Sequential prostate magnetic resonance imaging in newly diagnosed high-risk prostate cancer treated with neoadjuvant enzalutamide is predictive of therapeutic response

Fatima Karzai, Stephanie M. Walker, Scott Wilkinson, Ravi A. Madan, Joanna H. Shih, Maria J. Merino, Stephanie A. Harmon, David J. VanderWeele, Lisa M. Cordes, Nicole V. Carrabba, John R. Bright, Nicolas T. Terrigino, Guinevere Chun, Marijo Bilusic, Anna Couvillon, Amy Hankin, Monique N. Williams, Rosina T. Lis, Huihui Ye, Peter L. ChoykeJames L. Gulley, Adam G. Sowalsky, Baris Turkbey, Peter A. Pinto, William L. Dahut*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Purpose: For high-risk prostate cancer, standard treatment options include radical prostatectomy (RP) or radiotherapy plus androgen deprivation therapy (ADT). Despite definitive therapy, many patients will have disease recurrence. Imaging has the potential to better define characteristics of response and resistance. In this study, we evaluated prostate multiparametric MRI (mpMRI) before and after neoadjuvant enzalutamide plus ADT. Patients and Methods: Men with localized intermediate- or high-risk prostate cancer underwent a baseline mpMRI and mpMRI-targeted biopsy followed by a second mpMRI after 6 months of enzalutamide and ADT prior to RP. Specimens were sectioned in the same plane as mpMRI using patient-specific 3D-printed molds to permit mpMRI-targeted biopsies to be compared with the same lesion from the RP. Specimens were analyzed for imaging and histologic correlates of response. Results: Of 39 patients enrolled, 36 completed imaging and RP. Most patients (92%) had high-risk disease. Fifty-eight lesions were detected on baseline mpMRI, of which 40 (69%) remained measurable at 6-month follow-up imaging. Fifty-five of 59 lesions (93%) demonstrated >50% volume reduction on posttreatment mpMRI. Three of 59 lesions (5%) demonstrated growth in size at follow-up imaging, with two lesions increasing more than 3-fold in volume. On whole-mount pathology, 15 patients demonstrated minimal residual disease (MRD) of <0.05 cc or pathologic complete response. Low initial mpMRI relative tumor burden was most predictive of MRD on final pathology. Conclusions: Low relative lesion volume at baseline mpMRI was predictive of pathologic response. A subset of patients had limited response. Selection of patients based on these metrics may improve outcomes in high-risk disease.

Original languageEnglish (US)
Pages (from-to)429-437
Number of pages9
JournalClinical Cancer Research
Volume27
Issue number2
DOIs
StatePublished - Jan 15 2021

Funding

The authors thank all the patients who participated in this study and their families. Enzalutamide, goserelin, leuprolide acetate, and degarelix were provided through the Center for Cancer Research, NIH. This project was supported by the Prostate Cancer Foundation (Young Investigator Awards to F. Karzai, S. Wilkinson, R.A. Madan, S.A. Harmon, D.J. VanderWeele, H. Ye, and A.G. Sowalsky), the Department of Defense Prostate Cancer Research Program (W81XWH-19-1-0712 to S. Wilkinson and W81XWH-16-1-0433 to A.G. Sowalsky), the NCI (HHSN261200800001E), and the Intramural Research Program of the NCI, NIH. The authors also thank Bonnie L. Casey for editorial assistance in the preparation of this article.

ASJC Scopus subject areas

  • General Medicine

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