Outcome Of Prostate Cancer Patients Research Articles

The epithelial-mesenchymal transition regulators Twist, Slug, and Snail are associated with aggressive tumour features and poor outcome in prostate cancer patients.

The prognostic importance of transcription factors promoting epithelial–mesenchymal transition (EMT) and angiogenesis has not been well explored in prostate cancer patients with long follow‐up, nor the interplay between these factors. The objective of this study was to assess the individual protein expression and co‐expression of Twist, Slug (Snai2), Snail (Snai1), and hypoxia‐inducible factor‐1 alpha (Hif‐1α) in prostate cancer in relation to EMT, angiogenesis, hypoxia, tumour features, disease recurrence, and patient survival. Immunohistochemical staining was performed on tissue microarray sections from 338 radical prostatectomies with long follow‐up. In addition, 41 cases of prostatic hyperplasia, 33 non‐skeletal metastases, 13 skeletal metastases, and 33 castration‐resistant prostate carcinomas were included. Our findings were validated in external gene expression data sets. Twist was overexpressed in primary prostate cancer and markedly reduced in distant metastases (p < 0.0005). Strong expression of Twist and Slug was associated with Hif‐1α in localised prostate cancer (p ≤ 0.001), and strong Twist was associated with Hif‐1α in castration‐resistant carcinomas (p = 0.044). Twist, Slug, and increased Snail at the tumour stromal border were associated with vascular factors (p ≤ 0.045). Each of the three EMT‐regulating transcription factors were associated with aggressive tumour features and shorter time to recurrence and cancer‐specific death. Notably, the co‐expression of factors demonstrated an enhanced influence on outcome. In the subgroup of E‐cadherinlow carcinomas, strong Slug was associated with shorter time to all end points and was an independent predictor of time to multiple end points, including cancer‐specific death (hazard ratio 3.0, p = 0.041). To conclude, we demonstrate an important relation between EMT, hypoxia, and angiogenesis and a strong link between the investigated EMT regulators and aggressive tumour features and poor patient outcome in prostate cancer. Despite the retrospective nature of this long‐term study, our findings could have a significant impact on the future treatment of prostate cancer, where tailored therapies might be directed simultaneously against epithelial–mesenchymal phenotypes, angiogenesis, and tumour hypoxia.

Downregulation of nc886 contributes to prostate cancer cell invasion and TGFβ1-induced EMT

Epithelial-to-mesenchymal transition (EMT) activation is important in cancer progression and metastasis. Evidence indicates that nc886 is a representative Pol III gene that processes microRNA products via Dicer and further downregulates its target gene transforming growth factor- β1 (TGF-β1), which is the most prominent inducer of EMT in prostate cancer (PC). Consistent with the previous literature, we found that nc886 downregulation was strongly associated with metastatic behavior and showed worse outcomes in PC patients. However, little is known about the association between nc886 and the EMT signaling pathway. We developed a PC cell model with stable overexpression of nc886 and found that nc886 changed cellular morphology and drove MET. The underlying mechanism may be related to its promotion of SNAIL protein degradation via ubiquitination, but not to its neighboring genes, TGFβ-induced protein (TGFBI) and SMAD5, which are Pol II-transcribed. TGF-β1 also override nc886 promotion of MET via transient suppression the transcription of nc886, promotion of TGFBI or increase in SMAD5 phosphorylation. Both nc886 inhibition and TGFBI activation occur regardless of their methylation status. The literature suggests that MYC inhibition by TGF-β1 is attributed to nc886 downregulation. We incidentally identified MYC-associated zinc finger protein (MAZ) as a suppressive transcription factor of TGFBI, which is controlled by TGF-β1. We elucidate a new mechanism of TGF-β1 differential control of Pol II and the transcription of its neighboring Pol III gene and identify a new EMT unit consisting of nc886 and its neighboring genes.

Survival outcomes in prostate cancer patients with a prior cancer

BackgroundTo shed light on the survival outcomes of prostate cancer (PCa) patients diagnosed after a prior cancer and identify prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in PCa patients.MethodsIn the primary group, a total of 1,778 PCa patients with a prior cancer were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2005 to 2015, retrospectively. Baseline characteristics and causes of death (COD) of these patients were collected and compared. In the second group, a total of 10,296 PCa patients [5,148 patients with PCa as the only malignancy and 5,148 patients with PCa as their second primary malignancy (SPM)] diagnosed between 2010 and 2011 were extracted to investigate the impact of prior cancers on survival outcomes.ResultsIn PCa patients with a prior cancer, the most common type of prior cancer was from gastrointestinal system (29.92%), followed by urinary system (21.37%). Patients were more likely to die of the prior caner, and those with prior cancer from respiratory system had the worst survival outcomes. Moreover, the overall ratios in patients with stage (PCa) I–II and III–IV diseases were 0.21 and 1.65, indicating that patients with higher stage diseases were more likely to die of PCa. In the second group, patients with PCa as the SPM had worse OS than those with PCa as the first primary cancer. Lastly, prognostic factors for OS and CSS in PCa patients were explored.ConclusionsPCa remains to be an important COD for patients with a prior malignancy, especially for those with high-stage diseases. PCa patients with a prior cancer had worse survival outcomes than those without.

Do androgen-directed therapies improve outcomes in prostate cancer patients undergoing radical prostatectomy? A systematic review and meta-analysis.

Approximately 50% of patients with non-metastatic prostate cancer are treated with radical prostatectomy (RP). While some men will be cured with surgery alone, a substantial proportion will experience cancer recurrence. Androgen-directed therapy (ADT) is an effective adjuvant therapy for patients treated with prostate radiation. Comparatively, the efficacy of ADT in surgical patients has not been well-studied. A systematic search of MEDLINE, Embase, and the Cochrane Library from inception to July 2020 was performed. Randomized trials comparing ADT with RP vs. prostatectomy alone in patients with clinically localized prostate cancer were included. Neoadjuvant ADT and adjuvant ADT interventions were assessed separately. The primary outcomes were cancer recurrence-free survival (RFS) and overall survival (OS). Pathological outcomes following neoadjuvant ADT were also evaluated. Fifteen randomized trials met eligibility criteria; 11 evaluated neoadjuvant ADT (n=2322) and four evaluated adjuvant ADT (n=5205). Neoadjuvant ADT (three months of treatment) did not improve RFS (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.74-1.11) or OS (HR 1.22, 95% CI 0.62-2.41). Neoadjuvant ADT significantly decreased the risk of positive surgical margins (relative risk [RR] 0.48, 95% CI 0.41-0.56) and extraprostatic tumor extension (RR 0.75, 95% CI 0.64-0.89). Adjuvant ADT improved RFS (HR 0.65, 95% CI 0.45-0.93) but did not improve OS (HR 1.02, 95% CI 0.84-1.24). Neoadjuvant ADT causes a pathological downstaging of prostate tumors but has not been found to delay cancer recurrence nor extend survival. Few studies have evaluated adjuvant ADT. Trials are needed to determine the benefits and harms of intermediate- or long-term adjuvant ADT for RP patients.

Tumor location on MRI determines outcomes of patients with prostate cancer after total prostate cryoablation

We investigated the association between tumor location on multiparametric magnetic resonance imaging (mpMRI) and outcomes of prostate cancer patients after primary total prostate cryoablation (PTPC). Between March 2010 and December 2012, consecutive 192 prostate cancer patients receiving PTPC were enrolled. Tumor locations were determined and classified as anterior apex (AA), anterior midgland (AM), anterior base (AB), posterior apex (PA), posterior midgland (PM) and posterior base (PB) using mpMRI. Midline location, central location, seminal vesicle invasion, extraprostatic extension, multiple tumors, and tumor volume were also identified. Prostate local recurrence and biochemical failure were considered as primary and secondary endpoints, respectively. Tumors on mpMRI were identified in 148 (77.1%) patients. Tumor locations were most frequently noted in PM (89, 46.4%), followed by AM (55, 28.6%), PB (53, 27.6%), PA (46, 24%), AA (35, 18.2%) and AB (31, 16.1%). Midline and central tumors were observed in 34 (17.7%) and 14 (7.3%) patients, respectively. During a median follow-up duration of 81 months (range, 2–114 months), 71 (37.0%) and 29 (40.8%) patients experienced biochemical failure and local recurrence, respectively. Multivariable analyses revealed only AA tumors increased the risk of local recurrences (HR = 2.98, 95% CI. 1.36–6.49). None of location-related parameters was associated with biochemical failure. Tumor location on mpMRI has a significant association with local tumor recurrence in patients receiving PTPC. Physicians should be cautious when conducting cryoablation for prostate tumors in AA location.

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.

Association of statins use and mortality outcomes in prostate cancer patients who received androgen deprivation therapy: a systematic review and meta-analysis.

IntroductionWhile several recent studies investigated the influence of statins on survival outcomes in prostate cancer (PCa) patients on androgen deprivation therapy (ADT), definitive conclusions are still missing. The present systematic review and meta-analysis aimed to develop an overarching framework for the association of statins use and survival outcomes in PCa patients who receive ADT.Material and methodsWe conducted a systematic review and meta-analysis of the literature assessing the survival outcomes for statin compared to non-statin users in PCa patients who received ADT. We searched PubMed and Web of Science for studies published before March 1, 2021. We used the random effect model in the presence of heterogeneity and the fixed-effects model in the absence of heterogeneity per the I 2 statistic. We did two meta-analyses; the primary meta-analysis was accomplished for articles reporting cancer-specific survival (CSS) as an outcome. A secondary meta-analysis was completed for articles reporting overall survival (OS) as an outcome.ResultsTen studies were eligible for inclusion. Nine studies included in the first meta-analysis comprising 136,285 patients showed no statistically significant difference in CSS (HR 0.77; 95% CI 0.49–1.21) between statin users and non-users in PCa patients who received ADT. In four studies included in the second meta-analysis comprising 95,032 patients, statin users had a significantly better OS compared to non-users (HR 0.67; 95% CI 0.62–0.73).ConclusionsAlthough the combination of statins and ADT in PCa patients significantly improves OS, it seems not to be through an effect on cancer-specific factors.

The effect of HMGB1 and RAGE on the clinicopathological and prognostic features of prostate cancer

As a DNA-binding protein, high mobility group box 1 (HMGB1) has been shown be involved in various biological activities, including transcription regulation, DNA repair, genomic stability, and extracellular signaling. Accumulating evidence indicates that HMGB1 has an important role in biological processes in cancer. Moreover, HMGB1 has been shown to have intracellular and extracellular roles, activating key cancerogenic signaling pathways. The main signal pathway is activated via the interaction of HMGB1 with its receptor, receptor for advanced glycation end-products (RAGE). In addition, overexpression of HMGB1/RAGE occurs in certain types of primary tumors and has been linked to increased metastasis and poorer prognosis. In our previous research, we demonstrated that co-expression of HMGB1 and RAGE is associated with cancer progression and poor patient outcome in prostate cancer (PCa). Together with the recent published evidence, we describe and speculate on the character of the HMGB1/RAGE axis in PCa progression and elaborate on future prospects for the application of potential strategies to target HMGB1 in PCa therapy.

Church Attendance and Mobility Limitation Among Black and White Men With Prostate Cancer

Prostate cancer is a significant impediment that can reduce physical functional status. Mobility is fundamental for quality of life and church attendance to be associated with improved physical functioning. Few studies have examined how religious participation have implications for mobility limitation among men in general and among prostate cancer survivors in particular. The purpose of this study was to assess the association between church attendance and mobility limitation among Black and White prostate cancer patients and survivors. Data for this investigation were drawn from the Diagnosis and Decisions in Prostate Cancer Treatment Outcomes Study that consisted of 804 Black and White men with complete information on the primary outcome and predictor variables. Mobility limitation was the primary outcome variable, and church attendance was the main independent variable. The analytic sample was almost equally divided between Black (N = 382) and White men (N = 422). The proportion of Black men reporting mobility limitation (30.09%) more than doubled the corresponding percentage for White men (14.7%). Black men had a higher proportion of individuals who reported weekly church attendance (49.2% vs. 45.0%). Fully adjusted modified Poisson regression models produced results indicating that respondents attending church weekly had a lower mobility limitation prevalence (PR = 0.56, 95% CI [0.39, 0.81]) than those never attending church. Results from this study contribute to the body of evidence asserting the health benefits of church attendance. These findings suggest that health providers should consider how religion and spirituality can present opportunities for improved outcomes in prostate cancer patients and survivors.

Cribriform architecture in radical prostatectomies predicts oncological outcome in Gleason score 8 prostate cancer patients

The Gleason score is an important parameter for clinical outcome in prostate cancer patients. Gleason score 8 is a heterogeneous disease including Gleason score 3 + 5, 4 + 4, and 5 + 3 tumors, and encompasses a broad range of tumor growth patterns. Our objective was to characterize individual growth patterns and identify prognostic parameters in Gleason score 8 prostate cancer patients. We reviewed 1064 radical prostatectomy specimens, recorded individual Gleason 4 and 5 growth patterns as well as presence of intraductal carcinoma, and evaluated biochemical recurrence- and metastasis-free survival. Gleason score 8 disease was identified in 140 (13%) patients, of whom 76 (54%) had Gleason score 3 + 5, 46 (33%) 4 + 4, and 18 (13%) 5 + 3 disease. Invasive cribriform and/or intraductal carcinoma (n = 87, 62%) was observed more frequently in Gleason score 4 + 4 (93%) than 3 + 5 (47%; P < 0.001) and 5 + 3 (44%; P < 0.001) patients. Gleason pattern 5 was present in 110 (79%) men: as single cells and/or cords in 99 (90%) and solid fields in 32 (29%) cases. Solid field pattern 5 coexisted with cribriform architecture (23/32, 72%) more frequently than nonsolid pattern 5 cases (36/78, 46%, P = 0.02). In multivariable analysis including age, prostate-specific antigen, pT-stage, surgical margin status, and lymph node metastases, presence of cribriform architecture was an independent parameter for biochemical recurrence-free (hazard ratio (HR) 2.0, 95% confidence interval (CI) 1.0–3.7; P = 0.04) and metastasis-free (HR 3.5, 95% CI 1.0–12.3; P = 0.05) survival. In conclusion, invasive cribriform and/or intraductal carcinoma occurs more frequently in Gleason score 4 + 4 prostate cancer patients than in Gleason score 3 + 5 and 5 + 3, and is an independent parameter for biochemical recurrence and metastasis. Therefore, cribriform architecture has added value in risk stratification of Gleason score 8 prostate cancer patients.

Clinical Outcome of Salvage Radiotherapy for Locoregional Clinical Recurrence After Radical Prostatectomy.

Objectives: To assess the clinical outcomes of prostate cancer patients treated with salvage radiotherapy (SRT) for locoregional clinical recurrence (CR) after radical prostatectomy (RP). Methods: Records of 60 patients with macroscopic locoregional recurrence after prostatectomy and referrals for SRT were retrospectively investigated in the multi-institutional database. The median radiation dose was 70.2 Gy. Biochemical failure was defined as the prostate-specific antigen (PSA) ≥ nadir + 2 or initiation of androgen deprivation therapy (ADT) for increased PSA. Results: Median recurrent tumor size was 1.1 cm and pre-radiotherapy PSA level was 0.4 ng/ml. At a median follow-up of 83.1-month after SRT, 7-year biochemical failure-free survival (BCFFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 67.0%, 89.7%, 83.6%, and 91.2%, respectively. Higher Gleason's scores were associated with unfavorable BCFFS, DMFS, and OS. Pre-SRT PSA ≥0.5 ng/ml predicted worse BCFFS, LRFFS, and DMFS. In multivariate analyses, a Gleason's score of 8 to 10 was associated with decreased BCFFS (hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.11-8.74, P = .031) and OS (HR 17.72, 95% CI 1.75-179.64, P = .015), and combined ADT decreased the risks of distant metastasis (HR 0.18, 95% CI 0.04-0.92, P = .039). Two patients (3.3%) experienced late grade 3 urinary toxicity. Conclusions: SRT for locoregional CR after RP achieved favorable outcomes with acceptable long-term toxicities. Higher Gleason's scores and pre-radiotherapy PSA level were unfavorable prognostic variables. Combined ADT may decrease the risks of metastases.

Pharmacological inhibition of noncanonical EED-EZH2 signaling overcomes chemoresistance in prostate cancer.

Rationale: Chemoresistance is a major obstacle in prostate cancer (PCa) treatment. We sought to understand the underlying mechanism of PCa chemoresistance and discover new treatments to overcome docetaxel resistance.Methods: We developed a novel phenotypic screening platform for the discovery of specific inhibitors of chemoresistant PCa cells. The mechanism of action of the lead compound was investigated using computational, molecular and cellular approaches. The in vivo toxicity and efficacy of the lead compound were evaluated in clinically-relevant animal models.Results: We identified LG1980 as a lead compound that demonstrates high selectivity and potency against chemoresistant PCa cells. Mechanistically, LG1980 binds embryonic ectoderm development (EED), disrupts the interaction between EED and enhancer of zeste homolog 2 (EZH2), thereby inducing the protein degradation of EZH2 and inhibiting the phosphorylation and activity of EZH2. Consequently, LG1980 targets a survival signaling cascade consisting of signal transducer and activator of transcription 3 (Stat3), S-phase kinase-associated protein 2 (SKP2), ATP binding cassette B 1 (ABCB1) and survivin. As a lead compound, LG1980 is well tolerated in mice and effectively suppresses the in vivo growth of chemoresistant PCa and synergistically enhances the efficacy of docetaxel in xenograft models.Conclusions: These results indicate that pharmacological inhibition of EED-EZH2 interaction is a novel strategy for the treatment of chemoresistant PCa. LG1980 and its analogues have the potential to be integrated into standard of care to improve clinical outcomes in PCa patients.

Extended Versus Limited Pelvic Lymph Node Dissection During Radical Prostatectomy for Intermediate- and High-risk Prostate Cancer: Early Oncological Outcomes from a Randomized Phase 3 Trial

BackgroundThe role of extended pelvic lymph node dissection (EPLND) in the surgical management of prostate cancer (PCa) patients remains controversial, mainly because of a lack of randomized controlled trials (RCTs). ObjectiveTo determine whether EPLND has better oncological outcomes than limited PLND (LPLND. Design, setting and participantsThis was a prospective, single-center phase 3 trial in patients with intermediate- or high-risk clinically localized PCa. InterventionRandomization (1:1) to LPLND (obturator nodes) or EPLND (obturator, external iliac, internal iliac, common iliac, and presacral nodes) bilaterally. Outcome measurements and statistical analysisThe primary endpoint was biochemical recurrence–free survival (BRFS). Secondary outcomes were metastasis-free survival (MFS), cancer-specific survival (CSS), and histopathological findings. The trial was designed to show a minimal 15% advantage in 5-yr BRFS by EPLND. Results and limitationsIn total, 300 patients were randomized from May 2012 to December 2016 (150 LPLND and 150 EPLND). The median BRFS was 61.4 mo in the LPLND group and not reached in the EPLND group (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.63–1.32; p = 0.6). Median MFS was not reached in either group (HR 0.57, 95% CI 0.17–1.8; p = 0.3). CSS data were not available because no patient died from PCa before the cutoff date. In exploratory subgroup analysis, patients with preoperative biopsy International Society of Urological Pathology (ISUP) grade groups 3–5 who were allocated to EPLND had better BRFS (HR 0.33, 95% CI 0.14–0.74, interaction p = 0.007). The short follow-up and surgeon heterogeneity are limitations to this study. ConclusionThis RCT confirms that EPLND provides better pathological staging, while differences in early oncological outcomes were not demonstrated. Our subgroup analysis suggests a potential BCRFS benefit in patients diagnosed with ISUP grade groups 3–5; however, these findings should be considered hypothesis-generating and further RCTs with larger cohorts and longer follow up are necessary to better define the role of EPLND during RP. Patient summaryIn this study, we investigated early outcomes in prostate cancer patients undergoing prostatectomy according to the anatomic extent of lymph node resection. We found that extended removal of lymph nodes did not reduce biochemical recurrence of prostate cancer in the expected range.

Role of SPTSSB-Regulated de Novo Sphingolipid Synthesis in Prostate Cancer Depends on Androgen Receptor Signaling.

SummaryAnti-androgens are a common therapy in prostate cancer (PCa) targeting androgen receptor (AR) signaling. However, these therapies fail due to selection of highly aggressive AR-negative cancer cells that have no therapeutic options available. We demonstrate that elevating endogenous ceramide levels with administration of exogenous ceramide nanoliposomes (CNLs) was efficacious in AR-negative cell lines with limited efficacy in AR-positive cells. This effect is mediated through reduced de novo sphingolipid synthesis in AR-positive cells. We show that anti-androgens elevate de novo generation of sphingolipids via SPTSSB, a rate-limiting mediator of sphingolipid generation. Moreover, pharmacological inhibition of AR increases the efficacy of CNL in AR-positive cells through de novo synthesis, while SPTSSB knockdown limited CNL's efficacy in AR-negative cells. Alluding to clinical relevance, SPTSSB is upregulated in patients with advanced PCa after anti-androgens treatment. These findings emphasize the relevance of AR regulation upon sphingolipid metabolism and the potential of CNL as a PCa therapeutic.

Pathologic response to neoadjuvant therapy of high risk prostate cancer

Background. The role of pathological response, which develops as a result of systemic therapy for localized and locally advanced high risk prostate cancer, is not still fully understood. There are no clear indications for neoadjuvant therapy and no data on the relationship between neoadjuvant therapy and median of overall or progression free survival. According to increasing interest for neoadjuvant chemohormonal therapy followed by radical prostatectomy, we evaluated the features of pathological response and its effects on overall and progression free survival rates.Objective. Estimating residual disease and pathologic response to neoadjuvant therapy of high risk prostate cancer and its relationship with oncological results.Materials and methods. This was a prospective randomized study: patients with prostate cancer of high and very high-risk groups (prostate specific antigen levels &gt;20 ng/ml and/or Gleason score ≥8 and/or clinical stage ≥T2c) were treated with neoadjuvant chemohormonal therapy followed by radical prostatectomy (n = 36). The neoadjuvant course included the intravenous administration of docetaxel once every 21 days (75 mg/m2 up to 6 cycles) and the antagonist of the gonadotropin releasing hormone degarelix according to the standard scheme (6subcutaneous injections every 28 days). The prostate tissue was evaluated for the residual disease, features of pathological response according to the ABC system. Additionally, the expression of IHC markers (p53, bcl-2, p16, Ki-67, androgen receptors, c-MYC, ERG, PTEN) was evaluated on postoperative material using tissue microarray.Results. A totally of 480 H&amp;Epostoperative and 775 H&amp;E biopsy slides were analyzed. Group A included 10 (32.3 %) cases, group B — 16 (51.6 %), and group C — 5 (16.1 %). The variance analysis revealed a significant difference in the frequency of more localized forms of prostate cancer in group B (43.7 %) (p = 0.028). During assessment we did not found any relationship ABC system assignment and preoperative prostate specific antigen level, the presence of a positive surgical margin, the pathological stage of diseases or regional lymph nodes involvement. However, the values of relapse-free survival vary sharply between groups: the highest median of relapse-free survival was found in group B — 23.02 ± 12.61 months, patients of groups A/C could not achieve the level of median relapse-free survival — 11.7 ± 6.43 and 16.19 ± 16.54 months respectively.Conclusion. The effectiveness of neoadjuvant chemohormonal therapy for high risk prostate cancer can be assessed by the features of pathologic response through ABC system which has demonstrated own versatility and reproducibility in presented material. Neoadjuvant therapy with docetaxel and degarelix can improve the treatment outcomes of prostate cancer patients at high and very high risk of disease progression. The data on changes in the prostate tissue can be helpful in predicting the duration of the effect after chemohormonal therapy with subsequent surgery.

Abstract 17016: Cardiovascular Safety Profile of Gonadotropin Releasing Hormone (GnRH) Antagonist Compared to GnRH Agonist Among Patients With Prostate Cancer: A Meta-Analysis

Introduction: Androgen deprivation therapy (ADT) is the cornerstone of advanced prostate cancer therapy. The degree that ADT contributes to cardiovascular disease remains uncertain with conflicting studies. ADT can be achieved through the use of gonadotrophin releasing (GnRH) hormone agonist or, more recently, GnRH antagonists. The objective of this study was to determine whether cardiovascular events differ after the initiation of GnRH agonist compared with GnRH antagonist in randomized control trials. Methods: From PubMed, Cochrane Central, and Embase we identified all randomized studies comparing GnRH antagonists with GnRH agonists in patients with prostate cancer from 2000-2020. Outcomes studied included major adverse cardiovascular events (MACE), coronary artery disease (CAD), cerebrovascular accidents (CVA), atrial fibrillation (AF), and heart failure (HF). A random effects model using the Mantel-Haenszel method was used to assess outcomes. Results: Overall, we identified 7 studies (n = 3298) which reported outcomes in prostate cancer patients receiving GnRH antagonists (n = 2127) compared with those receiving GnRH agonists (n = 1171). When compared to men receiving GnRH agonists, the incidence of MACE (RR 0.52, 95% CI 0.35-0.76, p&lt;0.001) and CAD (RR 0.46, 95% CI 0.27 - 0.77, p=0.004) was lower in men receiving GnRH antagonists. There was no difference in the rates of CVA (RR 0.93, 95% CI 0.31-2.77, p=0.89), AF (RR 0.49, 95% CI 0.09-2.72, p=0.41), or HF (RR 0.55, 95% CI 0.19-1.59, p=0.52) between the two groups. Conclusion: For men with prostate cancer receiving ADT, GnRH antagonists decreased the incidence of MACE and coronary artery disease by half compared to men treated with GnRH agonists. GnRH antagonists have a more favorable cardiovascular safety profile than GnRH agonists.

P051 - The clinical, radiological, pathological and oncological outcomes of prostate cancer patients undergoing PSMA PET/CT imaging for initial staging; comparing those with PSMA-avid Lesions suspicious for prostate cancer to those who have not

P051 - The clinical, radiological, pathological and oncological outcomes of prostate cancer patients undergoing PSMA PET/CT imaging for initial staging; comparing those with PSMA-avid Lesions suspicious for prostate cancer to those who have not

PO-1170: Long-Term testosterone levels and its influence in treatment outcomes in prostate cancer patients

PO-1170: Long-Term testosterone levels and its influence in treatment outcomes in prostate cancer patients

Depression, anxiety, and suicidality in patients with prostate cancer: a systematic review and meta-analysis of observational studies.

Psychiatric implications of prostate cancer are increasingly recognised, having important effects on oncological and functional outcomes. However, findings for co-occurring depression, anxiety, and suicidality remain variable. Therefore, this review of observational studies aimed to establish best estimates of the prevalence and rates of these outcomes in prostate cancer patients. A systematic literature search was conducted using MEDLINE, Scopus, PsycInfo, and Cochrane Library databases from inception up to 26 May 2020. Observational studies using validated methods for evaluating prevalences of depression, anxiety and suicidal ideation, or suicide mortality rates post prostate cancer diagnosis were included. Random effect models were used to calculate pooled prevalences of depressive and anxiety symptoms or disorders, and suicidal ideation post diagnosis. Additionally, pooled crude suicide mortality rates per 100,000 person years were calculated. Heterogeneity was explored using a stratified analysis. Of 3537 articles screened, 117 were included. Pooled prevalence for depressive disorders was 5.81% (95% CI 4.36-7.46) in 11 studies, representing 655,149 patients. Significant depressive symptoms were identified in 17.07% (15.14-19.09) across 32,339 patients and 76 studies. In total, 16.86% (14.92-18.89) had significant anxiety symptoms in 56 studies combining 24,526 patients. In 6,173 patients and eight studies, recent suicidal ideation was present in 9.85% (7.31-12.70). Crude suicide mortality rate after diagnosis was 47.1 (39.85-54.96) per 100,000 person years in 12 studies. Significant heterogeneity was seen with potential sources identified through our sensitivity analysis including diagnostic method utilised, study size and location of study. The mental health impact in patients with prostate cancer is significant. Depressive, anxiety, and suicidal symptoms were common. Additionally, a high suicide mortality rate was identified when compared to general population estimates. Screening of patients and integration of physical and mental health care should be evaluated further to improve quality of life and functional outcomes.

A systematic review of tools used to assess body image, masculinity and self-esteem in men with prostate cancer.

Masculinity, body image and self-esteem are important interlinked factors affecting prostate cancer (PCa) patients' quality of life. The aim of this systematic review was to identify and evaluate all tools measuring these domains in men with PCa. This review was conducted according to PRISMA guidelines with a priori protocol registered. Pubmed, Embase, Medline and Psychinfo were searched from inception to May 2020. Studies using a predefined tool which measured any body image, self-esteem or masculinity construct in men with PCa were included, as well as validation studies of these. Reliability, validity and responsiveness of tools identified were objectively evaluated against the COSMIN taxonomy of measurement properties. From 1416 records screened, a final 46 studies consisting of 17 different tools were included in the systematic review. Seven tools were identified assessing body image, nine masculinity and one self-esteem, varying widely in their number of items, possible responses and domains assessed. Most tools had evaluated internal consistency through Cronbach's alpha analysis; however, structural and discriminative validity, and responsiveness were lacking for many. Additionally, only one tool identified was specifically developed and evaluated in patients with PCa: The Masculinity in Chronic Disease Inventory. Numerous tools have been used for the measurement of body image, masculinity and self-esteem in men with PCa. However, few were developed specifically for these patients. More research is therefore needed to ascertain specific factors affecting these outcomes in PCa patients, so valid, reliable and clinically relevant tools can be developed.