Soft tissue sarcoma (Retroperitoneal Sarcoma)

Shaukat Khanum Memorial Cancer Hospital and Research Centre
Jibran Mohsin
Soft tissue Sarcoma
(Retroperitoneal Sarcoma)
Fellow Surgical Oncology
SKMCH & RC, Lahore

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Outline
 Introduction
 Clinical Presentation
 Evaluation
 Surgery
 Radiotherapy
 Chemotherapy
 Targeted therapy
 Recurrent disease

Introduction
 15 – 20 % of adult STS
 Retroperitoneal tumor (mostly malignant)
 lymphoma,
 germ cell tumors, and
 undifferentiated carcinomas
 RPS (1/3rd cases)

Introduction
 RPS
 liposarcomas (50% to 65%, mainly well-differentiated or
dedifferentiated liposarcomas),
 leiomyosarcomas (20% to 25%), and
 undifferentiated/unclassified sarcomas (previously
categorized as MFH)

Introduction
 Histology remains a key component to overall
prognosis
MDACC Database
5-year OS rates
Well differentiated liposarcoma 95%
Other liposarcomas
(mostly dedifferentiated liposarcoma)
25%
Other histologies
(mainly leiomyosarcoma and
undifferentiated/unclassified sarcomas)
43%

Introduction
 Histology remains a key component to overall
prognosis
Retrospective studies
• MSKCC
• European Multi-Institutional Collaborative RPS Working Group
Local recurrence rate Metastatic rate
Liposarcoma 35 % - 60 % 30 % (dedifferentiated)
Leiomyosarcoma < 20 % 60 %

Clinical Presentation
 Asymptomatic large masses
 nearly 50% are > 20 cm at the time of diagnosis.
 Symptomatic if compress or invade contiguous
structures
 neurological (compression of lumbar or pelvic nerves) or
 GI obstruction (direct invasion vs displacement)

Evaluation
 History
 exclude signs and symptoms of lymphoma (e.g., fever,
night sweats)
 Examination
 all nodal basins
 testicular examination

Evaluation
 Investigations
 Hematological
 LDH (lymphoma)
 AFP and β hCG (Germ cell tumors)

Evaluation
 Investigations
 Radiological
 CT abdomen/pelvis
 extent and relation to surrounding structures
 Liver metastases
 Discontinuous abdominal disease
 Bilateral renal function
 Thorax CT (High grade tumors)

Evaluation
 CT-guided core-needle biopsy
 equivocal history,
 unusual-appearing mass,
 unresectable tumor, or
 distant metastasis and
 in patients who are potentially eligible for preoperative
therapy

Surgery
 Mainstay treatment for Primary RPSs.
 Complete surgical resection/excision with wide negative
margins ( RO or R1) (40 – 60 % cases)
 Incomplete or debulking (R2) resection
 Anatomic constraints
 Improves local symptoms with no survival benefit

Surgery
 Quality of surgical resection is important for
outcomes
 Local recurrence (often the cause of mortality)
 Distant metastasis ( 4 x)
 Survival

Surgery
outcomes
MDACC (83 patients; surgery + radiotherapy)
Margin positive resection margin-negative resection
Five-year local control rates 33% 62%
Mortality
• 42 % cases (local recurrence was the sole site of disease)
• 11 % cases (local recurrence was a component of progression)

Surgery
outcomes
MSKCC (500 patients)
complete
resection
incomplete
resection
observation
without resection
median survival duration 103 months 18 months

Surgery
 Careful preoperative planning
 Multi organ resection
 Multidisciplinary surgical teams (especially vascular) for
complete resection

Surgery
 How extensive the surgical resection should be?
 Standard (simple complete) resection
vs
 Extended or compartmental resection

Surgery
 Extended or compartmental resection
French retrospective study (382 patients) (Bonvalot et al. ) (2009)
nephrectomy 42%
colectomy 30%
local recurrence rate 44% (a 3.29 times lower than with simple complete
resection)
Overall survival No difference
Surgical complications 16 % (half required another surgery)
Mortality 13 (3 %) perioperatively due to surgical complications
3 (1%) intraoperatively

Surgery
Gronchi et al. (Italian)
“standard” resection compartmental resection
Local recurrence rate
(p = 0.007)
48% 28% (shorter follow up)
Distant metastasis rate
(p = 0.013)
13% 22%
Overall 5 year survival rate
(p = 0.47)
51% 60%

Surgery
 Multi-visceral resection
 Exponential increase in morbidity and mortality
 difficult to justify the resection of uninvolved “adjacent”
organs (e.g., kidney, pancreas, duodenum)
 MDACC recommends
 to resect adjacent structures with evidence of
invasion, either radiographically or at the time of
surgical exploration.

Surgery

Multimodality Therapy
 High local and distant recurrence rates in RPS
 shift in treatment strategies for localized RPS toward
multimodality therapy
 perioperative use of chemotherapy and/or radiation
therapy
 No level I evidence (rarity of disease)
 limited retrospective studies
 data extrapolated from extremity sarcoma

Radiotherapy
 Nussbaum et al. (National Cancer Data Base)
 compared 563 (preoperative radiation) or 2,215
(postoperative radiation) patients vs 6,290 (no radiation)
 Radiation therapy, either by the preoperative or
postoperative approach, improved OS compared with
surgery alone

Radiotherapy
 Postoperative radiotherapy
 Difficult because the bowel and other organs are
frequently located in the resected area
 Preoperative Intensity Modulated Radiation
Therapy (IMRT)
 tumor often displaces adjacent radiosensitive organs
 Improved 5 year SR and rate of complete resection

Radiotherapy

Radiotherapy
 Preoperative radiotherapy
MDACC and colleagues from Toronto ( 2 Prospective trails)
72 patients with intermediate- or high grade RPS
Only two patients (3%) did not complete the planned radiation dose
(supported the feasibility of the preoperative approach)
5-year local recurrence-free
survival rate of 60%
95% complete resection rate

Radiotherapy
 Preoperative radiation therapy + intraoperative
radiation
Stucky et al. (Mayo Clinic-Arizona) (retrospective study)
5-year local control rate
(p = 0.03)
Overall survival
Preoperative radiation, surgery, plus
intraoperative radiation (37 cases)
89% no impact
Surgery alone (26 cases) 46%

Radiotherapy
 Preoperative radiotherapy + Postoperative
brachytherapy
 Smith et al
 long-term follow-up of a phase II trial of 40 patients
 unacceptable toxicity profile, typically associated with
duodenitis/duodenal stricture and death
 Neither recurrence-free survival nor OS was
improved

Radiotherapy
 STRASS trial (EORTC 62092)
 prospective randomized phase III study
 Comparing preoperative radiation (50.4 Gy in 28
fractions) plus surgery to surgery alone.
 Results are expected in 2020.

Chemotherapy
 Medical College of Wisconsin (National Cancer
Database)
 preoperative chemotherapy (11% cases)
 postoperative chemotherapy (7% cases)
 intermediate/high-grade,
 leiomyosarcoma, or UPS histology
 R2 resection status

Chemotherapy
 Medical College of Wisconsin (National Cancer
Database)
 median OS was shorter in patients who received
chemotherapy (40 vs. 52 months; p = 0.002).
 Supported by
 Singer et al. (1995)
 Bremjit et al. (2014)
 Innate selection bias

Chemotherapy
 MDACC
 safety of preoperative chemotherapy
 No increase in surgical complication rates in patients
with RPS (29% vs. 34% in the upfront surgery group; p
= 0.66)
 Radiographic response was sufficient to decrease the
extent of surgery in 13%.

Chemotherapy
 MDACC
 Radiographic responders
 Higher negative-margin resection rate,
 Better local recurrence-free survival rate, and
 Better OS rate

Chemotherapy
 most commonly used regimen
 Doxorubicin + Ifosfamide (nephrotoxic)

Targeted Therapy
 Liposarcomas
 inhibitors of CDK4, a cyclin-dependent kinase
 Dickson et al. from MSKCC (phase II trial)
 57 % overall progression-free survival at 12 weeks
 MDM2 inhibitors

MDACC Current practice
 Multidisciplinary sarcoma conference
 Individualized treatment strategies
 Pretreatment biopsy and histologic confirmation
are mandatory before initiating any preoperative
therapy

MDACC Current practice
 Careful use of preoperative chemotherapy and/or
radiation therapy
 High risk of distant metastasis, such as
 intermediate- or high-grade histology and
 large or
 recurrent tumors.

Recurrent Disease
 66 % recurrence rate after complete surgical
resection
 Local recurrence (tumor bed)
 Distant
 Lungs
 Liver (leiomyosarcoma)
 Soft tissue distant from primary site
 diffusely throughout the peritoneal cavity (sarcomatosis)

Recurrent Disease
 Change in the biology of the disease
 25% of well-differentiated liposarcoma recur in a poorly
differentiated form or develop areas of dedifferentiation
 aggressive with a greater propensity for distant
metastasis.

Recurrent Disease
 Salvage surgery
 Ability to adequately resect a recurrent RPS declines
precipitously with each recurrence
 Survival benefit (if careful patient selection)

Recurrent Disease
 Salvage surgery
 Predictive factors
 Size
 Growth rate
 Subtype
 Disease free survival period

Recurrent Disease
 Park et al (MSKCC)
 Retrospective analysis of 105 first recurrent
retroperitoneal liposarcoma
 61 underwent salvage surgery
 incidence of a second local recurrence/poor outcome
 Size
 Growth rate (>0.9 cm / month)
 enrolled in clinical trials rather than undergo second re-
resection.

Recurrent Disease
 Resection of distant recurrence (metastasectomy)
 Survival benefit (leiomyosarcoma)
 MDACC
 disease-free interval of >1 year from primary resection
to recurrence --> better outcome after salvage surgery

THANK YOU

Soft tissue sarcoma (Retroperitoneal Sarcoma)

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