PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) is used widely for prostate cancer (PCa) evaluation. Approximately 35% of aggressive tumors, however, are not visible on mpMRI. We sought to identify the molecular alterations associated with mpMRI-invisible tumors and determine whether mpMRI visibility is associated with PCa prognosis.

METHODS: Discovery and validation cohorts included patients who underwent mpMRI before radical prostatectomy and were found to harbor both mpMRI-visible (Prostate Imaging and Reporting Data System 3 to 5) and -invisible (Prostate Imaging and Reporting Data System 1 or 2) foci on surgical pathology. Next-generation sequencing was performed to determine differential gene expression between mpMRI-visible and -invisible foci. A genetic signature for tumor mpMRI visibility was derived in the discovery cohort and assessed in an independent validation cohort. Its association with long-term oncologic outcomes was evaluated in a separate testing cohort.

RESULTS: The discovery cohort included 10 patients with 26 distinct PCa foci on surgical pathology, of which 12 (46%) were visible and 14 (54%) were invisible on preoperative mpMRI. Next-generation sequencing detected prioritized genetic mutations in 14 (54%) tumor foci (n = 8 mpMRI visible, n = 6 mpMRI invisible). A nine-gene signature (composed largely of cell organization/structure genes) associated with mpMRI visibility was derived (area under the curve = 0.89), and the signature predicted MRI visibility with 75% sensitivity and 100% specificity (area under the curve = 0.88) in the validation cohort. In the testing cohort (n = 375, median follow-up 8 years) there was no significant difference in biochemical recurrence, distant metastasis, or cancer-specific mortality in patients with predicted mpMRI-visible versus -invisible tumors (all P > .05).

CONCLUSION: Compared with mpMRI-invisible disease, mpMRI-visible tumors are associated with underexpression of cellular organization genes. mpMRI visibility does not seem to be predictive of long-term cancer outcomes, highlighting the need for biopsy strategies that detect mpMRI-invisible tumors.

Authors: Simpa S. Salami, MD, MPH1,2; Jeremy B. Kaplan1; Srinivas Nallandhighal, MS1; Mandeep Takhar, MS3; Jeffrey J. Tosoian, MD, MPH1; Matthew Lee, MD1; Junhee Yoon, MS4; Daniel H. Hovelson, PhD1; Komal R. Plouffe, MS1; Samuel D. Kaffenberger, MD1,2; Edward M. Schaeffer, MD, PhD5; R. Jeffrey Karnes, MD6; Tamara L. Lotan, MD7; Todd M. Morgan, MD1,2; Arvin K. George, MD1,2; Jeffrey S. Montgomery, MD, MHSA1,2; Matthew S. Davenport, MD1; Sungyong You, PhD4; Scott A. Tomlins, MD, PhD1,2; Nicole E. Curci, MD1; Hyung L. Kim, MD4; Daniel E. Spratt, MD2,1; Aaron M. Udager, MD, PhD1,2; and Ganesh S. Palapattu, MD1,2,8
J.B.K., S.N., and M.T. contributed equally to this work; D.E.S., A.M.U., and G.S.P. share co-senior authorship.

Author Affiliation: 
1. Michigan Medicine, Ann Arbor, MI
2. University of Michigan Rogel Cancer Center, Ann Arbor, MI
3. GenomeDx Biosciences, San Diego, CA
4. Cedars-Sinai Medical Center, Los Angeles, CA
5. Northwestern University Feinberg School of Medicine, Chicago, IL
6. Mayo Clinic, Rochester, MN
7. Johns Hopkins Medical Institute, Baltimore, MD
8. Medical University of Vienna, Vienna, Austria

Salami, S., Kaplan, J., Nallandhighal, S., Takhar, M., Tosoian, J., & Lee, M. et al. (2019). Biologic Significance of Magnetic Resonance Imaging Invisibility in Localized Prostate Cancer. JCO Precision Oncology, (3), 1-12. doi: 10.1200/po.19.00054