Mortality In Prostate Cancer Patients Research Articles

Glycemic control was associated with nonprostate cancer and overall mortalities in diabetic patients with prostate cancer.

Diabetes mellitus (DM) can worsen the prognosis or survival in prostate cancer (PC) patients. We investigated whether glycemic control impacts mortality in PC patients with existing diabetes. All PC patients with or without preexisting DM were enrolled from 2006 to 2017. Mean hemoglobin A1c (HbA1c) values (<7%, 7%-9%, ≥9%) were used to represent glycemic control. Major outcomes included all-cause, PC-specific, and non-PC mortalities. Statistical analyses were performed using Cox regression models with adjusted mean HbA1c and other related confounders. A total of 831 PC patients were enrolled (non-DM group, n = 690; DM group with a record of mean HbA1c values, n = 141). Results showed that the DM group with mean HbA1c level ≥ 9% (n = 14) had significantly increased risk for all-cause and non-PC mortality (hazard ratio [HR], 3.09; 95% CIs, 1.15-8.32; p=0.025 and HR, 5.49; 95% CIs, 1.66-18.16; p = 0.005, respectively), but not for PC-specific mortality (HR, 1.03; 95% CIs, 0.13-8.44; p = 0.975), compared with the non-DM group. Our findings indicate that PC patients with DM who had a mean HbA1c level ≥ 9% had higher risks of all-cause and non-PC mortality compared with non-DM subjects. Further large and long-term studies are needed to verify the effect of glycemic control in PC patients with DM.

Impact of Frailty on Survivals of Prostate Cancer Patients Treated with Radiotherapy

BACKGROUND: Frailty has been linked to an increased risk of adverse outcomes among older men with prostate cancer (PCa), which in turn impacts survival. We evaluated the associations between frailty and risks of all-cause mortality and cancer-specific mortality in PCa patients treated with radiotherapy (RT). METHODS: We conducted a retrospective cohort study using the Taiwan Cancer Registry Database and National Health Insurance Research Database. Patients aged ≥65 years with newly-diagnosed PCa, and receiving RT as initial treatment between 2011 and 2015 were identified in the study. Frailty was measured using the multimorbidity frailty index (mFI), categorized as fit, mild frailty, moderate frailty, and severe frailty. Cox regression models were used to examine the association between frailty and mortality. RESULTS: Among 4,291 men with a median age of 75 years at PCa diagnosis, 21.87% were categorized as fit, 44.72% were mild frailty, 23.02% were moderate frailty, and 10.42% were severe frailty. With the mean follow-up duration of 4.8 years, patients in the severe frailty group had a significantly higher all-cause mortality risk (HR 1.86; 95% CI, 1.48–2.32) and cancer-specific mortality risk (HR 1.44; 95% CI, 1.05–1.98) than patients in the fit group, whereas no such association was found in the mild frailty group after adjustment. CONCLUSIONS: This is the first population-based cohort study to evaluate the feasibility of mFI on mortality of PCa patients treated with RT. We found that severe frailty was associated with a higher risk of both all-cause mortality and cancer-specific mortality.

The Effects of Statins on Prostate Cancer Patients Receiving Androgen Deprivation Therapy or Definitive Therapy: A Systematic Review and Meta-Analysis.

Mortality associated with statin use has been reported in prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) or definitive therapy in several observational studies, although the results have varied. This study aimed to analyze the association of statin use with all-cause mortality and cancer-specific mortality among PCa patients receiving ADT or definitive therapy as their primary treatment and to examine the effect of statin initiation (pre-ADT) timing on outcomes. A systematic literature search of PubMed, the Cochrane library, and Embase was conducted from database inception to 4 October 2021. In total, 12 eligible studies from 976 references were included in the final analysis. The results showed that statin use was associated with a significant reduction in the risks of all-cause mortality (hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.64–0.84, p < 0.0001) and cancer-specific mortality (HR = 0.61, 95% CI = 0.49–0.77, p < 0.0001) in PCa patients receiving ADT. However, statin use before ADT initiation did not significantly lower the risk of all-cause mortality (HR = 0.87, 95% CI = 0.66–1.16, p = 0.35) or cancer-specific mortality (HR = 0.84, 95% CI = 0.62–1.13, p = 0.25) in advanced PCa patients receiving ADT. In contrast, statin use was not associated with a significantly reduced risk of all-cause mortality (HR = 0.69, 95% CI = 0.39–1.21, p = 0.20), but it was associated with a reduced risk of cancer-specific mortality (HR = 0.82, 95% CI = 0.68–0.98, p = 0.03) in PCa patients receiving definitive therapy. This review indicated that statin use in combination with ADT was correlated with better all-cause and cancer-specific mortality in PCa patients. However, the beneficial effect might not come from statin use before ADT initiation. In addition, statin use in combination with definitive therapy was correlated with a reduced risk of cancer-specific mortality in PCa patients. In the future, randomized controlled trials are needed to validate the efficacy of statin use in combination with primary treatment for PCa among PCa patients.

Impact of androgen deprivation therapy on mortality of prostate cancer patients with COVID-19: a propensity score-based analysis

BackgroundPrevious studies hypothesized that androgen deprivation therapy (ADT) may reduce severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infectivity. However, it is unknown whether there is an association between ADT and a higher survival in prostate cancer patients with COVID-19.MethodsWe performed a retrospective analysis of prostate cancer (PC) patients hospitalized to treat COVID-19 in Brazil’s public health system. We compared patients with the active use of ADT versus those with non-active ADT, past use. We constructed propensity score models of patients in active versus non-active use of ADT. All variables were used to derive propensity score estimation in both models. In the first model we performed a pair-matched propensity score model between those under active and non-active use of ADT. To the second model we initially performed a multivariate backward elimination process to select variables to a final inverse-weight adjusted with double robust estimation model.ResultsWe analyzed 199 PC patients with COVID-19 that received ADT. In total, 52.3% (95/199) of our patients were less than 75 years old, 78.4% (156/199) were on active ADT, and most were using a GnRH analog (80.1%; 125/156). Most of patients were in palliative treatment (89.9%; 179/199). Also, 63.3% of our cohort died from COVID-19. Forty-eight patients under active ADT were pair matched against 48 controls (non-active ADT). All patients (199) were analyzed in the double robust model. ADT active use were not protective factor in both inverse-weight based propensity score (OR 0.70, 95% CI 0.38–1.31, P = 0.263), and pair-matched propensity score (OR 0.67, 95% CI 0.27–1.63, P = 0.374) models. We noticed a significant imbalance in the propensity score of patients in active and those in non-active ADT, with important reductions in the differences after the adjustments.ConclusionsThe active use of ADT was not associated with a reduced risk of death in patients with COVID-19.

Association between Helicobacter pylori infection and mortality risk in prostate cancer patients receiving androgen deprivation therapy: A real-world evidence study.

Purpose Helicobacter pylori (H. pylori) is a major risk factor for gastric cancer and may affect androgen activity in men. The association between H. pylori and androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) remains unclear.MethodsThis retrospective cohort study linked National Health Insurance (NHI) data to Taiwan Cancer Registry (TCR) and Taiwan Death Registry (TDR) between 1995 and 2016. PCa patients who received ADT were classified into H. pylori infection and non‐H. pylori infection groups. The outcomes were overall mortality, prostate cancer‐specific mortality, and castration‐resistant prostate cancer (CRPC). Propensity score matching was adopted for the primary analysis and inverse probability of treatment weighting (IPTW) was used for the sensitivity analysis.ResultsOf the 62,014 selected PCa patients, 23,701 received ADT, of whom 3516 had H. pylori infections and 20,185 did not. After matching, there were 3022 patients in the H. pylori infection group and 6044 patients in the non‐H. pylori infection group. The mean follow‐up period for the matched cohort was 4.8 years. Compared to the non‐H. pylori group, the H. pylori group was significantly associated with decreased risks of all‐cause mortality (hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.84–0.96) and prostate cancer‐specific mortality (HR 0.88; 95% CI 0.81–0.95) in the matched analysis.Conclusions H. pylori infection was associated with a reduced risk of mortality in PCa patients receiving ADT.

CdGAP promotes prostate cancer metastasis by regulating epithelial-to-mesenchymal transition, cell cycle progression, and apoptosis

High mortality of prostate cancer patients is primarily due to metastasis. Understanding the mechanisms controlling metastatic processes remains essential to develop novel therapies designed to prevent the progression from localized disease to metastasis. CdGAP plays important roles in the control of cell adhesion, migration, and proliferation, which are central to cancer progression. Here we show that elevated CdGAP expression is associated with early biochemical recurrence and bone metastasis in prostate cancer patients. Knockdown of CdGAP in metastatic castration-resistant prostate cancer (CRPC) PC-3 and 22Rv1 cells reduces cell motility, invasion, and proliferation while inducing apoptosis in CdGAP-depleted PC-3 cells. Conversely, overexpression of CdGAP in DU-145, 22Rv1, and LNCaP cells increases cell migration and invasion. Using global gene expression approaches, we found that CdGAP regulates the expression of genes involved in epithelial-to-mesenchymal transition, apoptosis and cell cycle progression. Subcutaneous injection of CdGAP-depleted PC-3 cells into mice shows a delayed tumor initiation and attenuated tumor growth. Orthotopic injection of CdGAP-depleted PC-3 cells reduces distant metastasic burden. Collectively, these findings support a pro-oncogenic role of CdGAP in prostate tumorigenesis and unveil CdGAP as a potential biomarker and target for prostate cancer treatments.

Abstract 780: Racial disparities in death from cardiovascular disease for patients with prostate cancer: A population-based study

Abstract Introduction: Prostate cancer (PCa) is the most common cancer diagnosis among men in the United States. However, a vast majority of patients with PCa die of causes other than PCa, the most common being cardiovascular disease (CVD). We hypothesize that CVD-related mortality in PCa patients is disproportionately higher among Blacks as compared to Whites. Methods: We identified patients with PCa from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked files between 1/1/2004 and 12/31/2015. The PCa risk groups were created based on the National Comprehensive Cancer Network criteria: low, intermediate, and high risk. The primary endpoint was CVD-related mortality. The following CVD conditions were included in the CVD-specific mortality: acute myocardial infarction, stroke, congestive heart failure, atrial fibrillation, and ischemic heart disease. A proportional hazards model that considered the competing risks was fitted to address the hypothesis. The model was adjusted for age, year of diagnosis, marital status, income level, SEER-region, state buy-in, radiation, surgery, and education level. Results: We identified 394,323 patients with PCa. Among these 80% were Whites, 15% were Blacks, and 5% were other races. The median age at diagnosis for Whites, Blacks, and other races was 69, 66, and 70 years, respectively. The incidence of CVD-related mortality was 5.6%, 6.6%, and 5% among Whites, Blacks, and Other races, respectively. Compared to Whites, Blacks had a significantly higher risk of mortality due to CVD across all PCa risk groups (Table). Similar results were not seen when the Other races was compared to Whites. Conclusion: Blacks with PCa have a significantly higher risk of mortality due to CVD as compared to Whites across all PCa risk groups. Our study highlights the importance of cardio-oncology in the setting of PCa. Further studies are warranted to confirm the findings. Table: Risk of CVD-related mortality among PCa patients; stratified by PCa risk group.Low-Risk (N=84,367)Intermediate-Risk(N=146,411)High-Risk(N=96,502)HR (95%CI); p-valueHR (95%CI); p-valueHR (95%CI); p-valueWhites(N=316,803)RefRefRefBlacks(N=58,046)1.23 (1.09-1.39); p&amp;lt;0.0011.24 (1.14-1.34); p&amp;lt;0.0011.09 (1.01-1.20); p=0.029Other Races(N=19,474)0.79 (0.60-1.04); p=0.0890.87 (0.74-1.03); p=0.1120.79 (0.69-0.91); p&amp;lt;0.001 Citation Format: Nikita Nikita, Joshua Banks, Scott Keith, Kosj Yamoah, Ulhas P. Naik, Felix J. Kim, David M. Shipon, Wm Kevin Kelly, Timothy R. Rebbeck, Grace Lu Yao. Racial disparities in death from cardiovascular disease for patients with prostate cancer: A population-based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 780.

Decreased ATM Protein Expression Is Substantiated with PTEN Loss in Defining Aggressive Phenotype of Prostate Cancer Associated with Lethal Disease

BackgroundAtaxia Telangiectasia Mutated (ATM) serine/threonine protein kinase is a known tumor suppressor, involved in DNA damage repair. It has prognostic and predictive therapeutic implications and is associated with aggressive prostate cancer (PCa). ObjectiveTo investigate the prognostic value of ATM protein expression in PCa patients and assessed the combined value of ATM, ERG, and PTEN status. Design, setting, and participantsThis study consisted of 303 patients with incidental, locally advanced, and castrate-resistant PCa by transurethral resection of the prostate (TURP). Outcome measurements and statistical analysisTURP samples from 303 PCa patients were assessed by immunohistochemistry (IHC for ATM, ERG, and PTEN. Individual and combined marker status were correlated with International Society of Urological Pathology Gleason grade group, overall survival (OS), and PCa-specific mortality (PCSM). Results and limitationsDecreased ATM expression (negative/weak intensity) occurred in 164/303 (54.1%) patients, and was associated with shorter OS and higher PCSM (p = 0.015 and p = 0.001, respectively). Negative/weak ATM expression was significantly associated with PCSM with a hazard ratio of 2.09 (95% confidence interval 1.34–3.27, p = 0.001). Assessment of Combined ATM/PTEN expression showed improved prognostic power to predict OS and PCSM, independent of Gleason grade groups. ConclusionsDecreased ATM protein expression is associated with poor outcomes in advanced PCa patients. Patients with combined low ATM/PTEN negative expression are at the highest risk for reduced OS and PCSM. Assessing the combined status of ATM/PTEN by IHC in PCa patients may aid in risk stratification relative to OS and PCSM. Moreover, since ATM plays an integral role in DNA damage response pathways, future studies will enhance our understanding of how outcomes of patients with altered ATM and PTEN expression can be improved further with poly-ADP ribose polymerase inhibitors (PARPi), combinations of PARPi and androgen receptor–targeted therapies, as well as platinum-based chemotherapies. Patient summaryLower ATM intensity is associated with increased cancer-specific mortality in prostate cancer patients. Patients with lower ATM and PTEN negative expression showed decreased overall survival and increased cancer mortality compared with controls.

Disparities in prostate cancer diagnosis, treatment, and survival among men with disabilities: Retrospective cohort study in South Korea

BackgroundDisparities in cancer care have not been well documented for individuals with disability. ObjectiveTo investigate potential disparities in the diagnosis, treatment, and survival of prostate cancer (PC) patients according to disability status. MethodsA retrospective cohort study using disability registration data linked to Korean National Health Insurance and national cancer registry data. Totals of 7924 prostate cancer cases among patients with disabilities (diagnosed between 2005 and 2013) and 34,188 PC patients without disability were included. ResultsWhile overall PC stage distribution at diagnosis was similar, unknown stage was more common in patients with severe disabilities compared to those without disabilities (18.1% vs. 16.2%, respectively). People with disabilities were less likely to undergo surgery (33.1% vs. 38.6%, respectively; adjusted odds ratio [aOR] 0.79, 95% confidence interval [CI] 0.74–0.84), and more likely to receive androgen deprivation therapy (ADT) (57.9% vs. 55%, respectively; aOR 1.10, 95% CI 1.04–1.16) compared to those without disabilities. This was more evident for people with severe brain/mental impairment (aORs 0.29 for surgery; 1.52 for ADT). Patients with disabilities had higher overall mortality (adjusted hazard ratio [aHR] 1.20; 95% CI, 1.15–1.25), but only slightly higher PC-specific mortality after adjustment for patient factors and treatment (aHR 1.11, 95% CI 1.04–1.18) than people without disability. ConclusionsPC patients with disabilities underwent less staging work-up and were more likely to receive ADT than surgical treatment. Overall mortality of PC patients with disabilities was greater than those of PC patients without disability, but PC-specific mortality was only slightly worse.

Impact of androgen deprivation therapy on mortality of prostate cancer patients with COVID-19: A propensity score-based analysis.

5067 Background: Previous studies suggested that androgen deprivation therapy (ADT) may reduce severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infectivity. However, it is unknown whether there is an association between ADT and a higher survival in prostate cancer patients with COVID-19. Methods: We performed a retrospective analysis of prostate cancer (PC) patients hospitalized to treat COVID-19 in Brazil’s public health system. We compared patients with the active use of ADT versus those with non-active ADT, past use. We constructed propensity score models of patients in active versus non-active use of ADT. All variables were used to derive propensity score estimation, and for the outcome analysis we performed a multivariate backward elimination process to select variables to add to the propensity score model. Results: We analyzed 109 PC patients with COVID-19 that presented past or current use of ADT. In total, 52.8% of our patients were less than 75 years old, 44.0% (48/109) were in active ADT, and most were using a GnRH analog (73%, 35/48). Also, 63.3% of our cohort died from COVID-19. ADT active use were protective factor in our logistic regression model (OR 0.28, 95% CI 0.12–0.66, P = 0.0036). We noticed a significant imbalance in the propensity score of patients in active and those in non-active ADT. Then, when we performed a propensity score-based inverse weight double robust estimation model, we observed that ADT remained statistically associated with improved overall survival (average treatment effect [ATE] -0.26, 95% CI -0.45 to -0.08, P = 0.0058). Conclusions: The active use of ADT was associated with a reduced risk of death in patients with COVID-19.

PH-0120: The influence of telomere length on mortality in prostate cancer patients treated with radiotherapy.

PH-0120: The influence of telomere length on mortality in prostate cancer patients treated with radiotherapy.

Abstract 343: Identifying a novel and aggressive CD52+ve type of prostate cancer: Phenotype distinguishing biomarker and therapeutic target

Abstract Metastatic prostate cancer (PCa) and the development of CRPC are the major causes of mortality in PCa patients. The poor prognosis and failure of therapies in metastatic PCa could be associated to the heterogeneous nature of tumor cells. We previously showed that S100A4 protein drives the metastasis of PCa in preclinical models. On the basis of recent genomic data of &amp;gt;1000 patients, we now provide evidence that S100A4 in association with CD52 forms a unique and aggressive class of PCa in patients. The tumor genome data of patients show a direct correlation between S100A4 and CD52, a small glycoprotein expressed on T, B, NK, dendritic cells and monocytes. We posit that aggressive type of PCa cells during progression acquire immunosuppressive properties. Here, by employing a progressive panel of human PCa cell lines and primary prostate tumors and metastatic tumors, we show the presence of a subpopulation of PCa cells that express high levels of CD52 and S100A4. We were successful in isolating CD52+/S100A4+ subpopulation of aggressive PCa cells from DU145 (brain metastasis model) and PC3 (bone metastasis model). On analysis the CD52+/S100A4+ metastatic cells exhibited higher degree of invasiveness than the parental cells. These cells are characterized by the high expression of S100A4, VEGF and MMP9, phosphorylated-NFκB-p65 and phosphorylated-ERK. By using IHC, we observed that metastatic tumors (brain, bone, testis) exhibiting high S100A4 levels also exhibited high expression of CD52. A marked increase in the number of CD52+/S100A4+ metastatic PCa cells were found in brain in patient Met specimens, that well explains the increased number of such tumor cell types found in DU145 model (isolated from brain). We provide data showing that genetic suppression CD52 (by using siRNA) significantly reduces the growth, migration and invasive potential of metastatic cells. However, suppressing CD52 has no bearing on S100A4 expression. On the contrary, modulation of S100A4 expression could bring changes in the expression of CD52 in PCa cells. These data suggest a potential link between the S100A4 and immunosuppressive type PCa cells human disease. In conclusion, the novelty of this study is that we for the first time identified a new PCa subtype that is aggressive and resistant to existing therapies. Another novel finding is that we identified CD52 as a novel target for treating metastatic PCa. These findings warrant future clinical studies in investigating CD52+/S100A4+ signature as a biopsy biomarker to identify patients (at diagnosis) who are prone to develop metastasis (particularly bone metastasis). In addition our data opens the opportunity to develop new therapies targeting CD52/S100A4 for treating aggressive metastatic PCa which otherwise remains a non-treatable disease. Grant Support: R01CA193739 Citation Format: Adrian Pablo Mansini, Marina G. Ferrari, Arsheed Ganaie. Identifying a novel and aggressive CD52+ve type of prostate cancer: Phenotype distinguishing biomarker and therapeutic target [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 343.

Haptoglobin polymorphism and prostate cancer mortality

Prostate cancer is a common malignancy in men worldwide and it is known that oxidative stress is a risk factor for cancer development. A common functional haptoglobin (Hp) polymorphism, originating from a duplication of a gene segment spanning over two exons, results in three distinct phenotypes with different anti-oxidative capacities: Hp1-1, Hp1-2, and Hp2-2. The aim of the study was to investigate the relationship between this Hp polymorphism and prostate cancer mortality. The study was performed on 690 patients with histologically confirmed prostate cancer, recruited between January 2004 and January 2007. Hp genotypes were determined by a TaqMan fluorogenic 5′-exonuclease assay. Hp1-1 was present in 76 (11%), Hp1-2 in 314 (45.5%), and Hp2-2 in 300 (43.5%) patients. During a median follow-up of 149 months, 251 (35.3%) patients died. Hp genotypes were not significantly associated with higher overall mortality (HR 1.10; 95% CI 0.91–1.33; p = 0.34). This remained similar in a multivariate analysis including age at diagnosis, androgen deprivation therapy, and risk group based on PSA level, GS, and T stage (HR 1.11; 95% CI 0.91–1.34; p = 0.30). We conclude that the common Hp polymorphism does not seem to be associated with overall mortality in prostate cancer patients.

PT136 - Young age associated with increased risks of disease progression and cancer-specific mortality in prostate cancer patients

PT136 - Young age associated with increased risks of disease progression and cancer-specific mortality in prostate cancer patients

Association of polymorphisms in androgen production, uptake, and conversion chain (APUC) genes with mortality of prostate cancer patients.

5528 Background: Genes involved in APUC may affect prognosis in PC. We tested the association of four SNPs involved in the APUC pathway: hydroxy-delta-5-steroid dehydrogenase, 3 beta-and steroid delta-isomerase 1 ( HSD3B1), 5α reductase enzyme ( SRD5A), and solute carrier organic ion ( SLCO2B1) with all-cause and PC mortality 596 in the Atherosclerosis Risk in Communities (ARIC) study. Methods: Between 1987 &amp; 2015 596 men were diagnosed with PC. Median age at diagnosis was 70 (range 53-86) years; 21% of all PC patients were African American. After diagnosis, follow-up was median 8.4 years (max 26.7 years) until PrC death (N = 60), death from any cause (N = 253), or end of 2015. SNPs were genotyped using the Affymetrix Genome-Wide Human SNP Array 6.0 and imputed to the 1000 Genomes Phase 3 reference panel. To examine survival, we used Kaplan-Meier curves and Cox proportional hazards regression. Hazard ratios (HR) and 95% confidence intervals (CI) were adjusted for age, field center, stage and grade at diagnosis. We also controlled for confounding by ancestry by adjusting for genetic principal components. The analyses were conducted in all PrCa patients and in Whites PrCa patients only. Polymorphisms tested included rs1047303 (A = &gt; C, also called 1245C); rs523349 (C = &gt; G); and rs1789693 (A = &gt; T) and rs12422149 (G = &gt; A), located in the aforementioned genes. Results: The A allele for SLCO2B1 rs1789693 (A = &gt; T) was significantly associated with an increased risk of PC mortality (versus T): multivariable-adjusted HRs (95%CI) were (2.06, 1.14-3.74; p = 0.02) and all-cause mortality (1.29, 1.00-1.66; p = 0.05) among Whites. The associations were similar when Whites and African-Americans were combined and when accounting for ancestry. The C allele for HSD3B1 rs1047303 (C = &gt; A) was not statistically significantly associated with either PC or all-cause mortality in the whole cohort (which included localized disease), although HRs were increased for men diagnosed with stage 4 disease (n = 35) in both additive and dominant models. For carriers of the C allele (gain of function) versus AA, HRs were 5.32 (1.16-24.33; p = 0.03) and 6.13 (1.51-24.86; p = 0.01) for PC and all-cause mortality, respectively. All associations with SRDA2 (rs12422149) and SLCO2B1 (rs12422149) were not significant. Conclusions: The gain of function allele in HSD3B1 rs1047303 (1245C) was associated with increased PC and all-cause mortality in men diagnosed with metastatic PC, paralleling prior findings. Associations with SLCO2B1 SNP rs1789693 require validation in larger studies.

Ability of cell-cycle progression score to predict risk for progression to metastatic disease and disease-specific mortality in prostate cancer patients after prostatectomy.

5524 Background: Prostate cancer treatment aims to prevent metastatic disease (METS) and disease-specific mortality (DSM). A major challenge is to identify those at highest risk so additional intervention can be initiated earlier when it has a better chance of success. Pathologic parameters alone have limited ability to predict METS and DSM, but data suggests biomarkers can improve risk discrimination. Methods: Eligible patients had: (1) prostate cancer treated with radical prostatectomy (RP; 1988-1995); (2) available tissue for cell-cycle progression (CCP) testing that resulted in a valid score; (3) preoperative prostate-specific antigen (PSA); (4) no neoadjuvant therapy; and (5) clinical follow-up (N = 360). Cancer of the prostate risk assessment post-surgical (CAPRA-S) was combined with CCP into a combined cell-cycle risk score (CCR = 0.38 × CAPRA-S + 0.57 × CCP). Results: Median follow-up was 23.5 years for patients alive at last follow-up. Overall, 11% (41/360) developed METS and 9% (33/360) had DSM. CCP score added significant information to CAPRA-S when predicting METS (p = 0.001) and DSM (p = 0.001). CCR score was also a significant predictor of METS and DSM (p-values &lt; 1×10−8). CCP and CCR scores were prognostic of METS in patients with rising post-RP PSA. Of patients with biochemical recurrence (BCR), 25% (41/163) developed METS. CAPRA-S alone was predictive of these events (p = 0.01) but was significantly improved with the addition of CCP (Hazard Ratio [HR] = 1.69 [95% Confidence Interval (CI) 1.13, 2.52], p = 0.014). CCR was also highly prognostic (HR = 1.56 [95% CI 1.20, 2.03], p = 0.001). CCR score discriminated risk of METS both post-RP and after post-RP BCR (Table). Conclusions: Overall, the CCR score significantly predicted METS and DSM in prostate cancer post-RP and was also highly prognostic in those with a post-RP rising PSA. It is therefore a useful tool for determining who is at greatest risk of treatment failure and may benefit from earlier intervention. [Table: see text]

Эпидемиологические особенности рака предстательной железы в Дальневосточном федеральном округе

Background. Recent decades in the Far East Federal District have been characterized by a constant increase in the number of patients with oncological pathology, in the structure of which prostate tumors are the second largest cause of mortality in men. The goal of this study was a scientific assessment of the main rates of morbidity and mortality of prostate cancer in the male population in the Far East Federal District for the last ten years (2009–2018). Material and methods. During the study, the indicators of morbidity and mortality, reporting forms of statistical registration of oncological patients and regulatory documents of higher-level organizations, information on ten-year observations of the dynamics of changes in digital indicators of the investigated pathology were used. Results of the research. The main rates of morbidity and mortality of prostate cancer patients in the Far East Federal District are given, where 33,111 new cases of malignant neoplasms were registered in 2018, that is 24,6 % higher than ten years ago (20 191 people in 2009). In Russia, such increase was 21,6 % higher. 9 324 patients, i.e. 0,12 % population of the region, were under medical supervision. The number of patients with I-II stages of the disease (60,9 %) increased during the investigated period with simultaneous reduction of the number of patients with neglected forms (38,1 %) of the disease. Morbidity and mortality rates have been increasing steadily over the past 10 years. The percentage of actively identified patients has increased, as well as the year-end accumulation index. Morphological confirmation of the diagnosis (over 95 %) did not exceed the average republican indicators (95,9 %). The proportion of patients registered for 5 years or more was lower than averagely in Russia, but mortality rates improved in the first year from the time of the initial diagnosis (2009 – 17,3 %; 2018 – 10,1 %; Russian Federation – 7,8 %). As far as the localizations in the male reproductive organs, neglected prostate cancer remains at the highest level.

Disparities in Prostate Cancer Diagnosis, Treatment, and Survival Among Men with Disabilities

Background: Disparities in the diagnosis, treatment, and survival of prostate cancer (PC) patients according to disability status have not been widely investigated. Methods: A retrospective cohort study using disability registration data linked to Korean National Health Insurance and national cancer registry data. 7,924 PC patients with disabilities and 34,188 age-matched PC patients without disability were included. Results: While stage distribution at diagnosis was similar, unknown stage was more common in patients with severe disabilities compared to those without disabilities (18·1% vs. 16·2%, respectively). People with disabilities were less likely to undergo surgery (33·1% vs. 38·6%, respectively; adjusted odds ratio [aOR] 0.79, 95% confidence interval [CI] 0.74-0.84), and more likely to receive androgen deprivation therapy (ADT) (57·9% vs. 55.0%, respectively; aOR 1·10, 95% CI 1·04-1·16) compared to those without disabilities. This was more evident for people with severe brain/mental impairment (aORs 0·29 for surgery; 1·52 for ADT). Patients with disabilities had higher overall mortality (adjusted hazard ratio [aHR] 1·20; 95% CI, 1·15-1·25), but only slightly higher PC-specific mortality after adjustment for patient factors and treatment (aHR 1·11, 95% CI 1·04-1·18) than people without disability. Interpretation: PC patients with disabilities underwent less staging work-up and were more likely to receive ADT than surgical treatment. Overall mortality of PC patients with disabilities was greater than those of PC patients without disability, but PC-specific mortality was only slightly worse. Unequal clinical care in this vulnerable population suggests the presence of disability-related barriers that need to be addressed. Funding Statement: This work was supported by an R&D grant (No. 2016007) from the Korea National Rehabilitation Center Research Institute, Ministry of Health & Welfare, and the National Research Foundation of Korea(NRF) grant funded by the Ministry of Education (No.2016R1D1A3B03931142) and by the Korea government(MSIT) (No. 2019R1H1A2080180, 2019R1A2C1087507). Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: Institutional Review Board approval was obtained from Chungbuk National University (IRB No. CBNU-201708-BM-501-01).

SEX STEROIDS AND ADIPOKINES IN MEN WITH PROSTATE CANCER AND THEIR RELATIONSHIP WITH OBESITY AND METABOLIC SYNDROME

Prostate cancer is the most commonly diagnosed cancer among men in the world and in Poland it is the second cause of death in men suffering from cancer. Recent evidence suggests that obesity is associated with prostate cancer. Increased BMI correlates with aggressive disease and with higher risk of recurrence and mortality in prostate cancer patients. Obesity can promote the progression of prostate cancer through endocrine disturbances, mainly in sex steroids, through chronic inflammation resulting in altered production of adipokines, peripheral insulin resistance with hyperinsulinemia and oxidative stress. Diagnosis of metabolic syndrome can be used in the global assessment of prognosis in patients with prostate cancer. The aim of the paper is to present current state of knowledge about connections between obesity, metabolic syndrome, sex steroids and adipokines in men with prostate cancer.

P063 - Relative telomere length is associated with mortality in prostate cancer patients

P063 - Relative telomere length is associated with mortality in prostate cancer patients