Received: 2 November 2017
Accepted: 2 November 2017
Systemic therapy in retroperitoneal sarcoma management
Robin L. Jones
Medical School University of Cyprus &
The BoC Oncology Centre, Nicosia, Cyprus
The Royal Marsden NHS Foundation Trust,
The Institute of Cancer Research, London, UK
Robin L. Jones, Sarcoma Unit, The Royal
Marsden NHS Foundation Trust, The Institute
of Cancer Research, Fulham Road, London
SW3 6JJ, UK.
There is paucity of randomized controlled data on the role of systemic therapy in
retroperitoneal sarcomas. The type of systemic therapy used is guided by the
histological subtype. The majority of retroperitoneal sarcomas comprising lip-
osarcomas and leiomyosarcomas are by and large chemotherapy insensitive. There
is an urgent need for more efficacious systemic therapies in the management of early
and advanced stage retroperitoneal sarcomas.
adjuvant, neoadjuvant, palliative, retroperitoneal sarcoma, systemic therapy
Retroperitoneal sarcomas constitute a rare group of tumors with
propensity to grow locally in the retroperitoneal space and less often to
spread hematogenously. About 20-25% of retroperitoneal sarcomas
will develop distant metastases resulting in a dismal median overall
survival of 13 months.
The role of surgery for local control is well
established in the management of these tumors
while the role of
radiotherapy, particularly in the neoadjuvant setting, is currently being
addressed in randomized controlled trials.
The role of systemic
therapy, however, is yet to be defined although systemic therapy has
been used both in the adjuvant/neoadjuvant setting as well as in the
advanced/metastatic setting in the management of these tumors.
The main purpose of systemic treatment in the neoadjuvant
setting is to reduce the size of the primary tumor in order to facilitate
R0 resection often reducing the need for extensive multiorgan
In addition, neoadjuvant systemic therapy is used to
control micrometastatic disease, to assess in vivo chemosensitivity and
prevent prolonged administration of ineffective treatment. In the
adjuvant setting, drug therapy is given to treat micrometastatic disease
and ultimately reduce the risk of recurrence.
In the advanced setting
the aim of systemic therapy is to reduce disease bulk, alleviate
symptoms, and if possible prolong survival.
The performance of prospective randomized controlled clinical
trials has been limited by the small numbers of patients, and the
heterogeneity of histological subtypes arising in the retroperitoneum.
The majority of data on systemic therapy arise from retrospective
studies or from a small number of prospective studies which however,
lump various subtypes together to secure study power, and
subsequently analyze outcomes separately according to different
histology. The histological subtype is the most important factor
influencing recurrence (both distant and local) and disease- specific
death, as documented in large retrospective series of retroperitoneal
However, retroperitoneal sarcomas often demonstrate
similar natural history characteristics, despite their differing histology;
for example, they are usually asymptomatic and of a large size (>5 cm)
by the time they are diagnosed. These factors influence their
management in terms of type of therapy used (surgery, radiotherapy,
systemic therapy) and the most appropriate timing for each therapy
(neoadjuvant, adjuvant, palliative) taking into consideration each
modality's toxicity profiles and quality of life patient reported
outcomes, beyond the survival outcomes.
The type of systemic therapy used is guided by the histological
subtype of the retroperitoneal sarcoma. The majority of retroperito-
neal sarcomas comprising liposarcomas and leiomyosarcomas are by
and large chemotherapy insensitive, although some subtypes (ie,
myxoid liposarcomas) have demonstrated higher sensitivity.
less frequently occurring sarcoma subtypes including synovial sarcoma
and Ewing's sarcoma may be more chemosensitive.
In this article, we discuss the role of systemic therapy separately
for each of the commonest subtypes with reference to the specific
drugs used for each subtype, the treatment intent in each case and the
available supporting evidence. Because of the rarity of retroperitoneal
sarcoma and consequently the paucity of randomized controlled data,
data on chemotherapy and biological therapy, are often extrapolated
from studies on extremity sarcomas.
J Surg Oncol. 2018;117:87–92. wileyonlinelibrary.com/journal/jso © 2017 Wiley Periodicals, Inc.