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

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.

Keywords: benign prostatic hyperplasia; isogeometric analysis; mathematical oncology; patient-specific; prostate cancer.

Fig. 1.

Patient-specific local anatomy of the prostate. From a radiological perspective, the prostate is divided into central gland (CG) and peripheral zone (PZ). BPH takes place in the CG and most cases of PCa arise in the PZ. We extracted the geometry of the patient’s prostate and CG from their corresponding segmentations provided on axial T2-weighted MR images. The volumes of the prostate, CG, and PZ at MRI date are 52.81 cc, 33.15 cc, and 19.66 cc, respectively. The major diameters of the prostate at MRI date have a length of 53.49 mm, 38.35 mm, and 52.01 mm in lateral, anteroposterior, and craniocaudal directions, respectively.

Fig. 2.

Deformation of the prostate caused by BPH over 1 y. (A) Length of the displacement field vector over original anatomy at $t=1$ y. (B) Original and deformed geometries of the prostate at $t=1$ y.

Fig. 3.

Deformation of the prostate over 1 y produced by a tumor originated on basal PZ (A1–C1), apical PZ (A2–C2), and median CG (A3–C3). (A1–A3) Tumor growth over the original prostate geometry. (B1–B3) Length of the displacement field vector over original anatomy at $t=1$ y. The contour of the tumor is depicted with black curves. (C1–C3) Original and deformed geometries of the prostate at $t=1$ y.

Fig. 4.

Growth of the patient’s tumor over 1 y without the influence of BPH (A1 and B1) vs. considering the patient’s history of benign prostatic enlargement (A2 and B2). (A1 and A2) Tumor growth over the original prostate geometry. (B1 and B2) Time history of tumor volume (solid line) and serum PSA (dashed line).

Fig. 5.

Deformation of the prostate over 1 y produced by the patient’s tumor without the influence of BPH (A1 and B1) vs. considering the patient’s history of benign prostatic enlargement (A2 and B2). (A1 and A2) Length of the displacement field vector over original anatomy at $t=1$ y. The contour of the tumor is depicted with black curves. (B1 and B2) Original and deformed geometries of the prostate at $t=1$ y.