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Computer simulations suggest that prostate enlargement due to benign prostatic hyperplasia mechanically impedes prostate cancer growth

Guillermo Lorenzo, Thomas J. R. Hughes, Pablo Dominguez-Frojan, Alessandro Reali, and Hector Gomez
PNAS January 22, 2019 116 (4) 1152-1161; published ahead of print January 22, 2019 https://doi.org/10.1073/pnas.1815735116
Guillermo Lorenzo
aDepartamento de Matemáticas, Universidade da Coruña, 15071 A Coruña, Spain;bDepartment of Civil Engineering and Architecture, University of Pavia, 27100 Pavia, Italy;
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  • For correspondence: hughes@ices.utexas.eduguillermo.lorenzo@unipv.it
Thomas J. R. Hughes
cInstitute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX 78712-1229;
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  • For correspondence: hughes@ices.utexas.eduguillermo.lorenzo@unipv.it
Pablo Dominguez-Frojan
dSchool of Mechanical Engineering, Purdue University, West Lafayette, IN 47907
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Alessandro Reali
bDepartment of Civil Engineering and Architecture, University of Pavia, 27100 Pavia, Italy;
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Hector Gomez
dSchool of Mechanical Engineering, Purdue University, West Lafayette, IN 47907
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  1. Contributed by Thomas J. R. Hughes, October 30, 2018 (sent for review September 13, 2018; reviewed by Krishna Garikipati and Ellen Kuhl)

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Significance

Benign prostatic hyperplasia (BPH) is a common disease in aging men that causes the prostate to enlarge progressively. Men with larger prostates tend to harbor prostatic tumors with more favorable features. The underlying mechanisms that explain this interaction between BPH and prostate cancer (PCa) are largely unknown. Here, we propose that BPH may mechanically impede PCa growth by producing increasingly intense mechanical stresses in the prostate over time, which are known to slow down tumor dynamics. To explore this hypothesis, we ran a qualitative simulation study using an extension of our mathematical model of PCa growth including the mechanical deformation of the prostate under BPH and PCa. The proposed mechanism suggests relevant shifts in clinical management of PCa and BPH.

Abstract

Prostate cancer and benign prostatic hyperplasia are common genitourinary diseases in aging men. Both pathologies may coexist and share numerous similarities, which have suggested several connections or some interplay between them. However, solid evidence confirming their existence is lacking. Recent studies on extensive series of prostatectomy specimens have shown that tumors originating in larger prostates present favorable pathological features. Hence, large prostates may exert a protective effect against prostate cancer. In this work, we propose a mechanical explanation for this phenomenon. The mechanical stress fields that originate as tumors enlarge have been shown to slow down their dynamics. Benign prostatic hyperplasia contributes to these mechanical stress fields, hence further restraining prostate cancer growth. We derived a tissue-scale, patient-specific mechanically coupled mathematical model to qualitatively investigate the mechanical interaction of prostate cancer and benign prostatic hyperplasia. This model was calibrated by studying the deformation caused by each disease independently. Our simulations show that a history of benign prostatic hyperplasia creates mechanical stress fields in the prostate that impede prostatic tumor growth and limit its invasiveness. The technology presented herein may assist physicians in the clinical management of benign prostate hyperplasia and prostate cancer by predicting pathological outcomes on a tissue-scale, patient-specific basis.

  • prostate cancer
  • benign prostatic hyperplasia
  • mathematical oncology
  • patient-specific
  • isogeometric analysis

Footnotes

  • ↵1To whom correspondence may be addressed. Email: hughes{at}ices.utexas.edu or guillermo.lorenzo{at}unipv.it.
  • Author contributions: G.L., T.J.R.H., A.R., and H.G. designed research; G.L., T.J.R.H., A.R., and H.G. performed research; G.L., P.D.-F., and H.G. contributed new reagents/analytic tools; G.L., T.J.R.H., A.R., and H.G. analyzed data; and G.L., T.J.R.H., A.R., and H.G. wrote the paper.

  • Conflict of interest statement: H.G., T.J.R.H., and G.L. are listed as coinventors in a patent application that has been filed by The University of Texas at Austin. The invention leverages part of the technology presented in this paper.

  • Reviewers: K.G., University of Michigan; and E.K., Stanford University.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1815735116/-/DCSupplemental.

Published under the PNAS license.

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Computer simulations suggest that prostate enlargement due to benign prostatic hyperplasia mechanically impedes prostate cancer growth
Guillermo Lorenzo, Thomas J. R. Hughes, Pablo Dominguez-Frojan, Alessandro Reali, Hector Gomez
Proceedings of the National Academy of Sciences Jan 2019, 116 (4) 1152-1161; DOI: 10.1073/pnas.1815735116

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Computer simulations suggest that prostate enlargement due to benign prostatic hyperplasia mechanically impedes prostate cancer growth
Guillermo Lorenzo, Thomas J. R. Hughes, Pablo Dominguez-Frojan, Alessandro Reali, Hector Gomez
Proceedings of the National Academy of Sciences Jan 2019, 116 (4) 1152-1161; DOI: 10.1073/pnas.1815735116
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