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364
Metastases to the Retroperitoneum in Patients with
Extremity Soft Tissue Sarcoma
An Unusual Metastatic Pattern
Dina Lev-Chelouche, M.D.1
Richard Nakache, M.D.1
Dror Soffer, M.D.1
Ofer Merimsky, M.D.2
Joseph M. Klausner, M.D.1
Mordechai Gutman, M.D.1
1
Department of Surgery B, Tel Aviv Sourasky
Medical Center, Sackler Faculty of Medicine, Tel
Aviv University, Tel Aviv, Israel.
2
Department of Oncology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv
University, Tel Aviv, Israel.
BACKGROUND. Extremity soft tissue sarcoma (STS) metastasizes preferentially to
the lungs via the hematogenous route. Metastases in extrapulmonary sites such as
bone, brain, and subcutaneous tissues are observed less frequently. To the authors’
knowledge, limb STS primarily metastasizing to the retroperitoneum has not been
described to date. The current study reviews the clinical course, management, and
patient prognosis in such a pattern of metastasis.
METHODS. Records of patients with retroperitoneal metastases originating from an
extremity STS between 1994 –1998 were reviewed. Patient demographics, primary
tumor site, other tumor sites, local recurrence, distant metastasis, treatment, and
survival were analyzed.
RESULTS. Ten patients were included in the study. All had primary STS of different
histologic types and high histologic grade confined to a lower limb. The retroperitoneal metastases were diagnosed between 6 –120 months (mean, 45 months) after
diagnosis of the primary sarcoma. At that time, one patient had evidence of local
recurrence of the primary tumor site, two patients had lung metastases, and one
patient had diffuse bone metastases. Eight patients were eligible for surgery. In six
of these patients the metastases were excised completely. The median follow up
was 12 months. Of the six patients who underwent complete resection, 3 were alive
at last follow-up with no evidence of disease after 12 months, 14 months, and 24
months, respectively. Two patients with recurrent retroperitoneal disease and one
patient with retroperitoneal and lung metastases died despite systemic chemotherapy.
CONCLUSIONS. Extremity STS can metastasize hematogenously to the retroperitoneum, a fact that mandates a high index of suspicion and abdominal imaging
studies during the follow-up of such patients. Retroperitoneal metastases necessitate aggressive surgical resection to enable prolongation of survival. Cancer 2000;
88:364 – 8. © 2000 American Cancer Society.
KEYWORDS: soft tissue sarcoma, limb, retroperitoneum, metastasis, treatment,
survival.
oft tissue sarcomas (STS) are relatively rare, comprising ⬍ 1% of
all adult solid malignancies. This low incidence rate, together with
the multitude of histologic subtypes, is responsible for the relatively
obscure knowledge regarding their natural history. Approximately
60% of STS occur in the extremities, mainly in the lower limb. At the
time of diagnosis, the majority of patients do not have detectable
distant metastases, and initial therapy therefore is directed at definitive treatment of the primary lesion.1 Use of a multimodality approach– (surgery, chemotherapy, and radiation) has resulted in a
significantly lower local recurrence rate and improved local control.2,3
S
Address for reprints: Mordechai Gutman, M.D.,
Department of Surgery B, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239,
Israel.
Received April 23, 1999; accepted September 27,
1999.
© 2000 American Cancer Society
Sarcoma Metatasizing to the Retroperitoneum/Lev-Chelouche et al.
365
TABLE 1
Patient and Tumor Characteristics
Patient
no.
Age
(yrs)
Gender
Histology/grade
1
2
3
4
5
6
7
8
9
10
43
42
22
38
34
58
35
83
75
47
M
M
M
M
M
F
M
F
F
F
Liposarcoma/2
Liposarcoma/2
Malignant schwannoma/2
Leiomyosarcoma/2
Synovial sarcoma/2
Malignant fibrous histiocytoma/2
Malignant fibrous histiocytoma/3
Malignant fibrous histiocytoma/3
Liposarcoma/2
Liposarcoma/2
Primary site
TNM staging of
primary tumor8
Time to retroperitoneal
metastases from
primary diagnosis (mos)
Local recurrence/other
metastatic sites
Thigh
Thigh
Thigh and calf
Thigh
Calf
Thigh
Thigh
Thigh
Thigh
Thigh
IIB
IIB
IIB
IIB
IIB
IIB
IIIB
IIIB
IIB
IIB
37
12
32
96
36
24
6
72
120
12
No
Local recurrence
No
No
No
Lung
Lung
No
No
Bone
M: male; F: female.
However, mortality remains high and largely is attributed to the well recognized propensity of STS for hematogenous dissemination.
Extremity STS appear to metastasize preferentially
to the lungs and indeed the lung is the first site of
spread, accounting for up to 80% of all metastases in
the majority of series reported to date.4,5 This led to
the recommendation that during follow-up of patients
after resection of an STS of a limb, the physician’s
attention should focus on the local site of the tumor
and the lungs. Less frequently, metastases in extrapulmonary sites such as bone, brain, and, occasionally,
subcutaneous tissues are observed. This pattern will
develop in approximately 14% of patients as the initial
manifestation of metastatic disease.4 Lymphatic metastases are uncommon and occur in ⬍ 5% of sarcoma
patients.6 The low rate of lymph node involvement
occurs as a result of the limited lymphatic supply to
mesodermal structures resulting from the unusual involvement of these tissues in a host defense against
invasion by pathogens.7 To our knowledge, the retroperitoneum, although a rather common site for primary STS, is a rare and poorly described target for the
spread of extremity STS. Encountering patients with
this disease entity led us to undertake the current
study to examine the natural history, treatment, and
prognosis of patients with this unique metastatic pattern.
MATERIALS AND METHODS
The records of patients with retroperitoneal metastases originating from an extremity STS treated in our
surgical department between 1994 and 1998 were reviewed. Included were all patients with a history of
histologically proven primary STS confined to the limb
who developed a histologically identical secondary
retroperitoneal mass. Charts and histopathologic
slides were reviewed to determine clinical presentation, size, histologic type, and grade of both the extremity and the retroperitoneal tumor, treatment of
the primary tumor, time to development of retroperitoneal metastasis, extent of surgical resection and use
of chemotherapy, pattern of recurrence and metastases, and survival.
RESULTS
Ten patients were included in the study; 6 were male
and 4 were female, ages 22– 83 years (mean, 48 years)
(Table 1). All had primary STS confined to the lower
limb, with no evidence of metastases at time of diagnosis. There were four liposarcomas, three malignant
fibrous histiocytomas, one synovial sarcoma, one
leiomyosarcoma, and one malignant schwannoma. All
tumors were of high histologic grade (1997 AJCC
Grades II–III). Staging according to the TNM system is
reported in Table 1.8 The primary tumors were treated
via a multimodality limb-sparing approach including
complete resection plus radiotherapy (seven patients),
systemic chemotherapy (four patients), and isolated
limb perfusion with chemotherapeutics and/or tumor
necrosis factor (four patients). Prior to the diagnosis of
retroperitoneal metastases, three patients experienced
local recurrence that necessitated further treatment;
none underwent amputation.
The retroperitoneal metastases were diagnosed
between 6 –120 months (mean, 45 months) after diagnosis of the primary sarcoma. The most common presenting symptoms were abdominal pain and a palpable abdominal mass. Other symptoms included
anorexia, nausea, emesis, and weight loss. Four patients were asymptomatic and were diagnosed inci-
366
CANCER January 15, 2000 / Volume 88 / Number 2
TABLE 2
Treatment and Follow-Up
Patient
no.
Treatment
Follow-up
Status (D/A)
1
Complete resection, colectomy, and nephrectomy
D, 12 mos
2
Resection of recurrent extremity STS and complete retroperitoneal
metastases resection
Laparotomy - biopsy, chemotherapy
Complete resection, colectomy, splenectomy, and distal
pancreatectomy
Laparotomy - biopsy, chemotherapy
Complete resection, nephrectomy, and lung metastectomy
Chemotherapy
Complete resection, sigmoidectomy, iliac vessel resection, and
reconstruction
Complete resection
Chemotherapy
Recurrent retroperitoneal and lung metastases
(8 mos)
Recurrent retroperitoneal metastases (12 mos)
D, 18 mos
NED
D, 6 mos
A, 14 mos
3
4
5
6
7
8
9
10
NED
NED
Recurrent retroperitoneal metastases (12 mos)
D, 8 mos
A, 12 mos
D, 6 mos
A, 24 mos
D, 24 mos
A, 3 mos
D: dead; A: alive; STS: soft tissue sarcoma; NED: no evidence of disease.
dentally through imaging studies performed during
the follow-up of patients with a history of STS.
At the time of diagnosis of the retroperitoneal
mass, one patient had evidence of local recurrence of
the primary site, two patients were found to have lung
metastases (one had two lung lesions and the other
had diffuse bilateral disease), and a fourth patient had
diffuse bone metastases. The remaining six patients
had no evidence of any other metastatic spread and
the disease was confined to the retroperitoneum,
which was the initial site of disease spread.
Treatment was based on the extent of disease
(Table 2). The two patients with diffuse extraabdominal disease (lung and bone) were treated with doxorubicin-based chemotherapy. The patient with limited
lung disease and the patient with simultaneous local
recurrence underwent combined surgery to resect all
evident disease. The six patients with metastases confined to the retroperitoneum were referred for curative
surgical resection.
Surgical Treatment
Prior to abdominal resection surgery, all eight patients
had undergone preoperative assessment including ultrasonography, computed tomography, or magnetic
resonance imaging, and all were considered to have
resectable disease according to these imaging techniques. Six patients were found to have single lesions
with an average dimension of 15 cm; all underwent
complete resection necessitating en bloc excision of
adjacent structures in four patients: colectomy (three
patients), nephrectomy (two patients), splenectomy
(one patient), distal pancreatectomy (one patient),
and iliac vessel excision and reconstruction (one patient). Two patients were found to have nonresectable
diffuse metastatic disease infiltrating the root of the
mesentery and only a biopsy was performed. These
patients later received systemic chemotherapy. There
was no perioperative mortality. Two patients had
wound infections but no other major complications
were observed.
According to the pathologic examinations performed by two separate pathologists, all resected tumors were comprised of clean microscopic margins
and histologically were identical with regard to tumor
type and grade to the primary extremity STS, as were
those tumors that were biopsied only. There was no
evidence of lymph node involvement.
Follow-up
The median follow-up period to date was 12 months.
Of the six patients who underwent complete resection,
two had recurrent retroperitoneal disease that was
found to be nonresectable and one patient had retroperitoneal and lung metastases. All 3 patients received
systemic chemotherapy but all died at 12 months, 18
months, and 24 months, respectively, after the initial
diagnosis of retroperitoneal metastases. The remaining 3 patients were alive with no evidence of disease at
12 months, 14 months, and 24 months, respectively,
after undergoing curative resection (Table 2).
Both patients who underwent biopsy alone died 6
months and 8 months, respectively, after surgery. Of
the 2 patients with diffuse metastatic disease who
were treated with chemotherapy alone, 1 patient died
Sarcoma Metatasizing to the Retroperitoneum/Lev-Chelouche et al.
6 months after diagnosis and the second patient was
alive after 3 months.
DISCUSSION
The fact that sarcomas spread hematogenously, and
that the lung is the most common site for such spread,
has been well established in the literature.4-6 However,
to the best of our knowledge, extremity STS primarily
metastasizing to the retroperitoneum has not been
described previously. In the current study we reviewed
the clinical course of ten patients with such a pattern
of metastasis. Although this was a small group of patients, they should be viewed differently given the
rarity of STS. The estimated annual incidence rate of
STS of the limb in Israel is approximately 70 patients
among the entire population.
The diagnosis of retroperitoneal metastases is difficult because the symptoms are vague and manifest only
when the disease is very extensive. In the current study,
tumors had reached a mean dimension of 15 cm at the
time of diagnosis, and many patients were asymptomatic. Although the majority of systemic failures in STS
occur within the first 2 years,4 the time to development
of metastatic disease in the current series was 6 –120
months (mean, 45 months), emphasizing the need for
the prolonged follow-up of sarcoma patients.
Are we dealing with metastasis or is it a multifocal
sarcoma?
Blair et al.9 described six patients with multifocal
sarcoma, six of whom had recurrent extremity STS with
a sarcoma present in the retroperitoneum as well. However, all these patients had other sites of involvement
concurrently, whereas in the majority of the patients in
the current study (seven of ten patients), the retroperitoneum was an isolated and initial site of metastasis.
Moreover, all retroperitoneal sarcomas in the current
study were identical histologically to the primary extremity STS, making the metastatic theory more likely.
We theorize that the dissemination of sarcoma
from the extremity to the retroperitoneum most likely
occurred via a hematogenous route because there was
no evidence of direct extension from the leg to the
retroperitoneum and, although the lymphatic channels also are a potential metastatic route, it is unlikely
in the ten patients described in the current study
because no lymph node involvement was found.
Treatment of metastatic sarcoma to the retroperitoneum mainly is based on surgical resection. Experience with surgical resection of pulmonary metastases
indicate that this approach may prolong patient survival.10,11 Only a small number of patients with isolated sites of involvement other than the lung (bone,
subcutaneous tissue, liver, and lymph nodes) will be
amenable to surgical resection and remain disease
367
free for a prolonged period. Thus the prognosis for the
majority of patients developing this pattern of metastasis is far less favorable than that for patients developing an isolated pulmonary metastasis.4
The current study suggests that one could adopt
the approach used for lung metastases to retroperitoneal metastases also, because 50% (3 of 6 patients) of
the patients in the current study with resectable disease were alive with no evidence of disease at last
follow-up, whereas those patients with nonresectable
disease had a short survival period of only several
months’ duration.
Surgery for retroperitoneal metastases should be
identical to surgery for primary retroperitoneal sarcoma,
in which the main goal is complete resection of all tumor
masses with macroscopic negative surgical margins.12,13
This can be accomplished using a policy of liberal en
bloc resection even when contiguous organs are not
invaded directly, but approximate the margin of resection. However, even this aggressive surgical approach
does not eliminate the possibility of recurrence, which in
our study reached 50% (3 of 6 patients).
Comparing our patients with retroperitoneal metastases with those patients with primary retroperitoneal STS, we found a lower resectability rate for the
former group (60% vs. 80 –95%).12,13 These results are
similar to the resectability rate of recurrent retroperitoneal sarcomas, a fact that most likely reflects a more
aggressive disease.
Current chemotherapy modalities are not effective against retroperitoneal sarcomas, and radiation is
limited by toxicity to adjacent structures. It would
appear that the same can be said with regard to retroperitoneal metastases because none of the patients
in the current series who were treated by chemotherapy showed improved survival.
According to the literature, multiple sites of metastasis are described as developing in 14% of patients
with extremity STS.4 Only 6.6% of these patients were
found to be surgically rendered disease free and none
enjoyed prolonged survival. In the current series, three
patients developed recurrence at more than one site,
one of which was found to be resectable (lung metastasectomy and complete retroperitoneal sarcoma resection). At last follow-up this patient was still alive
with no evidence of disease 1 year later. Thus, we
believe that, if possible, all sites of malignancy should
be resected to enable prolonged survival.
Abdominal imaging studies, in contrast to those of
the chest, are not performed routinely during the follow-up of patients with extremity STS. However, after
gathering further information regarding the true incidence rate of retroperitoneal metastases, it may prove
logical to recommend the addition of such studies in
368
CANCER January 15, 2000 / Volume 88 / Number 2
the future to diagnose retroperitoneal disease as early
as possible and enable efficient treatment.
Our conclusions are that extremity STS can metastasize hematogenously to the retroperitoneum, a
fact that mandates a high index of suspicion and may
support the performance of abdominal imaging studies during the follow-up of patients with such sarcomas. Retroperitoneal metastases necessitate the same
aggressive surgical treatment as retroperitoneal sarcomas to enable prolonged survival.
5.
6.
7.
8.
9.
10.
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