Clinicopathologic characteristics
Among the 90 cases of RPLPS treated, 46 cases were diagnosed as PR RPLPS and 44 cases were diagnosed as LR RPLPS. Patient demographics and tumor characteristics are listed in Table 1. The median age of patients was 54 years (ranging from 30 to 87 years) and there was a slightly higher population of men (58.9%) compared to women. The median tumor diameter was 19.5 cm (ranging from 5 to 80 cm). All cases were classified according to FNCLCC criteria. Compared to the PR group (41.3% of grade 1; 21.7% of grade 2; 37.0% of grade 3), there was an increased number of poorly differentiated and highly malignant patients in the LR group (18.2% of grade 1; 22.7% of grade 2; 59.1% of grade 3, p = 0.042).
Table 1
Clinicopathological factors for 90 RPLPS patients
Characteristics | All patients | | Primary retroperitoneal liposarcoma | | Recurrent retroperitoneal liposarcoma | | P-valueb |
N(% of total or IQR a) | N(% of total or IQR a) | N(% of total or IQR a) |
Total number of patients | 90(100) | 46(100) | 44(100) | |
Age(years) <60 ≥60 | 63(70.0) 27(30.0) | 29(63.0) 17(37.0) | 34(77.3) 10(22.7) | 0.141 |
Gender Female | 37(41.1) | 16(34.8) | 21(47.7) | 0.212 |
Male | 53(58.9) | 30(65.2) | 23(52.3) | |
Modus operandi R0 resection R1 resection R2 resection | 46(51.1) 30(33.3) 14(15.6) | 31(67.4) 12(26.1) 3(6.5) | 15(34.1) 18(40.9) 11(25.0) | 0.004* |
Subtype Well-differentiated Dedifferentiated Myxoid Pleomorphic Mixed | 34(37.8) 24(26.7) 16(17.8) 9(10.0) 7(7.8) | 17(37.0) 11(23.9) 9(19.6) 5(10.9) 4(8.7) | 17(38.6) 13(30.0) 7(15.9) 4(9.0) 3(6.8) | 0.960 |
Blood loss(ml) <1500 ≥1500 | 60(66.7) 30(33.3) | 36(78.3) 10(21.7) | 24(54.5) 20(45.5) | 0.017* |
FNCLCC 1 2 3 | 27(30.0) 20(22.2) 43(47.8) | 19(41.3) 10(21.7) 17(37.0) | 8(18.2) 10(22.7) 26(59.1) | 0.042* |
Tumor size(cm) <20 ≥20 | 45(50.0) 45(50.0) | 24(52.2) 22(47.8) | 21(47.7) 23(52.3) | 0.673 |
Adjuvant therapy Yes No | 15(16.7) 75(83.3) | 3(6.5) 43(93.5) | 12(27.3) 32(72.7) | 0.008* |
Median adjacent organs resected | 1.0(0.0–2.0) | 1.0(0.0-1.3) | 1.0(0.0–2.0) | 0.322 |
*Significant. |
a Inter-quartile range (IQR). |
bComparison between patients who were primary retroperitoneal liposarcoma and patients who were recurrent retroperitoneal liposarcoma using Pearson's chi-squared test for categorical variables and Wilcoxon-Mann-Whitney test for continuous variables. |
Treatment strategy
A total of 51.1% (46/90) of patients underwent R0 resection, 33.3% (30/90) underwent R1 resection and 15.6% (14/90) underwent R2 resection. The primary group (R0 67.4%, R1 26.1%, R2 6.5%) showed a higher complete resection rate compared to the relapsed group (R0 34.1%, R1 40.9%, R2 25%) (p = 0.004). In order to obtain a higher rate of complete tumor resection or to reduce tumor burden, 65.6% (59/90) of patients underwent at least 1 adjacent organ resection during surgery (Table S1).The most frequent organ resection performed was for the colon (32.2%), followed by the kidney (18.9%), spleen (10.0%) and small intestine (7.8%). The median blood loss in the PR group was 800 ml (95% CI 897.7, 1541.3) and 1200 ml (95% CI 1127.1, 2811.6) in the LR group. Assigning 1500 ml of blood volume as a boundary, the LR group was more prone to blood loss during the operation (p = 0.009). In 16 patients, tumors were closely associated with abdominal blood vessels, including the iliac vessels (11.1%), inferior vena cava (8.9%) and abdominal aorta (5.6%). Postoperative complications included hemorrhagic shock (3cases), postoperative abdominal infections (3cases), pancreatic fistulas (2cases), intestinal fistula (1case), ureteral fistula (1case) and incisional liquefaction (2cases). Adjuvant therapy was performed on 15 patients (12 in the relapse group), where5 were treated with intraoperative radiotherapy, 6 with radiofrequency ablation, and 4 with chemotherapy.
Outcomes
Median follow-up time was 28 months. A total of 59 patients who underwent R0 / R1 resection showed recurrence at a rate of 77.6%, with median recurrence time being 12 months. A total of 57 patients passed away, including 43 who died of relapse after R0 / R1 resection and 14 patients who passes away after R2 resection. The OS at 1, 3 and 5 years were 68.9%, 45.6%, and 33.3%, respectively. The PFS at 1, 3 and 5 years were 50.0%, 32.2%, and 18.9%, respectively. Due to a differential course of the disease, the OS in the PR group was 80.4%, 60.9%, and 45.7% at 1, 3 and 5 years, respectively, while the OS in the LR group was 56.8%, 29.5% and 20.5%, respectively. Differences between the two groups were statistically significant (p = 0.004, Fig. 1A). Similarly, the PFS at 1, 3 and 5 years in the PR group were 63.0%, 43.5% and 28.3%, compared to 36.4%, 15.9% and 9.1% in the LR group (p = 0.015, Fig. 1B).
Among the 46 cases diagnosed with PR RPLPS, univariate analysis (Table S2) revealed that R0 resection results in longer OS than R1 and R2 resections(R0 resection median OS, 65months, 95% CI 50.02–69.52 months vs. R1 resection median OS, 19months, 95% CI 13.53–56.14 months vs. R2 resection median OS, 8months, 95% CI 1.24–20.09 months, p < 0.001). Similarly, the median PFS of patients in the R0 resection group was 53 months (95% CI 36.77–58.06 months) and 12 months for the R1 resection group (7.18-38.0 months).Assigning 1500 ml of blood loss as a limit, a large amount of intraoperative bleeding indicates poor prognosis (OS, p = 0.006; PFS, p = 0.008). The FNCLCC subtype was also a significant indicator of the postoperative survival time. The median OS times observed for FNCLCC grades 1, 2 and 3 were 70(58.23–80.93), 66(34.42–75.38) and 20(13.28–37.54) months (p < 0.001), respectively. The median PFS were 55(37.17–61.57), 36(14.73–60.07) and 12(8.51–33.14) months (p = 0.022), respectively. Multivariate analysis using the Cox proportional hazards model revealed that blood loss (OS: p = 0.003, Fig. 2B; PFS: p = 0.035, Fig. 2D) and tumor grade (OS: p = 0.000, Fig. 2C; PFS: p = 0.027, Fig. 2E) were significant prognostic factors associated with the postoperative survival time. However, extent of resection was a prognostic factor associated with OS (p = 0.035, Fig. 2A), but not with PFS (Table 2).
Table 2
Multivariate associations between clinicopathologic and treatment factors and survival for PR RPLPS patients.
Variable | | Analyses by survival type |
| OS | | PFS |
| HR | 95% CI | p Value | | HR | 95% CI | p Value |
Modus operandi (R0 vs R1 vs R2resection) | | | | 0.035* | | | | 0.326 |
R0 vs R1 | | 3.02 | 0.96-9.48 | 0.058 | | 1.69 | 0.68-4.23 | 0.260 |
R0 vs R2 | | 6.89 | 1.49-31.86 | 0.014* | | 2.51 | 0.65-9.67 | 0.182 |
Blood loss (< 1500 ml vs ≥ 1500 ml) | | 0.19 | 0.06-0.57 | 0.003* | | 2.59 | 0.16-0.94 | 0.035* |
FNCLCC (1 vs 2 vs 3) | | | | 0.000* | | | | 0.027* |
1 vs 2 | | 4.08 | 0.87-19.21 | 0.075 | | 1.57 | 0.57-4.29 | 0.383 |
1 vs 3 | | 17.68 | 4.70-66.56 | 0.000* | | 3.06 | 1.35-6.93 | 0.007* |
*Significant. |
FNCLCC, French Federation of Cancer Centers Sarcoma Group; OS, overall survival; PFS, progression-free survival; R0 resection, Complete resection + clean microscopic margins; R1 resection, Complete resection + positive microscopic margins; R2 resection, macroscopically incomplete resection. |
Among the 44 cases diagnosed as LR RPLPS, univariate analysis (Table S3) showed that a R0 resection results in longer OS (median OS, 61 months, 95% CI 38.32–72.61 months) and PFS (median PFS, 26 months, 95% CI 20.44–53.29 months). Patients with tumor diameters < 20 cm showed longer OS than patients with tumor diameters ≥ 20 cm(median OS, 30 months, 95% CI 25.27–51.97 months vs. 9months, 95% CI 8.80-32.59 months, p = 0.024). Differences of PFS between the two groups were not statistically significant (p = 0.077). Patients with low-grade disease showed favorable OS and PFS compare to those with intermediated-grade and high-grade disease (median OS: 72 months, 95% CI 42.55–94.95 months vs. 23 months, 95% CI 9.00-45.40 months vs. 12 months, 95% CI 10.31–25.46 months, p = 0.001; median PFS: 60 months, 95% CI 25.56–79.44 months vs. 12 months, 95% CI 5.58-18.43months vs. 8.5 months, 95% CI 7.00-21.30 months, p = 0.005). Multivariate analysis using the Cox proportional hazards model revealed that resection extent was a significant prognostic factor associated with OS (p = 0.001, Fig. 3A), whereas tumor grade was associated with PFS (p = 0.044, Fig. 3B) (Table 3).
Table 3
Multivariate associations between clinicopathologic and treatment factors and survival for LR RPLPS patients.
Variable | | Analyses by survival type |
| OS | | PFS |
| HR | 95% CI | p Value | | HR | 95% CI | p Value |
Modus operandi (R0 vs R1 vs R2 resection) | | | | 0.001* | | | | 0.157 |
R0 vs R1 | | 3.94 | 1.32-11.78 | 0.014* | | 2.21 | 0.99-4.94 | 0.054 |
R0 vs R2 | | 10.51 | 3.16-34.96 | 0.000* | | 0.00 | 0.00-5.74 | 0.963 |
Tumor size (< 20 cm vs ≥ 20 cm) | | 0.49 | 0.22-1.09 | 0.081 | | 0.73 | 0.34-1.58 | 0.422 |
FNCLCC (1 vs 2 vs 3) | | | | 0.090 | | | | 0.044* |
1 vs 2 | | 4.82 | 0.55-42.46 | 0.157 | | 5.58 | 1.29-24.14 | 0.021* |
1 vs 3 | | 8.19 | 1.03-65.40 | 0.047* | | 4.14 | 1.27-13.53 | 0.019* |
*Significant. |
FNCLCC, French Federation of Cancer Centers Sarcoma Group; OS, overall survival; PFS, progression-free survival; R0 resection, Complete resection + clean microscopic margins; R1 resection, Complete resection + positive microscopic margins; R2 resection, macroscopically incomplete resection. |