
==== Front
Sci Rep
Sci Rep
Scientific Reports
2045-2322
Nature Publishing Group UK London

39245685
71862
10.1038/s41598-024-71862-w
Article
MRI-measured periprostatic to subcutaneous adipose tissue thickness ratio as an independent risk factor in prostate cancer patients undergoing radical prostatectomy
Jiang Shanshan 12
Li Yi 12
Guo Yusheng 12
Gong Bingxin 12
Wei Chengcheng 34
Liu Weiwei 12
Chen Chao 12
Pan Feng 12
Song Jiyu 5
He Qingliu heqingliu163@163.com

46
Yang Lian yanglian@hust.edu.cn

12
Zhou Guofeng Zhouguofeng69@126.com

12
1 grid.33199.31 0000 0004 0368 7223 Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1277 Jiefang Avenue, Wuhan, 430022 China
2 grid.412839.5 0000 0004 1771 3250 Hubei Key Laboratory of Molecular Imaging, Wuhan, 430022 China
3 https://ror.org/033vnzz93 grid.452206.7 0000 0004 1758 417X Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400000 China
4 grid.33199.31 0000 0004 0368 7223 Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
5 grid.33199.31 0000 0004 0368 7223 Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022 China
6 https://ror.org/03wnxd135 grid.488542.7 0000 0004 1758 0435 Department of Urology, The Second Affiliated Hospital of Fujian Medical University, No.34 North Zhongshan Road, Quanzhou, 362000 China
8 9 2024
8 9 2024
2024
14 208969 5 2024
2 9 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
The purpose of this study is to evaluate whether the periprostatic adipose tissue thickness (PPATT) is an independent prognostic factor for prostate cancer patients after laparoscopic radical prostatectomy (LRP). This retrospective cohort study included consecutive prostate cancer patients who underwent LRP treatment at Wuhan Union Hospital from June 2, 2016, to September 7, 2023. PPATT was defined as the thickness of periprostatic fat and was obtained by measuring the shortest vertical distance from the pubic symphysis to the prostate on the midsagittal T2-weighted MR images. Subcutaneous adipose tissue thickness (SATT) was obtained by measuring the shortest vertical distance from the pubic symphysis to the skin at the same slice with PPATT. The primary outcome of the study was biochemical recurrence (BCR), and the secondary outcome was overall survival (OS). Multivariable Cox regression analysis was used to identify independent prognostic factors for prostate cancer survival and prognosis. Based on the optimal cutoff value, 162 patients were divided into a low PPATT/SATT group (n = 82) and a high PPATT/SATT group (n = 80). During the entire follow-up period (median 23.5 months), 26 patients in the high PPATT/SATT group experienced BCR (32.5%), compared to 18 in the low PPATT/SATT group (22.0%). Kaplan–Meier curve analysis indicated that the interval to BCR was significantly shorter in the high PPATT/SATT group (P = 0.037). Multivariable Cox regression analysis revealed that an increase in the PPATT/SATT ratio was associated with BCR (hazard ratio: 1.90, 95% CI, 1.03–3.51; P = 0.040). The PPATT/SATT ratio is a significant independent risk factor for BCR after LRP for prostate cancer patients.

Keywords

Periprostatic adipose tissue thickness
Subcutaneous adipose tissue thickness
Laparoscopic radical prostatectomy
Prostate cancer
Biochemical recurrence
Prognosis
Subject terms

Oncology
Cancer
Urological cancer
Prostate cancer
Fundamental Research Funds for the Central Universities20242422 Guo Yusheng National Key Research and Development Program of China2023YFE0113300 Yang Lian National Natural Science Foundation of China82172034 Yang Lian issue-copyright-statement© Springer Nature Limited 2024
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pmcIntroduction

Prostate cancer (PCa) is the most common malignant tumor in the male genitourinary system, and its incidence is significantly increasing in men over the age of 55 years. In 2023, PCa was estimated to have the highest number of new cases among all cancers and ranked second in mortality, after only lung cancer, with an increasing trend year by year1. Family history, genetic and environmental factors (such as obesity, smoking, exercise, and diet) play roles in its etiology2–4.

Obesity is a global issue in this century and is a risk factor for poor treatment outcomes and increased mortality in various types of cancer, including esophageal cancer, gynecologic cancer, and colorectal cancer. Recent studies have also revealed a relationship between obesity and the aggressiveness of prostate cancer, including increased risks of biochemical recurrence (BCR) and higher mortality rates after radical prostatectomy (RP)5–7. However, the relationship between adipose tissue and clinical outcomes in prostate cancer remains uncertain8–10. These controversial results may be due to the use of body mass index (BMI) as the most common obesity metric, which doesn't show the distribution of adipose tissue, and there is still limited understanding of the impact of adipose tissue on the development and progression of prostate cancer.

Adipose tissue is a metabolically active organ with diverse distributions in the body, classified based on anatomical location into subcutaneous and visceral adipose tissue. Visceral adipose tissue primarily surrounds the mesentery and omentum11,12. Based on morphological and functional characteristics, it is differentiated into white adipose tissue (WAT) and brown adipose tissue (BAT). The activity of adipose tissue is associated with the occurrence of various tumors13,14.

Periprostatic adipose tissue thickness (PPATT) is defined as the thickness of fat surrounding the prostate15. This periprostatic adipose tissue located in the pelvic region and mainly enclosed by the prostate capsule, is the closest to PCa. One-third of the prostate directly contacts the periprostatic adipose tissue16,17. Compared to subcutaneous adipose tissue, periprostatic adipose tissue has unique morphological and functional characteristics. The adipocytes in periprostatic adipose tissue are smaller, have the same basal rate of lipolysis, but release fewer types of polyunsaturated fatty acids and are more sensitive to the lipolysis induced by isoproterenol18. Therefore, its role differs from other adipose tissue, making its study significant.

Periprostatic adipose tissue can impact various prostate-related diseases such as prostatitis, benign prostatic hyperplasia (BPH), erectile dysfunction, urethral dysfunction, and PCa19–21. As an active endocrine organ, periprostatic adipose tissue can influence the lipid microenvironment and inflammatory state in PCa, although the precise mechanism is not fully determined. It is known to produce hormones and cytokines like tumor necrosis factor-α, interleukin-6, and adiponectin, playing a role in the growth and migration of prostate cancer22. Currently, RP is the preferred treatment for PCa, but the 10-year biochemical recurrence rate post-RP is as high as 27%23. Therefore, accurately identifying the risk of BCR before RP can assist clinicians in making individualized and comprehensive treatment decisions for those at high risk of recurrence. Previous studies have confirmed that periprostatic adipose tissue can serve as a predictive marker for assessing the Gleason scores and tumor aggressiveness in patients undergoing RP24–27. however, research on clinical indicators predicting BCR after RP remains relatively limited. In this study, we aim to investigate whether MRI-measured PPATT is an independent prognostic factor for PCa patients undergoing laparoscopic radical prostatectomy (LRP) and to assess its predictive value for postoperative BCR.

Materials and methods

This retrospective cohort study was approved by the local ethics committee and the institutional review board of Tongji Medical College, Huazhong University of Science and Technology (Institutional Review Board No. S187). The study procedures were conducted in accordance with good clinical practice and the Declaration of Helsinki. The institutional review board waived the requirement for written informed consent.

Study design and patient selection

This is a single-center, cross-sectional and retrospective study. We conducted a computer search of our electronic medical records to identify patients who met the following inclusion criteria. The study included consecutive prostate cancer patients who underwent LRP treatment at Wuhan Union Hospital from June 2, 2016, to September 7, 2023.

The inclusion criteria are as follows: (1) Diagnosed with prostate cancer through prostate biopsy or transurethral resection of the prostate (TURP) specimens, and underwent evaluation with prostate MRI and serum prostate-specific antigen (PSA) levels before prostate biopsy or TURP. (2) Aged ≥ 18 years old. (3) Underwent laparoscopic radical prostatectomy. (4) No history of other malignant tumors.

Exclusion criteria: (1) Incomplete or unevaluable clinical or imaging data. (2) Palliative resection, previous neoadjuvant treatment, radiation therapy, or other forms of treatment. (3) Patients lost to follow-up.

Procedures

We retrospectively collected baseline data from electronic medical records of patients before LRP, including age, BMI, diabetes, hypertension, smoking, t PSA, f PSA, PSA%, and clinical stages of the tumor. Additionally, information from the pathology report, including pathological T stages, Gleason scores, and surgical margins positivity, was obtained from the pathology database. We classify phases T1 and T2 as Stage I and phases T3 and T4 as Stage II. The pathology reports were written by a pathologist with 10 years of experience in urological pathology who analyzed step-section histological slides obtained every 4 mm from radical prostatectomy specimens28. Data related to hypertension and diabetes included patients diagnosed during hospitalization and using related medications.

MRI technique

All MRI examinations in this study were performed at a 3.0 T MRI system (Skyra, Siemens Healthcare, Erlangen, Germany) using the same parameters. A standard 18-channel phased body coil was selected, the body position was supine, and the scan included the entire pelvic. Only the sagittal T2-weighted images were evaluated in this study. T2-weighted imaging parameters were as follows: TR range/TE range 3400–4500/100–140; layer thickness 3 mm; layer spacing 3 mm; 346 × 384 matrix; FOV 180 × 180 mm; flip angle 160 degrees, NEX = 2.

PPATT/SATT measurement and assessment

Two independent radiologists with 3 and 25 years of experience in prostate MRI conducted consistent reviews of the images using the PACS system (Yi Li, Guofeng Zhou). Both were aware that all patients had undergone LRP but were blinded to the clinical, surgical, and pathological outcomes. The thicknesses of the subcutaneous and periprostatic adipose tissues were measured on sagittal T2-weighted images. The average of the two radiologists' measurements was used in the analysis, and the assessment was repeated 30 days later. Using the intraclass correlation coefficient (ICC) to test for intra- and inter-observer reliability, and the intra- and inter-observer agreements were 0.94 and 0.90. Any differences were resolved through discussion and consensus. The PPATT and the subcutaneous adipose tissue thickness (SATT) were determined by measuring the shortest vertical distances from the pubic symphysis to the prostate and from the pubic symphysis to the skin, as shown in Fig. 1. The shortest vertical distances were used to avoid overestimation of these measurements.Fig. 1 Men with prostate cancer aged 64-year-old with BMI 22.2 (A) and 61-year-old with BMI 29.4 (B) . Midsagittal T2-weighted MR images show the measurement of SATT and PPATT. SATT and PPATT were measured as the perpendicular shortest range between skin-symphysis pubis and symphysis pubis-prostate on the midsagittal section of the T2-weighted MRI (yellow line). BMI, body mass index; PPATT, periprostatic adipose tissue thickness; SATT, subcutaneous adipose tissue thickness.

Using X-tile software (version 3.6.1; URL: https://medicine.yale.edu/lab/rimm/research/software/ ) to determine the optimal cutoff value, and dividing the patients into high PPATT/SATT group (PPATT/SATT ratio > 0.22) and low PPATT/SATT group (PPATT/SATT ≤ 0.22), as illustrated in Fig. 2.Fig. 2 Optimal cutoff value obtained from X-tile software (version 3.6.1).

Follow-up and endpoints

Follow-up data were obtained from clinical case records (including outpatient and inpatient records), imaging data (MRI), and telephone interviews. All patients were followed until February 22, 2024, or until their death. The primary outcome of the study was BCR, defined as two consecutive prostate-specific antigen (PSA) levels > 0.2 ng/mL after RP [0.2 µg/L]29. If postoperative PSA levels did not drop below 0.2 ng/mL, the date of RP was considered the BCR date. Biochemical recurrence free survival (BFS) was calculated from the date of surgery to the date of BCR or the last follow-up. Patients without BCR were reviewed at the last follow-up. The secondary outcome was overall survival (OS), defined as the time from undergoing RP to death from any cause.

Statistical analysis

In our study, continuous variables that were normally distributed were presented as mean (SD) with standard deviations and compared using the t-test. Continuous variables that were not normally distributed were presented as median (IQR) and compared using the Mann–Whitney U-test. Categorical variables were compared using the Chi-square test or Fisher's exact test. Differences in BCR and OS between high PPATT/SATT and low PPATT/SATT groups were compared using Log-rank test, and results were presented in Kaplan–Meier survival curves. Univariate and multivariate Cox regression analyses were used to calculate the hazard ratios and 95% confidence intervals for BCR and OS between the two groups, based on PPATT/SATT ratios and other clinical and pathological factors, to identify independent prognostic factors. Variables with a p-value < 0.1 in univariate analysis were included in multivariate Cox regression analysis. Unstratified univariate Cox models with clinically significant covariates were used to calculate the risk ratios for BCR and OS for each subgroup. Statistical analyses were performed using SPSS version 26.0 (IBM, Chicago, IL, USA; URL: https://www.ibm.com/spss ) and R software version 4.3.0 (R Foundation; URL: https://www.r-project.org/ ). A p-value < 0.05 was considered statistically significant.

Results

Patient characteristics

A total of 162 patients who underwent LRP for prostate cancer were included in this retrospective cohort study. This included 82 patients with a PPATT/SATT ratio ≤ 0.22 and 80 patients with a PPATT/SATT ratio > 0.22. The median age was 69 years old, and the median BMI was 23.61 kg/m2. Normal weight (BMI < 25 kg/m2) accounts for 66%, and overweight (BMI ≥ 25 kg/m2) accounts for 34%. The median PPATT measured on MRI was 5.77 mm, the median SATT was 25.75 mm, and the median prostate volume was 79.38 ml. Pathological examination of the radical prostatectomy specimens showed that 61 patients (39.6%) had positive surgical margins. Pathological stages T3 and T4 included 64 cases (42.4%). In Stage I (pathological stages T1 and T2), the low PPATT/SATT group comprised 39 cases (44.8%), while the high PPATT/SATT group had 48 cases (55.2%). In Stage II (pathological stages T3 and T4), the low PPATT/SATT group had 36 cases (56.2%) and 28 cases (43.8%) in the high PPATT/SATT group. There was no significant difference in the pathological stage distributions between the two groups. Gleason scores ≤ 7 was found in 40 cases (50.6%) in the low PPATT/SATT group and 39 cases (49.4%) in the high PPATT/SATT group. Gleason scores > 7 was observed in 41 cases (51.9%) in the low PPATT/SATT group and 38 cases (48.1%) in the high PPATT/SATT group. 59 patients (37.3%) had a Gleason score of 9 or above. Patients in the high PPATT/SATT group had relatively higher Gleason scores (total score ≥ 9, 81.6% vs. 68.3%). The baseline demographic, clinical, radiological, and pathological characteristics of the patients are shown in Table 1. There were no significant differences in baseline characteristics between the two groups.Table 1 Demographic, clinical, radiological and pathological characteristics of patients who underwent laparoscopic radical prostatectomy.

Characteristics	Low-PPATT/SATT group	High-PPATT/SATT group	P value	
Patient characteristics	
 Patients, n	82	80		
Age, n (%)			0.744	
 < 69	39 (24.1%)	36 (22.2%)		
 ≥ 69	43 (26.5%)	44 (27.2%)		
Body mass index (kg/m2), n (%)			0.135	
 < 24.8	36 (22.2%)	26 (16%)		
 ≥ 24.8	46 (28.4%)	54 (33.3%)		
Diabetes, n (%)	14 (8.6%)	15 (9.3%)	0.781	
Hypertension, n (%)	21 (13.0%)	15 (9.3%)	0.294	
Smoking, n (%)	19 (11.7%)	16 (9.9%)	0.624	
Clinical T stages, n (%)			0.197	
Stage I	44 (27.5%)	52 (32.5%)		
Stage II	36 (22.5%)	28 (17.5%)		
Pathological T stages, n (%)			0.432	
Stage I	
 T2	39 (25.8%)	47 (31.1%)		
Stage II	
 T3	27 (17.9%)	21 (13.9%)		
 T4	9 (6.0%)	7 (4.6%)		
Pathological Gleason scores, n (%)			0.592	
6	5 (3.2%)	8 (5.1%)		
7	35 (22.2%)	31 (19.6%)		
8	13 (8.2%)	7 (4.4%)		
9	26 (16.5%)	29 (18.4%)		
10	2 (1.3%)	2 (1.3%)		
Prostate volume (mL), median (IQR)	80.89 (54.84,128.23)	79.12 (57.65,104.32)	0.763	
t PSA (ng/mL), median (IQR)	18.89 (9.94,65.19)	19.62 (8.66,52.51)	0.535	
f PSA (ng/mL), median (IQR)	2.69 (1.38,7.47)	2.40 (0.96,8.03)	0.443	
PSA%, median (IQR)	0.12 (0.10,0.24)	0.16 (0.08,0.36)	0.729	
Surgical margin positivity, n (%)	35 (22.7%)	26 (16.9%)	0.176	
PPATT, periprostatic adipose tissue thickness; SATT, subcutaneous adipose tissue thickness; PSA, prostate specific antigen; t PSA, total PSA; f PSA, free PSA; Stage I, T1 and T2; Stage II, T3 and T4.

Survival analysis

The entire cohort had a median follow-up of 23.5 months (IQR 13.0, 32.1), and 44 patients (27.2%) reported BCR postoperatively. In the high PPATT/SATT group, 26 patients (32.5%) experienced BCR, compared to 18 patients (22.0%) in the low PPATT/SATT group. The hazard ratios (HR) for BCR and OS between the high and low PPATT/SATT groups were 1.90 (95% CI, 1.03 to 3.51; P = 0.040) and 2.15 (95% CI, 0.69 to 6.75; P = 0.188) respectively. Kaplan–Meier curve analysis showed that the BFS was significantly shorter in the high PPATT/SATT group (P = 0.037), as shown in Fig. 3.Fig. 3 Kaplan–Meier curve analysis of BCR (A) and OS (B) in low PPATT/SATT group (blue) and high PPATT/SATT group (red). PPATT, periprostatic adipose tissue thickness; SATT, subcutaneous adipose tissue thickness; BCR, biochemical recurrence; OS, overall survival.

Due to the insufficient follow-up period, the median BFS for the two groups could not be obtained.

Univariate and multivariate analysis

In the univariate analysis for BCR, a high PPATT/SATT ratio was identified as a potential predictive factor and was further included in the multivariate model. In the multivariate Cox regression model, a high PPATT/SATT ratio (HR, 1.902 [95% CI, 1.031–3.507]; P = 0.040) was identified as an independent risk factor for BCR after LRP, as shown in Table 2. Similarly, the final multivariate Cox regression model for OS demonstrated that a larger prostate volume (PV) (HR, 1.003 [95% CI, 1.001–1.004]; P < 0.001) was an independent risk factor associated with decreased OS, as shown in Table 3.Table 2 Effects of the PPATT/SATT ratio on BCR for prostate cancer patients after laparoscopic radical prostatectomy in univariate and multivariate Cox regression models.

Parameter	Univariate analysis	Multivariate analysis	
Hazard ratio (95% CI)	P value	Hazard ratio (95% CI)	P value	
Groups	
 Low-PPATT/SATT group	Reference		Reference		
 High-PPATT/SATT group	1.902 (1.031−3.507)	0.040	1.902 (1.031−3.507)	0.040	
Age	
 < 69	Reference				
 ≥ 69	1.135 (0.625−2.061)	0.678			
Body mass index (kg/m2)	
  < 24.8	Reference				
  ≥ 24.8	1.134 (0.617−2.083)	0.686			
Diabetes	
 No	Reference				
 Yes	1.626 (0.800−3.311)	0.179			
Hypertension	
 No	Reference				
 Yes	1.735 (0.799−3.767)	0.163			
Smoking	
 No	Reference				
 Yes	1.328 (0.680−2.591)	0.406			
Surgical margin positivity	
 No	Reference				
 Yes	1.115 (0.605−2.058)	0.727			
Clinical T stages	
 Stage I	Reference				
 Stage II	1.055 (0.572−1.944)	0.865			
Pathological T stages	
 Stage I	Reference				
 Stage II	1.103 (0.591−2.061)	0.758			
Pathological Gleason scores	
  ≤ 7	Reference				
  > 7	1.189 (0.641−2.203)	0.583			
Prostate volume (mL)	1.001 (1.000−1.002)	0.147			
 t PSA (ng/mL)	1.000 (0.997−1.003)	0.957			
 f PSA (ng/mL)	1.004 (0.977−1.030)	0.790			
 PSA%	0.972 (0.803−1.177)	0.772			
BCR, biochemical recurrence; 95% CI, 95% Confidence Interval; PPATT, periprostatic adipose tissue thickness; SATT, subcutaneous adipose tissue thickness; PSA, prostate specific antigen; t PSA, total PSA; f PSA, free PSA; Stage I, T1 and T2; Stage II, T3 and T4.

Table 3 Effects of the PPATT/SATT ratio on OS for prostate cancer patients after laparoscopic radical prostatectomy in univariate and multivariate Cox regression models.

Parameter	Univariate analysis	Multivariate analysis	
Hazard ratio (95% CI)	P value	Hazard ratio (95% CI)	P value	
Groups	
 Low-PPATT/SATT group	Reference				
 High-PPATT/SATT group	2.155 (0.688−6.748)	0.188			
Age	
  < 69	Reference				
  ≥ 69	0.689 (0.228−2.080)	0.509			
Body mass index (kg/m2)	
  < 24.8	Reference				
  ≥ 24.8	1.355 (0.453−4.065)	0.587			
Diabetes	
 No	Reference				
 Yes	1.067 (0.236−4.831)	0.932			
Hypertension	
 No	Reference				
 Yes	1.195 (0.138−10.338)	0.872			
Smoking	
 No	Reference				
 Yes	1.610 (0.494−5.236)	0.430			
Surgical margin positivity	
 No	Reference				
 Yes	1.082 (0.351−3.344)	0.890			
Clinical T stages	
 Stage I	Reference				
 Stage II	0.708 (0.208−2.408)	0.580			
Pathological T stages	
 Stage I	Reference				
 Stage II	1.062 (0.313−3.605)	0.923			
Pathological Gleason scores	
  ≤ 7	Reference				
  > 7	1.467 (0.422−5.096)	0.547			
 Prostate volume (mL)	1.003 (1.001−1.004)	 < 0.001	1.003 (1.001−1.004)	 < 0.001	
 t PSA (ng/mL)	1.000 (0.994−1.006)	0.964			
 f PSA (ng/mL)	0.995 (0.938−1.055)	0.854			
 PSA%	0.972 (0.695−1.360)	0.869			
OS, overall survival; 95% CI, 95% Confidence Interval; PPATT, periprostatic adipose tissue thickness; SATT, subcutaneous adipose tissue thickness; PSA, prostate specific antigen; t PSA, total PSA; f PSA, free PSA; Stage I, T1 and T2; Stage II, T3 and T4.

Subgroup analysis

Differences between the BCR and OS groups were consistently observed across subgroups based on baseline characteristics, as illustrated in Figs. 4 and 5. In all subgroups, the high PPATT/SATT group exhibited a higher risk of BCR compared to the low PPATT/SATT group. In the analysis of OS, except for subgroups such as fatter body (BMI ≥ 24.8), smoking, earlier pathological T stages, and lower Gleason scores, the high PPATT/SATT group demonstrated a higher risk of shortened OS.Fig. 4 Subgroup analyses of BCR between the low PPATT/SATT and high PPATT/SATT groups. Hazard ratios were derived from univariate cox model for each subgroup. Dashed line indicates Hazard ratio of 1. PPATT, periprostatic adipose tissue thickness; SATT, subcutaneous adipose tissue thickness; BCR, biochemical recurrence; OS, overall survival.

Fig. 5 Subgroup analyses of OS between the low PPATT/SATT and high PPATT/SATT groups. Hazard ratios were derived from univariate cox model for each subgroup. Dashed line indicates Hazard ratio of 1. PPATT, periprostatic adipose tissue thickness; SATT, subcutaneous adipose tissue thickness; BCR, biochemical recurrence; OS, overall survival.

Discussion

This article retrospectively analyzes the relationship between MRI-measured PPATT and the prognosis after LRP. By using the PPATT/SATT ratio as a grouping standard, the influence of obesity on PPATT can be reduced and the predictive efficacy of PPATT on BCR after LRP can be better shown. In clinical practice, experienced clinicians have accuracy in predicting BCR post-RP, but when assessing critical patients, clinicians tend to rely on personal knowledge and experience, which can influence diagnostic outcomes and vary among different clinicians. The conclusion of our study, that the PPATT/SATT ratio is an independent risk factor for post-RP BCR, can compensate for the shortcoming of subjective clinical analysis, providing auxiliary information to determine treatment strategies for prostate cancer patients30, improving risk stratification for PCa, and avoiding unnecessary biopsies and overtreatment31,32.

Peritumoral adipose tissue promotes cancer growth through different mechanism, including the release of growth factors, inflammatory signaling activator, and as fatty acids33. In prostate cancer, periprostatic adipose tissue is an essential component of the prostate microenvironment and may be a key source of fatty acids that influence the pathogenesis of prostate cancer15. Laurent et al.34 reported that adipocytes from periprostatic fat support the directed migration of prostate cancer cells. This process relies on adipocytes secreting the chemokine CCL7, which diffuses from the periprostatic fat to the periphery of the prostate, stimulating tumor cells expressing the CCR3 receptor to migrate, mediated by the CCR3/CCL7 axis. In prostate cancer, they demonstrated that upregulated expression of the CCR3 receptor in obese patients is associated with the expansion of aggressive prostate cancer. Another study showed that men with more periprostatic fat had higher activity of matrix metalloproteinases 2 and 9, which has been shown to increase the proliferation and migration capabilities of prostate cancer cells in conditioned media35.

Based on these biological pathways, we hypothesize that PPATT may independently influence the aggressiveness of prostate cancer, separate from factors such as PSA, PSA density (PSAD), and International Society of Urological Pathology (ISUP). However, it is necessary to account for the effect of obesity. To date, most studies investigating the role of obesity in prostate cancer have used BMI as a marker and have provided controversial results8,36–38. While Amling et al. suggest that BMI is associated with higher-grade cancer and higher rate of BCR post-RP, Pfitzenmaier et al. argue that BMI has not been proven as a predictive marker for BCR. In our research, BMI also could not be demonstrated as an independent predictor of BCR. Furthermore, BMI is significantly correlated with subcutaneous adipose tissue, and Delouya et al.39 reported that increased SATT is associated with the aggressiveness of prostate cancer. In order to cope with this uncertainty, we used the PPATT/SATT ratio as a grouping standard to minimize the impact of obesity. To our knowledge, this is the first study to analyze the predictive value of PPATT/SATT for BCR in patients undergoing LRP.

Many studies have indicated that periprostatic adipose tissue may be a crucial source influencing the pathogenesis and prognosis of prostate cancer40,41. Unlike other adipose tissue , Periprostatic adipose tissue does not significantly increase in obese patients42. Additionally, PPATT measured by MRI or similar techniques is not correlated with BMI43. Wu et al. found that a high VAT/SAT ratio is significantly associated with shorter OS in prostate cancer patients with normal weight, although this relationship was not observed in overweight or obese patients44. To address the impact of obesity on the prognosis of prostate cancer patients, we used the PPATT/SATT ratio as a grouping criterion. In our study, multifactorial Cox regression analysis shows that a PPATT/SATT ratio > 0.22 is an independent risk factor for BCR after LRP. Similar to our results, Iemura et al.15 demonstrated that the thickness of periprostatic adipose tissue measured by mpMRI is an independent risk factor for BCR in patients treated with RARP.

Additionally, Iemura et al.15 found the prostate volume to be an independent risk factor for OS. In our research, the multivariate Cox regression model indicated that a larger prostate volume (HR, 1.003 [95% CI, 1.001–1.004]; P < 0.001) is an independent risk factor associated with decreased OS, which is comparable to findings in the literature.

In our study, we used measurement techniques similar to those used by Woo et al.24, getting consistent results. The method of measuring the shortest vertical distances from the skin to the pubic symphysis and from the prostate to the pubic symphysis is easily applicable in clinical work25,45,46. Bhindi et al. found that the TRUS-measured thickness of periprostatic adipose tissue is a risk factor for prostate cancer, particularly high-grade prostate cancer. On the other hand, Roermund et al. indicated that CT-measured periprostatic fat was not related to the aggressiveness of prostate cancer. We believe there are more advantages to using MRI instead of CT and TRUS. TRUS is highly operator-dependent and susceptible to variability, and the pressure applied to the prostate during TRUS can affect the thickness of periprostatic adipose tissue. And CT carries the risk of ionizing radiation. MRI is commonly used for the diagnosis, localization, and risk stratification of prostate cancer patients and does not involve ionizing radiation. Furthermore, this method is relatively simple and easy to use.

In our study, a high PPATT/SATT ratio was an independent risk factor for BCR after LRP. This indicates that patients with thicker PPATT and thinner SATT have a higher probability of BCR. This study highlights the role of PPATT and overall fat distribution in predicting BCR and OS in PCa patients after LRP. A lower BMI and less subcutaneous adipose tissue may reflect cancer-related cachexia. Furthermore, Dahran et al. found no correlation between BMI, abdominal fat area, SATT, and the aggressiveness of PCa47. In this study, we also found no statistically significant difference in baseline BMI between the low and high PPATT/SATT groups, and BMI did not show predictive value in the multivariate COX regression analysis. Considering that obese patients may have thicker SATT, we used SATT as the denominator to minimize the confounding effect of obesity on this study. By using PPATT as the numerator and SATT as the denominator, and employing SATT as an internal control for comparison, we better demonstrated the association between PPATT and BCR or OS. We recognize that our study patients did not include many overweight patients, with the majority (66%) being of healthy weight (BMI < 25 kg/m2). In contrast, previous reports have indicated that only 27.7–37.2% of patients were of normal weight25,45,46. This may partially explain why BMI has been identified as a risk factor for severe disease in other studies but not ours. Therefore, it is necessary to conduct further research that includes a sufficient number of overweight patients to validate the predictive value of the PPATT/SATT ratio in obese patients.

Our study has several limitations. Firstly, it is a single-center retrospective analysis with a small sample size, which could lead to potential selection bias. Future studies should be conducted in larger patient groups across multiple centers. Secondly, our study only included patients who had undergone LRP, which may introduce selection bias and limit the generalizability of our findings to a broader patient population. Thirdly, the number of deaths in our study population was relatively low (n = 13), which might be why we did not find statistical significance in the relationship between the PPATT/SATT ratio and OS. Fourthly, for convenience, we measured the thickness of periprostatic and subcutaneous adipose tissue in a single plane. Because our main objective was to determine the relationship between the two markers. Finally, further research is needed to evaluate the biological activity of periprostatic adipose tissue and their association with BCR, to better understand the precise role of periprostatic adipose tissue in prostate cancer. Currently, there is limited research in this area.

Conclusion

Our study indicates that a higher PPATT/SATT ratio is associated with poorer clinical outcomes, however, the majority of patients in this cohort had normal weight, indicating the need for large-scale, multicenter studies in the future to validate the predictive value of the PPATT/SATT ratio in obese patients. The PPATT/SATT ratio holds promise as an important marker for assessing the prognosis of patients after LRP for prostate cancer. This assessment can help identify which patients are likely to benefit from the surgery and which might benefit more from alternative treatment strategies.

Acknowledgements

The authors thank everyone who participated in this project and helped with this project. We also thank the reviewers’ helpful comments and suggestions.

Author contributions

Conception and design:S.J., L. Y. and G. Z.; Administrative support: G. Z., Q.H. and F. P.; Collection of data: C. C., J.S. and Y.L.; Data analysis and interpretation: S. J., C.W.and W. L.; Manuscript writing: S. J., Y. G., and B. G.; Responsible for the overall content: G. Z.; Final approval of manuscript: All authors.

Funding

This study was supported by grants from the National Key Research and Development Program of China (2023YFE0113300), the National Natural Science Foundation of China (82172034), and the Fundamental Research Funds for the Central Universities (20242422).

Data availability

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. If someone wants to request the data, he can contact corresponding author by email, upon reasonable request.

Competing interests

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

The studies involving humans were approved by the Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (Institutional Review Board No. S187).

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

These authors contributed equally: Shanshan Jiang, Yi Li and Yusheng Guo.
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