Official Title
REtroperitoneal SArcoma Registry (RESAR): Prospective Collection of Primary Retroperitoneal Sarcoma Patient's Data, Radiological and Pathological Material for the TransAtlantic Retroperitoneal Sarcoma Working Group
Summary:
Surgery is currently the only potentially curative treatment modality for localized
retroperitoneal sarcoma (RPS). Available studies regarding oncologic outcomes are mainly
retrospective in nature, and RPS are recognized as a rare disease. Therefore, prospective
analysis of high quality data is a top priority.
Primary Objectives of this study are:
- to prospectively collect standardized clinical data and radiological and pathological
material from primary RPS patients treated with surgery at reference centres.
- 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).
Secondary Objectives:
- to estimate the efficacy and safety of surgical treatment, including extended surgical
approach to primary RPS;
- to prospectively evaluate the impact of multimodality therapy, including radiation
therapy and chemotherapy;
- to identify clinical, radiological and pathological characteristics that may influence
the oncological outcome or may be used as predictors of LR/DM/OS. These may be important
biomarkers of disease;
- to utilize collected pathological material for research collaborations.
Trial Description
Primary Outcome:
Secondary Outcome:
- Overall Survival
- Crude cumulative incidence of Local recurrence
- Crude cumulative incidence of Distant metastasis
- Morbidity
Retroperitoneal sarcomas (RPS) are rare tumours 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 tumour (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 tumours
(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
favourable overall survival. These tumours 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 tumours 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 tumour 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 tumour 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.
Radiation Therapy is an option for RPS, especially in the preoperative setting, but currently the
best evidence for efficacy comes form retrospective, mainly single-centre, 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 tumours. So far, there is no agreement on the optimal treatment
strategy, even within reference centres, regarding the use of both chemo- and radiation therapy.
In the recent years European and North-American centres 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 centres 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 tumours. 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 centres.
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 tumour-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 centres.
Each participating reference centre 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 tumour). 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 centre 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 centre
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 multicentre 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 centre. Data will be
collected in a standardized database, stored by every participating centre, 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.
View this trial on ClinicalTrials.gov
