the latest guide line

1. Management of Recurrent
Retroperitoneal Sarcoma

2. INTRODUCTION
• Soft-tissue sarcomas have an incidence of 3–4 cases per 100 000 inhabitants/year;
• 15% are located in the retroperitoneum, which is the second most frequent location after the
extremities.
• Retroperitoneal sarcomas (RPS) are rare tumors, with an expected incidence of .5-1 new
case/100,000 inhabitants per year.
• Although in this location there is a great variety of histological subtypes (>70);
• the most frequent are well-differentiated liposarcoma (WD-LPS), dedifferentiated lipo-sarcoma (DD-
LPS) and leiomyosarcoma (LMS).
• Fibrosarcoma and undifferentiated pleomorphic sarcoma, rhabdomyosar- coma,
lymphangiosarcoma, malignant schwannoma or hemangiosarcoma are less common.
Lo´pez-Pousa A, Martin Broto J, Martinez Trufero J, Sevilla I, Valverde C, A´lvarez R, et al. SEOM Clinical Guideline of management of soft-tissue sarcoma (2016). Clin Transl Oncol. 2016;18:1213–20. http://dx.doi.org/10.1007/s12094- 016-1574-1. 2. Garcı´a
del Muro X, de Alava E, Artigas V, Bague S, Bran˜ a A, Cubedo R, et al. Clinical practice guidelines for the diagnosis and treatment of patients with soft tissue sarcoma by the Spanish group for research in sarcomas (GEIS). Cancer Chemother Pharmacol.
2016;77:133–46. http://dx.doi.org/ 10.1007/s00280-015-2809-5. 3. Martin J, Cruz J, Valverde C, Cubedo R. Capı´tulo 15-17. Tratado de sarcoma de partes blandas. Madrid (Espan˜ a): Nature Publishing Group Iberoame´ rica; 2015

3. • Surgery is the mainstay of curative therapy and local control is critical for cure.2–13
• Overall local/abdominal recurrence is common( 50 % at 5 years overall) following resection of
primary retroperitoneal sarcoma (RPS).2–13
• A high proportion of recurrences occur late (after 5 years), mandating ongoing follow-up.13–
15
. 4. Tseng WW, Seo HJ, Pollock RE, Gronchi A. Historical perspectives and future directions in the surgical managenet of
retroperitoneal sarcoma. J Surg Oncol. 2018;117:7–11

5. Preoperative evaluation/treatment ( out lines )
• As a rare and complex malignancy, RPS is best managed by an experienced multidisciplinary team
in a specialized reference center (IVA)
• Staging and Preoperative Assessment
• The optimal management of RPS is facilitated by pretreatment diagnosis and staging.
• Thorough review of cross-sectional imaging by a specialized sarcoma tumor board is required (IVA).
• The standard method for staging is contrast tomography (CT) scan of the chest/abdomen/ pelvis
with IV contrast
• Magnetic resonance imaging (MRI) is an option for patients with IV CT contrast allergy or other
contraindication, Li- Fraumeni syndrome, or pelvic tumors and for assessing the extent of tumor to
specific sites (i.e., vertebral foramina, sciatic notch) that is not clear on the CT scan (VA).
• Functional assessment of the contralateral kidney typically is necessary for planning treatment of
the ipsilateral RPS. This may be achieved using CT with IV contrast or differential renal scanning
(VA).
• Bone scan, head CT, brain MRI, and positron emission tomography (PET) scanning usually are
NOT required (VD).

6. • Biopsy
• Image-guided percutaneous coaxial core needle biopsy (14 or 16 gauge) is strongly recommended
unless the imaging is pathognomonic (e.g., heterogeneous dedifferentiated/well-differentiated
liposarcoma) and no preoperative treatment is planned (IVA).
• Multiple needle cores should be obtained to allow for histologic and molecular subtyping (VA).
• Repeat core biopsy with more aggressive sampling may be required (VB).
• Sampling of the more solid, dedifferentiated tumor component represented by well-perfused areas
in contrast-enhanced CT or contrast-enhanced MRI is encouraged (IVA).
• If [18F]Fluorodeoxyglucose ([18F]FDG)-PET is available, hot spots with high standard uptake value
(SUV) are the target areas of biopsy (IVA).
• Risk of needle track seeding is minimal and should not be a reason to avoid a biopsy (IVA)
• Laparotomy and open biopsy and Laparoscopic biopsy of suspected RPS shouldbe avoided. This
practice exposes the peritoneal cavity to contamination by sarcoma, distorts subsequent planes of
dissection, may not provide diagnostic tissue due to lack of three-dimensional image guidance, and
may put vital neurovascular structures at risk (VE).

7. Determination of resectability
• For patients without any evidence of distant metastasis on staging imaging studies,
complete resection offers the only chance for cure. All patients with localized RPS should
therefore be offered surgery unless the surgeon identifies the following findings on the
preoperative imaging review, which would preclude resection:
●Peritoneal implants (sarcomatosis)
●Bilateral renal involvement
●Extensive spine involvement
●Extensive mesenteric root involvement
●Extensive liver hilar involvement
●Extensive major vascular involvement (aorta, vena cava, and/or iliac vessels), although
involvement of the vena cava and iliac veins is a relative, rather than absolute,
contraindication as these vessels can often be ligated or replaced with interposition grafts)
• Patient age and comorbidities should also be considered when determining whether to
proceed with resection.

8. Consideration of nonsurgical therapies
• multidisciplinary tumor board to determine if there may be a benefit for
nonsurgical therapies (eg, chemotherapy, radiation therapy).
• Especially for "borderline resectable" patients (eg, vascular involvement with
comorbidities).
• tumor shrinkage with neoadjuvant therapy may facilitate resection.
• radiation therapy is to be given, this should be done in the neoadjuvant setting to
limit the toxicity to bowel that would, after tumor resection, fall into the
treatment field.
• intraoperative radiation therapy, is an alternative in limited centers
• Retrospective data exist that suggest some benefit with radiation therapy in
patients with RPS [6];
• however, the data are somewhat conflicting [7]. Results of a prospective clinical
trial (STRASS) has been published …

9. • Primary Surgical Approach:
• Complete gross resection is the cornerstone of management (IIIA).
• In the case of primary RPS, surgery should be aimed at achieving macroscopically complete
• resection, with a single specimen encompassing the tumor and involved contiguous organs, and at
minimizing microscopically positive margins.
• This is best achieved by resecting the tumor en bloc with adherent structures even if not overtly
infiltrated (IIIA)
• In primary RPS, preservation of specific organs (e.g., kidney, duodenum, bladder) should be
• considered on an individualized basis and mandates specific expertise in the disease for
appropriate decisions to be made given the overall tumor extent/expected biology and given the
individual patient’s characteristics (VA).
• Judgment must be used in deciding which neurovascular structures to sacrifice, with the potential
for local control weighed against the potential for long-term dysfunction.
• Judgment must similarly be exercised in determining appropriateness of en bloc resection of liver
and pancreas (VA)
• Complete
• resection of all RP fatty tissue at risk for harbouring tumor is ideal (IIIA)

10. Recurrence retroperitoneal sarcoma
• Overall local/abdominal recurrence is common (50 % at 5 years overall) following resection of
primary retroperitoneal sarcoma (RPS).
• To date, there are minimal data to guide treatment decisions when a patient with RPS develops
recurrent disease.
• An understanding of the consequences of disease recurrence is vital in deciding upon an
appropriate management strategy
• A high proportion of recurrences occur late (after 5 years), mandating ongoing follow-up
• is there a Variability in Patterns of Recurrence ???
• The parameter that increasing disease free survival ( is there a rule for neoadjuvant treatment ) ??
• How to mange recurrent ???

11. • All consecutive patients with primary RPS treated at 6 European and 2 North American institutions between
January 2002 and December 2011 were included.
• Five, 8, and 10-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and
distant metastasis (DM) were calculated.
• Multivariate analyses for OS, CCI of LR, and DM were performed.

13. • In all, 316 patients developed LR. In 249 patients, this was the first event, whereas 47 patients developed
concurrent LR and DM, and 20 patients developed LR after DM.
• Five, 8, and 10-year CCI of LR were 25.9 (95% CI, 23.1,29.1), 31.3 (95% CI, 27.8, 35.1), and 35% (95% CI,
30.5, 40.1),
The median time to first LR was 39 months.
• excluded patients who underwent macroscopically incomplete resections, 5, 8, and 10-year
CCI of LR were 24% (95% CI, 21.2,27.3), 29.2% (95% CI, 25.7,33.1), and 33.1% (95% CI, 28.5,38.4), respectively.
Factors significantly predicting LR were patients’ age, size of the tumor,
completeness of surgical resection, malignancy grade, tumor rupture, multifocality, administration of RT, and
histological subtype

14. • Retroperitoneal sarcoma is not a single disease, and the spectrum of histologies is quite variable.
• WD LPS, deaths were all related to locoregional recurrences, which were observed in nearly one-third of
patients as the only modeof failure.
• as most local recurrences of WD LPS can be managed by subsequent resections, especially when the first one
had been limited.
• LMS, most deaths in patients with RP LMS were related to metastatic spread, occurring in as many as 50% of
patients.
• Interestingly, in contrast with the LR risk of WD LPS, which is mainly related to anatomic constraints, the
metastatic risk is linked to the biology of the disease and seemed to flatten out after 5 years. In other words,
patients with a retroperitonealLMS who survived without any disease recurrence for 8 years were likely cured.

15. • Solitary fibrous tumor and DD LPS displayed a pattern of LR and DM that lay within the biological
spectrum of behavior defined by WD LPS and LMS.
• SFT has low LR and DM rates. This reflects the predominance of the classical variant of SFT at this
site.
• DD LPS was the most common histology, accounting for 35% of all cases. Deaths were more
related to the LR risk, which was over 40% at 8 years, whereas the DM risk was less than 20%.
• Interestingly, grading the dedifferentiated component was very helpful to further delineate 2 distinct
entities.
• Grade II DD LPS was associated with an 8-year OS of 50%, almost exclusively related to LR risk
• (which was approximately 50%, compared with a DM risk of less than 10%).
• Patterns of failure were similar to WD LPS, although disease intervals were shorter and the
likelihood of death at the 8- year time point was higher.
• Grade III DD LPS was associated with a 30% 8-year OS, the worst of the entire group of RPS.
• At variance with WD LPS and GII DD LPS, deaths were both related to LR and DM.
• In fact, the latter was over 30% at 8 years, similar to LMS

16. • EORTC-62092 is an open-label, randomised, phase 3 study done in 31 research institutions, hospitals, and cancer
centres in 13 countries in Europe and North America.
• Between Jan 18, 2012 and April 10, 2017, 266 patients were enrolled, of whom 133 were randomly assigned to each group.
The median follow-up was 43·1 months (IQR 28·8–59·2). 128 (96%) patients from the surgery alone group had surgery, and
119 (89%) patients in the radiotherapy and surgery group had both radiotherapy and surgery.

18. • Median abdominal recurrence-free survival was 4·5 years (95% CI 3·9 to not estimable) in the radiotherapy plus surgery
group and 5·0 years (3·4 to not estimable) in the surgery only group (hazard ratio 1·01, 95% CI 0·71–1·44; log rank p=0·95).
• Preoperative radiotherapy should not be considered as standard of care treatment for retroperitoneal sarcoma.

19. • retrospective study, analyzed the medical records of patients who underwent salvage surgery and
IORT for isolated rRPTs between June 2004 and April 2015.
• patients with retroperitoneal sarcoma, the 2-, 5-, and 8-year LC rates
were 86, 62, and 62%, respectively.
• Regional failure is commonly observed among patients with retroperitoneal sarcoma, including 5 patients ,an
additional 5 patients experienced DF

20. Management of Recurrent Retroperitoneal Sarcoma (RPS)( NCCN )

21. Management of Recurrent Retroperitoneal Sarcoma (RPS)in the Adult: A Consensus Approach from
the Trans-Atlantic RPS Working Group
• Prior to undertaking a management decision, patients with recurrent RPS should be presented at a Multi-
Disciplinary Case Conference with participation by surgical oncologists, medical oncologists, radiation
oncologists, pathologists and radiologists with expertise in sarcoma (VA).

22. Pretreatment Assessment
• Imaging
• Pathology
• Patient evaluation
• Review of Previous Treatment
• Patient Selection for Resection of Recurrence

23. • Imaging
• All relevant imaging studies performed prior to resection of the primary RPS should be
obtainedreviewed, as should all subsequent imaging studies, in particular the initial postoperative
baseline imaging to determine whether prior resection was in fact grossly incomplete (R2) (VA).
• Current extent of local and distant disease should be determined using oral and intravenous (IV)
contrast
• enhanced computed tomography of the chest, abdomen and pelvis (CT-CAP) (IVA).
• Current imaging should be compared to all prior imaging to ascertain the extent and progression of
recurrent disease, with attention to pattern of relapse (locoregionalvs. peritoneal) and rate of
progression (IVB.)
• The risk of invasion into adjacent organ(s)/critical structure(s) with further progression should be
evaluated,
• and taken into account when deciding on the best management approach (VB).
• MRI may be a useful ancillary modality in selected cases to define extent of adjacent
organ/structure
• involvement that is not clear on CT but is not required in most cases (IVB).
• MRI may be helpful in operative planning for pelvic tumors or tumors that abut/involve bone or
psoas or oblique muscles or vertebral foramen.
• MRI also is an option in patients with IV contrast allergy or other serious contraindication to ct(IVB)
• PET scan is rarely indicated

24. • Pathology
• Histopathology of the primary tumor should be reviewed by a pathologist specialized in
theevaluation of soft tissue tumors; molecular subtyping should be performed where appropriate (VA).
• Percutaneous core biopsy confirmation of recurrence is often useful, for a number of reasons:
• 1) to provide a definitive diagnosis, because a variety of other entities can be mistaken for
recurrence of the original primary RPS, for example desmoid ,fibromatosis radiation-associated
osteosarcoma, or angiosarcoma in the bed of original LPS;
• 2) to guide selection of preoperative therapies, including potential targeted therapies;
• 3) as part of a translational research program or clinical trial;
• 4) because resection often is challenging and may be morbid and should not be undertaken without
due cause (VB).

25. • Patient Evaluation
• The patient’s symptoms, and pace of symptom progression, should be noted
• The patient’s current performance status should be recorded.
• Physical examination should include notation of previous incisions, and the relationship of new
tumor mass(es) to previous incisions, including port sites (VB).
• Renal function and nutritional status must be assessed (VB).

26. • Review of Previous Treatment
• The operative note describing the resection of theprimary tumor should be obtained and reviewed,
as should notes describing any subsequent operative or other interventional procedures (VB).
• Timing from previous surgery should be noted, as well as factors that precluded macroscopically
complete resection; if not described, these should be elicited through personal communication with
the referring surgeon (VB).
• Previous pathology reports, and if possible any tissue slides/blocks, from previous resection(s)
should be obtained and reviewed (VB).
• The nature of previous surgery should be categorized as
• (1) Macroscopically complete (en bloc resection).
• (2) Macroscopically incomplete (gross residual disease as noted on operative report or on
immediate postoperative cross-sectional imaging
• (3) Piecemeal and/or associated with tumor rupture or morcellation (VB).
• Details of any previously administered radiotherapy or systemic therapy should be reviewed (VA).

27. • Patient Selection for Resection of Recurrence
• While complete gross resection can be viewed as the only curative-intent option in patients with
recurrent RPS, the chance of long term disease-free survival is limited and this must be recognized
in multidisciplinary evaluation and planning of management for the individual patient (IVA)
• The decision to pursue curative resection is multifactorial and often nuanced.
• A nomogram to assist in this decision is presently lacking.
• Variables to be considered(abdominal recurrence , extra abdominal recurrence ) .

28. Abdominal Recurrence
• In the case of isolated locoregional recurrence , especially if the previous resection was incomplete,
the goal of resection should be curative, and the extent of resection should be as required to
achieve complete gross resection (IVB).
• A total of 75 patients underwent 115 resectional procedures as part of the management of retroperitoneal soft-tissue
sarcoma.
• The 30-day operative mortality was zero and the 90-day mortality rate was 1.33% (1/75).
• Follow-up ranged from 16–131 months.
• The median disease-free survival was 69 months (range, 59-78 months).
• Recurrences developed in 46 patients; median time to overall recurrence was 13 months (range, 3-71 months).
• Of these 46,22 developed localised recurrence, which was amenable to further resection.
• In the cohort of patients with recurrent disease, median survival in those who underwent surgery was 53 months
median survival in those who did not undergo surgery was 30 months and this difference was statistically significant
(log rank, P = 0.01).
• localised recurrences are amenable to surgery and this can lead to improved survival.

29. • For local recurrence of WD-LPS within the field of previous resection(s), the surgeon may rationally wait for an
increase in tumor size in order to space out the interval between operations (IVB)
• From a prospective sarcoma database selected 105 patients who had at least one local recurrence following
complete resection of a primary retroperitoneal liposarcoma between July 1982 and December 2005.
• Of these patients, 61 underwent complete resection of their first local recurrence.
• Study endpoints included second local recurrence-free survival for these 61 patients and disease-specific
survival for all 105 patients.
• Local recurrence growth rate was defined as the radiographic size of the local recurrence divided by the time to
local recurrence from the primary resection.
• Median follow-up was 65 months.
• Local recurrence size, primary histologic variant and grade, and local recurrence growth rate were independent
predictors of disease-specific survival.
• For those undergoing reresection, local recurrence size and local recurrence growth rate independently
influenced development of a second local recurrence.
• Only patients with local recurrence growth rates of less than 0.9 cm/mo were associated with improved survival
after aggressive resection of the local recurrence.

30. • Multifocal intra-abdominal disease is difficult to resect completely, will almost certainly recur again,
and carries a poor prognosis particularly with resection alone. The prognosis following resection
worsens with increasing number of intraperitoneal deposits.
• Any resection should be with the goal of avoiding complications of progression and preserving
function (i.e., limited resection) or with palliative intent. Because the oncologic benefit of surgery is
likely to be limited and the risk of morbidity may be substantial, a very careful approach to patient
selection for surgical intervention is required (IVA).
• A history of previous piecemeal resection/ tumor rupture indicates a strong potential for multifocal
peritoneal recurrence and curative-intent resection is generally not appropriate.
• Histopathologic subtype should factor into the decision to pursue re-resection, because outcomes
differ (e.g., WDLPS would be favored for re-resection) (IVA).
• A period of observation and reimaging may help to select more favorable candidates for resection,
particularly for asymptomatic WD-LPS (rate of growth of less than 1 cm per month is associated
with better duration of disease control) (IVB).
• Long-term survival may be achieved in well-selected patients (e.g. no history of tumor rupture, low
grade,
• long DFI, solitary local recurrence), however there is a very limited chance of cure and this must be
considered when offering aggressive therapy (IVB).
• Risk of mortality and serious morbidity after radical resection of recurrent RPS are significant; good
performance status is important to recovery.

31. Distant Recurrence
• Selected patients with limited oligo-metastatic recurrence of RPS may have prolonged survival
following metastasectomy (e.g., LMS) (IVB)
• In general, synchronous abdominal and distant recurrence should not be resected, and the patient
should be considered for systemic therapy as part of a multimodality approach based on tumor
histology/ molecular subtyping (IVB)

32. Preoperative Therapy
• Cytotoxic and/or targeted systemic therapies may be of benefit in downsizing recurrent disease to
improve resectability, especially in the case of LMS, DD-LPS, UPS, SFT, and synovial sarcoma, and
also may facilitate assessment of tumor biology/prognosis, especially when a high grade RPS has
recurredafter a short disease-free interval, and when resection of locally recurrent disease is
anticipated to be morbid (VB).
• .Preoperative XRT should be considered, particularly
• if no previous XRT has beenadministered and the recurrence is isolated,although its value in
improving disease control has not been studied, and toxicity may bemagnified in the setting of prior
resection (VB).
• Response to treatment varies by histological subtypeof RPS and the management plan should be
developed
• in recognition of this and in conjunction with amultidisciplinary care team (VB).
• Preoperative treatment of recurrent RPS should ideally be given within the context of a clinical trial.

33. Resection
• The technical challenge of resection is typically compounded following curative-intent en bloc
• resection of primary RPS (VA).
• Loss of the original planes increases the difficulty of determining the extent of disease
• and the optimal extent of resection (VA).
• Distortion of anatomical relationships due to prior resection can lead to injury of important
structures(e.g., IVC, duodenum, femoral nerve) (VA).
• Vascular involvement by recurrent disease may necessitate vessel resection and reconstruction;
this should be done in a planned manner and as part of curative-intent resection, at a specialized
center (VA).
• The use of intraoperative frozen sections on marginaltissues as a guide to extent of resection is
generally not advised.

34. Postoperative Systemic Therapy and Other
Locoregional Therapies
• There is no proven role for prophylactic systemic therapy after complete resection of recurrent RPS
(IVC)
• There is no proven role for brachytherapy or postoperative XRT after resection of recurrent RPS,
and each may lead to increased morbidity (IVE).
• IORT may be considered following resection of recurrent RPS, although the evidence is
• weak (IVD).
• There is no proven role for intraperitoneal chemotherapy (IVD)
• There is no proven role for regional hyperthermia (IIID)

35. Outcome
• All consecutive patients who underwent macroscopically complete resection for primary RPS at 8 high volume
centers from January 2002 to December 2011 were identified, and those who developed local recurrence (LR) only,
distant metastasis (DM) only, or synchronous local recurrence and distant metastasis (LR1DM) during the follow-up
period were included.
• Overall survival (OS) was calculated for all groups, as was the crude cumulative incidence of a second recurrence
after the first LR. Multivariate analyses for OS were performed.
• Of the 1007 patients who underwent resection for primary
RPS, 408 experienced disease recurrence.

36. • Survival for the group of patients who underwent resection of LR versus the group that did not, the 2-year OS
of 73% (95% CI, 64.5%-83.0%) and 43% (95% CI, 33.6%-55.5%), and 5-year OS of 43% (95%CI, 32.5%-
57.7%) and 11% (95% CI, 3.8%-31.5%), respectively (P<.0001).
• The CCI of further LR for the 105 patients who underwent resection of LR was calculated to be 40% (95% CI,
30.1%-51.8%) at 2 years and 58% (95% CI, 47.5%-71.8%) at 5 years.
• Resection of recurrent disease offers the only possibility of long-term survival and can result in prolonged OS
for selected patients

37. Predicting Survival in Patients Undergoing Resection for Locally Recurrent
Retroperitoneal Sarcoma: A Study and Novel Nomogram from TARPSWG
(http://www.sarculator.com)
A nomograms predictive of DFS and OS for patients undergoing curative intent
second surgery for RPS-LR1.
These nomograms provide individualized and diseaserelevant estimation of DFS and
OS and will assist in clinical decision-making.
Both nomograms were internally validated and perform well for patients irrespective of
site of initial surgery for primary RPS

38. Patterns of Recurrence and Survival Probability After Second Recurrence of
Retroperitoneal Sarcoma
• Data from patients undergoing resection of a first LR from January 2002 to December 2011were
collected from 22 sarcoma centers.
• The primary outcome was overall survival (OS) after second recurrence.
• A total of 567 patients met the inclusion criteria of the current study and underwent macroscopic
complete surgical resection of a first LR of an RPS after initial macroscopic resection of the
primary RPS.

39. • Of these 567 patients, 400 patients (70.5%) developed recurrent disease, including
323 patients (80.8%) who had LR only, 55 patients (13.8%)who developed DM only, and 22 patients who
had

40. • Second recurrences occurred in 400 of 567 patients (70.5%) after an R0/R1 resection of a first
locally recurrent RPS.
• Patterns of disease recurrence were LR in 323 patients (80.75%), distant metastases (DM) in 55
patients (13.75%), and both LR and DM in 22 patients (5.5%).
• The main subtype among the LR group was liposarcoma (77%), whereas DM mainly were
leiomyosarcomas (43.6%). In patients with a second LR only, a total of 200 patients underwent re-
resection (61.9%). The 5-year OS rate varied significantly based on the pattern of failure (P < .001):
45.6% for the LR group, 25.5% for the DM group, and 0% for the group with LR and DM.
• The only factors found to be associated with improved OS on multivariable analysis were both time
between second surgery and the development of the second recurrence (32 months vs 8 months:
hazard ratio, 0.44 [P < .001]) and surgery for second recurrence (yes vs no: hazard ratio, 3.25 [P <
.001]).
• The 5-year OS rate for patients undergoing surgery for a second LR was 59% versus 18% in the
patients not deemed suitable for surgical resection.
• Survival rates after second recurrence of RPS varied based on patterns of disease recurrence and
treatment.
• Durable disease-free survivors were identified after surgery for second LR in patients selected for
this intervention.

41. Conclusion

42. THANK YOU