- Retroperitoneal sarcomas are a heterogeneous group of tumors, with the most common subtypes being well-differentiated liposarcoma, dedifferentiated liposarcoma, and leiomyosarcoma. - Biopsy is essential for diagnosis and should target the most solid areas on imaging. Neoadjuvant radiotherapy may help with resectability but data is limited. - Complete surgical resection remains the mainstay of treatment when possible. Adjuvant therapies have not proven beneficial. - Advanced disease is treated based on histology with chemotherapy, targeted therapies like pazopanib or trabectedin, and immunotherapy showing some promise particularly for liposar

1. Retroperitoneal sarcoma –
Evidence based approach
Sameer Rastogi
Additional Prof,
Sarcoma Medical Oncology Clinic
Dept of Medical Oncology
Samdoc_mamc@yahoo.com

2. Flow of presentation
• Introduction –Types /Differential diagnosis /
Radiology/Pathology for Clinicians / Biopsy
where and when
• Neoadjuvant approaches
• Adjuvant therapies
• Advanced disease- targeted
therapy,immunotherapy etc

3. Retroperitoneal sarcomas distribution
• Well differentiated Liposarcoma – 26%
• Dediff. Liposarcoma – 37%
• Leiomyosarcoma – 20%
• Solitary fibrous tumor and MPNST – 10%
• Others – UPS/ DSRCT etc.
J Clin Oncol. 2013 May 1;31(13)

4. Radiology
• CECT scan abdomen- multiple core biopsies from more solid areas of the
tumor are needed.
• MRI abdomen – in a known case of Li Fraumeni syndrome.
• PET CT –
• Intra tumoral locations with high SUV value are preferred target for
biopsy1
• In case of MPNST - PET-CT might have some utility in diagnosing
neurofibromatosis 1 (NF1) associated malignant peripheral nerve sheath
tumours (MPNST)
1. Consensus Approach from the Transatlantic Australasian RPS Working Group
2. UK Guidelines for management of STS 2016

5. Can biopsy be avoided??
• Under the umbrella of tumor board if imaging is judged
pathognomic of Dediff LPS / WD liposarcoma by expert
radiologist in the expert multidisciplinary tumor board & NO
Neoadjuvant therapy is planned.
1. Consensus Approach from the Transatlantic Australasian RPS Working Grou
2. UK Guidelines for management of STS 2016

7. To delineate area of biopsy (more solid
area)

8. Neurofibromatosis with MPNST

9. Differential Diagnosis
• Desmoid
• Paraganglioma
• Germ cell tumor
• Other sarcomas like DSRCT
• Angiomyxoma / other rare tumors

10. Paraganglioma on DOTANOC PET CT

11. Fibromatosis showing T2 hypointensity

12. Pathology
• Multiple core needle biopsy to be obtained
• EXPERT SARCOMA PATHOLOGY
• IHC
• MDM2- Staining for MDM2 is minimal standards for the
diagnosis of well diff/ Dediff LPS +/- CDK 4 +/- MDM2 FISH
• STAT 6 IHC –For Solitary fibrous tumor +/- Nab2 stat6
translocation
• Grading should be according to FNCLCC scoring

13. Flow of presentation
• Introduction –Types/ Differential diagnosis
/Radiology/Pathology for Clinicians / Biopsy
where and when
• Neoadjuvant approaches
• Adjuvant therapies
• Advanced disease- targeted
therapy,immunotherapy etc

14. Pattern of recurrences (heterogenous)
Subtype Local recurrence 5
years (%)
Distant mets at 5
years (%)
OS 5 year survival
(%)
Well diff. LPS 19 0 87
Dediff- Grade 2 LPS 44 10 54
Dedifferentiated
Grade 3 LPS
33 44 41
LMS 10-20 56 58
SFT 5 17 85
MPNST 20 13 67
Dingley et al.Expert Review of Anti therapy. 2019

15. Why RT in retroperitoneal sarcoma
• LR is the cause of death of
the majority of RPS
• The results of
retrospective studies
evaluating RT are
contradictory and possibly
biased
1
5
Ann Surg 2016, TARPSWG
SYLVIE BONVALOT INSTITUT CURIE
PARIS FRANCE

16. Preoperative radiation therapy has several
potential advantages including
• Gross tumor volume can clearly be demarcated
• Tumor acts a tissue expander, displacing adjacent normal tissue
including small bowel that may lie in the treatment field postop
• Tissue oxygenation is better
• The risks of tumor seeding and consequent peritoneal
sarcomatosis are lower.
Kelly et al. Ann Surg. 2015 Jul; 262(1): 156–162.

17. Why pre operative radiotherapy
Theoritically,The advantages of pre-op vs post op RT
• Smaller treatment volumes,
• Easier tumor volume delineation
• Radiobiologically superior normal
vasculature/oxygenation
• Lesser toxicities to vital organs like bowel

18. Evidence pre STRASS trial
• The only randomized multicenter trial in USA
(ACOSOG Z9031) for pre operative RT –
stopped

19. STRASS
A phase III randomized study of preoperative
radiotherapy plus surgery versus surgery alone for
patients with
retroperitoneal sarcoma
EORTC protocol [62092-22092]
Bonvalot S (Institut Curie Paris, STBSG)
Gronchi A, Le Péchoux C
Swallow C, Strauss D, Meeus P, van Coevorden F
Stoldt S, Stoeckle E, Rutkowski P
Rastrelli M, Raut C, Sangalli C, Honoré C, Chung P, Fiore M
Litière S, Marreaud S, Gelderblom H
Haas R (NKI Amsterdam, ROG) 1
9
SYLVIE BONVALOT INSTITUT CURIE
PARIS FRANCE

20. Randomization
Surgery arm
Pre operative radiotherapy +
Surgery arm
Max 4 wks
Surgery
Max 8 wks
Radiotherapy 3D-CRT or IMRT
dose 50.4 Gy/28 daily fractions)
6-7 wks
CT /MRI)
4-8 wks
Surgery
266
patients
Stratification by institution and performance status (0-1 vs 2)
SYLVIE BONVALOT INSTITUT CURIE
PARIS FRANCE
STRASS: Study design

21. ARFS
ARFS definition
During or after surgery Before surgery
Local relapse after
macroscopically complete
resection
Development of distant
metastases while on
preoperative RT
Peritoneal sarcomatosis found
at laparotomy
Local progression of primary
tumor while on preoperative
RT
Macroscopic local disease left
behind at laparotomy (R2
Becoming American Society of
Anesthesiologist (ASA)
score=3,involvement of
superior mesenteric artery or
aorta or bone

22. 2
2
Surgery alone
(N=133)
Preoperative RT
(N=133)
Total
(N=266)
N (%) N (%) N (%)
Age: Median /Range 61 (26 – 81) 61 (24 – 83) 61 (24 – 83)
WHO performance status
0/1 100 (75.2)/33 (24.8) 110 (82.7)/ 22
(16.5)
210 (78.9)/ 55 (20.7)
2 0 (0.0) 1 (0.8) 1 (0.4)
Tumor size (mm) Median 167 160 160
Histological subtype
Well-differentiated
liposarcoma
42 (31.6) 46 (34.6) 88 (33.1)
Dedifferentiated
liposarcoma
54 (40.6) 51 (38.3) 105 (39.5)
Other liposarcoma 4 (3.0) 1 (0.8) 5 (1.9)
Leiomyosarcoma 22 (16.5) 16 (12.0) 38 (14.3)
Other 11 (8.3) 18 (13.5) 29 (10.9)
Missing 0 (0.0) 1 (0.8) 1 (0.4)
Grade
Low 43 (32.3) 44 (33.1) 87 (32.7)
Intermediate 38 (28.6) 47 (35.3) 85 (32.0)
High 19 (14.3) 12 (9.0) 31 (11.7)
Not evaluable 21 (15.8) 17 (12.8) 38 (14.3)
Missing 12 (9.0) 13 (9.8) 25 (9.4)
Patient characteristics (January 2012- April 2017)
SYLVIE BONVALOT INSTITUT CURIE
PARIS FRANCE
75%
24%

23. Results
• RECIST version 1.1
• PR 4/119 (3%)
• Stable disease 98/119 (82%)
• Progressive disease 19/ 119 (16%)
• Not evaluable 11/ 119 (9%)

24. Results: primary endpoint = ARFS
2
4
Median Follow up 43
months
Preoperative RT 3 y ARFS: 60.4
Surgery 3 y ARFS: 58.7%
SYLVIE BONVALOT INSTITUT CURIE
PARIS FRANCE

25. Liposarcoma subgroup

26. Different behavior different subtypes
• WDLPS - rarely metastasize, but exhibit a steady LR
rate of 4% to 5% per year of follow-up. (3 Year follow
up might be thus inadequate)
• Grade 1 to 2 DDLPS - rapid local failures (20% at 2
years and 40% at 5 years)whereas the DM rate at 5
years most likely is <10%
• Grade 3 DDLPS and leiomyosarcoma 50% risk of
distant metastasis
Dingley et al.Expert Review of Anti therapy. 2019

27. STRASS Questions
• Was there central assessment of surgery ?
• Missing data for the grades of the patients ?
• 20% difference in abdominal recurrence free survival A bit too
optimistic – Difference might exist and might be lesser than that.
• Long term follow up might be needed for subtypes
Shishak S, Rastogi S, Kalra K, Parisa M. STRASS trial: Preoperative radiotherapy in
retroperitoneal sarcoma: A commentary. J Can Res Ther 2021;17:1138-9

28. STRASS 2 trial

29. Pitfalls of neoadjuvant therapies
• Change of histology !
• Grade !
• What if patient progresses from resectable to
unresectable. – Difficult to explain patient
when the evidence is not too sound

30. • Introduction –types Differential diagnosis /
pathology for Clinicians / Biopsy where and when
• Neoadjuvant approaches
• Adjuvant therapies
• Advanced disease- targeted
therapy,immunotherapy etc

31. Adjuvant therapy
• Postoperative/adjuvant external beam radiation after
complete gross resection is of no proven benefit and is
associated with significant short and long term
toxicities.
• Postoperative/adjuvant chemotherapy after complete
gross resection is of no proven benefit (IE)
1. Consensus Approach from the Transatlantic
Australasian RPS Working Group 2021

32. Outside FNAC suggestive of ? MPNST

34. SMA S100P

35. MDM2 Immunostaining

36. Gronchi et al. J Clin Oncol 31:1649-1655
Grade 1- Grade 1
Grade 1 60
Grade 2 120
Grade 3 160

37. Adjuvant chemotherapy challenges
• Post nephrectomy/ post multiorgan resection
– Giving chemotherapy is difficult
• In STRASS trial 78% and 83% in surgery arm
and preoperative arm had kidney resection.

38. Follow up
• Risk of recurrence after complete excision of
RPS doesn’t platue even after 15 years –
INDEFINITE FOLLOW UP
Consensus Approach from the Transatlantic Australasian
RPS Working Group 2021

39. Pattern of recurrences (heterogenous)
Subtype Local recurrence 5
years (%)
Distant mets at 5
years (%)
OS 5 year survival
(%)
Well diff. LPS 19 0 87
Dediff- Grade 2 LPS 44 10 54
Dedifferentiated
Grade 3 LPS
33 44 41
LMS 10-20 56 58
SFT 5 17 85
MPNST 20 13 67
Dingley et al.Expert Review of Anti therapy. 2019

40. • Introduction –types Differential diagnosis /
pathology for Clinicians / Biopsy where and when
• Neoadjuvant approaches
• Adjuvant therapies
• Advanced disease- targeted
therapy,immunotherapy etc

41. Advanced RP sarcoma
Histology tailored
• Leiomyosarcoma- chemotherapy/pazopanib trabectedin/
eribulin*
• Liposarcoma - chemotherapy / trabectedin/ eribulin
• MPNST- Chemotherapy/ pazopanib/ tramatenib in NF associated
MPNST
• SFT – low grade – tem/ bevacizumab, axitinib, temozolamide,
trabectedin
• Immunotherapy –Liposarcoma / Leiomyosarcoma

42. `
Rastogi S, Sankhala KK and Chawla SP. Recent Advances in Advanced Sarcoma Therapy: Medical Oncologist’s Perspective
. SM J Orthop. 2016; 2(3): 1040.

43. No cross over was permitted
Quality of life assessment was
done and reported

44. PALETTE Trial

45. Toxicities of pazopanib
Toxicities * Grade 3 and 4
Fatigue 13%
Hypertension 7%
Diarrhoea 5%
Vomiting 3%
Rash 1%
*Graaf et al. Lancet 2012/ PALETTE trial

46. Cross over to trabectidin was not permitted

47. 4.2 vs 1.5 months

48. Eribulin in L - Sarcomas

50. PFS- 2.6 months vs 2.6 months

51. Pre and post trabectedin in
liposarcoma
A B
C D
E F
Fig. Axial CT (A) and axial fused PET-CT (B) images of the pre-treatment scan. Axial
CT (C) and axial fused PET-CT (D) images of the post-treatment scan. Coronal fused
PET-CT images of the pre-treatment scan (E) and the post-treatment scan. Tumor is
denoted by arrows.

52. Solitary Fibrous tumor with liver mets
STAT 6 IHC

53. Solitary Fibrous tumor with liver mets
axitinib and temozolamide

54. Immunotherapy in Soft tissue
sarcomas and LMS
• Sarc 028 study – 7 out of 40 patients had
objective response rate (UPS, LPS, SS)1
• In SARC 028 no patient with leiomyosarcoma
had any response (n=10)
• ASPS – Immunotherapy sensitive – RR 42% 2
1.Tawbi et al. SARC 028 Lancet 2017
2.CTOS 2018

55. Expanded cohorts SARC 028
Melissa Burgess et al. ASCO 2019

57. 47 year old gentleman with RP LMS
Baseline 2017

58. 1a 1b
1d
1c
1e
1f 1g
1a – Maximum intensity projection image of FDG PET-CT showing multiple areas of tracer
uptake corresponding to lytic skeletal lesions on axial CT (1b) showing increased FDG uptake
in fused PET-CT (1c), lung metastases (1d) with FDG uptake in fused PET-CT (1e), intramuscular
deposits (1f) with FDG uptake in fused PET-CT image (1g)
PDL1 < 1%
After 5 lines of therapy extensive metastatic

59. 2a 2b 2c
2d 2e
2f 2g
2a – Maximum intensity projection image of FDG PET-CT showing few areas of
tracer uptake corresponding to resolution of lytic skeletal lesions on axial CT (2b)
showing no FDG uptake in fused PET-CT (2c), lung metastases (2d) with mild FDG
uptake in fused PET-CT (2e), resolution of intramuscular deposits (2f) with no
FDG uptake in fused PET-CT image (2g) – findings suggestive of partial response.
POST 1 year
pembrolizumab

60. • Introduction –types Differential diagnosis /
pathology for Clinicians / Biopsy where and when
• Neoadjuvant approaches
• Adjuvant therapies
• Advanced disease- targeted
therapy,immunotherapy etc

61. Any questions?