Evaluating the influence of prostate-specific antigen kinetics on metastasis in men with PSA recurrence after partial gland therapy Martin T. King 1,2, * , Paul L. Nguyen 1,2 , Ninjin Boldbaatar 1 , David D. Yang 1,2 , Vinayak Muralidhar 1,2 , Clare M. Tempany 2,3 , Robert A. Cormack 1,2 , Mark D. Hurwitz 4 , W. Warren Suh 5,6 , Mark M. Pomerantz 7 , Anthony V. D’Amico 1,2 , Peter F. Orio III 1,2 1 Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, MA 2 Harvard Medical School, Boston, MA 3 Department of Radiology, Brigham and Women’s Hospital, Boston, MA 4 Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA 5 Ridley-Tree Cancer Center, Santa Barbara, CA 6 Department of Radiation Oncology, University of California at Los Angeles, Los Angeles, CA 7 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA ABSTRACT PURPOSE: Although current Delphi Consensus guidelines do not recommend a specific definition of biochemical recurrence after partial gland therapy, these guidelines acknowledge that serial prostate-specific antigen (PSA) tests remain the best marker for monitoring disease after treatment. The purpose of this study was to determine whether PSA velocity at failure per the Phoenix (nadir þ 2 ng/mL) definition is associated with metastasis and prostate cancer-specific mortality (PCSM) in a cohort of patients who experienced PSA failure after partial gland therapy. METHODS: Between 1997 and 2007, 285 patients with favorable risk prostate cancer underwent partial prostate brachytherapy to the peripheral zone. PSA velocity was calculated for 94 patients who experienced PSA failure per the Phoenix (nadir þ 2) definition. Fine and Gray competing risks regression was performed to determine whether PSA velocity and other clinical factors were asso- ciated with metastasis and PCSM. RESULTS: The median time to PSA failure was 4.2 years (interquartile range: 2.2, 7.9), and the median followup time after PSA failure was 6.5 years (3.5e9.7). Seventeen patients developed me- tastases, and five experienced PCSM. On multivariate analysis, PSA velocity $3.0 ng/mL/year (adjusted hazard ratio 5.97; [2.57, 13.90]; p ! 0.001) and PSA nadir (adjusted hazard ratio 0.39; [0.24, 0.64]; p ! 0.001) were significantly associated with metastasis. PSA velocity $3.0 ng/mL/year was also associated with PCSM (HR 15.3; [1.8, 128.0]; p 5 0.012) on univariate analysis. CONCLUSIONS: Rapid PSA velocity at PSA failure after partial gland treatment may be prognostic for long-term outcomes. Ó 2018 American Brachytherapy Society. Published by Elsev- ier Inc. All rights reserved. Keywords: Focal therapy; Brachytherapy; PSA kinetics; Metastasis Received 25 October 2018; received in revised form 9 December 2018; accepted 12 December 2018. Financial disclosures: P.F.O. reports personal fees from Augmenix, outside the submitted work. P.L.N. reports personal fees from Medivation, personal fees from GenomeDx, personal fees from Ferring, personal fees from Nanobiotix, personal fees from Dendreon, grants from Astellas, grants from Janssen, personal fees and other from Augmenix, and personal fees from Blue Earth, outside the submitted work. C.M.T. reports grants from AdMeTech/Massachu- setts Department of Health, personal fees from Insightec, personal fees from Profound, outside the submitted work. Funding sources: This work was supported in part by Grants NIH P41-EB 015898 and BRP-CA111288 and the Prostate Cancer Foundation Young Inves- tigator Award. * Corresponding author. Martin King, Brigham and Women’s Hospital, ASB1-L2, 75 Francis Street, Boston, MA 02115. Tel.: 617-732-7936; fax: 617- 975-0912. E-mail address: martin_king@dfci.harvard.edu (M.T. King). 1538-4721/$ - see front matter Ó 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.brachy.2018.12.001 Brachytherapy - (2019) -