Retroperitoneal sarcomas (RPS) are rare tumors accounting for 10-15% of all soft tissue
sarcomas (STS). They arise between retroperitoneal organs and among vital structures (ie
major abdominal vessels) in an anatomical compartment that is not readily accessible by
physical examination. Four main histotypes account for about 80% of all cases:
well-differentiated liposarcoma (WDLPS), dedifferentiated liposarcoma (DDLPS),
leiomyosarcoma (LMS) and solitary fibrous tumor (SFT).
Compared to sarcomas at other anatomic sites, RPS are burdened by a higher local
recurrence (LR) rate (50% at 5 years) and a poorer overall survival (OS) rate (50% at
5-years). The natural history of RPS as a whole group reflects the strong tendency of
lipomatous tumors (WDLPS and DDLPS, which account for about 50% of RPS) to recur locally.
Indeed, outcome of primary RPS is highly related to the histological subtype.
WDLPS are characterized by a relatively lower LR rate, negligible metastatic potential
and a favorable overall survival. These tumors however, still may recur locally even
years after the primary resection. Intermediate grade DDLPS are characterized by a strong
tendency to recur locally and low metastatic potential. High grade DDLPS has a high risk
of both local recurrence and distant metastasis. LMS are usually intermediate or
high-grade tumors with a strong tendency to develop distant metastasis; with an adequate
resection, it is relatively common to obtain a durable local control. Classic SFT usually
fare well after surgery, with a low rate of local recurrence and distant metastasis.
Historically, surgery emerged as the only potentially curative option in the localized
setting. In the last few years there has been lively debate as to how far should a
surgeon resect in order to obtain a margin that could be considerate adequate. This issue
is particularly challenging in this anatomical compartment where widening the surgical
margins means resecting adjacent organs.
Since 2002 an 'extended' surgical approach has been proposed for primary RPS patients.
The concept was that surgical margins could be improved by encompassing the tumor with
en-bloc resection of adjacent organs. The aim was to obtain reduced local recurrence and
improved survival. This approach has proven to be effective. In particular, this surgical
approach has been supported by an experimental model, retrospective comparisons,
pathology studies demonstrating adjacent organ involvement, and reports of high rates of
residual tumor at re-excision after conventional (non-extended) primary surgery. Finally,
this approach has been shown to be safe after both short and long term follow-up.
Radiotherapy is an option for RPS, especially in the preoperative setting, but currently
the best evidence for efficacy comes form retrospective, mainly single-center, small size
series. The results of such studies are controversial and high quality data are lacking.
A randomized prospective study led by EORTC (STRASS) is ongoing but results are not
expected for several years.
The role of chemotherapy in the localized disease is also still under investigation,
especially in high grade tumors. So far, there is no agreement on the optimal treatment
strategy, even within reference centers, regarding the use of both chemo- and
radiotherapy. In the recent years European and North-American centers joined the panel of
expert and this led to the formation of the TransAtlantic Retroperitoneal Sarcoma Working
Group (TARPSWG), which now consists of more than 50 representatives from sarcoma centers
from all over the world.
The aim of this collaboration is to expand the knowledge of the disease and formulate
shared, standardized principles of treatment. A retrospective study has been carried out
and recently published by the group to better define patients' outcome and prognostic
factors after surgical resection of primary tumors. Other retrospective studies have been
published focusing on post-relapse outcome, postsurgical morbidity and local recurrence
treatment. This collaboration has also just recently led to the development of consensus
guidelines for the treatment of primary and recurrent and metastatic RPS.
To take advantage of the group collaboration, TARPSWG promoted a prospective collection
of clinical, radiological and pathologic data for RPS.
This study is aimed to prospectively collect standardized clinical data and radiological
and pathological material from primary RPS patients treated with surgery at reference
centers. Patient outcome will be evaluated in terms of overall survival (OS),
disease-free survival (DFS), crude cumulative incidence (CCI) of local recurrence (LR)
and distant metastasis (DM).
STUDY DESIGN
This is a prospective, multicentric observational study under the supervision of TARPSWG
(TransAtlantic Retroperitoneal Sarcoma Working Group) aimed to prospectively collect
clinical data and prospectively store radiological and pathological material from
patients affected by primary RPS treated with surgery.
Patients with a diagnosis of primary RPS who meet the eligibility criteria will be
invited to participate to the current study.
Eligible patients will receive full information on the type of surgery proposed and on
the data and material (radiological and pathological) that will be collected. Eligible
and informed patients who give their consent to participate will be included in the
Prospective Cohort Study (PCS) and will be followed-up prospectively.
A data collection form including patient and tumor-related factors, treatment variables,
follow-up findings, development of and time to local recurrence and status at follow-up
has been constructed and shared among all the participating centers.
Each participating reference center will individually be able to have access to both
cross sectional imaging (CT or MRI images) and pathological material (a representative
formalin block of the tumor). Whenever possible patient identifiers will be removed and
patient confidentiality will be maintained. Any data shared between institutions will be
deidentified and all measures to conceal patient identifiers will be taken.
Each center will be responsible for data-entry and storage of its own patients' data,
radiological examinations and pathological samples. At the time of the analysis each
center is committed to provide the requested updated data to the group.
Follow-up will be based on clinical evaluation and on cross sectional imaging (CT scan of
the thorax and abdomen and/or contrast enhanced MRI of the abdomen) every 4 months for
the first 2 years, every 6 months until the 5th year and yearly thereafter.
The overall duration of the project has not been fixed.
Sample size
The number of patients we plan to include in this prospective multicenter study will be
400 patients per year.
STATISTICAL CONSIDERATIONS Continuous variables will be summarized with appropriate
summary statistics such as the mean, median, standard deviation, minimum and maximum.
Categorical variables will be tabulated with frequencies and percentages. We will
evaluate OS, DFS, CCI of DM and LR and correlate this with clinicopathologic factors such
as histology, grade, type of surgery, etc.
DATA COLLECTION Data entry will be performed by every participating center. Data will be
collected in a standardized database, stored by every participating center, and shared
with the group at the time of future studies. Data shared between institutions will be
deidentified and whenever possible all measures to conceal patient identifiers and
maintain patient confidentiality will be taken.
ETHICS It is the responsibility of the investigator to have prospective approval of the
trial protocol, informed consent forms, and other relevant documents, from the IRB/IEC.
All correspondence with the IRB/IEC should be retained in the Investigator File.
