Among men with metastatic castration-resistant prostate cancer (mCRPC) whose disease is responding to enzalutamide, new unconfirmed bone lesions detected on posttreatment technetium 99m–labeled methylene diphosphonate bone scans likely represents pseudoprogression, a healing response, researchers reported in JAMA Oncology. Men previously treated with docetaxel might be an exception, however.

Andrew J. Armstrong, MD, ScM, of Duke University Medical Center in Durham, North Carolina, and colleagues conducted a post hoc analysis of 1672 enzalutamide-treated (160 mg once daily) men from 2 randomized phase 3 trials of men with mCRPC: PREVAIL in the docetaxel-naïve setting and AFFIRM in the post-docetaxel setting. The investigators observed new unconfirmed bone lesions on the first or second bone scan in 27.5% of pre-docetaxel patients and 18.1% of post-docetaxel patients. Among chemotherapy-naïve patients, median radiographic progression-free survival (37%) and overall survival (25%) were similar between men with and without new bone lesions. For docetaxel-treated patients, however, median overall survival (94%) was worse among men with new unconfirmed bone lesions (although median radiographic progression-free survival was not). Quality of life did not differ among patients.

“These results suggest that new unconfirmed lesions detected on follow-up bone scans may represent pseudoprogression in men with mCRPC and are indicative of a favorable treatment response to enzalutamide,” Dr Armstrong’s team wrote. “The detection of new unconfirmed bone lesions in men with mCRPC that responded to treatment with enzalutamide after docetaxel appears to be associated with worse overall survival and may represent true progression, thus highlighting the need for improved functional bone metastasis imaging.”

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In an accompanying editorial, Umang Swami, MD, of Huntsman Cancer Institute in Salt Lake City, Utah, and coauthors highlighted the need to precisely assess bone metastases to decide on treatment continuation. The editorialists suggested that novel imaging modalities—whole-body magnetic resonance imaging, positron emission tomography using radiopharmaceuticals, and prostate-specific membrane antigen (PSMA) positron-emission tomography—be incorporated into prospective clinical trials to evaluate bone metastasis burden.

The PREVAIL and AFFIRM studies were funded by Pfizer and Astellas Pharma, the codevelopers of enzalutamide.

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Armstrong AJ, Al-Adhami M, Lin P, et al. Association between new unconfirmed bone lesions and outcomes in men with metastatic castration-resistant prostate cancer treated with enzalutamide: Secondary analysis of the PREVAIL and AFFIRM randomized clinical trials [published online December 12, 2019]. JAMA Oncol. doi:10.1001/jamaoncol.2019.4636

Swami U, Yap JT, Agarwal N. Radioisotope imaging and therapy for bone metastasis in men with castration-resistant prostate cancer [published online December 12, 2019]. JAMA Oncol. doi:10.1001/jamaoncol.2019.4635