Genomic and clinical characterization of pulmonary-only metastatic prostate cancer: A unique molecular subtype

Eugene Shenderov, Pedro Isaacsson Velho, Anas H. Awan, Hao Wang, Nooshin Mirkheshti, Tamara L. Lotan, Michael A. Carducci, Drew M. Pardoll, Mario A. Eisenberger, Emmanuel S. Antonarakis

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Isolated pulmonary involvement is uncommon in metastatic hormone-sensitive prostate cancer (mHSPC). To characterize outcomes and molecular alterations of this unique patient subset, we conducted a retrospective review of patients with hormone-naïve prostate cancer presenting with lung-only metastases. Methods: This was a retrospective single-institution study. Medical records of 25 patients presenting with pulmonary-only metastases before receiving androgen deprivation therapy (ADT) were analyzed. Germline and/or somatic genomic results, where available (n = 16), were documented. Tumor tissue was analyzed using clinical-grade next-generation DNA sequencing assays. Clinical endpoints included complete prostate-specific antigen (PSA) response to ADT (<0.1 ng/mL), median overall survival (OS) from time of ADT initiation, median PSA progression-free survival (PSA-PFS), and failure-free survival (FFS) at 4 years. Results: Baseline characteristics were notable for 48% of men (12 of 25) having first or second-degree relatives with prostate cancer, compared with 20% expected. Complete PSA responses to ADT were noted in 52% of men, with a median PSA-PFS of 66 months, a 4-year FFS rate of 72%, and a median OS that was not reached after 190 months. In evaluable patients, molecular drivers were enriched for mismatch repair mutations (4 of 16, 25%) and homologous-recombination deficiency mutations (4 of 16, 25%). These results are limited by the small sample size and retrospective nature of this analysis. Conclusions: This exploratory study represents one of the largest cohorts of lung-only mHSPC patients to-date. The prevalence of actionable DNA-repair gene alterations was higher than anticipated (any DNA-repair mutation: 8 of 16, 50%). Compared to historical data, these patients appear to have exceptional and durable responses to first-line ADT. This study suggests that pulmonary-tropic mHSPC biology may be fundamentally different from nonpulmonary mHSPC.

Original languageEnglish (US)
Pages (from-to)1572-1579
Number of pages8
JournalProstate
Volume79
Issue number13
DOIs
StatePublished - 2019
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by the Bloomberg‐Kimmel Institute for Cancer Immunotherapy and the NCI NIH SKCCC core grant P30CA006973. ES is partially supported by an ASCO Conquer Cancer Foundation Young Investigator Award. ESA is partially supported by National Institutes of Health grants R01CA185297 and P30CA006973, and Department of Defense Prostate Cancer Research Program grants W81XWH‐15‐2‐0050.

Funding Information:
This research was supported by the Bloomberg-Kimmel Institute for Cancer Immunotherapy and the NCI NIH SKCCC core grant P30CA006973. ES is partially supported by an ASCO Conquer Cancer Foundation Young Investigator Award. ESA is partially supported by National Institutes of Health grants R01CA185297 and P30CA006973, and Department of Defense Prostate Cancer Research Program grants W81XWH-15-2-0050.

Publisher Copyright:
© 2019 Wiley Periodicals, Inc.

Keywords

  • DNA repair
  • homologous recombination
  • mismatch repair
  • prostate cancer
  • pulmonary metastases

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