not with the expectation of a reduction in the risk of progression.

Discovery of PTN as a serum-based biomarker of pro-metastatic prostate cancer

Distinguishing clinically significant from indolent prostate cancer (PC) is a major clinical challenge. We utilised targeted protein biomarker discovery approach to identify biomarkers specific for pro-metastatic PC. Serum samples from the cancer-free group; Cambridge Prognostic Group 1 (CPG1, low risk); CPG5 (high risk) and metastatic disease were analysed using Olink Proteomics panels. Tissue validation was performed by immunohistochemistry in a radical prostatectomy cohort (n = 234). We discovered that nine proteins (pleiotrophin (PTN), MK, PVRL4, EPHA2, TFPI-2, hK11, SYND1, ANGPT2, and hK14) were elevated in metastatic PC patients when compared to other groups. PTN levels were increased in serum from men with CPG5 compared to benign and CPG1. High tissue PTN level was an independent predictor of biochemical recurrence and metastatic progression in low- and intermediate-grade disease. These findings suggest that PTN may represent a novel biomarker for the presence of poor prognosis local disease with the potential to metastasise warranting further investigation.

Erratum to: Oncological outcome of neoadjuvant low-dose estramustine plus LHRH agonist/antagonist followed by extended radical prostatectomy for Japanese patients with high-risk localized prostate cancer: a prospective single-arm study.

Background Patients with advanced high-risk prostate cancer (PCa) are prone to have worse pathological diagnoses of positive surgical margins and/or lymph node invasion, resulting in early biochemical recurrence (BCR) despite having undergone radical prostatectomy (RP). Therefore, it is controversial whether patients with high-risk PCa should undergo RP. The purpose of this study was to evaluate the efficacy of neoadjuvant chemohormonal therapy (NAC) followed by RP. Methods A total of 87 patients with high-risk PCa prospectively underwent extended RP after NAC; most of the patients underwent 6 months of estramustine phosphate (EMP) 140 mg twice daily, along with a luteinizing hormone-releasing hormone agonist/antagonist. We developed our surgical technique to reduce the rate of positive surgical margins. We aimed to approach the muscle layer of the rectum by dissecting the mesorectal fascia and continuing the dissection through the mesorectum until the muscle layer of the rectum was exposed. Results More than 1 year had elapsed after surgery in all 86 patients, with a median follow-up period of 37.7 months. The 3-year BCR-free survival was 74.9%. Multivariate Cox-regression analysis revealed that a positive core ratio of 50% or greater and pathological stage of pT3 or greater were independent predictors for BCR. About 17 of 23 cases received salvage androgen deprivation therapy and concurrent external beam radiotherapy, and showed no progression after the salvage therapies. Conclusions NAC concordant with extended RP is feasible and might provide good cancer control for patients with high-risk PCa.

Increased Cytoplasmic CD138 Expression Is Associated with Aggressive Characteristics in Prostate Cancer and Is an Independent Predictor for Biochemical Recurrence.

Syndecan-1 (CD138) is a transmembrane proteoglycan expressed in various normal and malignant tissues. It is of interest due to a possible prognostic effect in tumors and its role as a target for the antibody-drug conjugate indatuximab ravtansine. Here, we analyzed 17,747 prostate cancers by immunohistochemistry. Membranous and cytoplasmic CD138 staining was separately recorded. In normal prostate glands, CD138 staining was limited to basal cells. In cancers, membranous CD138 positivity was seen in 19.6% and cytoplasmic CD138 staining in 11.2% of 12,851 interpretable cases. A comparison with clinico-pathological features showed that cytoplasmic CD138 staining was more linked to unfavorable tumor features than membranous staining. Cytoplasmic CD138 immunostaining was associated with high tumor stage (p < 0.0001), high Gleason grade (p < 0.0001), nodal metastases (p < 0.0001), positive surgical margin (p < 0.0001), and biochemical recurrence (p < 0.0001). This also holds true for both V-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion positive and ERG fusion negative tumors although the cytoplasmic CD138 expression was markedly more frequent in ERG positive than in ERG negative tumors (p < 0.0001). Comparison with 11 previously analyzed chromosomal deletions identified a conspicuous association between cytoplasmic CD138 expression and 8p deletions (p < 0.0001) suggesting a possible functional interaction of CD138 with one or several 8p genes. Multivariate analysis revealed the cytoplasmic CD138 expression as an independent prognostic parameter in all cancers and in the ERG positive subgroup. In summary, our study indicates the cytoplasmic CD138 expression as a strong and independent predictor of poor prognosis in prostate cancer. Immunohistochemical measurement of CD138 protein may thus—perhaps in combination with other parameters—become clinically useful in the future.

Association between CD8 and PD-L1 expression and outcomes after radical prostatectomy for localized prostate cancer.

Characterization of markers of both immune suppression and activation may provide more prognostic information than assessment of single markers in localized prostate cancer. We therefore sought to determine the association between CD8 and PD-L1 expression in localized prostate tumors and biochemical recurrence (BCR) and metastasis-free survival (MFS). Tissue microarrays were constructed on 109 men undergoing radical prostatectomy (RP) for localized prostate cancer at Dana-Farber Cancer Institute between 1991 and 2008. Fluorescence immunohistochemistry was used to evaluate the expression of six immune markers (CD3, CD4, CD8, PD-1, PD-L1, FOXP3). Quantitative multispectral imaging analysis was used to calculate the density of each marker, which was dichotomized by the median as "high" or "low." Cox proportional hazards regression models and Kaplan-Meier analyses were used to analyze associations between immune marker densities and time to BCR and MFS. Over a median follow-up of 8.1 years, 55 (51%) and 39 (36%) men developed BCR and metastases, respectively. Median time to BCR was shorter in men with low CD8 (hazard ratio [HR] = 2.27 [1.27-4.08]) and high PD-L1 expression (HR = 2.03 [1.17-3.53]). While neither low CD8 or high PD-L1 alone were independent predictors of BCR or MFS on multivariable analysis, men with low CD8 and/or high PD-L1 had a significantly shorter time to BCR (median 3.5 years vs. NR) and MFS (median 10.8 vs. 18.4 years) compared to those with high CD8 and low PD-L1 expression. The main limitation is the retrospective and singe-center nature of the study. The presence of higher CD8 and lower PD-L1 expression in prostatectomy specimens was associated a low risk of biochemical relapse and metastatic disease. These findings are hypothesis-generating and further study is needed.

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.

Detectable Prostate-specific antigen value between 0.01 and 0.1ng/ml following robotic-assisted radical prostatectomy (RARP): does it correlate with future biochemical recurrence?

The aim of the study is to evaluate the impact of having a nadir and persistently detectable ultrasensitive prostate-specific antigen (uPSA) between 0.01 and 0.1ng/ml post-robot-assisted radical prostatectomy (RARP), on future biochemical recurrence (BCR). We conducted a retrospective analysis of a prospectively maintained cohort of 1359 men who underwent RARP, between 2006 and 2019. Patients were followed with uPSA at 1, 3, 6, 9, 12, 18, 24, 30, 36months and annually thereafter. We included patients with PSA nadir values between 0.01 and 0.1ng/ml within 6months of surgery and with at least 2 follow-up measurements within the same range. We divided patients based on their BCR status and analyzed uPSA changes. Multivariable Cox-regression models (CRMs) were used to analyze variables predicting BCR-free survival (BCR-FS). We identified 167 (12.3%) patients for analyses, with a mean follow-up time of 60.2 ± 31.4months. In our cohort, 5-year BCR-FS rate was 86%. Overall, 32 (19.1%) patients had BCR, with a mean time to BCR of 43.7 ± 24.3months. BCR-free patients had stable mean uPSA values ≤ 0.033ng/ml, while patients who developed BCR showed a slowly rising trend over time, with a significant difference between groups starting at 9months (p < 0.02). In multivariable CRMs, a rising uPSA starting at 9months was an independent predictor of BCR (HR: 2.7; 95% CI 1.6-3.82; p = 0.013). In the present cohort, our results demonstrated that a considerable number of men have detectable uPSA values ranging between 0.01 and 0.1ng/ml post-RARP. They can still be followed regularly to avoid patients' anxiety and salvage radiotherapy. Close follow-up is still required.

Increased nuclear factor I/B expression in prostate cancer correlates with AR expression.

Most prostate cancers express androgen receptor (AR), and our previous studies have focused on identifying transcription factors that modify AR function. We have shown that nuclear factor I/B (NFIB) regulates AR activity in androgen-dependent prostate cancer cells in vitro. However, the status of NFIB in prostate cancer was unknown. We immunostained a tissue microarray including normal, hyperplastic, prostatic intraepithelial neoplasia, primary prostatic adenocarcinoma, and castration-resistant prostate cancer tissue samples for NFIB, AR, and synaptophysin, a marker of neuroendocrine differentiation. We interrogated publically available data sets in cBioPortal to correlate NFIB expression and AR and neuroendocrine prostate cancer (NEPCa) activity scores. We analyzed prostate cancer cell lines for NFIB expression via Western blot analysis and used nuclear and cytoplasmic fractionation to assess where NFIB is localized. We performed co-immunoprecipitation studies to determine if NFIB and AR interact. NFIB increased in the nucleus and cytoplasm of prostate cancer samples versus matched normal controls, independent of Gleason score. Similarly, cytoplasmic AR and synaptophysin increased in primary prostate cancer. We observed strong NFIB staining in primary small cell prostate cancer. The ratio of cytoplasmic-to-nuclear NFIB staining was predictive of earlier biochemical recurrence in prostate cancer, once adjusted for tumor margin status. Cytoplasmic AR was an independent predictor of biochemical recurrence. There was no statistically significant difference between NFIB and synaptophysin expression in primary and castration-resistant prostate cancer, but cytoplasmic AR expression was increased in castration-resistant samples. In primary prostate cancer, nuclear NFIB expression correlated with cytoplasmic NFIB and nuclear AR, while cytoplasmic NFIB correlated with synaptophysin, and nuclear and cytoplasmic AR. In castration-resistant prostate cancer samples, NFIB expression correlated positively with an AR activity score, and negatively with the NEPCa score. In prostate cancer cell lines, NFIB exists in several isoforms. We observed NFIB predominantly in the nuclear fraction of prostate cancer cells with increased cytoplasmic expression seen in castration-resistant cell lines. We observed an interaction between AR and NFIB through co-immunoprecipitation experiments. We have described the expression pattern of NFIB in primary and castration-resistant prostate cancer and its positive correlation with AR. We have also demonstrated AR interacts with NFIB.

Contrast-enhanced transrectal ultrasound can reduce collection of unnecessary biopsies when diagnosing prostate cancer and is predictive of biochemical recurrence following a radical prostatectomy in patients with localized prostate cancer

BackgroundTo investigate the value of using contrast-enhanced transrectal ultrasound (CETRUS) to reduce unnecessary collection of biopsies during prostate cancer diagnosis and its utility in predicting biochemical recurrence in patients with localized prostate cancer.MethodsThis was a prospective study of suspected prostate cancer patients who were evaluated with CETRUS followed by a prostate biopsy. Prostate blood flow via CETRUS was graded using a 5-point scale. The relationship between CETRUS score and biopsy outcome was then analyzed for all patients; univariate and multi-variate analyses were used to determine the probable prognostic factors for biochemical recurrence in patients with localized prostate cancer that underwent a radical prostatectomy.ResultsA total of 347 patients were enrolled in the study. Prostate cancer was found in 164 patients. A significant positive correlation (r = 0.69, p < 0.001) was found between CETRUS scores and prostate cancer incidence. Using CETRUS scores ≥2 as the threshold for when to biopsy could have safely reduced the number of biopsies taken overall by 12.1% (42/347) and spared 23.0% (42/183) of patients from undergoing an unnecessary biopsy. 77 patients with localized prostate cancer underwent a radical prostatectomy. The median follow-up time was 30 months (range: 8–56 months) and 17 of these 77 patients exhibited biochemical recurrence during the follow-up period. 3-year biochemical recurrence-free survival rates were 86% for patients with low CETRUS scores (≤ 3) and 59% for patients with high scores (> 3; p = 0.015). Multivariate Cox regression analysis indicated that CETRUS score was an independent predictor of biochemical recurrence (HR: 7.02; 95% CI: 2.00–24.69; p = 0.002).ConclusionsCETRUS scores may be a useful tool for reducing the collection unnecessary biopsy samples during prostate cancer diagnosis and are predictive of biochemical recurrence in patients with localized prostate cancer following a radical prostatectomy.

MiR-196a-mediated downregulation of p27kip1 protein promotes prostate cancer proliferation and relates to biochemical recurrence after radical prostatectomy.

Dysregulation of microRNAs has performed vital gene regulatory functions in the genesis, progression, and prognosis of multiple malignant tumors. This study aimed to elucidate the regulatory mechanism of miR-196a in prostate cancer (PCa) and explore its clinical significance. Quantitative real-time polymerase chain reaction was implemented to examine miR-196a and p27kip1 messenger RNA expression in PCa. Cell proliferation was evaluated via Cell Counting Kit-8, colony formation, and nude mouse tumorigenicity assays. Luciferase reporter assay was applied to identify target genes. p27kip1 protein expression in PCa was investigated using Western blot analysis and immunohistochemistry. There was a dramatic upregulation of miR-196a in PCa. Upregulated miR-196a was related to worse Gleason score (GS), later pathological stage, and poor biochemical recurrence (BCR)-free survival. In vivo and in vitro experiments exhibited that miR-196a promoted PCa proliferation and expedited G1/S-phase progression through the downregulation of p27kip1 protein. Additionally, p27kip1 protein was distinctly downregulated in PCa. Low p27kip1 protein expression had a strong correlation with increased GS and was an independent predictor of BCR after radical prostatectomy (RP). Excessive expression of miR-196a and subsequent downregulation of p27kip1 protein play essential roles in promoting PCa proliferation and leading to BCR after RP. miR-196a and its target p27kip1 may become novel molecular biomarkers and therapeutic targets for PCa.

Specific spatial distribution patterns of tumor foci are associated with a low risk of biochemical recurrence in pT2pN0R0 prostate cancer.

The previous attempts for pT2 substaging of prostate cancer (PCa) were insufficient in providing prognostic subgroups and the search for new prognostic parameters to subcategorize pT2 PCa is, therefore, needed. Therefore, the current study investigated the association between tumor distribution patterns and the biochemical recurrence (BCR)-free survival rate in pT2pN0R0 PCa. Following radical prostatectomy, the anatomical distribution of PCa in 743 men with pT1-pT3pN0 disease was analyzed to determine 20 types of PCa distribution patterns. Then, 245 men with pT2pN0R0 PCa was considered for prognostic evaluation with a mean follow-up period of 60months. The spatial distribution patterns of PCa were evaluated using a cMDX©-based map model of the prostate. An analysis including 552,049 comparison operations was performed to assist in the evaluation of the similarity levels of the distribution patterns. A k-mean cluster analysis was applied to determine groups with similar distribution patterns. A decision-tree analysis was performed to divide these groups according to frequency of BCR. The BCR-free survival rate was analyzed using Kaplan-Meier curves. Predictors of progression were investigated using a Cox proportional hazards model. BCR occurred in 8.2% of the 245 men with pT2pN0R0 PCa. The median time of recurrence was 60months (interquartile range [IQR]: 42-77). In univariate and multivariate analyses, the prostate volume and the distribution patterns were independent predictors for BCR, whereas the sub-staging of pT2 tumors, Gleason grading, prostate-specific antigen (PSA) level, and relative tumor volume were not. In the patients with pT2pN0R0 disease, PCa distribution patterns with the apical involvement were significantly associated with the risk of BCR (P = 0.001). The spread tumor patterns with the apical involvement are associated with a high-risk of BCR in the pT2 tumor stage. The vertical tumor spread could be considered in developing improved prognostic pT2 sub-categories.

Predicting factors for progression to castration resistance prostate cancer after biochemical recurrence in patients with clinically localized prostate cancer who underwent radical prostatectomy.

To determine prognostic factors associated with progression to castration-resistant prostate cancer following biochemical recurrence which is lethal prostate cancer and establish a risk stratification model of progression to castration-resistant prostate cancer. We retrospectively reviewed the data of 550 patients who experienced biochemical recurrence after radical prostatectomy. The endpoint of the present study was progression to castration-resistant prostate cancer. The actuarial probabilities of progression to castration-resistant prostate cancer-free survival were determined using Kaplan-Meier analysis. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors of biochemical recurrence. Fifty-two patients experienced progression to castration-resistant prostate cancer during the follow-up period. The progression to castration-resistant prostate cancer-free survival rate after biochemical recurrence at 10years was 76.8%. In multivariate analysis, pathological Gleason score ≥ 9, lymphovascular invasion, and prostate-specific antigen velocity ≥ 0.4ng/mL/year were independent predictive factors for progression to castration-resistant prostate cancer. The patients were stratified into three groups using a risk stratification model incorporating these variables. The 10-year progression to castration-resistant prostate cancer-free survival rates were 96.7% in the low-risk group, 84.7% in the intermediate-risk group, and 24.5% in the high-risk group. The present results suggest that the pathological Gleason score, lymphovascular invasion, and prostate-specific antigen velocity were independent predictive factors for progression to castration-resistant prostate cancer. The risk stratification model established in the present study could be useful for patient counseling and in identifying patients with a poor prognosis.

Abstract B047: Advanced glycation end products promote prostate tumor growth and are a potential biologic consequence of lifestyle factors contributing to cancer disparity

Abstract Advanced glycation end-products (AGEs), are reactive metabolites produced endogenously as a consequence of glucose uptake during glycolysis. AGEs accumulate in tissues and organs as we grow older to promote multiple chronic disease phenotypes. AGE pathogenic effects are mediated through modification of protein function, genetic fidelity, stress responses and cellular signaling pathways. Critically, cancer disparity factors such as a sedentary lifestyle, obesity and an unhealthy diet are external influences that also contribute to the AGE accumulation pool in the body. This research group examined circulating and tumor AGE levels in clinical specimens of prostate cancer and identified a race specific, tumor-dependent pattern of accumulation. AGE levels were highest in aggressive tumors, especially those from men with African ancestry. Increased AGE levels correlated with an upregulation in the receptor for advanced glycation end products (RAGE) and activated NFkB. In a syngeneic subcutaneous prostate cancer mouse model, chronic consumption of AGE resulted in a 3-fold increase in tumor growth. Strikingly, dietary-AGE mediated increases in tumor growth were accompanied by a cytoplasmic accumulation of AR, elevation in MYC, RAGE, and AGE as well as increased cell proliferation. Cytoplasmic accumulation of AR is elevated in CRPC tissue and is an independent predictor of biochemical recurrence. Our data show that treatment of prostate cancer cells with AGEs induces a neuroendocrine differentiated phenotype by promoting a more mesenchymal morphology and increasing the expression of associated marker genes including ENO2, MYC and SYP and the prostate cancer stem cell marker CD44 as well as the downregulation of AR. The aberrant activation and recruitment of immune cells is a major pathogenic consequence of AGE accumulation, and a series of studies have highlighted the tumor-associated immune response as a critical pathway contributing to cancer disparity. Using patient-derived primary tumor cells, the investigators found that AGEs released into the extracellular matrix may recapitulate the tumor-associated immune response observed in ancestry-specific prostate tumor tissues. Further preliminary studies indicate that AGE treatment of prostate cancer cells can alter how cancer cells metabolize glucose to promote an aggressive phenotype. The investigators' studies support the concept that AGE metabolites represent a biologic consequence of the socioeconomic and environmental factors that promote cancer health disparity. As our understanding of tumor biology advances, it is becoming increasingly clear that these inter-related lifestyle factors have distinct molecular consequences on the biologic makeup of tumors, altering cell signaling events and gene expression profiles to contribute to cancer disparity outcomes such as its earlier development or its progression to more aggressive disease. Citation Format: Pamela Woods, Bradley A. Krisanits, Dion Foster, Lourdes M. Nogueira, Laura Spruill, Marvella E. Ford, Michael B. Lilly, Victoria J. Findlay, David P. Turner. Advanced glycation end products promote prostate tumor growth and are a potential biologic consequence of lifestyle factors contributing to cancer disparity [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B047.

PD43-07 IMPACT OF POSITIVE SURGICAL MARGIN LENGTH AND GLEASON GRADE AT THE MARGIN ON ONCOLOGIC OUTCOMES IN PATIENTS WITH NON-ORGAN-CONFINED PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy II (PD43)1 Apr 2020PD43-07 IMPACT OF POSITIVE SURGICAL MARGIN LENGTH AND GLEASON GRADE AT THE MARGIN ON ONCOLOGIC OUTCOMES IN PATIENTS WITH NON-ORGAN-CONFINED PROSTATE CANCER Felix Preisser*, Alexander Heinze, Raisa Pompe, Felix Chun, Markus Graefen, Hartwig Huland, and Derya Tilki Felix Preisser*Felix Preisser* More articles by this author , Alexander HeinzeAlexander Heinze More articles by this author , Raisa PompeRaisa Pompe More articles by this author , Felix ChunFelix Chun More articles by this author , Markus GraefenMarkus Graefen More articles by this author , Hartwig HulandHartwig Huland More articles by this author , and Derya TilkiDerya Tilki More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000930.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Positive surgical margins (PSM) represent a poor prognostic factor at radical prostatectomy (RP). To investigate the impact of PSM, its length, the focality and the Gleason grade at the PSM, on the oncologic outcomes in non-organ-confined RP patients. METHODS: Within a high-volume center database we identified patients who harbored non-organ-confined (pT3) prostate cancer (PCa) at RP between 2010 and 2016. Only patients without lymph node invasion were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of PSM on biochemical recurrence (BCR), metastasis and death after RP in patients without adjuvant radiotherapy. RESULTS: Overall, 3,706 patients were identified. Of those, 27.2% (n=1,008) harbored PSM. Patients with PSM had higher median PSA values (11.0 vs. 7.9ng/ml, p<0.001), higher proportion of primary Gleason ≥4 (56.0 vs. 38.7%, p<0.001) and more frequently harbored seminal vesicle invasion (45.9 vs. 22.0%, p<0.001). At 72 months after RP, BCR-free, metastasis-free and overall survival was 44.4 vs. 64.7%, 63.3 vs. 79.4% and 91.2 vs. 93.4% for patients with vs. without PSM (all p<0.001). BCR-free, metastasis-free and overall survival rates at 72 months were 49.3 vs. 32.7% (p=0.1), 60.9 vs. 76.5% (p=0.7) and 91.3 vs. 98.4% (p=0.3) for unifocal vs. multifocal PSM; 62.7 vs. 25.8% (p<0.001), 88.5 vs. 36.1% (p<0.001) and 98.4 vs. 83.7% (p<0.01) for Gleason pattern 3 vs. ≥4 at the margin and 48.4 vs. 37.3% (p=0.03), 63.6 vs. 63.1% (p=0.3) and 91.7 vs 93.9% (p=0.9) for <4mm vs. ≥4mm length of margin. In multivariable Cox models PSM was an independent predictor for BCR (Hazard ratio [HR]: 1.25, p<0.01) and overall survival (HR:1.94, p=0.02). In subgroups of patients with PSM only, length of PSM (HR: 1.03, p=0.03) and Gleason ≥4 at the margin (HR:1.76, p<0.01) represented independent predictors for BCR. CONCLUSIONS: PSM represents an independent predictor for worse oncologic outcome in non-organ-confined PCa at RP. Gleason ≥4 at the margin was an independent predictor for BCR and associated with development of metastasis and death after RP. Moreover, length of PSM was an independent predictor for BCR. Next to margin status, Gleason at the margin and its length carry important information that should be reported for the specimen. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e903-e903 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Felix Preisser* More articles by this author Alexander Heinze More articles by this author Raisa Pompe More articles by this author Felix Chun More articles by this author Markus Graefen More articles by this author Hartwig Huland More articles by this author Derya Tilki More articles by this author Expand All Advertisement PDF downloadLoading ...

MP64-09 DUCTAL ADENOCARCINOMA OF THE PROSTATE IS ASSOCIATED WITH SHORTER METASTASIS-FREE SURVIVAL

MP64-09 DUCTAL ADENOCARCINOMA OF THE PROSTATE IS ASSOCIATED WITH SHORTER METASTASIS-FREE SURVIVAL

Retrospective Cohort Analysis from a High-Volume Center of Prognostic Factors Affecting Biochemical Relapse in Patients with Encapsulated, Margin-Negative, Isolated Seminal Vesicle Invasion After Robot-Assisted Laparoscopic Prostatectomy: A Novel Study.

Purpose: Specimen pathology findings collectively impact the long-term outcomes of robot-assisted laparoscopic prostatectomy. Since seminal vesicle invasion (SVI) is an important independent predictor of biochemical recurrence (BCR), this study was designed to evaluate the influence of isolated SVI in the absence of capsular/margin invasion on BCR. Material and Methods: Pathology reports of 2009 robot-assisted laparoscopic prostatectomy specimens were analyzed retrospectively excluding capsular breach and/or margin-positive cases to include 1409 patients in the study. Factors predicting SVI and BCR in this select group of patients were assessed and statistically analyzed. Survival analysis for PSA (prostate-specific antigen) failure probability and binomial regressions for variable predictability were performed. Results: The African American race was associated with SVI (p < 0.05). PSA had a directly proportional correlation with the occurrence of SVI and BCR. SVI was found to be an independent predictor of BCR, leading to higher odds of BCR at 5 years (odds ratio [OR] 8.2, 95% confidence interval [CI] 4.5-14.6, p < 0.0001). When the seminal vesicle was invaded, the specimen Gleason grade group (SGGG; OR 1.9, 95% CI 1.02-3.7, p = 0.04), PSA (OR 1.2, 95% CI 1.01-1.4, p = 0.03), and BMI (body mass index) (OR 1.2, 95% CI 1.04-1.5, p = 0.01) predicted BCR. Seminal vesicle involvement was not found in SGGG 1. Risk stratification of significant predictors of BCR with isolated SVI identified a subgroup with BMI ≤27.9 kg/m2, PSA ≤8.6 ng/mL, and SGGG 2, which had a significantly better prognosis (p = 0.029, log-rank test). Conclusions: Seminal vesicles are infrequently involved with SGGG 1. Select groups of patients with isolated SVI who have low-grade disease with relatively lower PSA and BMI do not have an aggressive biological behavior and are unlikely to have a BCR, thereby circumventing unnecessary adjuvant therapy with its attendant side effects. The BMI significantly predicted PSA failures and should be considered as an additional risk assessment tool.

External validation of the Gleason grade group system in Argentinian patients that underwent surgery for prostate cancer.

IntroductionThe aim of this article was to evaluate the effectiveness of the Gleason grade groups (GGG) system on a group of Argentinian patients with prostate cancer (PC) who underwent radical prostatectomy (RP).Material and methodsWe retrospectively studied 262 patients who underwent RP between 1996 and 2014. To determine the performance and validity of the GGG system, a Kaplan-Meier analysis and multivariate analysis with Cox proportional method were performed to evaluate biochemical recurrence, distance metastases and specific cancer mortality. The area under the curve (AUC) was calculated to compare new groups of degrees of the GGG system with the classical scheme of stratification into 3 groups.ResultsThe median follow-up was 84 months. As the groups ascend, there is less confined organ disease (p <0.001) and greater extraprostatic extension (p <0.001), greater invasion of seminal vesicles (p <0.001) and greater lymph node involvement (p <0.001). The biochemical recurrence-free survival at 5 years was 68%, 55%, 22%, 9%, 0% of the 1–5 groups, respectively. Ten-years cancer-specific survival was 96%, 95%, 78%, 64%, 25% for group 1–5, respectively. In the multivariate analysis, the GGG system is presented as the only independent predictor of biochemical recurrence and specific cancer mortality. The AUC indicates that the GGG system has a higher prognostic discrimination compared to the classic 3-group system (6, 7, ≥8).ConclusionsThe International Society of Urological Pathology (ISUP) GGG system is an independent predictor of biochemical recurrence and mortality from prostate cancer in patients treated with RP. The classification into 5 groups shows greater discrimination in the prognosis than the traditional Gleason classification.

Determining the cut-off values of tumor diameter, degree of extraprostatic extension, and extent of surgical margin positivity with regard to biochemical recurrence of prostate cancer after radical prostatectomy

BackgroundThe pre-biopsy (bx) prostate-specific antigen (PSA) level, tumor volume/diameter, degree of extraprostatic extension (EPE), and extent of surgical margin positivity have been shown to be significant prognostic parameters of biochemical recurrence (BCR) after radical prostatectomy. The present study assessed the cut-off values of the pre-bx PSA level, maximum tumor diameter, radial and circumferential distances of EPE, and circumferential length of surgical margin (SM) positivity with regard to BCR. Material and methodsThe study included 445 radical prostatectomy specimens, and the cut-off values of all parameters were determined using receiver operating characteristic curve analysis. ResultsAn ISUP grade group ≥ 3, radial distance of EPE >1 mm, and circumferential length of SM positivity ≥2 mm were identified as independent predictors of BCR after radical prostatectomy. The parameters that showed statistical significance in univariate analysis, such as pre-bx PSA level ≥ 7.20 ng/mL, tumor diameter ≥ 19.5 mm, presence of seminal vesicle invasion, and circumferential distance of EPE >3 mm, did not have independent prognostic values for BCR. ConclusionsAn ISUP grade group ≥ 3, radial distance of EPE >1 mm, and circumferential length of SM positivity ≥2 mm are predictors of BCR. Our findings might have significance in risk classification and adjuvant therapy consideration among patients with localized prostate cancer.

Cell cycle progression score improves risk stratification in prostate cancer patients with adverse pathology after radical prostatectomy.

To assess the use of the cell cycle progression (CCP) score versus actual risk stratification practice in making treatment decisions for prostate cancer patients with locally adverse pathology after radical prostatectomy (RP). Men with adverse pathologic features, pT3 or positive surgical margins who underwent RP in 2010-2014 at Renji hospital were retrospectively analyzed. The primary outcome was biochemical recurrence (BCR) after RP. RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. The prognostic utility of the CCP score was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards model. Among the 100 men identified, 5-year BCR-free survival for the low- (< 0), intermediate- (0-1) and high- (> 1) CCP score groups was 89.3%, 38.8%, and 12.9%, respectively. In multivariable models adjusting for clinical and pathological variables with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score, both continuous CCP score [hazard ratio (HR) 1.373 per unit score, 95% confidence interval (CI) 1.006-1.874; p = 0.046) and the categorized CCP score (p < 0.001)were independent predictors of BCR. The present study provides insights into the role the CCP score plays in risk stratification of this cohort and in determining candidacy for deferred secondary treatment. From our perspective, the CCP score allows better stratification and can help identifying patients at lower risk of disease recurrence who could benefit from a wait-and-see policy.

The significance of micro-lymphatic invasion and pathological Gleason score in prostate cancer patients with pathologically organ-confined disease and negative surgical margins after robot-assisted radical prostatectomy.

The development process of recurrence in prostate cancer patients with pathologically organ-confined (pT2) disease and negative surgical margins is unclear. The aim of the present study was to determine factors associated with the development of biochemical recurrence following robot-assisted radical prostatectomy among those prostate cancer patients. We retrospectively reviewed the data of patients who underwent robot-assisted radical prostatectomy without neoadjuvant endocrine therapy. We evaluated prognostic factors in 1096 prostate cancer patients with pT2 disease and negative surgical margins. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors for biochemical recurrence. Of the 1096 patients, 55 experienced biochemical recurrence during the follow-up period. The 5-year biochemical recurrence-free survival rate for patients with pT2 and negative surgical margins was 91.8%. On univariate analysis, clinical stage, biopsy Gleason score, percent of positive core, pathological Gleason score, and the presence of micro-lymphatic invasion were significantly associated with biochemical recurrence. On a multivariate analysis, the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 were significant prognostic factors for biochemical recurrence. Based on these factors, we developed a risk stratification model. The biochemical recurrence-free survival rate differed significantly among the risk groups. The prognosis of prostate cancer patients with pT2 disease and negative surgical margins is favorable. However, patients with the presence of micro-lymphatic invasion and a pathological Gleason score ≥ 4 + 3 tend to experience biochemical recurrence more often after surgery. Therefore, careful follow-up might be necessary for those patients.