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 Lotan, Michael A Carducci, Andrew Mark Pardoll, Mario Eisenberger, Emmanuel Antonarakis

Research output: Contribution to journalArticle

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 - Jan 1 2019

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Prostatic Neoplasms
Androgens
Prostate-Specific Antigen
Lung
Hormones
DNA Repair
Mutation
Survival
Neoplasm Metastasis
Therapeutics
DNA Mismatch Repair
Homologous Recombination
DNA Sequence Analysis
Sample Size
Disease-Free Survival
Medical Records
Survival Rate
Genes
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Genomic and clinical characterization of pulmonary-only metastatic prostate cancer : A unique molecular subtype. / Shenderov, Eugene; Isaacsson Velho, Pedro; Awan, Anas H.; Wang, Hao; Mirkheshti, Nooshin; Lotan, Tamara; Carducci, Michael A; Pardoll, Andrew Mark; Eisenberger, Mario; Antonarakis, Emmanuel.

In: Prostate, Vol. 79, No. 13, 01.01.2019, p. 1572-1579.

Research output: Contribution to journalArticle

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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-na{\"i}ve 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.",
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T2 - A unique molecular subtype

AU - Shenderov, Eugene

AU - Isaacsson Velho, Pedro

AU - Awan, Anas H.

AU - Wang, Hao

AU - Mirkheshti, Nooshin

AU - Lotan, Tamara

AU - Carducci, Michael A

AU - Pardoll, Andrew Mark

AU - Eisenberger, Mario

AU - Antonarakis, Emmanuel

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N2 - 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.

AB - 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.

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