Prediction of PSA Progression in Castration-Resistant Prostate Cancer Based on Treatment-Associated Change in Tumor Burden Quantified by 18F-Fluorocholine PET/CT

Abstract

Measurements of metabolically active tumor volume (MATV) can be applied to (18)F-fluorocholine PET/CT to quantify whole-body tumor burden. This study evaluated the serial application of these measurements as systemic treatment response markers and predictors of disease progression in patients with castration-resistant prostate cancer (CRPC).

Methods: Forty-two patients completed sequential (18)F-fluorocholine PET/CT scans before and 1-3 mo after starting treatment for CRPC. Whole-body tumor segmentation was applied to determine net MATV from each scan. Changes in net MATV were evaluated as predictors of time to prostate-specific antigen (PSA) progression by Kaplan-Meier and proportional hazards regression analysis.

Results: Treatments consisted of chemotherapy in 16 patients, antiandrogens in 19 patients, (223)Ra-dichloride in 5 patients, and sipuleucel-T in 2 patients. A significant MATV response (defined as a ≥30% decrease in net MATV) was observed in 20 patients on the basis of in-treatment PET/CT performed an average of 51 d (median, 49 d) into treatment. Significantly longer times to PSA progression were observed in patients who exhibited an MATV response (418 d vs. 116 d, P = 0.0067). MATV response was associated with a hazard ratio of 0.246 (P = 0.0113) for PSA progression, which remained significant when adjusted for treatment type.

Conclusion: Significant changes in whole-body tumor burden can be measured on (18)F-fluorocholine PET/CT over the course of contemporary treatments for CRPC. In this study, these changes were found to be predictive of PSA progression as a potential surrogate marker of treatment outcome. Because (18)F-fluorocholine PET/CT can also be used for localizing resistant tumors, this modality can potentially complement other measures of response in the precision management of advanced prostate cancer.

Trial registration: ClinicalTrials.gov NCT00928174 NCT00928252.

Keywords: PET/CT; castrate resistant prostate cancer; fluorocholine; treatment response; tumor volume.

© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Figures

Figure 1. Early MATV response discordant with PSA response

18F-fluorocholine PET (left column), PET/CT (middle column), and maximum intensity projection (MIP) (right column) images from a 74 year old patient receiving docetaxel. Color indicates MATV contours on the MIP images. Multiple bone metastases are evident on the pre-treatment PET/CT (arrow, row A; net MATV = 42.7 cm3, PSA = 39.3 ng/mL). Net MATV decreased after the second chemotherapy cycle to 21.6 cm3 (row B), while PSA increased to 41.7 ng/mL. After the 6th chemotherapy cycle, PET/CT (row C) demonstrated resolution of abnormal activity (net MATV = 0.0 cm3) and PSA level decreased to 8.1 ng/mL.

Figure 2. Cancer progression reflected by increasing net MATV

18F-fluorocholine PET (left column), PET/CT (middle column), and maximum intensity projection (MIP) (right column) images from a 65 year old patient receiving sipuleucel-T. Color indicates MATV contours on the MIP images. Pre-treatment PET/CT (row A) shows hyperactive vertebral metastases (arrows; net MATV = 42.9 cm3, PSA = 38.0 ng/mL). PET/CT obtained 36 days after initiating treatment (row B) demonstrates increasing activity and new lesions in the sternum and lumbar spine (arrows; net MATV = 338.4 cm3, PSA = 46.7 ng/mL). The PSA level after 4 months increased to 241.4 ng/mL.

Figure 3. Heterogeneous response on serial 18F-fluorocholine PET/CT

PET (left column), PET/CT (middle column), and maximum intensity projection (MIP) (right column) images from a 64 year old patient receiving sipuleucel-T. Pre-treatment images show abnormal activity in the prostate gland (red contour, top row A). PET/CT obtained 60 days after starting treatment shows significant decline in prostatic activity (arrow, top row B) but new abnormal activity in a left iliac lymph node and the ilium (red and blue contour, bottom row B). Net MATV increased from 32.5 to 34.0 cm3 and PSA increased from 35.0 to 47.9 ng/mL. PSA progression was confirmed 3 months later (PSA = 65.1 ng/mL). Excreted tracer in the right ureter was not confused as a lesion (arrow in bottom row A and yellow contour in bottom row B).

Figure 4. Probability of PSA progression over time based on MATV response

Median time to PSA progression was 418 days in MATV responders and 116 days in MATV non-responders. Both early and late differences in time to PSA progression were statistically significant on Kaplan-Meier analysis (Wilcoxon p = 0.0138 and Log-Rank p = 0.0067, respectively).