Retroperitoneal sarcomas (RPS) are rare malignant tumors arising from mesenchymal cells. The objective of this study was to review the treatment experiences and to identify prognostic factors for overall survival (OS) after primary resection and subsequent reoperations for recurrences.
The medical records of patients who underwent resection for RPS at our institution between June 2002 and December 2016 were retrospectively reviewed. Univariate and multivariable Cox proportional hazards modeling was used to assess the prognostic factors for OS.
A total of 48 patients were enrolled. On multivariable analysis in primary resection group, the FNCLCC (Fédération Nationale des Centres de Lutte Contre le Cancer) grade was a significant prognostic factor for OS (P=0.006). The patients who received chemotherapy after primary resection were significantly associated with poor prognosis (P=0.009). The 5-year OS rate after primary resection (n=48) were 58.1% and the 5-year cumulative reoperation rate after primary resection was 62.5%. After second resection for recurrence after primary resection (n=23), the 5-year OS rate was 64.3%. There was a tendency towards decreased surgery-free survival rate as the number of repeated resections for recurrent RPS increased. In the subset of patients (n=16) who underwent more than 3 repeated resections at our institute, the 5-year OS rate was 75.0%, indicating that repeated resections are not associated with worse outcome.
Only low tumor grade was an independent favorable prognostic factor for OS. Although the prognosis for RPS remains poor, repeated resections for recurrence are not associated with poor prognosis. Aggressive surgical strategies for recurred RPS patients are warranted.
Retroperitoneal sarcomas (RPS) are rare malignant tumors arising from mesenchymal cells of the retroperitoneum such as muscle, fat, and other connective tissue and have a low incidence of 0.5 to 1 cases per 100,000 [
The prognosis for patients with RPS is relatively poor, with 5-year overall survival (OS) rates reported in the range of 39% to 70% from series with long-term follow-up [
We retrospectively reviewed prospectively collected data of patients who underwent operations with curative intent for RPS at Seoul National University Hospital in Korea between June 2002 and December 2016. Retroperitoneal tumors other than sarcomas were excluded. This study was approved by the Institutional Review Board of Seoul National University Hospital (IRB No. 1906-014-1036). The informed consent was waived.
The following variables were evaluated: age, sex, initial presenting symptoms, duration of presenting symptoms, histologic type, tumor grade, tumor size, resection type (R0/R1, R2), radiation therapy and chemotherapy after resection, pathologic organ invasion and contiguous organ resection. The resection type was divided into complete gross resection (R0/R1) and incomplete resection (R2). Tumor grade was assessed according to the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system based on differentiation, necrosis, and mitotic rate [
Statistical analysis was conducted using SPSS version 25.0 for Windows (IBM Corp., Armonk, NY, USA). P-value <0.05 was considered statistically significant. OS rate was estimated using the Kaplan-Meier method. Univariate and multivariate prognostic factor analyses for OS were performed using the log-rank test and Cox proportional hazards model, and the multivariable analysis included factors with a P-value <0.1 in the univariable analysis.
Of the 50 patients with primary RPS, two patients were excluded from this study because of insufficient operation records or pathologic reports. Of the 48 patients who received primary resection at our institution, 23 patients (47.9%) underwent repeated resections for recurrences during the follow-up period (
The clinicopathologic characteristics of the 48 patients who underwent primary resection at our institution are shown in
The mean size of the resected tumors was 18.0±11.0 cm (range, 6.0–56.5 cm), and according to the FNCLCC grading system for RPS, the patients were classified as follows: nine patients (18.8%) as grade I, 15 patients (31.2%) as grade II, and 10 patients (20.8%) as grade III. Liposarcoma (70.8%) was the most common histology, followed by leiomyosarcoma (16.7%). Thirty-five patients (72.9%) underwent R0 or R1 resection, and three patients (6.3%) underwent R2 resection. No patients received neoadjuvant radiation therapy or chemotherapy. However, 10 patients (20.8%) received radiation therapy and eight patients (16.7%) received chemotherapy after primary resection. Approximately 56.3% of patients underwent contiguous organ resection, and 29.2% had pathologic organ invasion. The 5-year OS rate after primary resection was 58.1% as shown in
Among the 48 patients who underwent primary resection at our institution, 23 patients (47.9%) underwent secondary resection for recurrence. The clinicopathologic characteristics of these 23 patients are shown in
Of the 48 patients, 23 patients (47.9%) underwent 2nd resection for recurrence, 16 patients (33.3%) underwent 3rd reoperations, and nine patients (18.7%) underwent additional resections for repeated recurrences (
In the case of liposarcoma, well-differentiated liposarcoma can dedifferentiate, which is associated with more aggressive clinical behavior [
Previous studies have documented several factors which contribute to higher OS for RPS, and tumor grade was regarded as one of the most important independent predictive factors. Accordingly, our results also indicated that the FNCLCC tumor grade was the only independent prognostic factor for OS [
Currently, the role of systemic therapy or radiation therapy for RPS remains unclear [
It is generally recognized that another major prognostic factor related to survival outcome is whether complete resection of the tumor was performed [
The unique feature of this paper is that we studied the median surgery-free survival in 23 patients who underwent repeated resections for recurrence. After primary resection, the median surgery-free survival was 25.5 months (range, 3–109 months), and as the number of reoperations increased, the median surgery-free survival tended to decrease, indicating earlier recurrence after repeated resections for recurrence. However, a statistically significant difference was not noted. An interesting point of our study is that patients who underwent repeated resection for recurrence had better OS compared to patients who underwent single resection for RPS. In fact, our results indicated that patients who underwent resections more than three times for recurrence tended to have better OS compared to patients who were operated on once or twice, although statistical significance was not reached because of the small number of patients. This finding suggests that even when RPS recur, when the recurrent tumor is amenable to surgical resection, OS may be improved, in contrast to unresectable recurrence. Our finding again emphasizes the central and most important role of surgical intervention in management of RPS. Aggressive repeated surgical approach until the point of unresectable recurrence is warranted.
In some cases of liposarcoma, histologic changes from well-differentiated type to dedifferentiated type occurred. The clinical behavior of dedifferentiated liposarcoma involves aggressive local growth and increased risk of local recurrence and tumor-related death [
This study had some potential limitations. First, the retrospective design might have led to selection bias. Second, the number of patients included in this study was relatively small. Third, the proportion of patients who received radiation therapy or chemotherapy was small, limiting the evaluation of effectiveness of adjuvant therapy.
In conclusion, according to the results of this study, the 5-year OS rate after primary resection at our institution was 58.1%, and 5-year cumulative reoperation rate after primary resection at our institution was 62.5%. Only the FNCLCC grade was a significant prognostic factor for OS. The 5-year OS rate for patients who underwent more than 3 repeated resections was 75.0%, which is comparable to patients who underwent resection only once or twice. In addition, radiation therapy or chemotherapy after resection had no effect on survival. Although OS for patients with RPS remains poor, our study shows that repeated resection in comparison to single resection does not decrease the 5-year OS rate of patients with recurrent RPS. Therefore, aggressive surgical strategies for recurrent RPS patients are warranted.
No potential conflict of interest relevant to this article was reported.
Flowchart of patient management (June 2002 to December 2016). SNUH, Seoul National University Hospital.
Outcomes after primary resection of retroperitoneal sarcoma. (A) Overall survival rate. (B) Cumulative reoperation rate (n=48).
Overall survival rate after second resection of recurred retroperitoneal sarcoma (n=23).
A 51-year-old female patient at diagnosis who underwent repeated resections for dedifferentiated liposarcoma. (A) 3rd operation, (B) 4th operation, (C) 5th operation, and (D) 6th operation.
Median surgery-free survival in reoperations of recurred retroperitoneal sarcoma.
Overall survival rate of patients who underwent resection for retroperitoneal sarcoma.
Overall survival rate dependent on histologic type of liposarcoma (n=14). WD, well-differentiated; DD, dedifferentiated.
Clinicopathologic characteristics of patients who underwent primary resection for retroperitoneal sarcoma
Variable | Value (n=48) |
---|---|
Age (yr) | 54.0±16.1 (21–84) |
| |
Sex | |
Male | 22 (45.8) |
Female | 26 (54.2) |
| |
Initial presenting symptom | |
Abdominal/back/flank pain | 15 (31.3) |
GI symptom | 3 (6.2) |
Enlarging painless palpable mass | 15 (31.3) |
Incidental finding | 11 (22.9) |
Unknown | 4 (8.3) |
| |
Length of presenting symptom | |
≤6 month | 15 (31.3) |
>6 month | 5 (10.4) |
Unknown | 17 (35.4) |
No symptom | 11 (22.9) |
| |
Histology | |
Liposarcoma | 34 (70.8) |
Leiomyosarcoma | 8 (16.7) |
Others | 6 (12.5) |
| |
Grade (FNCLCC) | |
1 | 9 (18.8) |
2 | 15 (31.2) |
3 | 10 (20.8) |
Unknown | 14 (29.2) |
| |
Tumor size (cm) | 18.0±11.0 (6.0–56.5) |
| |
Resection type | |
R0/R1 | 35 (72.9) |
R2 | 3 (6.3) |
Unknown | 10 (20.8) |
| |
Radiation therapy after primary resection | 10 (20.8) |
| |
Chemotherapy after primary resection | 8 (16.7) |
| |
Pathologic organ invasion | 14 (29.2) |
| |
Contiguous organ resection | 27 (56.3) |
Values are presented as mean±standard deviation (range) or number (%).
GI, gastrointestinal; FNCLCC, Fédération Nationale des Centres de Lutte Contre le Cancer.
Prognostic factors for overall survival after primary resection for retroperitoneal sarcoma (n=48)
Characteristic | Univariate analysis | Multivariate analysis | |
---|---|---|---|
| |||
HR (95% CI) | P-value | ||
Age (≤54 vs. >54 yr) | 0.141 | ||
| |||
Sex (male vs. female) | 0.529 | ||
| |||
Histology | 0.089 | ||
Liposarcoma | |||
Leiomyosarcoma | |||
Others | |||
| |||
FNCLCC grade | 0.003 | 0.006 | |
1 | Reference | ||
2 | 4.083 (0.473–35.250) | 0.201 | |
3 | 16.605 (1.954–141.127) | 0.010 | |
| |||
Tumor size (≤18 vs. >18 cm) | 0.082 | ||
| |||
Resection type (R0/R1, R2) | 0.221 | ||
| |||
Radiation therapy after primary resection | 0.259 | ||
| |||
Chemotherapy after primary resection | 0.004 | 4.239 (1.432–12.548) | 0.009 |
| |||
Pathologic organ invasion | 0.791 | ||
| |||
Contiguous organ resection | 0.868 |
HR, hazard ratio; CI, confidence interval; FNCLCC, Fédération Nationale des Centres de Lutte Contre le Cancer.
Statistically significant, P<0.05.
Clinicopathologic characteristics of patients who underwent secondary resection for recurred retroperitoneal sarcoma
Variable | Value (n=23) |
---|---|
Age (yr) | 58.0±13.2 (28–75) |
| |
Sex | |
Male | 12 (52.2) |
Female | 11 (47.8) |
| |
Histology | |
Liposarcoma | 18 (78.3) |
Leiomyosarcoma | 2 (8.7) |
Others | 3 (13.0) |
| |
Grade (FNCLCC) | |
1 | 6 (26.0) |
2 | 4 (17.4) |
3 | 8 (34.8) |
Unknown | 5 (21.7) |
| |
Tumor size (cm) | 8.0±5.6 (2.5–23.0) |
| |
Resection type | |
R0/R1 | 21 (91.3) |
R2 | 2 (8.7) |
| |
Radiation therapy after second resection | 3 (13.0) |
| |
Chemotherapy after second resection | 5 (21.7) |
| |
Pathologic organ invasion | 9 (39.1) |
| |
Contiguous organ resection | 11 (47.8) |
Values are presented as mean±standard deviation (range) or number (%).
FNCLCC, Fédération Nationale des Centres de Lutte Contre le Cancer.
Prognostic factors for overall survival after secondary resection for recurred retroperitoneal sarcoma (n=23)
Characteristic | Univariate analysis | Multivariate analysis | |
---|---|---|---|
| |||
HR (95% CI) | P-value | ||
Age (≤58 vs. >58 yr) | 0.292 | ||
| |||
Sex (male vs. female) | 0.292 | ||
| |||
Histology | 0.146 | ||
Liposarcoma | |||
Leiomyosarcoma | |||
Others | |||
| |||
FNCLCC grade | 0.064 | 0.074 | |
1 | Reference | ||
2 | 2.111 (0.131–33.980) | 0.598 | |
3 | 7.221 (0.860–60.617) | 0.069 | |
| |||
Tumor size (≤8 vs. >8 cm) | 0.510 | ||
| |||
Resection type (R0/R1, R2) | 0.949 | ||
| |||
Radiation therapy after second resection | 0.590 | ||
| |||
Chemotherapy after second resection | 0.008 | ||
| |||
Pathologic organ invasion | 0.147 | ||
| |||
Contiguous organ resection | 0.022 |
HR, hazard ratio; CI, confidence interval; FNCLCC, Fédération Nationale des Centres de Lutte Contre le Cancer.