Association of prostate size with capsule thickness and glandular epithelial cell density: The possible clinical implications on prostate cancer development

Abstract

Objective:

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most common urologic diseases in aging males. The negative association between prostate/BPH size and incidence of PCa is well documented in the literature. However, the exact mechanism is not well understood. This study aims to further investigate the possible effect of prostate volume on prostate capsule thickness and glandular cell density in the prostatic peripheral zone (PZ).

Materials and Methods:

A total of 100 patients were selected that had undergone radical prostatectomy with prostate sizes ranging from 20 to 160 mL. Quantitative measurements of capsule thickness and density of epithelial glands within the peripheral zone not affected by cancer were analysed and calculated on histo-anatomical slides using computer-based imaging software. Associations between the different variables were calculated using Spearman correlation with 95% confidence intervals (CIs).

Results:

In the non-cancerous areas of the PZ, prostate volume and average capsule thickness are positively associated (r_s = +0.6526, 95% CI +0.5233 to +0.7526, p < 0.0001), while prostate volume and average glandular epithelial cell density of the PZ are negatively associated (r_s = −0.6011, 95% CI −0.7133 to −0.4589, p < 0.0001). These associations remain consistent on subgroup analysis.

Conclusion:

The findings of this study support the hypothesis that transition zone (TZ) growth in large BPH prostates may cause pressure on the outer PZ, leading to fibrosis and atrophy of the glandular tissue. This may provide a protective effect against PCa, as most PCa originates in the PZ of the prostate.

Level of evidence:

Not applicable

Keywords

Prostate benign prostatic hyperplasia prostate cancer histo-anatomical image processing

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References

McVary

. BPH: Epidemiology and comorbidities. Am J Manag Care 2006; 12(5 Suppl.): S122–S128.

Kelly

Anderson

Rosenberg

, et al. Past, current, and future incidence rates and burden of metastatic prostate cancer in the United States. Eur Urol Focus 2018; 4(1): 121–127.

Siegel

Naishadham

Jemal

. Cancer statistics, 2013. CA Cancer J Clin 2013; 63: 11–30.

Newton

Phillips

Chang

, et al. Smaller prostate size predicts high grade prostate cancer at final pathology. J Urol 2011; 184: 930–937.

Peng

Shen

Liao

, et al. MRI-based prostate volume-adjusted prostate-specific antigen in the diagnosis of prostate cancer. J Magn Reson Imaging 2015; 42(6): 1733–1739.

Alcaraz

Hammerer

Tubaro

, et al. Is there evidence of a relationship between benign prostatic hyperplasia and prostate cancer? Findings of a literature review. Eur Urol 2009; 55: 864–875.

Weaver

Smith

Sharma

, et al. Quantitative measurements of prostate capsule and gland density and their correlation to prostate size: Possible clinical implications in prostate cancer. Int Urol Nephrol 2019; 52: 1829–1837.

Fine

Reuter

. Anatomy of the prostate revisited: Implications for prostate biopsy and zonal origins of prostate cancer. Histopathology 2012; 60(1): 142–152.

Holder

Galvan

Knight

, et al. Possible clinical implications of prostate capsule thickness and glandular epithelial cell density in benign prostate hyperplasia. Investig Clin Urol 2021; 62(4): 423–429.

10.

Collins

. Imagej for microscopy. Biotechniques 2007; 43: 25–30.

11.

Ruifrok

Katz

Johnston

. Comparison of quantification of histochemical staining by hue-saturation-intensity (HSI) transformation and color-deconvolution. Appl Immunohistochem Mol Morphol 2003; 11(1): 85–91.

12.

Bhavsar

Verma

. Anatomic imaging of the prostate. Biomed Res Int 2014; 2014: 728539.

13.

Ayala

Babaian

, et al. The prostatic capsule. Am J Surg Pathol 1989; 13: 21–27.

14.

Semple

. Surgical capsule of the benign enlargement of the prostate. BMJ 1963; 1: 1640–1643.

15.

Lorenzo

Hughes

Dominguez-Frojan

, et al. Computer simulations suggest that prostate enlargement due to benign prostatic hyperplasia mechanically impedes prostate cancer growth. Proc Natl Acad Sci 2019; 116: 1152–1161.

16.

Moolupuri

Camacho

de Riese

. Association between prostate size and the incidence of prostate cancer: A meta-analysis and review for urologists and clinicians. Int Urol Nephrol 2021; 53(10): 1955–1961.

17.

Buie

De Riese

Sharma

. Smaller prostate volume is associated with adverse pathological features and biochemical recurrence after radical prostatectomy. Urol Sci 2019; 30(6): 255–261.

18.

Sellers

Wagstaff

Helo

, et al. Quantitative measurements of prostatic zones by MRI and their dependence on prostate size: Possible clinical implications in prostate cancer. Ther Adv Urol 2021; 13: 1–9.

19.

Tarle

Spajic

Kraljic

, et al. Continuous finasteride therapy for benign prostate hypertrophy upgrades both neuroendocrine differentiation and aggressive prostate cancer. Anticancer Res 2009; 29(5): 1797–1801.

20.

Lorenzo

Hughes

TJR

Reali

, et al. A numerical simulation study of the dual role of 5a-reductase inhibitors on tumor growth in prostates enlarged by benign prostatic hyperplasia via stress relaxation and apoptosis upregulation. Comput Methods Appl Mech Eng 2020; 362: 112843.