ARTICLE
Auteur(s) : Ming-zhou Qiao, Chang-ling Li
Department of Urology, Cancer Hospital, CAMS and PUMC, Beijing
100021, China
The retroperitoneum is the site of origin of 15 to 20% of soft
tissue sarcomas (STS) [1]. Surgical resection remains the mainstay
of treatment. Because retroperitoneal STS are often large and
locally advanced at presentation, and are adjacent to vital viscera
and major vascular structures, complete surgical resection is
possible in only 67% of patients who present with primary disease
[2]. Therefore, the outcome is characterized by a high local
recurrence rate leading to a poor overall survival.The aim of
present study was to investigate the factors affecting
postoperative recurrence and prognosis. A retrospective analysis
was performed in 77 patients who were affected by primary
Retroperitoneal Sarcoma and treated in Cancer Hospital, CAMS.
Patients and methods
Between January 1980 and December 2005, 161 patients with
retroperitoneal sarcoma were treated with surgery in Cancer
Hospital, CAMS. Recurrent tumors, visceral sarcomas, and uncertain
histological diagnoses were not included in this study. A total of
77 patients (36 men and 41 women) were eligible. The median age was
49 years (range 24-75). The mean size of the tumor was 19.4 (4-50)
cm. The tumor was completely resected in 44 cases (57.1%) and
incompletely resected in 33 cases (42.9%). During surgical
procedures, resection of adjacent organs was required in 24 (31.2%)
patients (table 1( Table 1 )). The
histological subtypes included liposarcoma (49 cases),
leiomyosarcoma (11 cases), fibrosarcoma (9 cases), and other
subtypes (8 cases). Tumor histological grade was classified as low
in 49 cases and high in 22 cases and was not available in 6
patients. Tumors invaded the adjacent organs in 14 patients. After
surgery, 18 patients received adjuvant chemotherapy and/or
radiotherapy.
Local recurrence was defined as the first clinically,
radiologically, or pathologically evident tumor of the same
histological type, within or contiguous to the previously treated
tumor bed, 3 or more months after primary therapy. According to
this criterion, 57 patients had local recurrence after surgery in
present study.
All data were analyzed with SPSS 10.0 software package.
Univariate analysis was performed with the Kaplan-Meier and
log-rank tests. Independent prognostic values were analyzed with
the Cox proportional hazards model, with relative risks and 95%
confidence intervals. In all statistical analyses, p < 0.05 was
considered significant.
Table 1 Resection of adjacent organ
|
Surgery procedure
|
No. of patients (%)
|
|
Tumor resection only
|
53 (68.8)
|
|
Resection of tumor and adjacent organs
|
24 (31.2)
|
|
Kidney
|
12
|
|
Colon (partial)
|
6
|
|
Spleen
|
2
|
|
Pancreas (partial)
|
2
|
|
Liver (partial)
|
2
|
|
Stomach (partial)
|
1
|
|
Ovary
|
1
|
|
Ureter (partial)
|
1
|
Results
After a median follow-up of 45.7 months (range 3.6-180.4, mean
59.5), there were 57 patients who had local recurrence. The
overall recurrence rate was 74%. The median time between initial
surgery and recurrence was 14.8 months (range 3.2-99.6). Three
patients had advanced disease with distant metastases. The
metastasis site was lung in two patients and liver in one patient.
A total of 32 patients died during follow-up, including 27 who died
of their sarcoma and 5 who died of other diseases. The median
survival time after surgery was 42.5 months. The 5- and 10-year
overall survival rates were 61.7 and 43.9%, respectively ( (figure 1) ). The
5- and 10-year recurrence-free survival rates were 22.7 and 16.8%,
respectively.
Overall survival
In univariate analysis, female sex (p = 0.034),
age < 45 years (p = 0.019), complete resection
(p < 0.001), no adjuvant therapy (p = 0.013), no adjacent organ
invasion (p = 0.019), and no local recurrence (p = 0.002) were
associated with an increased overall survival while resection of
adjacent organ involvement (p = 0.608) and high histological grade
(p = 0.523) were not correlated with overall survival. All these
factors except complete resection retained independent prognostic
value in the multivariate analysis (table 2( Table 2 )).
Table 2 Cox regression analysis
|
B
|
SE
|
Wald
|
df
|
Sig.
|
Exp(B)
|
95% CI for Exp(B)
|
|
Lower
|
Upper
|
|
Age
|
- 0.835
|
0.432
|
3.736
|
1
|
0.053
|
0.434
|
0.186
|
1.012
|
|
Complete resection
|
1.465
|
0.430
|
11.576
|
1
|
0.001
|
4.326
|
1.861
|
10.059
|
|
Adjuvant therapy
|
0.703
|
0.410
|
2.938
|
1
|
0.087
|
2.021
|
0.904
|
4.517
|
|
Organ invasion
|
- 0.138
|
0.469
|
0.087
|
1
|
0.768
|
0.871
|
0.348
|
2.182
|
|
Local recurrence
|
- 1.187
|
0.627
|
3.582
|
1
|
0.058
|
0.305
|
0.089
|
1.043
|
Tumor-related mortality
Female sex (p = 0.047), tumor size < 15 cm (p = 0.045),
complete resection (p < 0.001), no adjacent organ invasion
(p = 0.012), and no local recurrence (p = 0.001) were the factors
found to be correlated with a decreased risk of tumor mortality in
univariate analysis. When subjected to a Cox multivariate analysis,
the only factor found to decrease the risk of tumor mortality was
complete resection of the tumor.
Local recurrence
Univariate analysis showed that high pathological grade (p = 0.042)
and incomplete resection (p = 0.019) were associated with an
increased risk of local recurrence. Other factors such as tumor
size, adjacent organ invasion, resection of adjacent organ, and
adjuvant therapy had no prognostic significance.
Discussion
Generally, retroperitoneal STS cannot be diagnosed easily during
its early course because of its anatomical site and delayed disease
presentation. When the tumor grows and compresses adjacent organs,
it is diagnosed as a large tumor mass . It was reported that
complete resection of the tumor and obtaining a negative surgical
margin were difficult [3, 4]. In present study, the mean tumor size
is 19.4 cm. Complete surgical resection of the tumor was
achieved in 44 of the total group of 77 patients (57.1%), which was
less than the percentages reported in the literature [2].
This study demonstrates that complete surgical resection of the
tumor is the most important factor for increased overall survival
and may significantly decrease the local recurrence rate and tumor
mortality. We therefore conclude that complete resection at the
time of primary tumor presentation is the main means to cure
retroperitoneal STS. Incomplete surgical resection will increase
the probability of local recurrence and tumor mortality. To
identify patterns of recurrence and prognostic factors associated
with long-term survival after resection, the investigators of
Memorial Sloan-Kettering Cancer Center analyzed the data of 198
patients with retroperitoneal STS. This study demonstrated that
complete surgical resection was likely to afford the best chance
for long-term survival and incomplete gross resection was found to
increase the risk of mortality when extensive surgery was
performed.
In the present study, adjacent organ invasion, local recurrence
were negatively correlated with overall survival rate and it even
increase the risk of tumor mortality, though this trend was not
significant in a multiviarate analysis. Extensive invasion to vital
viscera and major vascular structures may lead incomplete surgical
resection and local recurrence. Local recurrence is the main cause
of treament failure. Surgical resection of the invaded organ at the
time of definitive operation will not significantly increase the
local recurrence rate and decrease the overall survival rate.
This study also demonstrated that female patients benefited from
a higher overall survival rate and a lower risk of tumor-related
mortality. To our knowledge, there is no report in the literature
concerning the prognostic difference of gender in retroperitoneal
STS patients. It has been reported that age less than 50 years may
increase the risk of distant metastasis although it didn’t show any
prognostic effect on tumor mortality [5]. In the present study, age
less than 45 years was found to be associated with an increased
overall survival rate. Stojadinovic et al. [6] reported that large
tumor size was associated with positive surgical margins which
could decrease the disease-free survival and cancer-specific
survival. The present study demonstrates that a tumor size larger
than 15 cm may increase the risk of tumor mortality.
It has been reported that pathological grade is an important
prognostic factor [5, 7, 8]. High grade tumors were associated with
increased risk of local recurrence and distant metastasis. In the
present study, pathological grade was associated with the local
recurrence rate. High tumor grade was found to significantly
increase the local recurrence rate, but did not affect the overall
survival rate and the risk of tumor-related mortality.
At present, randomized series that have examined both radiation
therapy and chemotherapy have not shown a survival benefit.
Conversely radiotherapy may delay the time to local recurrence [9].
In the present study, 18 patients received adjuvant chemo- or
radiotherapy. Their local recurrence rate did not differ from that
of patients who had not received adjuvant therapy, but their
overall survival rate was lower. Most of the patients having
received adjuvant therapy in this study were those with large size,
incompletely resected, or adjacent organ invading tumors.
In summary, the local recurrence rate is high after surgical
resection of retroperitoneal STS. Adjacent organ invasion and local
recurrence decrease the overall survival rates and increase the
risk of tumor-related mortality. Complete resection of the tumor
and invaded organs at the time of first surgery is the main means
to decrease local recurrence and afford the best chance for
long-term survival. Age < 45 years, female sex and tumor
size <15 cm are associated with prolonged survival. High
tumor grade appears to increase the local recurrence rate.
References
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