The prognostic biomarkers of the patients treated with platinum-based chemotherapy in treatment emergent or related neuroendocrine prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17576-e17576
Author(s):  
Takeo Kosaka ◽  
Hiroshi Hongo ◽  
Yota Yasumizu ◽  
Kazuhiro Matshumoto ◽  
Ryuichi Mizuno ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Univariate Analysis ◽  
Prognostic Biomarkers ◽  
Monocyte Count ◽  
Chemotherapy Treatment ◽  
Visceral Metastasis ◽  
Risk Of Death ◽  
Neuroendocrine Prostate Cancer ◽  
Pathologic Features ◽  
Platinum Based Chemotherapy

e17576 Background: Treatment emergent or related neuroendocrine prostate cancer (tNEPC) is an aggressive subtype of prostate cancer in patients previously treated with androgen receptor pathway inhibitor (ARPI) as a mechanism of resistance. These patients are typically treated platinum-based chemotherapy using small cell lung cancer (SCLC). The clinical features of tNEPC are poorly defined. The aim of the present study was to investigate the prognostic biomarkers of the patients treated with platinum-based chemotherapy in tNEPC. Methods: We reviewed baseline, treatment and outcome data of 41 patients with tNEPC. Clinicopathological factors and laboratory data before administering the first cycle of platinum-based chemotherapy were collected to assess the prognostic factors for overall survival (OS). Definition of tNEPC were based on NEPC morphology on the basis of any current or prior tissue sample, development of liver metastases in the absent of PSA progression, or elevated serum neuron specific enolase (NSE). Results: Median PSA and NSE were 119.8 ng/ml and 18.2 ng/ml, respectively. Twenty-four patients had pathologic features of NEPC. NSE were elevated above the 32 patients. The median OS from the start of platinum-based chemotherapy treatment was 10 months. Univariate analysis revealed that LDH (p = 0.003), absolute monocyte count < 280 (p = 0.022), visceral metastasis (p = 0.014) prior to platinum-based chemotherapy were significantly associated with shorter OS. Multivariate analysis revealed that LDH (p = 0.047), absolute monocyte count < 280, (p = 0.012), visceral metastasis (p = 0.005) prior to platinum-based chemotherapy treatment were independent prognostic indicators for OS. Based on the relative risk of death, NEPC patients before platinum-based chemotherapy were divided into 3 risk groups: low, intermediate and high ( p< 0.001). Conclusions: Our findings provide new insights into the practical implication of NEPC. Our results might be to tailor the management of NEPC treated with platinum-based chemotherapy.

Prevalence and predictors of active surveillance management for black males diagnosed with low risk prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18019-e18019
Author(s):  
Nicolette Taku ◽  
Vivek Narayan ◽  
Scarlett Bellamy ◽  
Neha Vapiwala
Keyword(s):  
Prostate Cancer ◽  
Active Surveillance ◽  
Private Insurance ◽  
Univariate Analysis ◽  
Low Risk ◽  
Consensus Guidelines ◽  
Pathologic Features ◽  
Significant Difference ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer

e18019 Background: Consensus guidelines recommend that active surveillance (AS) be considered in the management of men with low risk prostate cancer (LRPC). The evidence supporting this recommendation is largely derived from studies in which men of African descent were underrepresented; thus, the appropriate implementation of AS in this population remains controversial. The objective of our study was to evaluate the prevalence and clinical predictors of an AS approach in black men (BM) diagnosed with LRPC following the 2010 inclusion of AS in LRPC management consensus guidelines. Methods: BM (N = 15,242) and non-Hispanic white men (WM) (N = 86,655) diagnosed with LRPC (as defined by PSA ≤ 10 ng/ml, Gleason score ≤ 6, clinical stage T1 – T2a) between 2010 and 2013 were identified from the National Cancer Database. Logistic regression models were used to assess the likelihood of pursuing an AS strategy over time, as well as to examine associations between sociodemographic characteristics (SDCs) and the receipt of AS. Results: Overall, 9% of BM with LRPC were managed with AS. On univariate analysis, the likelihood of BM undergoing AS increased from 2010 and was statistically significant ( p < 0.001) for all subsequent years (2011: OR = 1.54, 95% CI 1.30-1.82; 2012: OR = 2.19, 95% CI 1.82-2.60; 2013: OR = 2.55, 95% CI 2.15-3.02). Uninsured BM were twice as likely as those with private insurance to pursue AS (OR 1.97, 95% CI 1.51-2.58, p < 0.001). BM seen at academic cancer programs were also more likely to be managed with AS, when compared to those seen at community cancer centers (OR 1.47, 95% CI 1.37-1.60, p < 0.001). BM were less likely than WM to receive AS (OR = 0.82, 95% CI 0.77 to 0.87, p < 0.001). On multivariate analysis adjusted for SDCs, there was no significant difference in AS utilization between the two ethnic groups. Conclusions: The utilization of AS for BM with LRPC appears to be increasing, may be influenced by SDCs, and may not differ from the AS utilization for WM with LRPC. Given the observed elevated rates of post-prostatectomy adverse pathologic features among BM, further evaluation of the determinants of AS utilization and scrutinous consideration of the appropriateness of AS in this population is warranted.

scholarly journals Identification of Novel Diagnosis Biomarkers for Therapy-Related Neuroendocrine Prostate Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Cuijian Zhang ◽  
Jinqin Qian ◽  
Yucai Wu ◽  
Zhenpeng Zhu ◽  
Wei Yu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Characteristics ◽  
Expression Profiles ◽  
Prostate Adenocarcinoma ◽  
Diagnostic Tools ◽  
Receptor Interaction ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Neuroendocrine Prostate Cancer ◽  
Platinum Based Chemotherapy

Background: Therapy-related neuroendocrine prostate cancer (NEPC) is a lethal castration-resistant prostate cancer (CRPC) subtype that, at present, lacks well-characterized molecular biomarkers. The clinical diagnosis of this disease is dependent on biopsy and histological assessment: methods that are experience-based and easily misdiagnosed due to tumor heterogeneity. The development of robust diagnostic tools for NEPC may assist clinicians in making medical decisions on the choice of continuing anti-androgen receptor therapy or switching to platinum-based chemotherapy.Methods: Gene expression profiles and clinical characteristics data of 208 samples of metastatic CRPC, including castration-resistant prostate adenocarcinoma (CRPC-adeno) and castration-resistant neuroendocrine prostate adenocarcinoma (CRPC-NE), were obtained from the prad_su2c_2019 dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was subsequently used to construct a free-scale gene co-expression network to study the interrelationship between the potential modules and clinical features of metastatic prostate adenocarcinoma and to identify hub genes in the modules. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression analysis was used to build a model to predict the clinical characteristics of CRPC-NE. The findings were then verified in the nepc_wcm_2016 dataset.Results: A total of 51 co-expression modules were successfully constructed using WGCNA, of which three co-expression modules were found to be significantly associated with the neuroendocrine features and the NEPC score. In total, four novel genes, including NPTX1, PCSK1, ASXL3, and TRIM9, were all significantly upregulated in NEPC compared with the adenocarcinoma samples, and these genes were all associated with the neuroactive ligand receptor interaction pathway. Next, the expression levels of these four genes were used to construct an NEPC diagnosis model, which was successfully able to distinguish CRPC-NE from CRPC-adeno samples in both the training and the validation cohorts. Moreover, the values of the area under the receiver operating characteristic (AUC) were 0.995 and 0.833 for the training and validation cohorts, respectively.Conclusion: The present study identified four specific novel biomarkers for therapy-related NEPC, and these biomarkers may serve as an effective tool for the diagnosis of NEPC, thereby meriting further study.

Correlation of statin use and duration with increased survival in hormone refractory prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14617-14617
Author(s):  
N. T. Rich ◽  
B. J. Smith ◽  
D. A. Vaena
Keyword(s):  
Prostate Cancer ◽  
Univariate Analysis ◽  
Time Dependent ◽  
Prescription Database ◽  
Hormone Refractory Prostate Cancer ◽  
Risk Of Death ◽  
Hormone Refractory ◽  
The Impact ◽  
Statin Use

14617 Background: Prior studies associated statin use with prevention and reduced progression of prostate cancer. (Platz et al, 96th AACR abst. 4374). However, the effects of statins in hormone refractory prostate cancer (HRPC) are unknown. We evaluated the impact of statins on survival of HRPC patients by comparing actual survival data with predicted survival using the Halabi nomogram (JCO 21:(7);1232). Methods: Using the Iowa City VA (ICVA) prescription database since 2001 along with chart review, we identified 28 consecutive patients who were prescribed statins when they had HRPC. Survival information, duration of statin use while HRPC, and Halabi nomogram variables were collected (Hb, PS, Alk Phos, Gleason, PSA). An LDH value of 90 U/L (low-normal at ICVA) was used for all patients, since LDH values were not available. Log-rank and and Cox regression analyses were performed. The outcome of interest was overall survival. Patients alive at last follow-up were censored. Statin use was treated as a time-dependent covariate in the regression analysis, and subject-specific predicted survival from the Halabi nomogram as another covariate. Results: 17 patients were alive and 11 had died. Median duration of follow-up for patients alive was 23 months. The observed vs. nomogram-predicted estimated median survivals were 36 vs. 17 months, respectively. Study patients significantly outlived their nomogram-predicted survival (p = 0.0004). Four patients had negative bone scans. 12 patients outlived their nomogram, 8 died before, and 8 were indeterminate (censored prior to their Halabi-predicted survival). Risk of death decreased with greater length of statin use (p = 0.02). When covariates for Halabi nomogram and statin use were both included in a multivariate regression model, neither was statistically significant, although similar point estimates for the relative risks were obtained. Conclusions: Statin use, and longer duration of use, significantly improved survival of HRPC patients in univariate analysis. The sample size limits the multivariate analysis. Evaluation of a time-dependent statin effect in HRPC could be considered in larger studies. No significant financial relationships to disclose.

scholarly journals Bone Scan Index: A Quantitative Treatment Response Biomarker for Castration-Resistant Metastatic Prostate Cancer

2012 ◽  
Vol 30 (5) ◽  
pp. 519-524 ◽  
Author(s):  
Elizabeth R. Dennis ◽  
Xiaoyu Jia ◽  
Irina S. Mezheritskiy ◽  
Ryan D. Stephenson ◽  
Heiko Schoder ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Scintigraphy ◽  
Bone Scan ◽  
Metastatic Prostate Cancer ◽  
Univariate Analysis ◽  
Imaging Biomarker ◽  
Bone Scan Index ◽  
Risk Of Death ◽  
Percent Change ◽  
Castration Resistant

Purpose There is currently no imaging biomarker for metastatic prostate cancer. The bone scan index (BSI) is a promising candidate, being a reproducible, quantitative expression of tumor burden seen on bone scintigraphy. Prior studies have shown the prognostic value of a baseline BSI. This study tested whether treatment-related changes in BSI are prognostic for survival and compared BSI to prostate-specific antigen (PSA) as an outcome measure. Patients and Methods We retrospectively examined serial bone scans from patients with castration-resistant metastatic prostate cancer (CRMPC) enrolled in four clinical trials. We calculated BSI at baseline and at 3 and 6 months on treatment and performed univariate and bivariate analyses of PSA, BSI, and survival. Results Eighty-eight patients were scanned, 81 of whom have died. In the univariate analysis, the log percent change in BSI from baseline to 3 and 6 months on treatment prognosticated for survival (hazard ratio [HR], 2.44; P = .0089 and HR, 2.54; P < .001, respectively). A doubling in BSI resulted in a 1.9-fold increase in risk of death. Log percent change in PSA at 6 months on treatment was also associated with survival (HR, 1.298; P = .013). In the bivariate analysis, change in BSI while adjusting for PSA was prognostic at 3 and 6 months on treatment (HR, 2.368; P = .012 and HR, 2.226; P = .002, respectively), but while adjusting for BSI, PSA was not prognostic. Conclusion These data furnish early evidence that on-treatment changes in BSI are a response indicator and support further exploration of bone scintigraphy as an imaging biomarker in CRMPC.

Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16501-e16501
Author(s):  
Igal Kushnir ◽  
Ranjeeta Mallick ◽  
Michael Ong ◽  
Christina Canil ◽  
Dominick Bossé ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Dose Reduction ◽  
Univariate Analysis ◽  
Dose Intensity ◽  
Cox Proportional Hazards ◽  
Significant Variable ◽  
Median Dose ◽  
Intensity Effect ◽  
Risk Of Death

e16501 Background: Several studies assessed the association of docetaxel dose intensity (DI) and efficacy in metastatic castrate-resistant prostate cancer (mCRPC) patients with contradicting conclusions. In this retrospective analysis we will assess whether the docetaxel DI used in patients with metastatic castrate-sensitive prostate cancer (mCSPC) is associated with overall survival (OS). Methods: We have identified all the patients with mCSPC treated at The Ottawa Hospital Cancer Centre that received docetaxel chemotherapy between June 2014 - September 2017. For each patient we calculated the relative dose intensity (RDI) and assessed whether it’s associated with OS using univariate and multivariate cox-proportional hazards analysis. Results: Eighty-0ne patients were included in the analysis. Nineteen patients (23.5%) had their body surface area capped at 2 which resulted with de facto median dose reduction of 7% (IQR 6% - 9%). Ten patients had upfront dose reduction (usually due to significant co-morbidities) with a median dose reduction of 20% (IQR 19.25 – 20.75). Only 35 patients (43.2%) were able to complete the planned treatment with a RDI of at least 90%. After a median follow-up of 29.4 months, 32 patients (39.5%) died. The median OS was 43.9 months. On a univariate analysis RDI and number of cycles of docetaxel received were found to be statistically significant associated with OS. For every 10% decrease in RDI the risk of death increased by 23% (HR 1.23, 95% CI 1.09 – 1.4, P = 0.0011). For every incremental cycle (up to a total of 6) the risk of death decreased by 27% (HR 0.73, 95% CI 0.61- 0.88, P = 0.001). On multivariate analysis we included age, Gleason score, burden of disease, visceral involvement and baseline PSA. Reduced RDI remained the only significant variable associated with OS (HR 1.2, 95% CI 1.04 – 1.39, P = 0.0117). Conclusions: Reduced docetaxel DI administrated to mCSPC patients is associated with worse survival. Therefore unnecessary docetaxel dose reductions, treatments delays and early discontinuation should be avoided. Granulocyte-colony stimulating factor should be considered in order help maintain standard DI.

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