Survival In Advanced Prostate Cancer Research Articles

The effect of human leukocyte antigen genotype on survival in advanced prostate cancer treated with primary androgen deprivation therapy: the KYUCOG-1401-A study.

Immune editing, in which human leukocyte antigens (HLA) have critical roles, has been suggested to shape the landscape of human cancer. This study prospectively investigated whether HLA gene zygosity is associated with the prognosis of primary androgen deprivation therapy in advanced prostate cancer. KYUCOG-1401-A was conducted in conjunction with a prospective clinical trial (KYUCOG-1401). Among the patients enrolled in KYUCOG-1401 and treated with primary androgen deprivation therapy, only Japanese patients were included. HLA genotypes of HLA-A, B, C, DRB1, DQB1, and DPB1 were determined. The effect of divergence of HLA genotypes on time to progression, prostate cancer-specific survival, and overall survival was evaluated. Among 127 patients, homozygosity for HLA-DRB1 (HR, 95% CI; 4.05, 1.54-10.7, P = 0.0047) and HLA-DQB1 (HR, 95% CI; 3.75, 1.47-9.58, P = 0.0058) was associated with an increased risk of prostate cancer-specific mortality. Patients with higher HLA evolutionary divergence scores at HLA-DQB1 (HR, 95% CI; 0.90, 0.82-0.97, P = 0.0093) had lower risks of prostate cancer-specific mortality. Androgen-responsive gene sets were upregulated in CD4low and CD8low tumors in the prostate cancer cohort, but not in the bladder and kidney cancer cohorts. This study suggested that the diversity of HLA-II loci including HLA-DRB1 and HLA-DQB1 plays an important role in advanced prostate cancer survival, contributing to improved risk stratification in advanced prostate cancer. Moreover, it was shown that CD4+ T cells play an important role in androgen deprivation therapy, suggesting that immunotherapy targeting CD4+ T cells is promising for prostate cancer.

Cardio-oncology in advanced prostate cancer.

Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.

Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer

Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies. To study the association between statin use and survival among men with prostate cancer receiving androgen deprivation therapy (ADT) or androgen receptor axis-targeted therapies (ARATs). This systemic review and meta-analysis used sources from MEDLINE, EMBASE, Epub Ahead of Print, Cochrane Clinical Trials, Cochrane Systematic Reviews, and Web of Science from inception to September 6, 2022. Observational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs]). Two authors independently abstracted all data. Summary estimates pooled multivariable HRs with 95% CIs using the generic inverse variance method with random-effects modeling. A priori specified subgroup and sensitivity analyses were undertaken, and heterogeneity, study quality, and publication bias were evaluated. Confidence in the evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Overall mortality and prostate cancer-specific mortality (PCSM). Twenty-five cohorts of 119 878 men (65 488 statin users [55%]) with more than 74 416 deaths were included. Concurrent statin use was associated with a 27% reduction in the risk of overall mortality (HR, 0.73 [95% CI, 0.66-0.82]; I2 = 83%) and a 35% reduction in the risk of PCSM (HR, 0.65 [95% CI, 0.58-0.73]; I2 = 74%), with substantial heterogeneity in both estimates. Subgroup analyses identified a PCSM advantage associated with statins for men receiving ARATs compared with ADT alone (HR, 0.40 [95% CI, 0.30-0.55] vs 0.68 [95% CI, 0.60-0.76]; P = .002 for difference). Confidence in the evidence was rated low for both outcomes. The findings of this meta-analysis show that concurrent statin use was associated with reduced overall mortality and PCSM among men receiving androgen-ablative therapies for advanced prostate cancer. These findings are limited by the observational nature of the data and residual unexplained interstudy heterogeneity. Randomized clinical trials are warranted to validate these results.

Statin use and survival in men receiving androgen-ablative therapies for advanced prostate cancer: A systematic review and meta-analysis of cohort studies.

83 Background: Mounting evidence support a role for statins in improving survival in advanced prostate cancer (PC), particularly among men on androgen-ablative therapies. This study aimed to systemically review and meta-analyze the relationship between statin use and survival among men with PC on androgen deprivation therapy (ADT) or androgen receptor-axis-targeted therapies (ARATs). Methods: This review was conducted in accordance with the Cochrane Handbook for Systematic Reviews and reported in compliance with the MOOSE guidelines. Medline, Embase, Epub Ahead of Print, Cochrane CT, Cochrane SR, and Web of Science were searched from inception to May 18, 2021, for observational studies reporting associations of postdiagnostic statin use and survival outcomes (hazard ratios [HRs]). Two authors independently abstracted all data. Study quality was assessed using the Newcastle-Ottawa Scale. The primary outcomes included overall mortality (OM) and Prostate cancer-specific mortality (PCSM). Summary estimates pooled multivariable HRs with 95% confidence intervals (CIs) using the generic inverse variance method with random-effects modelling. Heterogeneity was assessed and quantified. A priori subgroup and sensitivity analyses were undertaken, and publication bias was evaluated. Confidence in the evidence was assessed using GRADE. Results: Twenty-five cohorts of 119,878 men (64,717 statin users [54%]) with over 74,416 mortality events were included. Postdiagnostic statin use was associated with a 27% reduction in the risk of OM (19 cohorts, HR 0.73 [95%CI: 0.66 to 0.82], I2= 83%) and a 35% reduction in the risk of PCSM (14 cohorts, HR 0.65 [95%CI: 0.58 to 0.73], I2= 74%), with significant heterogeneity in both estimates. Subgroup analyses identified a PCSM-advantage of statins for men on ARATs compared to ADT (HR 0.40 [95%CI: 0.30 to 0.55] vs HR 0.68 [95%CI: 0.60 to 0.76], p-difference < 0.01). Confidence in the overall evidence was “low” for both outcomes. Conclusions: Postdiagnostic statin use reduced both overall and prostate cancer-specific mortality in men on androgen-ablative therapies for advanced PC. Randomized controlled trials are warranted to validate these findings.

Association of area social determinants of health with prostate cancer mortality.

49 Background: Validated clinical nomograms prognosticate survival for men with metastatic castrate resistant prostate cancer. In addition to clinical factors, significant disparities in survival in advanced prostate cancer are associated with social determinants of health (SDH). We performed a study of county-level data to evaluate SDH associated with prostate cancer mortality. Methods: County-level data regarding prostate cancer crude mortality rate (dependent variable) and crude incidence rate was extracted from the ten states with information at www.cancer-rates.info for the years 2006-2015. The 2014 Robert Wood Johnson County Health Rankings dataset was used for information regarding county demographics, clinical information, and available SDH(independent variables). A correlation analysis was performed between independent variables and only one variable was analyzed if a criterion of a correlation of ≥ 0.65 was present. All counties with ≤ 30 death in the specified time period or with incomplete independent variable information were excluded from analysis. A univariate linear regression analysis was performed. All individual independent variables with a statistically significant (p ≤ 0.05) association with the dependent variable were included in a multivariate linear regression model. Results: 275 counties were available for analysis. On multivariate analysis, independent variables statistically significantly associated with the crude rate of prostate cancer mortality included household income and the percentage of: a population ≥ 65 years of age, the population < 18 years of age, African Americans, the population classified as rural, women reporting a screening mammography, smokers, and uninsured patients. The multivariate model was associated with a R-squared of 0.62. Conclusions: In addition to differences in baseline clinical factors, prostate cancer quality metrics that evaluate survival should account SDH. Information from this study, if validated in subsequent work, could be used to develop a stepwise model to adjust for both clinical factors and SDH when measuring survival as a quality metric.

Predicting long-term results with circulating tumor cells in patients with de novo androgen sensitive prostate cancer treated with hTERT peptides vaccine.

98 Background: Androgen deprivation, radiotherapy and chemotherapy improves survival in advanced prostate cancer (PC), but many patients still progress and experience toxicity from treatment. We investigated the clinical utility of a medical wire, collecting circulating tumor cells (CTCs) from a peripheral vein, to predict oncologic outcomes prior to treatment with a hTERT peptide vaccine. Methods: Twenty-three patients with advanced PC with non-visceral spread and unselected HLA-type were eligible. One patient progressed before initiation of the vaccination (median FU 60 months). The hTERT peptides vaccine schedule started one week after inclusion with a total of 13 vaccinations (N=22). Patients with no signs of deterioration during the vaccine schedule received image-guided radiation to the prostate (2Gy/37f, n=20). Vaccine response was evaluated by T-cell proliferation assay. CTCs were enriched from the peripheral blood using EpCAM as antibody (CellCollector, Gilupi, Potsdam, Germany). Kaplan-Meier outcome curves were constructed for prostate cancer-specific survival (PCSS) and overall survival with stratification by immune response, CTCs (no/yes), PSA and comparison of patient subsets using the log-rank test. Results: Median age of the cohort was 67 years (range 51-78 years).The mean time from CellCollector after ADT to start vaccine was 2,95 months (SD+-1,78 months). The mean yield of CTCs was 3 cells (range 0 - 22). The detection of CTCs showed an inverse trend towards immune response (p=0.07). None of the patients with a positive CellCollector finding and a PSA below ≤0.2 (n=9) had died of prostate cancer during the observation period of 5 years, patients with no CTCS and a PSA >0.2 (n=14) had an estimated median PCSS of 39 months (log-rank test 0=0.007, Fig. 1). The overall survival analysis showed that 6 out of 9 patients with CTCs compared to 5 out of 14 patients in the CTCs negative group were alive at 5 years FU (log-rank-test=0.159). Conclusions: Patients with a de novo diagnozed metastatic prostate cancer and a positive CTC burden do better when subsequently treated with the hTERT vaccine than those with a negative CTC finding. Clinical trial information: NCT01784913.

Evaluation of the contribution of demographics, access to health care, treatment, and tumor characteristics to racial differences in survival of advanced prostate cancer.

Racial differences in prostate cancer (PCa) outcomes in the United States may be due to differences in tumor biology and race-based differences in access and treatment. We designed a study to estimate the relative contribution of these factors on Black/White disparities in overall survival (OS) in advanced PCa. We identified Black and White men aged ≥ 40 years with metastatic or locally advanced PCa (cN+ cM+ and/or T3/4) between 2004 and 2010 using the National Cancer Database. We employed sequential propensity score weighting procedures to generate simulated cohorts of Black and White patients with equal demographics, access to care, treatment, and tumor characteristics. Adjusted survival analyses were used to compare survival in these simulated cohorts. The changes in relative survival after each weighting procedure were used to infer the contribution of each set of variables on the excess risk of mortality in Blacks. In total, 35,611 men met inclusion criteria, 5927 (16.77%) of whom were Black. Survival was significantly worse for Black men after adjusting for demographics and comorbidities (hazard ratio (HR) 1.27, 95%-confidence interval (95%-CI) 1.2-1.34, p < 0.001). After simulating equal access to care, there was no significant difference in survival between races (HR 1.04, 95%-CI 0.97-1.12, p = 0.276), despite worse tumor characteristics in Blacks. After simulating equal treatment and equivalent tumor characteristics, Black men had a better survival than Whites (HR 0.93, 95%-CI 0.86-1.01, p = 0.071 and HR 0.92, 95%-CI 0.84-1.00, p = 0.043, respectively). Overall, access-related variables explained 84.7% of the excess risk of death in Black men. Our analysis of men with advanced PCa revealed worse OS among Blacks. However, when access to care, treatment, and cancer characteristics are accounted for, Black race was associated with better OS. These findings suggest that initiatives to improve access to care may represent an effective tool to reduce disparities in PCa outcomes.

A randomized phase III trial between adjuvant docetaxel and surveillance after radical radiotherapy for intermediate and high risk prostate cancer: Results of SPCG-13 trial.

5000Background: Docetaxel combined with androgen deprivation therapy (ADT) has improved survival in advanced prostate cancer (PCa). This randomized trial evaluates if six courses of docetaxel impro...

Effect of chemotherapy combined with bioimmune therapy on clinical efficacy and survival of advanced prostate cancer

Objective To investigate the effect of chemotherapy combined with biological immunotherapy on clinical efficacy and survival of advanced prostate cancer. Methods Ninety-six patients with advanced prostate cancer who were treated from September 2013 to March 2016 in our hospital were randomly divided into two groups. The control group was given chemotherapy alone, the observation group was given chemotherapy combined with biological immunity for treatment. The clinical efficacy and immunohistochemical response of patients with advanced prostate cancer were compared and analyzed. After 4 months of treatment, the patients were followed up for 1 year. The mortality, survival and time to disease progression (TTP) as well as the occurrence of adverse reactions of the two groups were observed. Results After treatment, the total effective rate of the observation group was 87.5% (42/48), which was significantly higher than that of the control group [68.8%(33/48]. There was significant difference between the two groups (P<0.05). The numbers of Tlymphocytes, T helper cells, Tsuppressor cells, natural killer cells and naturak killer T were significantly higher than that in the control group in the external T lymph. There was a significant difference between the two groups (P <0.05). After 1 year of follow-up, the mortality rate of the observation group was lower than that of the control group, and the survival time (36.6 ± 5.4) months was higher than that of the control group (20.7 ± 7.2) months, TTP of the observation group was higher than that of the control group [(29.8 ± 5.7) months vs.(19.7±9.3)months] (P<0.05). The adverse reaction rate (22.9%) in the observation group was significantly lower than that in the observation group (43.8%), and the difference between the two groups was statistically significant (P<0.05) . Conclusions Chemotherapy combined with biological immunotherapy is effective in advanced prostate cancer, which can effectively enhance the activity of immune function cells, prolong survival time, TTP, reduce mortality, reduce the incidence of adverse reactions and improve the quality of life after treatment. Key words: Prostatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Immunotherapy

The Novel Association of Circulating Tumor Cells and Circulating Megakaryocytes with Prostate Cancer Prognosis.

Purpose: To develop an approach for the investigation of different subtypes of circulating tumor cells (CTC) and other cells to evaluate their potential prognostic value of prostate cancer.Experimental Design: Malignancy of CTCs undergoing epithelial-to-mesenchymal transition (EMT) was confirmed by repeated FISH. Subgroups of CTCs in 81 patients with prostate cancer (43 castration resistant and 38 untreated localized) were correlated to disease aggressiveness parameters. AUC analysis was applied to compare the performance for metastasis prediction between serum PSA level alone and a combined risk score using both PSA and EMTing CTC count. Circulating megakaryocytes and cancer patient survival association was performed using Cox model.Results: The majority of vimentin (VIM)+/CD45- cells were malignant, with genomic alterations in several genomic regions. The number of cytokeratin (CK)-/VIM+/CD45- CTCs correlated with disease burden, tumor aggressiveness, and poorer survival. Meanwhile, CK+/VIM+/CD45- CTCs were associated with metastases better than other subtypes of CTCs in these limited samples. Combination of PSA level and the number of CK+/VIM+/CD45- CTCs enhanced the prediction of cancer metastases [AUC, 0.921; 95% confidence interval (CI), 0.858-0.985]. The number of circulating megakaryocytes was potentially associated with good patient survival in advanced prostate cancer (HR, 0.849; 95% CI, 0.628-1.146, per cell increase), and the difference between the number of mesenchymal CTCs and megakaryocytes strongly correlated to poor survival (HR, 10.17; 95% CI, 2.164-47.789, if score ≥2.0).Conclusions: This CTC analysis approach and the potential association of megakaryocytes with cancer prognosis may greatly enhance our ability to investigate the cancer metastasis process and to predict/monitor cancer progression. Clin Cancer Res; 23(17); 5112-22. ©2017 AACR.

Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer

Background:Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression.Methods:Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis.Results:ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival.Conclusions:Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.

Advanced prostate cancer survival in Spain according to the Gleason score, age and stage

ObjectivesThe aim of this study was to determine the overall and disaggregated survival based on the Gleason score, age and extent of a patient cohort diagnosed with advanced prostate cancer according to standard clinical practice. Material and methodWe used an observational and retrospective design for the study. For each patient, we recorded clinical variables such as the extent (metastatic or locally advanced), Gleason score, age, date of diagnosis, date of last contact with the health system and the vital status during the last contact. We used univariate and multivariate statistical techniques of survival. The parametric survival methods enabled us to calculate the mean survival using extrapolation.We analyzed 219 patients treated in the public health system between 2008 and 2011. The analysis showed statistically significant differences in survival depending on Gleason score, age and stage. The longest survival was in the subgroup younger than 75 years, with a local extent and a low-risk category on the Gleason scale (19.41 years), and the shortest survival (0.97 years) was in the 75 years or older group. The survival of the other subgroups ranged between these outliers. ConclusionThe main contribution of this study is that it is the first to calculate the mean survival of advanced prostate cancer in Spain in terms of the variables of our study population. This information helps clinicians predict the life expectancy of each patient according to their prognostic factors.

Supervivencia del cáncer de próstata avanzado en España según escala de Gleason, edad y estadio

ObjectivesThe aim of this study was to determine the overall and disaggregated survival based on the Gleason score, age and extent of a patient cohort diagnosed with advanced prostate cancer according to standard clinical practice. Material and methodWe used an observational and retrospective design for the study. For each patient, we recorded clinical variables such as the extent (metastatic or locally advanced), Gleason score, age, date of diagnosis, date of last contact with the health system and the vital status during the last contact. We used univariate and multivariate statistical techniques of survival. The parametric survival methods enabled us to calculate the mean survival using extrapolation.We analysed 219 patients treated in the public health system between 2008 and 2011. The analysis showed statistically significant differences in survival depending on Gleason score, age and stage. The longest survival was in the subgroup younger than 75 years, with a local extent and a low-risk category on the Gleason scale (19.41 years), and the shortest survival (0.97 years) was in the 75 years or older group. The survival of the other subgroups ranged between these outliers. ConclusionThe main contribution of this study is that it is the first to calculate the mean survival of advanced prostate cancer in Spain in terms of the variables of our study population. This information helps clinicians predict the life expectancy of each patient according to their prognostic factors.

Body mass index at mCRPC, weight change, and survival in advanced prostate cancer.

270 Background: Body mass index (BMI) at diagnosis is associated with increased risk of fatal prostate cancer, but the link between BMI at mCRPC and cancer progression is less clear. Cachexia, often defined as involuntary weight loss &gt; 5% over 6 months, is common in advanced cancers. The goal of this study was to examine the link between BMI at mCRPC and weight change as it relates to cancer progression, the outcomes of survival, and treatment use in a single-institution setting. Methods: 58 mCRPC patients treated at Tulane Hospital were identified, 41 of whom had an overweight BMI at mCRPC (BMI &gt; 25) and 17 with normal BMI at mCRPC (BMI &lt; 25). All patients had a confirmed prostate cancer death. Survival, treatment history, and percent weight change were compared according to BMI status. Rate of percent weight change was defined as the change in weight per day, from date of mCRPC diagnosis to the last treatment stop date or death date (“mCRPC days”). Linear regression, overall survival (OS), and nonparametric analyses were performed. Results: There was no significant difference between the normal and overweight BMI groups in overall survival, from date of diagnosis to death (median = 1835 days vs. 2710 days respectively). Additionally, the difference in survival from mCRPC to death was not statistically significant (median = 630 days vs. 799 days, p = 0.115). Use of Taxotere was not significantly different (47% vs. 68% respectively); however, overweight patients (n = 28) more likely received Abiraterone than normal BMI patients (n = 2) (p-value = 0.0001). The rate of percent weight change was significantly different for normal and overweight patients (mean = –0.050%/day vs. –0.019%/day, p = 0.003). Linear regression analysis showed that mCRPC days had a significant effect on percent weight change (p = 0.0109), and this effect was not significantly different between BMI groups (p = 0.6991). Conclusions: Survival after mCRPC was not significantly different between BMI groups. We observed a significant effect of mCRPC days on percent weight change, with a similar effect for both BMI groups. This outcome is expected, as more time would allow for greater weight changes to occur. Larger studies are needed to fully evaluate these observations.

Abstract 4495: Fisetin, a dietary flavonoid, binds to and disrupts microtubule dynamic instability in prostate cancer cells.

Abstract Taxanes are the first class of chemotherapy drugs shown to improve survival in advanced prostate cancer (PCa). Taxanes bind β-tubulin and stabilize microtubules, resulting in mitotic arrest and cell death. Therefore, disruption of microtubule function may provide an effective therapy for human PCa, which has been observed in clinical settings using paclitaxel. However, these drugs are associated with severe side effects and are sensitive to resistance mechanisms. Thus, search for novel and non-toxic tubulin targeting agents is urgently needed. We hypothesized that fisetin may offer PCa chemotherapeutic and/or chemopreventive effects by interfering with microtubule assembly, either by inhibiting or enhancing tubulin polymerization. Using an in vitro microtubule polymerization assay, we observed that fisetin enhanced tubulin polymerization whose kinetics paralleled that of paclitaxel. Because acetylation of α-tubulin is considered as a marker of stable microtubule structure, we next tested whether increased acetylated α-tubulin correlates with increased microtubule stability in PC-3 and DU-145 cells. We found that fisetin (20-80 μM) treatment increased α-tubulin acetylation in a dose dependent manner in PC-3 and DU-145 cells. To further investigate the stabilization of the microtubule network in fisetin-treated cells, we evaluated microtubule resistance to cold-induced depolymerization. Immunofluorescence labeling revealed that fisetin-treated PC-3 and DU-145 cells were resistant to cold-induced microtubule depolymerization. To identify microtubule-dependent tumor-specific pathways modulated by fisetin, we determined its effect on MAP2 expression in PC-3 and DU-145 cells. We found increased expression of MAP-2 with fisetin treatment. Stabilization of microtubules resulted in arrest of the cells in the G2/M phase of cell cycle and subsequent cell growth inhibition. Activation of microtubule-stabilizing proteins in PCa cells may inhibit their proliferation and correlate with a delay or inhibition of cell migration. Therefore, we investigated the efficacy of fisetin on the invasion and metastasis of PCa using scratch wound assay. We found that fisetin treatment (20-80 μM) for 24 hours inhibited PC-3 cells migration and invasion, which suggested fisetin as an anti-metastatic agent. As a mechanism for these effects we observed that fisetin increased the expression of nuclear migration protein Nud C in PC-3 and DU-145 cells in a dose dependent manner. Because Nud C protein regulates microtubule dynamics in the cell, the result reveal anti-microtubule effects of fisetin. The data reported here provide the first evidence of the dietary flavonoid fisetin as a microtubule stabilizing agent in PCa. Our observation suggests that fisetin could be used for the treatment of advanced PCa alone or as an adjuvant with other chemotherapy drugs. Citation Format: Eiman Mukhtar, Vaqar M. Adhami, Deeba N. Syed, Hasan Mukhtar. Fisetin, a dietary flavonoid, binds to and disrupts microtubule dynamic instability in prostate cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4495. doi:10.1158/1538-7445.AM2013-4495

Circulating tumor cell capture and analysis in a multicenter SWOG-coordinated prostate cancer trial.

TPS342 Background: Prostate cancer biomarkers are urgently needed to better inform treatment decisions. Recent studies have demonstrated that quantification of peripheral blood circulating tumor cells (CTCs) predicts response to therapy and overall survival in advanced prostate cancer. However, present methods for CTC collection are limited by low yield, complex techniques, and expensive equipment, and they provide little phenotypic information about the CTCs themselves. We have developed a new microfilter platform that simply and reliably traps and enriches the CTC population from peripheral blood, enabling enumeration and further study of these cells. To test whether our microfilter can serve as a simple yet reliable new predictive platform for CTC collection, quantification, and phenotypic analysis, we have activated a correlative CTC biomarker study that “piggybacks” onto S0421, a SWOG cooperative group national protocol studying atrasentan in combination with docetaxel in castration resistant prostate cancer. Methods: In this ongoing multicenter trial, blood samples are drawn at 3 time points before and during treatment. Each sample is processed through the microfilter, and the captured CTCs are analyzed in three ways: 1. Absolute and post-treatment changes in microfilter CTC counts with parallel analysis on the FDA-approved Cell Search platform. 2. Expression of relevant biomarkers on microfilter- trapped CTCs; specifically, endothelin receptor A for atrasentan response, type III β-tubulin for docetaxel response, and CD44 for an aggressive progenitor/metastatic phenotype. 3. Telomerase activity in microfilter-enriched cells. Data is relayed to SWOG Statistical Center for analysis and correlation with clinical outcomes and therapy response in S0421. As of 12/2009, 131 patients have been accrued, with a final goal of 600 samples from 200 patients. This large-scale correlative biomarker study will determine if the quantity and characteristics of CTCs captured on our novel platform can predict clinical outcome and response to therapy, thus enhancing our ability to assess therapeutic efficacy in real time and contributing to optimized, evidence-based, individualized patient management. No significant financial relationships to disclose.

Analysis of hormonal therapy for advanced metastatic prostate cancer

Objective To find the predictive factors that related to the effect of hormonal therapy and the survival of advanced metastatic prostate cancer. Methods Three hundred and Sixty-four cases of metastatic prostate cancer were treated with hormonal therapy in Cancer Hospital Fudan University in Shanghai from December 1996 to March 2008. The patients were followed up to the 31 March 2008 and the median follow-up time was 24 months. Two hundred and fifty cases have progressed into the stage of hormonal independent. The statistic software used in this study was SPSS 15. 0. Cumulative survival was analyzed by Kaplan-Meier method. Cox regression was used for univa-riate and multivariate analysis. Log-rank method was used for the significance test. The statistical difference was accepted when the P-value was lower than 0. 05. Results The effective rate of hormonal therapy for advanced metastatic prostate cancer was 98%. The median time of progression free survival of hormonal therapy was 20 months, and the one-year, two-year, three-year progression free survival rate was 69%, 39%, 27%, respectively. The survival analysis indicated that baseline PSA level more than 20ng/ml, with visceral organ metastasis, the PSA nadir more than Ing/ml during hormonal therapy, the time from the start of hormonal therapy to the PSA nadir less than 5 months were poor prognostic factors of progression free survival. Conclusions The baseline PSA level, clinicalstage, the PSA nadir during hormonal therapy and the time form the start of hormonal therapy to the PSA nadir could be the factors that predict the progression free survival time during hormonal therapy. Key words: Prostatic neoplasms; Carcinoma; Hormonal therapy; Prognosis

News &amp; Notes

AbstractVaccine prolongs prostate cancer survivalImmunisation with Prostvac vaccine prolonged overall survival in advanced prostate cancer by 8.5 months compared with placebo, a phase II trial has shown.Prostvac, a recombinant viral vaccine against prostate‐specific antigen and associated co‐stimulatory molecules, is being developed jointly by Bavarian Nordic and the US National Cancer Institute. Administered as a course of seven monthly subcutaneous injections, it has been shown to increase median overall survival from 16.6 months with placebo to 25.1 months after four years' follow‐up in 125 men with advanced prostate cancer. Bavarian Nordic says the tolerability profile is good, with local injection site reactions accounting for most adverse events.Breast cancer specialists not auditing NICE adherenceMost UK breast cancer specialists believe their units follow NICE guidance on treatment, but only 21 per cent have checked by auditing their practice. Further, 23 per cent do not have, or are unaware of, systems for recalling women treated with tamoxifen for reassessment after 2‐3 years. A quarter do not provide junior medical staff with a copy of treatment guidelines.The findings come from a survey of 100 breast cancer specialists presented at the National Cancer Research Institute Conference in Birmingham in October 2008. The authors concluded there is a clear need for a simple standardised system, in addition to normal clinical follow‐up, that would ensure timely recall of women on tamoxifen to review their treatment plans.Ovarian cancer statement raises awarenessClinicians, patients' representatives and policy makers have published a consensus statement designed to improve the diagnosis of ovarian cancer by raising awareness of its symptoms.Public awareness of ovarian cancer is low and patients often follow a convoluted care pathway because GPs fail to recognise the presenting symptoms. Although these are not specific, the statement emphasises that the persistence, frequency and severity of new‐onset pelvic and abdominal pain, increased abdominal size/persistent bloating, and difficulty eating and feeling full should alert doctors to the diagnosis.Copies of the statement can be downloaded at www.eveappeal.org.uk/consensus.HIV testing should be routineHIV testing should be a routine part of diagnosis for all health professionals in secondary care, according to a new guide.It is estimated that a third of HIV cases are undiagnosed and one‐third of diagnoses are late. Delayed diagnosis is believed to account for 35 per cent of HIV‐related deaths. The new guide, HIV for non‐HIV Specialists: Diagnosing the Undiagnosed, produced by the Medical Foundation for AIDS and Sexual Health (MedFASH) with funding from the Department of Health, provides practical help and advice for non‐specialists to help them consider the possibility of HIV infection in their differential diagnosis. The recommendations complement new national guidelines on HIV testing.MedFASH is a charity supported by the British Medical Association. The booklet can be downloaded at www.medfash.org.uk.OTC gel for bacterial vaginosisA new topical treatment for bacterial vaginosis is now available without prescription. Balance Activ Vaginal Gel contains lactic acid and glycogen; manufacturer Inverness Medical says this restores normal vaginal pH and promotes growth of lactobacilli. Further details are available at www.balanceactiv.com. Copyright © 2008 Wiley Interface Ltd

Treatment of prostate cancer: therapeutic potential of targeted immunotherapy with APC8015

The body's immune system has some capacity to recognize and attack cancerous growths, including prostate cancer. However, various intrinsic characteristics of tumor cells usually limit that capacity. Therapeutically administered immunologic stimuli, such as APC8015, an individualized, ex vivo stimulation of a patient's own antigen presenting cells (APC), are capable of boosting the anti-tumor response. Late phase clinical trials of APC8015 (now also called Sipuleucel-T) show evidence of slowing disease progression and increasing survival in advanced prostate cancer. Such immunotherapeutic approaches hold real promise to provide additional useful and welcome weapons against this common malignancy.

Clinical implication of vascular endothelial growth factor T-460C polymorphism in the risk and progression of prostate cancer

Vascular endothelial growth factor (VEGF), one of the most potent angiogenic factors, is suggested to play a crucial role in tumor neovascularization and is associated with tumor progression and metastasis in prostate cancer. This study evaluated the significance of the VEGF T-460C polymorphism in the risk and the progression of prostate cancer. In a case-control experiment, 270 patients with prostate cancer and 252 male controls were investigated to assess the association of the VEGF T-460C polymorphism with the risk of prostate cancer. Prostate-specific antigen (PSA) recurrence in 95 patients who underwent radical prostatectomy and survival in 99 patients with metastases at diagnosis were analyzed to evaluate the influence of the polymorphism in cancer progression. The CC and TC genotypes of the polymorphism were associated with significantly higher rates of PSA recurrence after radical prostatectomy than the TT genotype and were independent predictors of PSA recurrence (P=0.011) in a multivariate analysis. In contrast, metastatic prostate cancer patients with the TT genotype showed significantly worse survival as compared to the CC and TC genotypes. In a multivariate analysis, the TT genotype was an independent predictor of cancer-specific survival (P=0.006). The VEGF T-460C polymorphism may have a substantial impact on both PSA recurrence after radical prostatectomy and survival in advanced prostate cancer. The molecular mechanisms of the polymorphism on the differing status in prostate cancer should be elucidated in further studies.