Since primary retroperitoneal liposarcoma (PRPLS) is rare in the clinic, related clinical studies are lacking. The present study was designed to investigate the predictive factors of short-term (≤1 year) recurrence (STR) and construct a novel nomogram of local recurrence-free survival (LRFS) for surgically resected PRPLS. A total of 128 PRPLS cases who underwent radical surgery were retrospectively analyzed. Based on the interval from the operation to tumor recurrence, the predictors of STR were screened using univariate and multivariate logistic regression analyses. Cox proportional hazard regression models were applied to identify the predictors of LRFS. Furthermore, the independent predictors acquired from multivariate analyses were used to construct a nomogram. Multivariate logistic regression analysis revealed that age ≥55 years [odds ratio (OR)=5.607, P=0.010], operative time ≥260 min (OR=9.716, P=0.005) and tumor necrosis (OR=3.781, P=0.037) were independent risk factors of STR for PRPLS. In the Cox regression analysis, clinical symptoms [hazard ratio (HR)=1.746, P=0.017], resection method (OR=0.370, P=0.021) and de-differentiated histological subtype (HR=1.975, P=0.048) were identified as independent predictors of LRFS. Subsequently, the independent predictors acquired from multivariate analyses were used to construct a nomogram for LRFS. Age, operative time, tumor necrosis, clinical symptoms, resection method and histological subtype were related to recurrence for surgically resected PRPLS and a novel nomogram was constructed based on the above predictors.
As the most common primary retroperitoneal malignancy, primary retroperitoneal liposarcoma (PRPLS) originates from the adipose tissue in the retroperitoneal space. Although PRPLS accounts for <0.1% of all malignant tumors, it has hidden clinical symptoms and rapid progress (
To date, the mechanisms of PRPLS recurrence have remained largely elusive and the following factors are considered to have a role (
Since PRPLS is rare in the clinic, related clinical studies are lacking (
Patients with PRPLS who underwent radical operation at the First Medical Center of Chinese People's Liberation Army (PLA) General Hospital (Beijing, China) were included in this retrospective observational study. Relevant clinical data were collected using an electronic medical record (EMR) system. The inclusion criteria were as follows: i) Primary tumor with radical surgery (R0 resection) at our unit; ii) tumor originated from the retroperitoneal soft tissue and postoperative pathology confirmed liposarcoma; and iii) hospitalization period from January 2008 to December 2021. The exclusion criteria were as follows: i) Recurrent cases; ii) patients who did not undergo surgery, underwent palliative surgery (R2 resection) or with positive postoperative margin (R1 resection); iii) patients who died from surgical complications or other causes; and iv) cases lost to follow-up or refused to participate. This study was approved by the Medical Ethics Committee of the First Medical Center of the Chinese PLA General Hospital.
The following case data were collected from the EMR system: Sex, age, body mass index (BMI), preoperative neutrophil/lymphocyte ratio (NLR), abdominal operation history, clinical symptoms, tumor resection method, combined organ excision, operative time, intraoperative bleeding, application of intraperitoneal chemotherapy drug, transfer to intensive care unit (ICU), tumor diameter, multiple primary tumors, tumor shape, tumor capsule, histological subtype and tumor necrosis. The case data were acquired in three categories: Demographic characteristics, surgical characteristics and pathological characteristics. The preoperative clinical symptoms observed in the present study included abdominal pain and distension, gastrointestinal obstruction, back pain and lower limb paresthesia, which were caused by tumor compression or invasion. The sampling time to determine the preoperative NLR was 2–3 days prior to the surgery. Combined organ resection was selected if the tumor had invaded surrounding organs and piecemeal resection was considered only when complete resection was not feasible. A negative resection margin was defined as R0 resection and procedures with a positive postoperative margin were considered an R1 resection. R2 resection (palliative) was considered if there was any residual tumor observed during an operation. The intraperitoneal chemotherapy drug used in this study was mainly implantable sustained-release fluorouracil, which was placed in the abdominal cavity prior to closure. The tumor diameter was expressed as the largest tumor diameter after the postoperative assessment.
In the present study, patients had a follow-up every 3–4 months in the first 2 years after the surgery and every 6 months thereafter. During the follow-up period, routine physical examination and abdominopelvic magnetic resonance imaging or computerized tomography were performed to evaluate the recurrence of RPLS. Based on the interval from operation to neoplasm recurrence, the included PRPLS cases were divided into an STR (≤1 year) group and non-STR (>1 year) group. LRFS was defined as the period from radical operation to local recurrence.
SPSS software (version 26.0; IBM Corporation) and R software (version 4.2.2) were used for the statistical analyses. Categorical data were expressed as n (%) and compared using the two-sided χ2 test. The median (interquartile range, IQR) was used to illustrate continuous variables and comparison among groups was performed using the Mann-Whitney U-test. In addition, receiver operating characteristic (ROC) curves of continuous outcomes were drawn and dichotomous outcomes were obtained based on cut-off values. Subsequently, binary logistic regression analysis and Cox proportional hazard regression analysis were conducted to determine the predictors of STR and LRFS, respectively. Variables with P<0.15 in the univariate analysis were included in the multivariate analysis and variables with P<0.05 in the multivariate analysis were considered independent predictors. LRFS rates were estimated based on the Kaplan-Meier method and were compared between groups by the log-rank test. A nomogram was constructed using the independent predictors, aiming to predict 1-, 3- and 5-year LRFS of surgically resected PRPLS.
Initially, 396 patients with pathologically confirmed RPLS were retrieved using the EMR system. Of these, 64 did not undergo radical surgery, 196 were recurrent cases, three died from surgical complications or other causes and five were lost to follow-up. After excluding these patients, the data from the remaining 128 patients were finally included in the present analysis. At a median follow-up time of 30.0 (IQR, 14.3-67.5) months, 94 patients (73.4%) had tumor recurrence and 28 (21.9%) experienced STR (
According to the interval from surgery to neoplasm recurrence, the 128 PRPLS cases were divided into the STR (n=28) and non-STR (n=100) group. The demographic, surgical and pathological characteristics of the two groups were compared and statistically significant differences were found in preoperative NLR (P=0.040), clinical symptoms (P=0.012), resection method (P=0.034), operative time (P=0.015), intraoperative blood loss (P=0.002), transfer to ICU (P=0.003), tumor capsule (P=0.001), histological subtype (P=0.006) and tumor necrosis (P<0.001) (
Univariate and multivariate Cox proportional hazard regression models were constructed to identify the predictors of LRFS. Univariate analysis indicated that clinical symptoms [hazard ratio (HR)=1.947, P=0.002], complete resection (HR=0.239, P<0.001), operative time (HR=1.006, P<0.001), intraoperative blood loss (HR=1.001, P<0.001), transfer to ICU (HR=1.947, P
As a rare soft tissue sarcoma, PRPLS has a poor prognosis and poses a serious threat to human health. Owing to the unclear effects of radiotherapy and chemotherapy on RPLS, the application of adjuvant therapy is still controversial. Therefore, none of the cases included in the present study received radiotherapy or chemotherapy prior to or after surgery. The therapeutic effect and application time of radiotherapy and chemotherapy on RPLS still require to be further explored. At present, surgical resection remains the method of choice for PRPLS cases with indications to obtain potential cure opportunities (
Previous research has found a correlation between age and survival time for patients with PRPLS who underwent radical surgery, but a correlation between age and postoperative recurrence has not been reported (
Prolonged surgical duration was another important predictor for 1-year recurrence. Huge tumor volume, dense adhesion and tumor invasion of surrounding tissues and organs bring great difficulties to the radical operation, thus further prolonging the operation time, increasing the chance of residual tumor and tumor cells disseminating and spreading (
Histological subtypes, including well-differentiated, de-differentiated, mixed, mucinous and pleomorphic subtype, was also an important predictor for PRPLS recurrence (
Therefore, ensuring the integrity of the tumor resected by the first operation was particularly important and the tumor with its surrounding tissue should be excised as whole as possible to ensure a negative margin (
Although the present study was the first to explore prognostic factors of STR and construct a novel nomogram of LRFS for surgically resected PRPLS, it had certain limitations. First, the analysis was performed utilizing a retrospective database from a single center, affecting the quality of evidence. Furthermore, case data with a large time span may have been one of the sources of information bias. In addition, the small sample size caused by the low incidence also affected the reliability of the analysis results to a certain extent. In the future, multicenter prospective studies with large samples and long-term follow-up are required to further validate and complement the results of the present analysis.
In conclusion, age ≥55 years, operative time ≥260 min and tumor necrosis were identified as independent risk factors of STR for surgically resected PRPLS. Clinical symptoms, piecemeal resection and de-differentiated histological subtype may be used as independent predictors of LRFS. Based on the above variables, a nomogram with good calibration was constructed to predict the 1-, 3- and 5-year LRFS for surgically resected PRPLS.
Not applicable.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
ZY and PL conceived and designed the study and drafted the manuscript. ZY, XZ and SZ participated in writing the manuscript, as well as analyzing and interpreting the data. JG and NL collected and analyzed the data and produced the tables and figures. ZY and PL confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.
The present study was approved by the ethics committee of the Chinese PLA General Hospital (Beijing, China). This study was undertaken according to the provisions of the Declaration of Helsinki. The requirement for written informed consent was waived due to the retrospective nature of the study.
Not applicable.
The authors declare that they have no competing interests.
Flowchart of patient selection.
Kaplan-Meier curves of LRFS for (A) clinical symptoms, (B) resection method and (C) histological subtype. LRFS, local recurrence-free survival; sym, symptoms; differ, differentiation.
Nomogram for 1-, 3- and 5-year LRFS in patients with primary retroperitoneal liposarcoma. LRFS, local recurrence-free survival.
Calibration plots for internal validation of (A) 1-, (B) 3- and (C) 5-year LRFS nomogram. LRFS, local recurrence-free survival.
Characteristics of included primary retroperitoneal liposarcoma cases in STR group and non-STR group.
Variable | Total (n=128) | STR group (n=28) | Non-STR group (n=100) | P-value |
---|---|---|---|---|
Sex | 0.840 | |||
Male | 71 (55.5) | 16 (57.1) | 55 (55.0) | |
Female | 57 (44.5) | 12 (42.9) | 45 (45.0) | |
Age, years | 54 (48, 64) | 59 (51, 65) | 53 (47, 62) | 0.076 |
BMI, kg/m2 | 23.55 (21.49, 25.24) | 23.55 (21.08, 24.66) | 23.55 (21.57, 25.44) | 0.614 |
Preoperative NLR | 2.99 (1.95, 3.58) | 3.57 (2.56, 3.74) | 2.72 (1.74, 3.58) | 0.040 |
Previous abdominal surgery | 0.697 | |||
Yes | 31 (24.2) | 6 (21.4) | 25 (25.0) | |
No | 97 (75.8) | 22 (78.6) | 75 (75.0) | |
Clinical symptoms | 0.012 | |||
Yes | 74 (57.8) | 22 (78.6) | 52 (52.0) | |
No | 54 (42.2) | 6 (21.4) | 48 (48.0) | |
Resection method | 0.034 | |||
Piecemeal | 9 (7.0) | 5 (17.9) | 4 (4.0) | |
Complete | 119 (93.0) | 23 (82.1) | 96 (96.0) | |
Combined organ excision | 0.082 | |||
Yes | 73 (57.0) | 20 (71.4) | 53 (53.0) | |
No | 55 (43.0) | 8 (28.6) | 47 (47.0) | |
Operative time, min | 184 (140, 240) | 209 (163, 280) | 178 (136, 235) | 0.015 |
Intraoperative blood loss, ml | 475 (200, 1000) | 900 (313, 1800) | 400 (200, 875) | 0.002 |
Intraperitoneal chemotherapy drug application | 0.810 | |||
Yes | 62 (48.4) | 13 (46.4) | 49 (49.0) | |
No | 66 (51.6) | 15 (53.6) | 51 (51.0) | |
Transfer to ICU | 0.003 | |||
Yes | 25 (19.5) | 11 (39.3) | 14 (14.0) | |
No | 103 (80.5) | 17 (60.7) | 86 (86.0) | |
Pathological characteristics | ||||
Tumor diameter, cm | 25.0 (18.6, 32.0) | 25.8 (19.0, 32.8) | 25 (18.6, 32) | 0.723 |
Multiple primary tumors | 0.338 | |||
Yes | 24 (18.8) | 7 (25.0) | 17 (17.0) | |
No | 104 (81.2) | 21 (75.0) | 83 (83.0) | |
Tumor shape | 0.908 | |||
Irregular | 40 (31.3) | 9 (32.1) | 31 (31.0) | |
Regular | 88 (68.7) | 19 (67.9) | 69 (69.0) | |
Tumor capsule | 0.001 | |||
Intact | 98 (76.6) | 15 (53.6) | 83 (83.0) | |
Broken | 30 (23.4) | 13 (46.4) | 17 (17.0) | |
Histological subtype | 0.006 | |||
Well-differentiated | 45 (35.2) | 5 (17.9) | 40 (40.0) | |
De-differentiated | 18 (14.1) | 9 (32.1) | 9 (9.0) | |
Other subtypes | 65 (50.7) | 14 (50.0) | 51 (51.0) | |
Tumor necrosis | <0.001 | |||
Yes | 36 (28.1) | 16 (57.1) | 20 (20.0) | |
No | 92 (71.9) | 12 (42.9) | 80 (80.0) |
Values are expressed as the median (lower quartile, upper quartile) for continuous variables and n (%) for categorical variables. STR, short-term recurrence; BMI, body mass index; NLR, neutrophil/lymphocyte ratio; ICU, intensive care unit.
Multivariate analysis of predictors for short-term (≤1 year) recurrence.
Variable | β coefficient | OR (95% CI) | P-value |
---|---|---|---|
Age ≥55 years | 1.724 | 5.607 (1.517-20.726) | 0.010 |
Preoperative NLR ≥2.38 | 1.416 | 4.121 (0.889-19.096) | 0.070 |
Clinical symptoms | 1.000 | 2.717 (0.760-9.714) | 0.124 |
Complete resection | −0.812 | 0.444 (0.066-3.007) | 0.406 |
Combined organ excision | −0.308 | 0.735 (0.214-2.528) | 0.625 |
Operative time ≥260 min | 2.274 | 9.716 (1.975-47.791) | 0.005 |
Intraoperative blood loss ≥1,200 ml | −0.284 | 0.753 (0.162-3.492) | 0.717 |
Transfer to ICU | 0.577 | 1.781 (0.349-9.095) | 0.488 |
Intact tumor capsule | −0.761 | 0467 (0.124-1.764) | 0.262 |
Histological subtype | 0.088 | ||
De-differentiated vs. well-differentiated | 1.706 | 5.506 (0.833-36.376) | 0.077 |
Other subtypes vs. well-differentiated | 0.054 | 1.055 (0.229-4.871) | 0.945 |
Tumor necrosis | 1.330 | 3.781 (1.087-13.156) | 0.037 |
NLR, neutrophil/lymphocyte ratio; ICU, intensive care unit; OR, odds ratio; CI, confidence interval.
Further multivariate analysis for short-term (≤1 year) recurrence.
Variable | β coefficient | OR (95% CI) | P-value |
---|---|---|---|
Age ≥55 years | 1.690 | 5.421 (1.768-16.616) | 0.003 |
Operative time ≥260 min | 2.354 | 10.524 (3.131-35.374) | <0.001 |
Tumor necrosis | 1.978 | 7.231 (2.526-20.696) | <0.001 |
OR, odds ratio; CI, confidence interval.
Univariate and multivariate analyses of predictors for local recurrence-free survival.
Univariate analysis | Multivariate analysis | |||||
---|---|---|---|---|---|---|
Variable | HR | 95% CI | P-value | HR | 95% CI | P-value |
Sex (male) | 1.138 | 0.754-1.719 | 0.538 | |||
Age | 1.009 | 0.990-1.028 | 0.356 | |||
Preoperative NLR | 1.030 | 0.986-1.076 | 0.184 | |||
BMI (kg/m2) | 0.954 | 0.896-1.017 | 0.147 | 0.955 | 0.891-1.024 | 0.196 |
Previous abdominal surgery | 1.007 | 0.628-1.614 | 0.979 | |||
Clinical symptoms | 1.947 | 1.267-2.994 | 0.002 | 1.746 | 1.105-2.760 | 0.017 |
Complete resection | 0.239 | 0.116-0.492 | <0.001 | 0.370 | 0.159-0.861 | 0.021 |
Combined organ excision | 1.402 | 0.924-2.127 | 0.112 | 0.703 | 0.431-1.148 | 0.159 |
Operative time | 1.006 | 1.003-1.009 | <0.001 | 1.004 | 1.000-1.007 | 0.059 |
Intraoperative blood loss | 1.001 | 1.000-1.001 | <0.001 | 1.000 | 1.000-1.001 | 0.095 |
Intraperitoneal chemotherapy drug application | 0.936 | 0.624-1.405 | 0.749 | |||
Transfer to ICU | 1.947 | 1.178-3.220 | 0.009 | 1.026 | 0.567-1.856 | 0.933 |
Tumor diameter | 1.013 | 0.994-1.033 | 0.171 | |||
Multiple primary tumors | 1.589 | 0.966-2.614 | 0.068 | 1.379 | 0.796-2.390 | 0.252 |
Tumor shape | 1.458 | 0.949-2.240 | 0.085 | 0.998 | 0.594-1.677 | 0.993 |
Tumor capsule | 0.594 | 0.372-0.949 | 0.029 | 0.865 | 0.476-1.572 | 0.635 |
Histological subtype | 0.003 | 0.126 | ||||
De-differentiated vs. well-differentiated | 2.888 | 1.555-5.363 | 0.001 | 1.975 | 1.006-3.875 | 0.048 |
Other subtypes vs. well-differentiated | 1.638 | 1.029-2.608 | 0.037 | 1.423 | 0.875-2.314 | 0.155 |
Tumor necrosis | 1.647 | 1.055-2.573 | 0.028 | 1.253 | 0.761-2.064 | 0.375 |
BMI, body mass index; NLR, neutrophil/lymphocyte ratio; ICU, intensive care unit; HR, hazard ratio; CI, confidence interval.