Abstract Background: Fluorine-18 fluorocholine (FC) positron emission tomography/ computed tomography (PET/CT) is a promising molecular imaging technique for whole-body detection of prostate cancer that is under investigational status in the United States. This study explores the potential prognostic value of globally measuring metabolic tumor burden using FC PET/CT in castrate-resistant prostate cancer (CRPC). Methods: Following written informed consent, 30 patients with CRPC were enrolled into clinicaltrials.gov registered trials of FC PET/CT (NCT00928252 and NCT00928174). Whole-body FC PET/CT scans were obtained before and during treatment. The average time interval to follow-up FC PET/CT was 67 days, with intervening treatments consisting of chemotherapy in 11 patients and second-line androgen manipulation in 19 patients. Kaplan Meier analysis was applied to evaluate interval changes in prostate specific antigen (PSA) level, net metabolically active tumor volume (net MATV, calculated using automated image segmentation), and maximum standardized uptake value of the most active tumor found on each scan (matSUVmax) as survival factors. Declines of > 30% were prospectively evaluated as definitions of treatment response for these measures. Results: Baseline net MATV (range 0.12 cc to 1543.9 cc, median 52.6 cc) correlated significantly with baseline PSA level (r = 0.65, p = 0.0001) and matSUVmax (r = 0.42, p = 0.02). Baseline PSA level did not correlate with baseline matSUVmax (r = 0.11, p = 0.55). Change in net MATV (range +1294.93 to -1233.86 cc, median -2.59 cc), reflecting changes in whole body tumor volume ranging from 181% increase to 100% decrease, correlated significantly with change in matSUVmax (r = 0.41, p = 0.02) but not change in PSA (r = 0.17 , r = 0.36). Median duration of follow-up in surviving patients was 23 months (range 6 - 38 months). Longer overall survival was associated with treatment response based on net MATV (log-rank p = 0.04), but not PSA (log-rank p = 0.16) or SUV (log-rank p = 0.19). Conclusion: Whole-body quantification of the change in metabolically-active tumor volume using FC PET/CT may have therapeutic predictive value in CRPC. Translational Significance: Survival rates in CRPC may vary as a function of metastatic disease burden. FC PET/CT can globally depict the distribution of metastatic disease in CRPC and enables whole-body volumetric measurements of metastatic tumor activity. This preliminary study suggests that changes in overall tumor burden as depicted by this non-FDA approved PET tracer may have prognostic value in CRPC. Citation Format: Sandi Kwee, John Lim, Kathleen Kromer-Baker, Kyle Miyazaki, Miles Sato, Dayna Lucuab-Fegurgur, Marc N. Coel. Treatment-associated changes in whole-body metabolic tumor volume on 18F-fluorocholine PET/CT: potential prognostic value in castrate-resistant prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4708. doi:10.1158/1538-7445.AM2014-4708