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Genomic features of lung-recurrent hormone-sensitive prostate cancer

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Abstract
PURPOSE Pulmonary involvement is rare in metastatic hormone-sensitive prostate cancer (mHSPC) that recurs after treatment for localized disease. Guidelines recommend intensive systemic therapy, similar to patients with liver metastases, but some lung-recurrent mHSPC may have good outcomes. Genomic features of lung metastases may clarify disease aggression, but are poorly understood since lung biopsy is rarely performed. We present a comparative assessment of genomic drivers and heterogeneity in metachronous prostate tumors and lung metastases. METHODS We leveraged a prospective functional imaging study of 208 biochemically recurrent prostate cancers to identify 10 patients with lung-recurrent mHSPC. Histologic diagnosis was attained via thoracic surgery or fine-needle lung biopsy. We retrieved clinical data and performed multiregion sampling of primary tumors and metastases. Targeted and/or whole-exome sequencing was applied to 46 primary and 32 metastatic foci. RESULTS Unusually for mHSPC, all patients remained alive despite a median follow-up of 11.5 years. Several patients experienced long-term freedom from systemic treatment. The genomic landscape of lung-recurrent mHSPC was typical of curable prostate cancer with frequent PTEN, SPOP, and chromosome 8p alterations, and there were no deleterious TP53 and DNA damage repair gene mutations that characterize aggressive prostate cancer. Despite a long median time to recurrence (76.8 months), copy number alterations and clonal mutations were highly conserved between metastatic and primary foci, consistent with intrapatient homogeneity and limited genomic evolution. CONCLUSION In this retrospective hypothesis-generating study, we observed indolent genomic etiology in selected lung-recurrent mHSPC, cautioning against grouping these patients together with liver or bone-predominant mHSPC. Although our data do not generalize to all patients with lung metastases, the results encourage prospective efforts to stratify lung-recurrent mHSPC by genomic features. (C) 2022 by American Society of Clinical Oncology
Keywords
Cancer Research, Oncology, PRECISION MEDICINE, PROGRESSION, SITE

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MLA
Fonseca, Nicolette M., et al. “Genomic Features of Lung-Recurrent Hormone-Sensitive Prostate Cancer.” JCO PRECISION ONCOLOGY, vol. 6, 2022, doi:10.1200/po.21.00543.
APA
Fonseca, N. M., Van der Eecken, K., Herberts, C., Verbeke, S., Ng, S. W. S., Lumen, N., … Ost, P. (2022). Genomic features of lung-recurrent hormone-sensitive prostate cancer. JCO PRECISION ONCOLOGY, 6. https://doi.org/10.1200/po.21.00543
Chicago author-date
Fonseca, Nicolette M., Kim Van der Eecken, Cameron Herberts, Sofie Verbeke, Sarah W.S. Ng, Nicolaas Lumen, Elie Ritch, et al. 2022. “Genomic Features of Lung-Recurrent Hormone-Sensitive Prostate Cancer.” JCO PRECISION ONCOLOGY 6. https://doi.org/10.1200/po.21.00543.
Chicago author-date (all authors)
Fonseca, Nicolette M., Kim Van der Eecken, Cameron Herberts, Sofie Verbeke, Sarah W.S. Ng, Nicolaas Lumen, Elie Ritch, Andrew J. Murtha, Cecily Q. Bernales, Elena Schönlau, Lisa Moris, Jo Van Dorpe, Matti Annala, Alexander W. Wyatt, and Piet Ost. 2022. “Genomic Features of Lung-Recurrent Hormone-Sensitive Prostate Cancer.” JCO PRECISION ONCOLOGY 6. doi:10.1200/po.21.00543.
Vancouver
1.
Fonseca NM, Van der Eecken K, Herberts C, Verbeke S, Ng SWS, Lumen N, et al. Genomic features of lung-recurrent hormone-sensitive prostate cancer. JCO PRECISION ONCOLOGY. 2022;6.
IEEE
[1]
N. M. Fonseca et al., “Genomic features of lung-recurrent hormone-sensitive prostate cancer,” JCO PRECISION ONCOLOGY, vol. 6, 2022.
@article{8752058,
  abstract     = {{PURPOSE Pulmonary involvement is rare in metastatic hormone-sensitive prostate cancer (mHSPC) that recurs after treatment for localized disease. Guidelines recommend intensive systemic therapy, similar to patients with liver metastases, but some lung-recurrent mHSPC may have good outcomes. Genomic features of lung metastases may clarify disease aggression, but are poorly understood since lung biopsy is rarely performed. We present a comparative assessment of genomic drivers and heterogeneity in metachronous prostate tumors and lung metastases.

METHODS We leveraged a prospective functional imaging study of 208 biochemically recurrent prostate cancers to identify 10 patients with lung-recurrent mHSPC. Histologic diagnosis was attained via thoracic surgery or fine-needle lung biopsy. We retrieved clinical data and performed multiregion sampling of primary tumors and metastases. Targeted and/or whole-exome sequencing was applied to 46 primary and 32 metastatic foci.

RESULTS Unusually for mHSPC, all patients remained alive despite a median follow-up of 11.5 years. Several patients experienced long-term freedom from systemic treatment. The genomic landscape of lung-recurrent mHSPC was typical of curable prostate cancer with frequent PTEN, SPOP, and chromosome 8p alterations, and there were no deleterious TP53 and DNA damage repair gene mutations that characterize aggressive prostate cancer. Despite a long median time to recurrence (76.8 months), copy number alterations and clonal mutations were highly conserved between metastatic and primary foci, consistent with intrapatient homogeneity and limited genomic evolution.

CONCLUSION In this retrospective hypothesis-generating study, we observed indolent genomic etiology in selected lung-recurrent mHSPC, cautioning against grouping these patients together with liver or bone-predominant mHSPC. Although our data do not generalize to all patients with lung metastases, the results encourage prospective efforts to stratify lung-recurrent mHSPC by genomic features. (C) 2022 by American Society of Clinical Oncology}},
  articleno    = {{e2100543}},
  author       = {{Fonseca, Nicolette M. and Van der Eecken, Kim and Herberts, Cameron and Verbeke, Sofie and Ng, Sarah W.S. and Lumen, Nicolaas and Ritch, Elie and Murtha, Andrew J. and Bernales, Cecily Q. and Schönlau, Elena and Moris, Lisa and Van Dorpe, Jo and Annala, Matti and Wyatt, Alexander W. and Ost, Piet}},
  issn         = {{2473-4284}},
  journal      = {{JCO PRECISION ONCOLOGY}},
  keywords     = {{Cancer Research,Oncology,PRECISION MEDICINE,PROGRESSION,SITE}},
  language     = {{eng}},
  pages        = {{12}},
  title        = {{Genomic features of lung-recurrent hormone-sensitive prostate cancer}},
  url          = {{http://doi.org/10.1200/po.21.00543}},
  volume       = {{6}},
  year         = {{2022}},
}

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