NcXHF

ADJUVANT/NEOADJUVANT MEDICAL THERAPY OF ADULT SOFT TISSUE SARCOMAS
Adjuvant Chemotherapy for Soft Tissue Sarcoma
Paolo G. Casali, MD
OVERVIEW
Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option
for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several
randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available
meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was
suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality
of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation.
Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as
well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant
indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills
available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence.
Adult-type soft tissue sarcomas are a variegate group of
malignancies. They are highly heterogeneous, because
they are made up of several histologies and arise from virtually
all body sites. 1 In addition, they are rare, and their incidence is
approximately 4 per 100,000 per year. 2 This incidence does not
prevent controlled trials, but pooling together different histologies
and possibly different primary sites is often the price to pay.
It is true that more than half of STS cases are high-grade and
undifferentiated pleomorphic sarcomas, liposarcomas, leiomyosarcomas,
myxofıbrosarcomas, synovial sarcomas, or malignant
peripheral nerve sheath tumors, and more than half of
them arise in the limbs. However, a high degree of heterogeneity
remains, even after selecting a group of patients with these types
of STS, and other relevant subgroups (e.g., uterine sarcomas) are
left behind. This contributes to major limitations of available evidence
on adjuvant chemotherapy in STS and, thus, a considerable
degree of uncertainty on its clinical value, although several
randomized clinical trials have been performed in the last 40
years.
When one singles out high-grade STS, the mortality rate
exceeds 50%. In addition to the malignancy grade, other
main prognostic factors are size and presentation—for example,
deep fascial extension. By combining these three factors,
it is easy to select a population in which two-thirds of patients
may die of their disease. Prognostic nomograms are available to
refıne the prognosis with a view toward adjuvant decisions. 3-6
Currently, the treatment of metastatic disease is unsatisfactory.
Surgery of lung metastases is the main option when secondary
lesions are isolated in the lungs, and the number of
such lesions is relatively low. A cure may be achieved in a
minority of patients with these metastases, and the course of
disease may be slowed down in a subgroup of others; however,
most patients will experience relapse in a matter of
months. Chemotherapy is based on anthracyclines and ifosfamide,
though other cytotoxics and even molecularly targeted
agents are available, which have interesting antitumor
activity in selected histologies. Indeed, there is currently a
trend in favor of an histology-driven approach in the medical
therapy of STS. However, the effect of medical therapy in the
metastatic setting is essentially palliative, though improving
over the last years. The median survival of patients with metastatic
disease often has been reported to be in the range of 1
year. Undoubtedly, there are subgroups who benefıt from
surgery of lung metastases and currently available medical
therapies, but a cure is essentially precluded in most cases,
and—though possibly higher than once reported—overall
survival remains unsatisfactory, if one leaves aside the tails of
curves.
In addition, STS often pose challenging problems regarding
surgery of localized disease. In a minority of cases, one
may hope to convert mutilating surgery into limb-sparing
procedures by means of preoperative cytoreduction. In several
other cases, cytoreduction is felt by the surgeon to be potentially
useful to minimize sequelae and improve the local
control rate. This is why chemotherapy is resorted to preoperatively
in a proportion of patients, which may vary from an
From the Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Disclosures of potential conflicts of interest are found at the end of this article.
Corresponding author: Paolo G. Casali, MD, Adult Mesenchymal Tumour and Rare Cancer Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milano, Italy;
email: paolo.casali@istitutotumori.mi.it.
© 2015 by American Society of Clinical Oncology.
asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK
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