Diffusion-weighted Imaging as a Treatment Response Biomarker for Evaluating Bone Metastases in Prostate Cancer: A Pilot Study

Abstract

Purpose To determine the usefulness of whole-body diffusion-weighted imaging (DWI) to assess the response of bone metastases to treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). Materials and Methods A phase II prospective clinical trial of the poly-(adenosine diphosphate-ribose) polymerase inhibitor olaparib in mCRPC included a prospective magnetic resonance (MR) imaging substudy; the study was approved by the institutional research board, and written informed consent was obtained. Whole-body DWI was performed at baseline and after 12 weeks of olaparib administration by using 1.5-T MR imaging. Areas of abnormal signal intensity on DWI images in keeping with bone metastases were delineated to derive total diffusion volume (tDV); five target lesions were also evaluated. Associations of changes in volume of bone metastases and median apparent diffusion coefficient (ADC) with response to treatment were assessed by using the Mann-Whitney test and logistic regression; correlation with prostate-specific antigen level and circulating tumor cell count were assessed by using Spearman correlation (r). Results Twenty-one patients were included. All six responders to olaparib showed a decrease in tDV, while no decrease was observed in all nonresponders; this difference between responders and nonresponders was significant (P = .001). Increases in median ADC were associated with increased odds of response (odds ratio, 1.08; 95% confidence interval [CI]: 1.00, 1.15; P = .04). A positive association was detected between changes in tDV and best percentage change in prostate-specific antigen level and circulating tumor cell count (r = 0.63 [95% CI: 0.27, 0.83] and r = 0.77 [95% CI: 0.51, 0.90], respectively). When assessing five target lesions, decreases in volume were associated with response (odds ratio for volume increase, 0.89; 95% CI: 0.80, 0.99; P = .037). Conclusion This pilot study showed that decreases in volume and increases in median ADC of bone metastases assessed with whole-body DWI can potentially be used as indicators of response to olaparib in mCRPC. Online supplemental material is available for this article.

MRI biomarkers in osseous tumors

“…The use of ADC for therapeutic assessment of bone metastases has also been investigated because current response evaluation criteria like RECIST are of limited utility for bone metastasis. Consistently, studies have revealed an increase in ADC after therapy . This is thought to reflect greater water diffusivity from tumor cell death.…”

“…This is thought to reflect greater water diffusivity from tumor cell death. Because they are common and of clinical concern, metastases from prostate cancer were used in the majority of the studies . Sclerotic bone lesions may lower the sensitivity of DWI due to their low water content, although one study of sclerotic bone metastases showed no association between computed tomography (CT) radiodensity and mean ADC .…”

“…Another study analyzed the effect of postchemotherapeutic sclerosis of prostate cancer metastases on ADC but found no correlation . Although the definitions of responders are different, studies have shown a greater increase of mean ADC in responders after 12 weeks of treatment compared with nonresponders (+39.2% vs. +16.9% with undetailed chemotherapy, +35.4% vs. +7.5% with olaparib) . One study reported an ADC increase of 25% separated responders and progressors with 75% sensitivity and 66.6% specificity .…”

“…Consistently, studies have revealed an increase in ADC after therapy. [61][62][63][64][65] This is thought to reflect greater water diffusivity from tumor cell death.…”

“…Because they are common and of clinical concern, metastases from prostate cancer were used in the majority of the studies. [61][62][63][64][65] Sclerotic bone lesions may lower the sensitivity of DWI due to their low water content, although one study of sclerotic bone metastases showed no association between computed tomography (CT) radiodensity and mean ADC. 47 Another study analyzed the effect of postchemotherapeutic sclerosis of prostate cancer metastases on ADC but found no correlation.…”