Therapy For Metastatic Prostate Cancer Research Articles

Re: Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer.

Re: Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer.

Re: Enzalutamide with Standard First-line Therapy in Metastatic Prostate Cancer

Re: Enzalutamide with Standard First-line Therapy in Metastatic Prostate Cancer

Re: Enzalutamide with Standard First-line Therapy in Metastatic Prostate Cancer

Re: Enzalutamide with Standard First-line Therapy in Metastatic Prostate Cancer

Re: Enzalutamide with Standard First-line Therapy in Metastatic Prostate Cancer

Re: Enzalutamide with Standard First-line Therapy in Metastatic Prostate Cancer

Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer

BackgroundEnzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer.MethodsIn this open-label, randomized, phase 3 trial, we assigned patients to receive testosterone suppression plus either open-label enzalutamide or a standard nonsteroidal antiandrogen therapy (standard-care group). The primary end point was overall survival. Secondary end points included progression-free survival as determined by the prostate-specific antigen (PSA) level, clinical progression-free survival, and adverse events.ResultsA total of 1125 men underwent randomization; the median follow-up was 34 months. There were 102 deaths in the enzalutamide group and 143 deaths in the standard-care group (hazard ratio, 0.67; 95% confidence interval [CI], 0.52 to 0.86; P=0.002). Kaplan–Meier estimates of overall survival at 3 years were 80% (based on 94 events) in the enzalutamide group and 72% (based on 130 events) in the standard-care group. Better results with enzalutamide were also seen in PSA progression-free survival (174 and 333 events, respectively; hazard ratio, 0.39; P<0.001) and in clinical progression-free survival (167 and 320 events, respectively; hazard ratio, 0.40; P<0.001). Treatment discontinuation due to adverse events was more frequent in the enzalutamide group than in the standard-care group (33 events and 14 events, respectively). Fatigue was more common in the enzalutamide group; seizures occurred in 7 patients in the enzalutamide group (1%) and in no patients in the standard-care group.ConclusionsEnzalutamide was associated with significantly longer progression-free and overall survival than standard care in men with metastatic, hormone-sensitive prostate cancer receiving testosterone suppression. The enzalutamide group had a higher incidence of seizures and other toxic effects, especially among those treated with early docetaxel. (Funded by Astellas Scientific and Medical Affairs and others; ENZAMET (ANZUP 1304) ANZCTR number, ACTRN12614000110684; ClinicalTrials.gov number, NCT02446405; and EU Clinical Trials Register number, 2014-003190-42.)

Another dimension to the understanding of local therapy for metastatic prostate cancer.

Another dimension to the understanding of local therapy for metastatic prostate cancer.

Different therapeutic regimens in the treatment of metastatic prostate cancer by performing a Bayesian network meta-analysis

Although androgen deprivation therapy with or without chemotherapy are currently the mainstay of therapy for metastatic prostate cancer, accumulating data suggested the survival benefits from definitive local therapy such as radical prostatectomy or radiation therapy. Hence, this network meta-analysis was aimed to provide a hierarchy of different therapeutic regimens for mPCa. Relevant studies were retrieved comprehensively by searching the online databases of PubMed, EMBASE and Web of Science, published before July 1st, 2018. With the help of R-3.4.0 software and "gemtc-0.8.2" package, network meta-analysis was performed by random-effect model within a Bayesian framework. Hazard ratios and corresponding 95% credible intervals were calculated by Markov chain Monte Carlo methods. The surface under the cumulative ranking curve was also incorporated to rank the corresponding therapeutic regimens. A total of 55,363 cases from 17 studies were ultimately involved in this study. Ten different therapeutic regimens and three clinical endpoints were finally assessed. As illustrated by our results, local therapy (such as radical prostatectomy or radiation therapy) could provide a relatively more favorable survival rate than systematic therapies (no local therapy, androgen deprivation therapy or androgen deprivation therapy+chemotherapy). Meanwhile, in the comparison of radiation therapy, brachytherapy and intensity modulated radiation therapy were among the best two therapies. Furthermore, radical prostatectomy had a relatively lower cancer specific mortality or all-cause mortality than brachytherapy or intensity modulated radiation therapy, in the comparison of local therapy, whereas brachytherapy showed a relatively longer overall survival than radical prostatectomy. Our results indicated that local therapy was better than no local therapy. In a comprehensive comparison of three clinical endpoints (overall survival, cancer specific mortality or all-cause mortality), radical prostatectomy had a relatively lower cancer specific mortality or all-cause mortality than radiation therapy, whereas brachytherapy was superior to radical prostatectomy for overall survival.

Oligometastatic Prostate Cancer.

With advancements in diagnostic techniques, oligometastatic prostate cancer is diagnosed in patients who were, in the past, considered to have localized disease. Moreover, evidence of the effectiveness of treatment intensification for this disease is increasing, focusing on primary tumors as well as metastatic lesions. Thus, we can delay the start of systemic palliative treatment and improve overall survival. Many questions remain unclear, such as the definition of oligometastasis disease, or which patients should be offered aggressive treatment. Data are limited and come from small retrospective studies but show conclusively the benefits of survival in targeted primary prostate and metastatic prostate cancer therapy with surgery or radiotherapy. Often, stereotactic radiotherapy is used in this indication, with minimal side effects. In retrospective studies, 3-5 metastatic lesions were generally accepted for definition of oligometastatic disease, but patient subgroups were heterogeneous. A recent study attempts to better define oligometastatic disease and find out the right degree of intensification of treatment. When and in which patient to use metastasis-targeted therapy and when the standard systemic treatment is already meaningful. It is already clear that selected patients benefit from targeted personalized treatment. The purpose of this review is to offer an update of the problem of oligometastatic prostate cancer. The article presents an overview of data from contemporary literature, modern possibilities of diagnostic imaging methods and treatment options of oligometastatic prostate cancer including surgery and radiotherapy. authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 8. 2. 2019 Accepted: 5. 3. 2019.

Genetic Polymorphism in Sex Hormone-binding Globulin With a Prognosis of Androgen Deprivation Therapy in Metastatic Prostate Cancer Among Japanese Men.

Testosterone suppression in serum during androgen deprivation therapy (ADT) can affect the oncologic outcome of ADT. Although genetic variants in sex hormone-binding globulin (SHBG) were reported to be correlated with serum testosterone level, the association with serum testosterone during ADT remains unclear. Therefore, this study investigated the impact of a missense polymorphism in the SHBG gene among men treated with primary ADT for metastatic prostate cancer. This study included 104 Japanese men with metastatic prostate cancer. The association of SHBG gene polymorphism (rs6259, D356N) with clinicopathologic parameters including serum testosterone levels during ADT, as well as prognosis, including progression-free survival and overall survival, was examined. The serum testosterone levels during ADT were comparable between men carrying the homozygous wild-type (GG) and heterozygous/homozygous variant (GA/AA) in the SHBG gene. When adjusted for age, Gleason score, initial prostate-specific antigen, and clinical T-stage, the heterozygous/homozygous variant (GA/AA) in the SHBG gene was associated with a higher risk of progression (hazard ratio, 2.20; 95% confidence interval, 1.10-4.18; P= .027) and any-cause death (hazard ratio, 3.21; 95% confidence interval, 1.31-7.35; P= .012). This study suggested genetic variation in SHBG (rs6259) might be an independent prognostic biomarker among men treated with primary ADT for metastatic prostate cancer.

PD25-12 INPATIENT MORBIDITY AND COST OF CYTOREDUCTIVE RADICAL PROSTATECTOMY IN THE UNITED STATES

INTRODUCTION AND OBJECTIVES:Clinical trials are currently examining the role of local therapy in metastatic prostate cancer (mPCa). While the safety of RP in localized disease is proven, few studies have looked at perioperative complications and cost of cytoreductive RP (cRP). We used the National Inpatient Sample (NIS) to study the inpatient morbidity, and cost of cRP in the United States (US).METHODS:Analyzing the NIS dataset from 2008-2014, we identified 90,662 patients (weighted estimate 449,025 in the US) who underwent RP for nonmetastatic disease, and 1,173 patients (weighted estimate 5,835) who underwent cRP for mPCa (see Fig. 1). Outcomes of interest were inpatient complications, individual complications, hospital stay, and total cost. Covariates included age, race, Charlson Comorbidity score, insurance status, rural/semi-urban/urban location, income, hospital location (rural/urban), teaching status, geographical location of hospital, and hospital volume. Multivariable logistic regression was used...

Age-dependent overall survival benefit of androgen deprivation therapy for metastatic prostate cancer.

Androgen deprivation therapy (ADT) remains a standard of care in metastatic prostate cancer. Recent prospective trials have explored addition of chemotherapy to ADT. We retrospectively examined overall survival in metastatic prostate cancer patients treated with ADT, chemotherapy plus ADT (C + ADT), or observation from 2004 to 2010 using National Cancer Database data. Using the National Cancer Database, 21,977 patients with metastatic prostate cancer diagnosed from 2004 to 2010 were identified. Multivariate logistic regression, Kaplan-Meier survival analysis and Cox proportional hazards regression modeling were implemented, with overall survival as the primary endpoint. Five-year overall survival was 13.6% in patients aged ≥ 75 years vs. 30.1% (age 65-74) and 34.5% (age 18-64). Subgroup analysis of age-based cohorts (<65 and ≥65 years) showed poor overall survival for C + ADT vs. ADT alone, both in younger (HR 1.35, 95% CI 1.21-1.50; p < 0.0001) as well as older (HR 1.21, 95% CI 1.08-1.34; p = 0.0006) populations. Younger patients had no significant difference in overall survival for observation vs. ADT (HR 0.99, 95% CI 0.92-1.08; p = 0.9121). Besides age, other factors impacting overall survival included race, rural/urban settings, comorbidity score, income, PSA and radiation. Younger patients had no significant difference in overall survival between observation or ADT. This implies a group of younger patients in whom ADT does not confer any overall survival benefit. Future clinical trials with genetic and biologic markers are needed to delineate which subgroups would not benefit from C + ADT or ADT alone. This is of utmost clinical importance given the negative impact of ADT on quality of life and comorbidities.

An ALP-activatable and mitochondria-targeted probe for prostate cancer-specific bimodal imaging and aggregation-enhanced photothermal therapy.

Tumor-derived alkaline phosphatase (ALP) is over-expressed in metastatic prostate cancer. The development of selective probes for ALP detection is therefore critical for early diagnosis and therapy of metastatic prostate cancer. Herein, we develop a mitochondria-targeted near-infrared activatable fluorescent/photoacoustic (NIR FL/PA) probe for the selective detection of prostate cancer-derived ALP and aggregation-enhanced photothermal therapy. Upon dephosphorylation, the probes are activated and they provide a red-shifted strong absorption and emission in the NIR window and thus enable NIR FL and PA imaging of ALP activity in tumor tissues. Particularly, the activated probes self-assemble in situ into a supramolecular network structure which induces cell apoptosis and significantly enhances the photothermal therapy efficacy.

Abiraterone acetate to treat metastatic castration-resistant prostate cancer in combination with prednisone.

Prostate cancer is one of the most common cancers in the United States, with an estimated incidence of 164,690 cases, accounting for 9.5% of all new cancer diagnoses. The mainstay of therapy for metastatic prostate cancer involves suppressing testosterone production through androgen deprivation therapy. However, nearly all patients on androgen deprivation therapy will develop resistance to hormone therapy. An improved understanding of the biology of castration resistance has allowed for the development of novel inhibitors of the androgen axis. Agents such as abiraterone acetate, which provides additional androgen suppression by inhibiting cytochrome P450 17A (CYP17A), have improved survival outcomes of patients with advanced prostate cancer. The longest experience with abiraterone acetate is in the metastatic castration-resistant setting. However, more recent trials have demonstrated that abiraterone acetate is an option for treatment earlier in the prostate cancer paradigm. This review will cover the current use of abiraterone acetate in combination with prednisone for the treatment of castration-resistant prostate cancer.

Ectopic expression of CC chemokine receptor 7 promotes prostate cancer cells metastasis via Notch1 signaling.

There currently exists no satisfactory treatment for patients with prostate cancer with local evolution and distant metastasis. Previous studies have confirmed the importance of CC chemokine receptor 7 (CCR7) in the invasion and metastasis of prostate cancer. And increasing evidence prove that Notch1 can play diametrically opposite roles in the development and progression of different tumors. To demonstrate the correlation between CCR7 and Notch1, PC-3 cells were transfected with pcDNA3.1-CCR7 or CCR7 si-RNA, respectively. Then Western blot analysis was used to detect the expressions of Notch1, ERK, P38, JNK, NF-κB, MMP-9, and epithelial-mesenchymal transition (EMT)-related proteins. Moreover, matrigel invasion assays were performed to assess the migratory and invasive activities of PC-3 cells. PcDNA3.1-CCR7 increased the expression of Notch1, phospho-MAPK, phospho-P65, MMP-9, N-cadherin, and Snail in PC-3 cells, but decreased the expression of E-cadherin. PcDNA3.1-CCR7 also promoted the migration and invasion of PC-3 cells. However, CCR7 si-RNA reversed the effect of pcDNA3.1-CCR7 in PC-3 cells. And MAPK and NF-κB pathway inhibitors were used to testify that activation of Notch1 induces EMT through MAPK and NF-κB pathway. All these results indicate that upregulation of Notch1 by CCR7 can accelerate the evolution of EMT and develop the invasion and metastasis in prostate cancer cells by activating MAPK and NF-κB signaling pathways in prostate cancer cells, which provides a new molecular evidence for targeted therapy in metastatic prostate cancer.

Isoalantolactone induces apoptosis through ROS-mediated ER stress and inhibition of STAT3 in prostate cancer cells

BackgroundProstate cancer is one of the most commonly diagnosed cancers in men worldwide. Currently available therapies for metastatic prostate cancer are only marginally effective. Therefore, new therapeutic agents are urgently needed to improve patient outcome. Isoalantolactone (IATL), an active sesquiterpene naturally present in many vegetables and medicinal plants, is known to induce cell death and apoptosis in various cancer cell lines. Nevertheless, antitumor mechanisms initiated by IATL in cancer cells have not been fully defined.MethodsCell apoptosis and cellular ROS levels were analyzed by flow cytometry. Western blot and qRT-PCR were used to analyze the protein and mRNA levels of indicated molecules, respectively. Nude mice xenograft model was used to test the effects of IATL on prostate cancer cell growth in vivo.ResultsIn this study, we found that IATL dose-dependently inhibited cancer cell growth and induced apoptosis in PC-3 and DU145 cells. Mechanistically, our data found that IATL induced reactive oxygen species (ROS) production, resulting in the activation of endoplasmic reticulum stress pathway and eventually cell apoptosis in prostate cancer cells. IATL also decreased the protein expression levels of p-STAT3 and STAT3, and the effects of IATL were reversed by pretreatment with N-acetyl-L-cysteine (NAC). In vivo, we found that IATL inhibited the growth of prostate cancer xenografts without exhibiting toxicity. Treatment of mice bearing human prostate cancer xenografts with IATL was also associated with induction of ER stress and inhibtion of STAT3.ConclusionIn summary, our results unveil a previously unrecognized mechanism underlying the biological activity of IATL, and provide a novel anti-cancer candidate for the treatment of prostate cancer.

Mechanisms of Lysophosphatidic Acid-Mediated Lymphangiogenesis in Prostate Cancer.

Prostate cancer (PCa) is the most common noncutaneous cancer in men worldwide. One of its major treatments is androgen deprivation therapy, but PCa frequently relapses as aggressive castration resistant local tumors and distal metastases. Hence, the development of novel agents or treatment modalities for advanced PCa is crucial. Many tumors, including PCa, first metastasize to regional lymph nodes via lymphatic vessels. Recent findings demonstrate that the bioactive lipid lysophosphatidic acid (LPA) promotes PCa progression by regulating vascular endothelial growth factor-C (VEGF-C), a critical mediator of tumor lymphangiogenesis and lymphatic metastasis. Many of the underlying molecular mechanisms of the LPA–VEGF-C axis have been described, revealing potential biomarkers and therapeutic targets that may aid in the diagnosis and treatment of advanced PCa. Herein, we review the literature that illustrates a functional role for LPA signaling in PCa progression. These discoveries may be especially applicable to anti-lymphangiogenic strategies for the prevention and therapy of metastatic PCa.

Abstract B071: Circulating tumor cells as liquid biopsies of skeletal metastases from prostate cancer

Abstract Background: Circulating tumor cells (CTC) are promising biomarkers in advanced prostate cancer. Since they are seeded from metastases, they may also serve as liquid biopsies for skeletal metastases that are difficult to sample. The aim of the present study was to evaluate to which extent CTCs reflect the phenotype of skeletal metastases, and thereby their potential to serve as a clinical tool in individualizing treatment of metastatic prostate cancer. Materials and Method: CTC and tissue from skeletal metastases were sampled from 22 patients (8 GnRH-naïve and 14 castration-resistant) during surgery for spinal cord compression symptoms. CTCs were sampled prior to removal of metastatic tissue, and isolated with AdnaTest ProstateCancerSelect/Detect (Qiagen). Resulting cDNA was preamplified in a multiplex reaction and analyzed for expression of 37 genes related to prostate cancer progression and metastasis with qPCR. RNA was extracted from the metastatic tissue with RNeasy Plus Universal Mini kit (Qiagen), and gene expression was assessed in the same way as for CTCs. EPCAM expression level was used as internal control to enable normalization to epithelial content (CTCs or tumor tissue) of the samples. Correlation of detected signals between matched CTC and tissue was calculated with Pearson correlations. Results: 12 of the 37 genes displayed expression patterns that were correlating in paired CTC and metastatic samples. Using this subset of genes, the metastases could be grouped similarly to when all 37 genes were included in hierarchical clustering analyses. Using a smaller subset of genes and patients, defined by gene detection frequency in CTC samples, hierarchical clustering of gene expression in CTCs could group the patients similar to when expression data from the metastases were used. In addition, a subset of genes discriminating GnRH-naïve from castration-resistant metastases could be analyzed in CTCs, where it, to a large extent, could identify the same groups of patients. Conclusion: This study shows that gene expression patterns in CTCs can reflect those of metastases. However, careful selection of the genes to include is important. In addition, insufficient detection sensitivity in CTC analyses limits the range of the genes to be analyzed with current methodology. Taken together, the results imply that CTC phenotyping is a promising tool for individualized therapy in metastatic prostate cancer. Citation Format: Andreas Josefsson, Karin Larsson, Daniel Åhs, Helena Brisby, Jan-Erik Damber, Karin Welén. Circulating tumor cells as liquid biopsies of skeletal metastases from prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B071.

Prostate specific membrane antigen: the role in salvage lymph node dissection and radio-ligand therapy.

Prostate-specific membrane antigen (PSMA) is a receptor highly expressed on the membranes of prostate cancer (PCa) cells and provides a new opportunity for imaging and targeted therapy in metastatic prostate cancer. The use of radio-labelled peptides with high affinity for PSMA-receptor allows for localization of oligo-metastasis to guide salvage lymph node (LN) dissection, and effective delivery of radionuclide therapy to PCa cells. This review discusses the current statistics of PSMA-guided salvage lymph-node dissection. A non-systematic literature search of the Medline, Embase, and Scopus databases was performed in December 2017 using medical subject headings and free-text protocol. The properties of PSMA has enabled the timely detection of oligometastatic disease, potentially altering oncological outcomes of men with PCa. The utility of PSMA in directing sLND has been proven to have an impact in achieving modest biochemical response which is generally not durable. Larger randomized controlled trials are needed to validate the current findings, determine treatment protocols, and weigh up its benefits and determine its standing amongst the current management strategies for PCa.

Abstract 3016: Ezh2 is a dose-dependent mediator of prostate cancer aggressiveness and lineage transformation

Abstract Resistance to therapies for metastatic prostate cancer (PCa) causes patients to rapidly succumb to their disease, especially when resistance is associated with development of aggressive variant PCa. These PCa variants are found in 20-30% of patient autopsies relapsing from androgen deprivation therapy (ADT) and often lack androgen receptor (AR), aberrantly express alternative lineage markers, and have altered histology and clinical course. Of these PCa variants, neuroendocrine prostate cancer (NEPC) has been the most well-studied. Our recently published data show that Rb1 loss promotes NEPC transformation in the mouse and induces pervasive changes in gene expression characteristic of human NEPC. These changes include increased expression of histone methyltransferase Ezh2, a known PCa oncogene. In addition, treatment with Ezh2 inhibitors restores AR expression and ADT sensitivity in Rb1-deficient PCa. We hypothesize that Ezh2 is a driver of NEPC transformation in Rb1-deficient PCa. To test this hypothesis, we generated a new genetically engineered mouse model (GEMM) of Rb1-deficient PCa that also lacks Ezh2. Preliminary data suggest that overall survival of PBCre4:Ptenf/f:Rb1f/f:Ezh2f/+ (DKOE/+) mice with loss of one Ezh2 allele is increased compared to PBCre4:Ptenf/f:Rb1f/f (DKO). In prostate tumors from DKOE/+ mice, individual glands are apparent, characteristic of adenocarcinoma. Immunohistochemistry shows that expression of luminal markers, including AR, CK8, and CK18, are increased in DKOE/+ compared to DKO. NEPC markers synaptophysin and chromagranin A are decreased in DKOE/+ compared to DKO, suggesting that loss of one Ezh2 allele slows neuroendocrine transformation. To our surprise, overall survival of PBCre4:Ptenf/f:Rb1f/f:Ezh2f/f (DKOE/E) was decreased compared to DKO. Histological analysis of end-stage primary tumors from DKOE/E mice indicate they develop high grade lesions containing sheets of cells with minimal gland formation. These mice develop hemorrhagic ascites and metastases to the liver, lung, kidney, bone, thymus, and lymph node. AR expression in DKOE/E is decreased compared to both DKO and DKOE/+. When organoids were established from DKO, DKOE/+, and DKOE/E end-stage tumors, preliminary analysis suggest that DKOE/E have greater organoid renewal capability. Altogether, initial data from our new GEMMs show that loss of one allele of Ezh2 in DKOE/+ inhibits development of lethal NEPC transformation in Rb1-deficient PCa. Whereas, complete loss of Ezh2 in the context of Rb1-deficiency makes disease more aggressive. These data suggest that Ezh2's effect on PCa progression in the absence of Rb1 is dose-dependent. Future work is required to investigate of the exact mechanism of Ezh2's contribution to PCa aggressiveness and NEPC transformation. Citation Format: Kristine M. Wadosky, Yanqing Wang, Leigh Ellis, David W. Goodrich. Ezh2 is a dose-dependent mediator of prostate cancer aggressiveness and lineage transformation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3016.

Abstract 3671: Phenotypic heterogeneity within prostate cancer bone metastases measured by 18F-DCFBC PET/CT and 18F-NaF PET/CT

Abstract Purpose: The purpose of this study was to compare the spatial colocalization of prostate-specific membrane antigen (PSMA) targeting agent 18F-DCFBC PET/CT, a marker which demonstrates correlation with tumor aggressiveness, and 18F-NaF PET/CT, a marker of osteoblastic activity, within bone lesions of patients with metastatic prostate cancer. Methods: Twenty-eight metastatic prostate cancer patients received 18F-DCFBC PET/CT and 18F-NaF PET/CT scans (median interval 7 days, range 1-57). Tracer-specific regions of interest (ROI) were derived from threshold containing 80% of maximum SUV (SUV80%). Lesion detection and uptake was compared across the two PET/CT agents using non-parametric testing (Spearman correlation, Wilcoxon rank sum) accounting for intra-patient correlation. Lesion-specific registration was completed by global alignment of skeletal segments followed by local neighborhood optimization of area surrounding lesion. Spatial concordance was evaluated using overlap volume (OV), calculated as the volume of ROI intersection (shared volume) relative to the minimum volume of NaF-ROI or PSMA-ROI to account for differences in ROI volumes. Differences in uptake and CT Hounsfield units (HU) were compared within concordant (overlapping) and discordant (NaF-only, PSMA-only) regions of the same lesion using Wilcoxon signed rank test accounting for intra-patient correlation. Results: Twenty-six patients had positive NaF or DCFBC PET/CT scans, with a total of 241 metastatic sites identified. Lesion-level NaF SUV80% and DCFBC-2hr SUV80% were not significantly correlated at baseline (ρ=0.41, p&amp;gt;0.1). Lesion-level NaF-SUV80% was lower in bone lesions detected only by NaF (N=96) compared to NaF-SUV80% in bone lesions detected by both tracers (N=82), nearing significance (p=0.065). This pattern was not observed in DCFBC-SUV80% (p=0.5). To avoid bias from motion artifacts, only lesions in pelvis and spine were considered for voxel-based analysis (N=42). NaF and PSMA ROIs showing varying levels of spatial concordance (OV mean=0.26, range=0-1), which was modestly associated with higher sclerosis (ρ=0.4, p=0.01) and weakly associated with lower PSMA activity (ρ=0.3, p=0.07). Intra-lesion PSMA-only regions were significantly less sclerotic compared to concordant (p=0.04) and NaF-only (p=0.03) regions, indicating regions of active tumor seeding extend beyond regions of active bone remodeling within the tumor. Conclusions: Metastatic seeding and growth of prostate cancer in bone is biologically complex and dependent on bone microenvironment. We find regions of aggressive cellular activity (PSMA-targeting PET/CT) show heterogeneous colocalization with regions of rapid bone remodeling (NaF PET/CT) within sites of metastatic bone disease. These preliminary findings are important for consideration of targeted radionuclide therapies in metastatic prostate cancer. Citation Format: Stephanie A. Harmon, Esther Mena, Joanna Shih, Ethan Bergvall, Stephen Adler, Sherif Mehralivand, Ravi A. Madan, James L. Gulley, William L. Dahut, Baris Turkbey, Peter L. Choyke, M Liza Lindenberg. Phenotypic heterogeneity within prostate cancer bone metastases measured by 18F-DCFBC PET/CT and 18F-NaF PET/CT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3671.