Dataset Information

Role of Baseline and Post-Therapy 18F-FDG PET in the Prognostic Stratification of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated with Radium-223.

ABSTRACT: : Radium-223 dichloride (Ra223) represents the unique bone-directed treatment option that shows an improvement in overall survival (OS) in metastatic castrate resistant prostate cancer (mCRPC). However, there is an urgent need for the identification of reliable biomarkers to non-invasively determine its efficacy (possibly improving patients' selection or identifying responders' after therapy completion). 18F-Fluorodeoxyglucose (FDG)-avidity is low in naïve prostate cancer, but it is enhanced in advanced and chemotherapy-refractory mCRPC, providing prognostic insights. Moreover, this tool showed high potential for the evaluation of response in cancer patients with bone involvement. For these reasons, FDG Positron Emission Tomography (FDG-PET) might represent an effective tool that is able to provide prognostic stratification (improving patients selection) at baseline and assessing the treatment response to Ra223. We conducted a retrospective analysis of 28 mCRPC patients that were treated with Ra223 and submitted to bone scan and FDG-PET/CT for prognostic purposes at baseline and within two months after therapy completion. The following parameters were measured: number of bone lesions at bone scan, SUVmax of the hottest bone lesion, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). In patients who underwent post-therapy 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT), (20/28), PET Response Criteria in Solid Tumors (PERCIST), and European Organization for Research and Treatment of Cancer (EORTC) criteria were applied to evaluate the metabolic treatment response. The difference between end of therapy and baseline values was also calculated for Metabolic Tumor Volume (MTV), TLG, prostate-specific antigen (PSA), alkaline phosphatase (AP), and lactate dehydrogenase (LDH) (termed deltaMTV, deltaTLG, deltaPSA, deltaAP and deltaLDH, respectively). Predictive power of baseline and post-therapy PET- and biochemical-derived parameters on OS were assessed by Kaplan-Meier, univariate and multivariate analyses. At baseline, PSA, LDH, and MTV significantly predicted OS. However, MTV (but not PSA nor LDH) was able to identify a subgroup of patients with worse prognosis, even after adjusting for the number of lesions at bone scan (which, in turn, was not an independent predictor of OS). After therapy, PERCIST criteria were able to capture the response to Ra223 by demonstrating longer OS in patients with partial metabolic response. Moreover, the biochemical parameters were outperformed by PERCIST in the post-treatment setting, as their variation after therapy was not informative on long term OS. The present study supports the role of FDG-PET as a tool for patient's selection and response assessment in mCRPC patients undergoing Ra223 administration.

SUBMITTER: Bauckneht M

PROVIDER: S-EPMC7016706 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Role of Baseline and Post-Therapy 18F-FDG PET in the Prognostic Stratification of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated with Radium-223.

Bauckneht Matteo M Capitanio Selene S Donegani Maria Isabella MI Zanardi Elisa E Miceli Alberto A Murialdo Roberto R Raffa Stefano S Tomasello Laura L Vitti Martina M Cavo Alessia A Catalano Fabio F Mencoboni Manlio M Ceppi Marcello M Marini Cecilia C Fornarini Giuseppe G Boccardo Francesco F Sambuceti Gianmario G Morbelli Silvia S

Cancers 20191220 1

<b>:</b> Radium-223 dichloride (Ra223) represents the unique bone-directed treatment option that shows an improvement in overall survival (OS) in metastatic castrate resistant prostate cancer (mCRPC). However, there is an urgent need for the identification of reliable biomarkers to non-invasively determine its efficacy (possibly improving patients' selection or identifying responders' after therapy completion). 18F-Fluorodeoxyglucose (FDG)-avidity is low in naïve prostate cancer, but it is enhan ...[more]

PMID: 31861942

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Project description:BackgroundThe treatment of metastatic castration-resistant prostate cancer has changed with the introduction of radium-223, cabazitaxel, abiraterone and enzalutamide. To assess value for money, their cost effectiveness in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel from the Dutch societal perspective was investigated.MethodsA cost-effectiveness analysis was conducted using efficacy, symptomatic skeletal-related event and safety data obtained from indirect treatment comparisons. Missing skeletal-related event data for cabazitaxel were conservatively assumed to be identical to radium-223. A Markov model combined these clinical inputs with Dutch-specific resource use and costs for metastatic castration-resistant prostate cancer treatment from a societal perspective. Total quality-adjusted life-years and costs in 2017 euros were calculated over a 5-year (lifetime) time horizon.ResultsRadium-223 resulted in €6092 and €4465 lower costs and 0.02 and 0.01 higher quality-adjusted life-years compared with abiraterone and cabazitaxel, respectively, demonstrating dominance of radium-223. Sensitivity analyses reveal a 64% (54%) chance of radium-223 being cost effective compared with abiraterone (cabazitaxel) at the informal €80,000 willingness-to-pay threshold. Compared with enzalutamide, radium-223 resulted in slightly lower quality-adjusted life-years (-0.06) and €7390 lower costs, revealing a 61% chance of radium-223 being cost effective compared with enzalutamide. The lower costs of radium-223 compared with abiraterone and enzalutamide are driven by lower drug costs and prevention of expensive skeletal-related events. Compared with cabazitaxel, the lower costs of radium-223 are driven by lower costs of the drug, administration and adverse events.ConclusionRadium-223 may be a less costly treatment strategy offering similar gains in health benefits compared with abiraterone, cabazitaxel and enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel from the Dutch societal perspective.

Project description:BackgroundRadium-223 is a targeted alpha-particle therapy that improves survival in men with metastatic castration resistant prostate cancer (mCRPC), particularly in men with elevated serum levels of bone alkaline phosphatase (B-ALP). We hypothesized that osteomimicry, a form of epithelial plasticity leading to an osteoblastic phenotype, may contribute to intralesional deposition of radium-223 and subsequent irradiation of the tumor microenvironment.MethodsWe conducted a pharmacodynamic study (NCT02204943) of radium-223 in men with bone mCRPC. Prior to and three and six months after radium-223 treatment initiation, we collected CTCs and metastatic biopsies for phenotypic characterization and CTC genomic analysis. The primary objective was to describe the impact of radium-223 on the prevalence of CTC B-ALP over time. We measured radium-223 decay products in tumor and surrounding normal bone during treatment. We validated genomic findings in a separate independent study of men with bone metastatic mCRPC (n = 45) and publicly accessible data of metastatic CRPC tissues.ResultsWe enrolled 20 men with symptomatic bone predominant mCRPC and treated with radium-223. We observed greater radium-223 radioactivity levels in metastatic bone tumor containing biopsies compared with adjacent normal bone. We found evidence of persistent Cellsearch CTCs and B-ALP (+) CTCs in the majority of men over time during radium-223 therapy despite serum B-ALP normalization. We identified genomic gains in osteoblast mimicry genes including gains of ALPL, osteopontin, SPARC, OB-cadherin and loss of RUNX2, and validated genomic alterations or increased expression at the DNA and RNA level in an independent cohort of 45 men with bone-metastatic CRPC and in 150 metastatic biopsies from men with mCRPC.ConclusionsOsteomimicry may contribute in part to the uptake of radium-223 within bone metastases and may thereby enhance the therapeutic benefit of this bone targeting radiotherapy.

Project description:The aim of this prospective investigation was to assess the association of parameters derived from baseline (18)F-FDG PET/CT with overall survival (OS) in men with castrate-resistant metastatic prostate cancer.Eighty-seven men with castrate-resistant metastatic prostate cancer underwent (18)F-FDG PET/CT and were followed prospectively for OS. Median follow-up in patients who were alive was 22.2 mo (range, 1.6-62.5 mo). OS was defined as the time between the PET/CT imaging or the start of chemotherapy, whichever was later, and death, with patients who were alive censored at the last follow-up date. PET parameters included maximum standardized uptake value (SUV(max)) of the most active lesion, sum of SUV(max), and average SUV(max) of all metabolically active lesions, after subtraction of patient-specific background-liver average SUV. Comparison of OS was based on univariate and multivariable Cox regression analyses of continuous PET parameters adjusted for standard clinical parameters (age, serum prostate-specific antigen level, alkaline phosphatase, use of pain medication, prior chemotherapy, and Gleason score at initial diagnosis). Survival curves based on Kaplan-Meier estimates are presented.Among the 87 patients, 61 were dead at the time of last follow-up. Median OS was 16.5 mo (95% confidence interval [CI], 12.1-23.4 mo), and the OS probability at 24 mo was 39% ± 6%. For the univariate analysis, the hazard ratios associated with each unit increase were 1.01 (95% CI, 1.006-1.02) for sum of SUV(max) (P = 0.002), 1.11 (95% CI, 1.03-1.18) for maximum SUV(max) (P = 0.010), and 1.13 (95% CI, 0.99-1.30) for average SUV(max) (P = 0.095). For the multivariable analysis adjusting for relevant clinical parameters, the continuous parameter sum of SUV(max) remained significant (P = 0.053), with a hazard ratio of 1.01 (95% CI, 1.001-1.02). When sum of SUV(max) was grouped into quartile ranges, there was poorer survival probability for the patients in the fourth-quartile range than for those in the first-quartile range, with a univariate hazard ratio of 3.8 (95% CI, 1.8-7.9).Sum of SUV(max) derived from (18)F-FDG PET/CT contributes independent prognostic information on OS in men with castrate-resistant metastatic prostate cancer, and this information may be useful in assessing the comparative effectiveness of various conventional and emerging treatment strategies.

Dataset Information

Role of Baseline and Post-Therapy 18F-FDG PET in the Prognostic Stratification of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated with Radium-223.

Publications

Role of Baseline and Post-Therapy 18F-FDG PET in the Prognostic Stratification of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated with Radium-223.

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