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

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.

• Authors: 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
• Journal: The Prostate (Prostate) Vol. 79 Issue 13 Pg. 1572-1579 (09 2019) ISSN: 1097-0045 [Electronic] United States
• PMID: 31389628 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2019 Wiley Periodicals, Inc.

Topics

• Aged
• Cohort Studies
• Humans
• Lung Neoplasms (genetics, secondary)
• Male
• Middle Aged
• Mutation
• Prostatic Neoplasms (genetics, pathology)
• Prostatic Neoplasms, Castration-Resistant (genetics, pathology)
• Retrospective Studies