Retroperitoneal Sarcoma

Facts and Controversies

Ali Dabous.MD
Consultant Transplant & Surgical oncology
Fellowship Program Director
KHCC
• 15% of STS arise in the retroperitoneum
• 0.5 to 1 cases per 100,000
• Sporadic or part of hereditary cancer syndromes associated with
STS (Li-Fraumeni and neurofibromatosis type 1)
Diagnostic Challenges
• Most are asymptomatic and present with advanced disease
• Through history and physical examination
• Tumor markers (ie, LDH, AFP, bHCG)
• Percutaneous biopsy??
• Abdominal and pelvic CT scans plus staging CT chest
• MRI is used in cases where CT is contraindicated and/or when it may
complement CT
• PET scans (may be useful in staging other RP tumors)
Histologic subtypes of STS in the retroperitoneum
Common soft tissue sarcoma subtypes in the retroperitoneum with diagnostic markers
Histology Frequency (%) Immunohistochemistry Molecular
Liposarcoma 63 MDM2, CDK4, p16 MDM2 amplification
well-differentiated (WD LPS)
dedifferentiated (DD LPS)

myxoid round cell (MRC LPS)

pleomorphic
Leiomyosarcoma 19 Smooth muscle actin, Not applicable
desmin, H-caldesmin
Solitary fibrous tumour 6 CD34, CD99, BCL2, NAB2-STAT6 fusion
STAT6 product
Malignant peripheral 3 S100, SOX10, CD56, Not applicable
nerve sheath tumour CD57, PGP9.5
Undifferentiated 2 Not applicable Not applicable
pleomorphic sarcoma
Other 7 Diagnosis-dependent Diagnosis-dependent
Staging for STS
 Sarcoma-specific nomograms have been developed and validated to
predict postoperative survival
Histologic subtype

A population-based data

Grade

Invasion of
adjacent structures

Predictors of outcome
Management of Primary Retroperitoneal
Sarcomas

Surgery Lack of level one

evidence

Neoadjuvant CTx
and Rx
Expert sarcoma centers Multidisciplinary team
• Gross resection of tumor with en bloc removal of closely
associated/involved viscera and RP musculature
• Resection should also include complete removal of all ipsilateral RP
fat in patients with LPS.
• Extended RP resection
• Margin-negative excisions more technically challenging than for STS at
other sites
• Grossly incomplete resection is discouraged
 Primary Resection

Surgical planning Expertise

Required to perform multivisceral resections with

reconstruction while minimizing microscopically positive
margins
Recurrence rates in retroperitoneal sarcoma series

Margin of resection
Author, Year
Number
Resected
Margin (%)
R0/R1 vs R2
Median
Followup
Local
Recurrence(%)
Distant
Recurrenc(%) Notes
Gronchi et al, 2016 1007 95 58 5-y 26 5-y 21 8 expert centers
10-y 35 10-y 22
• •al,4
Tan et R0Duo resections
2016 haveofbeen
to large632size mostreported
90 RPS90(>20tocm),
be5-yassociated
the with
39 ability5-y decreased
to24achieve andexpert
Single
abdominal recurrence andassess
improved overall survival (OS) by
Gronchi accurately
et al,25 2015 pathologically
377 96 44 microscopically
5-y 24 clear
5-y 22(R0) margins is
2 expert centers
multivariate
limited analysis
Smith et al,21 2015 362 96 26 3-y LRFS 5-y DRFS 46 Single expert center
98 WD LPS 100 WD LPS
57 DD LPS 86 DD LPS
80 LMS 65 LMS
• So most RPS centers of excellence report gross margin clearance (R0
Toulemondeet al,2014 511 76 78 5-y LRFS 46 - 12 Frenchcenters
and R1) compared with grossly incomplete resections (R2)
Keung et al,2014 119 80 74 5-y LRFS 15 5-y DRFS 33 Single expert
DD LPS only
Bonvalotet al, 2010 249 93 37 5-y22 5-y DRFS 33 2 expert centers

Gronchi et al,2009 193 89 58 5-y LR 28 5-y DR 22 Single expert center

Lewis et al,1998 231 80 28 5-y LRFS 59 5-y DRFS 79 Single expert center
Survival rates in retroperitoneal sarcoma series
Outcomes and Recurrence Median
in Retroperitoneal
(Neo) Adjuvant
Therapy (%)
Sarcomas
Author, Year
Number Primary Follow-up Survival
Resected RPS (%) (mo) (%) Chemotherapy Radiation
Gronchi et al, 2016 1007 100 58 OS 5-y 67 18.2 32
10-y 46
Tan et al 2016 632 100 90 DSD 5-y 31 18 8
Gronchi et al 2015 377 100 44 OS 5-y 64 32 31
Smith et al 2015 362 100 26 DSS 3-y 81 3 8
Smith et al, 2014 40 73 73 OS 5-y 70 - 100
10-y 64
Toulemondeet al 2014 511 100 78 OS 5-y 66 17 29
Keung et al,2014 119 100 74 OS 5-y 42 12.6 28
Bonvalot et al 2010 249 100 37 OS 5-y 64 37 36
Gronchi et al, 2009 288 67 58 OS 10-y 36 32 31
Bonvalot et al, 2009 374 100 52 OS 5-y 57 34 32
van Dalen et al,2007 115 100 122 OS 5-y 39 18 16
Lewis et al, 1998 231 100 28 OS 5-y 54 - -
Predictive factors associated with survival include
• Age
• Tumor size
• Completeness of resection
• Grade
• Multifocality
Recurrence rates in retroperitoneal sarcoma series
Number Margin (%) Median Local Distant
Author, Year Resected R0/R1 vs R2 Followup Recurrence(%) Recurrenc(%) Notes
Gronchi et al, 2016 1007 95 58 5-y 26 5-y 21 8 expert centers
10-y 35 10-y 22
Tan et al,4 2016 632 90 90 5-y 39 5-y 24 Single expert

Gronchi et al,25 2015 377 96 44 5-y 24 5-y 22 2 expert centers

Smith et al,21 2015 362 96 26 3-y LRFS 5-y DRFS 46 Single expert center
98 WD LPS 100 WD LPS
57 DD LPS 86 DD LPS
80 LMS 65 LMS
Toulemondeet al,2014 511 76 78 5-y LRFS 46 - 12 Frenchcenters

Keung et al,2014 119 80 74 5-y LRFS 15 5-y DRFS 33 Single expert

DD LPS only
Bonvalotet al, 2010 249 93 37 5-y22 5-y DRFS 33 2 expert centers

Gronchi et al,2009 193 89 58 5-y LR 28 5-y DR 22 Single expert center

Lewis et al,1998 231 80 28 5-y LRFS 59 5-y DRFS 79 Single expert center
Predominant pattern of failure in RPS
- 25% to 50% at 5yrs
- 35% to 60% at 10 yrs
Median time to LR ranges from 24 to 41
months
Recurrence rates in retroperitoneal sarcoma series
Number Margin (%) Median Local Distant
Author, Year Resected R0/R1 vs R2 Followup Recurrence(%) Recurrenc(%) Notes
Gronchi et al, 2016 1007 95 58 5-y 26 5-y 21 8 expert centers
10-y 35 10-y 22
Tan et al,4 2016 632 90 90 5-y 39 5-y 24 Single expert

Gronchi et al,25 2015 377 96 44 5-y 24 5-y 22 2 expert centers

Smith et al,21 2015 362 96 26 3-y LRFS 5-y DRFS 46 Single expert center
98 WD LPS 100 WD LPS
57 DD LPS 86 DD LPS
80 LMS 65 LMS
Toulemondeet al,2014 511 76 78 5-y LRFS 46 - 12 Frenchcenters

Keung et al,2014 119 80 74 5-y LRFS 15 5-y DRFS 33 Single expert

DD LPS only
Bonvalotet al, 2010 249 93 37 5-y22 5-y DRFS 33 2 expert centers

Gronchi et al,2009 193 89 58 5-y LR 28 5-y DR 22 Single expert center

Lewis et al,1998 231 80 28 5-y LRFS 59 5-y DRFS 79 Single expert center
Distant recurrence (DR)
- 21% to 24% at 5 yrs
- 22% at 10 yrs
- The median OS post-DR is 20 months

Predictive factors associated with DR

- Size
- Grade
- Multifocality, and subtype.
OS with curative intent range from
- 39% to 70% at 5 yrs
- 20% to 64% at 10 yrs
Prospective long-term follow-up RPS consortium (Trans-Atlantic
databases RPS Working Group)

Better appreciation

• DD LPS had a high LR rate of 58% at 5 years & 62% at 15 years

• WD LPS and MRC LPS, had 39% and 60% incidence of LR at 5 and 15
years, Histologic subtype directs patterns of
• SFT 8%
failure
• MPNST patients occurred within 3 years.
Distant reccurence rate at 10 yrs
• high-grade LMS 58%
• SFT (41%)
• DD LPS (28%)
• MPNST (15%)
• WD LPS (8%)
CONTROVERSIES IN Managing RPS
Do we need Diagnostic Biopsies in all cases?
Role of Radiotherapy
• RT used should be administered neoadjuvantly in patients with RPS
that are be considered for curative intent surgery because it is well
tolerated and has limited toxicity

The limitation in translating the use of RT in patients with RPS is that there are no
high level evidence data that demonstrate the use of RT improves survival
 STRASS trial
randomized, multicentre, international trial

Preoperative RT (3D-CRT or IMRT) 50.4 Surgery alone

Gy followed by surgery

Primary endpoint is abdominal recurrence-free survival

Secondary endpoints
recurrence-free survival, overall survival, acute toxicity profile of
RT, perioperative and late complications, and QoL.
Role of Chemotherapy
• Adjuvant chemotherapy is not routinely recommended in high-grade
STS because of lack of sufficient evidence that it improves OS
• Neoadjuvant CTHx may be beneficial for chemosensitive histologies
(LMS and MRC LPS) or borderline resectable tumors where
cytoreduction may enhance the ability to achieve a gross resection
and potentially limit the need to resect critical structures
The routine use of extended compartmental
resection has not translated into RPS surgical
practice
Role of Extended Resection
• To achieve wider margins by performing a compartmental resection
Take Home Massages
• (RPS) are rare cancers whose work-up includes detailed radiologic
assessment and expert pathologic review.
• The overall goal of a primary RPS resection is gross resection of tumor
with en bloc removal of closely associated/involved viscera and
retroperitoneal musculature.
• Neoadj CTHx and/or Rx may be key components of the therapeutic
armamentarium in patients with RPS especially in chemosensitive
subtypes or borderline resectable tumors.
• The predominant pattern of failure in RPS is local recurrence
• Long-term surveillance should be in centers of expertise
From our experience at KHCC
A 42 year old Male

Biopsy : Dedifferentiated liposarcoma

EXPLORATION LAPARATOMY +RETRO PERITONEAL SARCOMA RESECTION ENBLOCK
WITH RT KIDNEY AND RT DIAPHRAGM
Pathology
• Dedifferentiated liposarcoma, 30.0cm with necrosis (treatment
related).
• The tumor is of intermediate grade (FNCLCC grade 2)
• Pathologic stage(yPT4Nx).
A 38 year old lady

Biopsy: Embryonal rhabdomyosarcoma

 Retroperitoneal mass excision enbloc with gerota fascia +
wedge resection and reconstruction of the IVC

Pathology

• Embryonal rhabdomyosarcoma, pT2bN0, completely excised.

 A 62 year old

Biopsy: high grade endometrial stromal sarcoma.

• laparotomy+excision of retroperitneal sarcoma+Uretric recestion and
reconstruction + sigmoidectomy

• Pathology: leiomyosarcoma pT4.

 A 72 year old Male

Biopsy : Malignant spindle cell tumor consistent with soft tissue sarcoma,
probably representing de-differentiated liposarcoma.
EXPLORATION LAPRATOMY, EN-BLOCK RESECTION OF RETROPERITONEAL MASS WITH SEGMENT II WEDGE LIVER RESECTION,
SPLENECTOMY, DISTAL PANCREATECTOMY & WEDGE RESESCTION FROM THE STOMACH and GEROTA FASCIA EXCISION +
SEGMENT IVb LIVER WEDGE RESECTION

Pathology : Leiomyosarcoma, high grade.

Thank You