A Prospective Study of Intraprostatic Inflammation, Focal Atrophy, and Progression to Lethal Prostate Cancer

Abstract

Background: Inflammation and focal atrophy are common features adjacent to prostate tumors. Limited evidence exists on whether these features have prognostic significance.Methods: In the Health Professionals Follow-Up Study and Physicians' Health Study, we studied 1,035 men diagnosed with prostate cancer. A genitourinary pathologist centrally reviewed tumor and normal areas of hematoxylin and eosin slides from prostate cancer specimens for the presence of acute and chronic inflammation, and four subtypes of focal atrophy. Cox proportional hazards models adjusted for potential confounders were used to estimate HRs and 95% confidence intervals (CI) for the association of these features with lethal prostate cancer, defined as development of metastatic disease or death during follow-up.Results: During a median of 12 years of follow-up, 153 men developed lethal prostate cancer. A total of 84% of men had histologic evidence of chronic inflammation and 30% had acute inflammation. Both chronic and acute inflammation were inversely associated with lethal prostate cancer in age-and lifestyle-adjusted models. Chronic inflammation remained inversely associated with lethal prostate cancer after additionally adjusting for prognostic clinical features (HR ¼ 0.45; 95% CI, 0.30-0.69 for mild and HR ¼ 0.51; 95% CI, 0.33-0.80 for moderate to severe). None of the atrophic lesions were associated with lethal prostate cancer.Conclusions: Our data suggest that the presence of inflammation, particularly chronic inflammation, in prostate cancer tissue is associated with better prognosis among patients with prostate cancer.Impact: This is the largest prospective cohort study to examine the association between inflammation, focal atrophy, and lethal prostate cancer.

Hematologic Markers and Prostate Cancer Risk: A Prospective Analysis in UK Biobank

“…Previous studies have reported that inflammatory markers were associated with an increased risk of several cancers (20,22,23), but the associations with prostate cancer were inconsistent (20,23,46). Furthermore, the associations of intraprostatic inflammation with prostate tumor prognosis remain unclear (47).…”

Why Do Epidemiologic Studies Find an Inverse Association Between Intraprostatic Inflammation and Prostate Cancer: A Possible Role for Colliding Bias?

“…A positive association between inflammation and prostate cancer is also supported by findings from rodent models suggesting that inflammation may contribute to prostate epithelial hyperproliferation, atrophy, dysplasia, and precursor lesions (3)(4)(5)(6)(7)(8)(9), as well as decreased expression of putative tumor suppressor genes (10) and acceleration of carcinogenesis (11,12). Finally, findings from patho-epidemiologic studies of intraprostatic inflammation and prostate cancer progression have also tended to be positive (13)(14)(15)(16).…”

Corpora amylacea in benign prostatic acini are associated with concurrent, predominantly low‐grade cancer

“…Numerous studies have been done, including mouse models, in search of inflammatory‐related prostate cancer pathways and for preventive and therapeutic purposes 32‐34 . On the other hand, several studies showed a negative association of inflammation with prostate cancer, whereby inflammation presence was associated with a lower risk or less aggressiveness of cancer, and better prognosis 35‐41 . A proposed explanation is inflammation being a host defense mechanism or protecting against prostate cancer.…”