Peri-prostatic adipose tissue measurements using MRI predict prostate cancer aggressiveness in men undergoing radical prostatectomy

Zhai, Ting‐Shuai; Hu, Lan-ting; G, W; Chen, X; Luo, Ming; Jin, Liang; Zhou, Zhen; Liu, X; Kang, Yuan; Zhang, J X; Liu, H; Lu, Jingyi; Yao, Xudong; Ye, L

doi:10.1007/s40618-020-01294-6

Cited by 10 publications

(13 citation statements)

References 37 publications

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“… 47 The PPFA/PA was also regarded as an independent predictor for lymph node metastasis in PCa patients undergoing radical prostatectomy. 48 In men with mCRPC treating with docetaxel, high volume of visceral fat was related to the decrease of survival. 49 Besides, the ratio of periprostatic fat thickness to subcutaneous fat thickness (PPFT/SFT) on MRI before treatment was an independent indicator of predicting the survival of males with hormone‐naïve advanced PCa.…”

Section: Discussionmentioning

confidence: 99%

Body composition parameters were associated with response to abiraterone acetate and prognosis in patients with metastatic castration‐resistant prostate cancer

You

Xue

et al. 2023

Cancer Medicine

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Objective To investigate the predictive value of body composition parameters for biochemical response to abiraterone acetate (AA) in metastatic castration‐resistant prostate cancer (mCRPC) patients with prior chemohormonal therapy. Methods We retrospectively evaluated the clinicopathologic information of 132 mCRPC cases receiving AA treatment after chemohormonal therapy at hormone‐sensitive stage from July 2018 to June 2021. All patients were divided into AA responders and non‐responders according to the biochemical response to AA (prostate‐specific antigen (PSA) reduction ≥50% than pretreatment). Multivariate Logistic analysis was used to determine the independent predictors and develop predictive model of biochemical response to AA. Cox regression analysis was utilized to investigate the prognostic factors for time to biochemical progression (TTBP), radiological progression‐free survival (rPFS), failure‐free survival (FFS), and overall survival (OS) after AA treatment. Results There were 57 AA responders and 75 AA non‐responders. Periprostatic fat area/prostate area (PPFA/PA) was decreased and skeletal muscle index (SMI) was increased in AA responders compared with AA non‐responders. Multivariable logistic analysis demonstrated that ADT duration ≥12 months, bone metastasis only, high SMI and low PPFA/PA were independent predictors of biochemical response to AA treatment. The FFS, TTBP, rPFS, and OS of patients with lower SMI or higher PPFA/PA was decreased compared with that of patients with higher SMI or lower PPFA/PA, respectively. Combining SMI, PPFA/PA, ADT duration and metastatic sites performed well in differentiating AA responders from non‐responders. Conclusions High SMI and low PPFA/PA could predict biochemical response to AA treatment and preferable prognosis in mCRPC patients with prior chemohormonal therapy at hormone‐sensitive stage.

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Section: Discussionmentioning

confidence: 99%

Body composition parameters were associated with response to abiraterone acetate and prognosis in patients with metastatic castration‐resistant prostate cancer

You

Xue

et al. 2023

Cancer Medicine

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“…Using this approach, we demonstrate that the volume of the PPAT correlates with that of the prostate. As prostate size is highly variable between individuals and often increases with age (Loeb et al, 2009), some previous studies used the ratio between the PPAT volume or area and the prostate size of the individual as a way of normalizing PPAT abundance (Zhai et al, 2021; Dahran et al, 2017). We show that this approach introduces a bias towards patients with smaller prostates being identified as having abundant PPAT, consistent with the findings of a previous study (Dahran et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Recent clinical studies have demonstrated that patients with large amounts of PPAT have more aggressive PCa than the patients with low amounts (Nassar et al, 2018), suggesting that the abundance of PPAT might be used to stratify patients’ risk. PPAT abundance correlates with prostate tumors with high Gleason scores and local dissemination (Nassar et al, 2018; Zhang et al, 2014; Woo et al, 2015; Van Roermund et al, 2011; Zhai et al, 2021), which are indicators of high risk progression. Measurement of PPAT abundance may be used in the early management of PCa patients since it predicts PCa aggressiveness in patients undergoing radical prostatectomy (RP) for localized disease (Dahran et al, 2019; Zhai et al, 2018) and predicts progression-free survival in men with indolent PCa who are under active surveillance (Gregg et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Collagen remodeling leads to inflammation-free expansion of periprostatic adipose tissue and promotes prostate cancer progression

Estève

Toulet

Roumiguié

et al. 2023

Preprint

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Periprostatic adipose tissue (PPAT) abundance correlates with prostate cancer progression, but the mechanism remains unexplained. Here, we used a statistical approach to define abundant PPAT by normalizing PPAT volume to prostate volume in a cohort of 351 patients with a linear regression model. Applying this definition, we find tumors specifically from patients with abundant PPAT exhibit several hallmarks of aggressiveness, suggesting that PPAT abundance might be used to improve risk stratification. We show that abundant PPAT expands by adipocyte hypertrophy but this does not result in inflammation. Extensive extracellular matrix remodeling, notably of the collagen network, and decreased expression of mechano-sensing proteins in adipocytes explains this inflammation-free expansion by decreasing the mechanical constraints on the adipocytes. Moreover, collagen VI degradation in abundant PPAT is associated with production of endotrophin, a matrikine that promotes cancer progression. We find high levels of endotrophin specifically in the urine of patients with abundant PPAT, indicating the clinical relevance of our findings.

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“…Indeed, there exists a significant correlation between increased PPAT volume and shortened progression-free survival in men with PCa [ 117 ]. Particularly, several studies demonstrated a significant positive correlation between PPAT size and, not only PCa aggressiveness, but also the development of castration-resistant PCa irrespective of treatment naivety and lymph node metastasis [ 118 , 119 , 120 , 121 ]. Nevertheless, these studies relied on the body mass index (BMI) as a marker for general obesity, and on PPAT size as a measure of its contribution to the hallmarks of PCa, rather than examining the inflammatory status of visceral fat, and particularly that of the PPAT.…”

Section: Periprostatic Adipose Tissue: a Microenvironmental Contribut...mentioning

confidence: 99%

Thromboinflammatory Processes at the Nexus of Metabolic Dysfunction and Prostate Cancer: The Emerging Role of Periprostatic Adipose Tissue

AlZaim

Al-Saidi

Hammoud

et al. 2022

Cancers

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The increased global prevalence of metabolic disorders including obesity, insulin resistance, metabolic syndrome and diabetes is mirrored by an increased incidence of prostate cancer (PCa). Ample evidence suggests that these metabolic disorders, being characterized by adipose tissue (AT) expansion and inflammation, not only present as risk factors for the development of PCa, but also drive its increased aggressiveness, enhanced progression, and metastasis. Despite the emerging molecular mechanisms linking AT dysfunction to the various hallmarks of PCa, thromboinflammatory processes implicated in the crosstalk between these diseases have not been thoroughly investigated. This is of particular importance as both diseases present states of hypercoagulability. Accumulating evidence implicates tissue factor, thrombin, and active factor X as well as other players of the coagulation cascade in the pathophysiological processes driving cancer development and progression. In this regard, it becomes pivotal to elucidate the thromboinflammatory processes occurring in the periprostatic adipose tissue (PPAT), a fundamental microenvironmental niche of the prostate. Here, we highlight key findings linking thromboinflammation and the pleiotropic effects of coagulation factors and their inhibitors in metabolic diseases, PCa, and their crosstalk. We also propose several novel therapeutic targets and therapeutic interventions possibly modulating the interaction between these pathological states.

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Peri-prostatic adipose tissue measurements using MRI predict prostate cancer aggressiveness in men undergoing radical prostatectomy

Cited by 10 publications

References 37 publications

Body composition parameters were associated with response to abiraterone acetate and prognosis in patients with metastatic castration‐resistant prostate cancer

Body composition parameters were associated with response to abiraterone acetate and prognosis in patients with metastatic castration‐resistant prostate cancer

Collagen remodeling leads to inflammation-free expansion of periprostatic adipose tissue and promotes prostate cancer progression

Thromboinflammatory Processes at the Nexus of Metabolic Dysfunction and Prostate Cancer: The Emerging Role of Periprostatic Adipose Tissue

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