Retroperitoneal Soft Tissue Sarcoma

Updated by David V. Eastham and Deborah A. Frassica

BACKGROUND

Describe the demographics of retroperitoneal soft tissue sarcoma (STS)?

There are a wide range of ages at presentation, but most pts are in their 50s with about equal numbers of men and women.

What % of STS are retroperitoneal?

10%–15% of STS are retroperitoneal.

What is the typical presentation of pts with retroperitoneal STS?

Pts with retroperitoneal STS typically present with vague abdominal complaints.

What is the median diameter of retroperitoneal STS at presentation?

The median diameter of retroperitoneal STS is 15 cm.

What are the boundaries of the retroperitoneal space?

Boundaries of the retroperitoneal space:

Superior: diaphragm

Inferior: pelvic diaphragm

Lateral: lat edge of quadratus lumborum, but lat edge of 12^th rib is also considered because it corresponds to origin of transversus abdominis aponeurosis

Anterior: parietal peritoneum where anchors to colon and small bowel

Posterior: muscular wall composed of psoas and quadratus lumborum in abdomen; iliacus, obturator internus, and pyriformis in pelvis

Which organs are retroperitoneal?

Retroperitoneal organs include the pancreas, kidneys, adrenal glands, and ureters.

What is the DDx of a retroperitoneal soft tissue mass? What % are malignant and what are the malignant and benign etiologies?

The DDx of a retroperitoneal mass includes either malignant or benign tumors. 80% of retroperitoneal neoplasms are malignant.

Malignant etiology includes:

1. Sarcoma

2. GI stromal tumor (GIST)

3. Lymphoma

4. Germ cell tumor

Benign etiology includes:

1. Desmoid tumor

2. Lipoma

3. Benign peripheral nerve sheath tumor (schwannoma, neurofibroma)

What are the 2 most common histologies of retroperitoneal sarcoma in adults?

The 2 most common histologies for retroperitoneal sarcoma in adults include liposarcoma and leiomyosarcoma.

What is the most common histology of retroperitoneal sarcoma in children?

The most common histology of retroperitoneal sarcoma in children is rhabdomyosarcoma.

WORKUP/STAGING

How does staging for retroperitoneal sarcoma differ from the general STS AJCC (7^th edition, 2011) staging?

Staging for retroperitoneal STS is according to the AJCC staging for STS except the retroperitoneal location is always considered deep and therefore the T stage will be designated with the letter “b.”

Do all pts with suspected retroperitoneal sarcoma require a preop Bx?

No. Preop Bx is not required if the suspicion for retroperitoneal sarcoma is high. However, CT-guided core Bx is necessary in pts undergoing neoadj chemo or RT.

What imaging studies should be performed to stage retroperitoneal sarcoma?

Recommended staging studies for retroperitoneal sarcoma include CT abdomen/pelvis with contrast, chest imaging, and optional MRI.

TREATMENT/PROGNOSIS

What is the primary Tx modality for retroperitoneal sarcoma?

Surgery (en bloc resection of the tumor with the goal of attaining –margins) is the primary Tx modality for retroperitoneal sarcoma.

What is the most important treatment factor which predicts survival for retroperitoneal sarcoma?

Postop margin status is the most important factor in predicting survival. MSKCC analysis of >500 pts showed MS= 103 mos if GTR vs. only 18 mos for less than GTR. (Lewis JJ et al., Ann Surg 1998)

What are the Tx paradigms for retroperitoneal STS?

Retroperitoneal STS Tx paradigms:

1. Surgery alone

2. Surgery (+/– IORT) → adj RT and/or chemo

3. Neoadj RT and/or chemo → surgery (+/– IORT)

Note: If RT will be included in the Tx, the authors’ strong institutional preference is for neoadj RT given the substantial morbidity of adj RT and the limited data supporting this approach.

What % of retroperitoneal sarcomas are amenable to a GTR?

<70% of retroperitoneal sarcomas are amenable to a GTR.

Is recurrence after surgery for retroperitoneal sarcoma more likely to be local or distant?

Most recurrences after surgery for retroperitoneal sarcoma are local.

What is the LR rate after GTR (R0 or R1) for retroperitoneal sarcoma?

LR ranges from 50%–95% in pts who have undergone GTR for retroperitoneal sarcoma.

Summarize the argument in favor of preop RT over PORT.

Preop RT may be superior to PORT for retroperitoneal sarcoma b/c it allows for better tumor volume definition, displacement of normal viscera by tumor (therefore, less normal tissue in Tx volume), smaller Tx fields, and the potential radiobiologic advantage of having normal vasculature/oxygenation in place. Although there has been no RCT comparing preop RT vs. PORT, Bolla et al. found significantly worse 5-yr RT-related complication rate with PORT (23% vs. 0%). (IJROBP 2007)

Is there a benefit of adding IORT with postop EBRT after the surgical management of retroperitoneal sarcoma?

Possibly. There are at least 2 studies that suggest IORT improves LC when added to EBRT, but it is unclear if this improves OS. An NCI trial (Sindelar WF et al., Arch Surg 1993) compared IORT + PORT to PORT alone for retroperitoneal STS. 35 pts were randomized to IORT (20 Gy) + postop EBRT (35–40 Gy) vs. PORT (50–55 Gy). Both groups rcvd chemo (doxorubicin/cyclophosphamide/methotrexate). At a min follow-up of 5 yrs, there was no difference in OS between the groups (MS was 3.7 yrs with IORT vs. 4.3 yrs with PORT). There was a significant improvement in “in-field” LR with IORT (40% IORT vs. 80% PORT). RT enteritis occurred in 13% of pts with IORT and 50% of pts with PORT. Peripheral neuropathy was found in 60% of pts with IORT vs. 80% of pts with PORT.

A Massachusetts General Hospital retrospective review included 29 pts: 16 treated with IORT (10–20 Gy with intraop electrons) and 13 treated without IORT. All pts rcvs 45 Gy EBRT. LC improved with the addition of IORT (83% vs. 61%). (Gieschen HL et al., IJROBP 2001)

What did ACOSOG Z9031 try to address?

ACOSOG Z9031 randomized pts to surgery alone vs. preop RT + surgery for primary retroperitoneal sarcoma. The target accrual was 370 pts in 4.5 yrs. The primary endpoint was PFS. This study closed due to poor accrual.

Summarize the outcomes of the Toronto Sarcoma Group and the MDACC prospective trials of preop EBRT for localized intermediate- or high-grade retroperitoneal sarcoma.

The Toronto Sarcoma Group and the MDACC prospective trials enrolled 72 pts with intermediate or high-grade retroperitoneal sarcoma. 75% were primary, and 25% were recurrent. Pts were treated preop to a median dose of 45 Gy with concurrent low-dose doxorubicin. 89% underwent laparotomy with curative intent 4–8 wks after RT. 60% had an intraop or postop boost. At median follow-up of 3.4 yrs, the RR was 52% after GTR. 5-yr LRFS was 60%, DFS was 46%, and OS was 61%. (Pawlik TM et al., Ann Surg Oncol 2006) Results compared favorably to historical controls.

What EBRT dose is typically used for preop RT for retroperitoneal sarcoma? What phase I study tested tolerability of this preop RT dose with concurrent doxorubicin?

Retroperitoneal STS is typically treated to 50.4 Gy preop. Based on the MDACC phase I trial enrolling 35 pts with potentially resectable intermediate- or high-grade retroperitoneal sarcoma, preop RT can be safely administered to 50.4 Gy with concurrent weekly doxorubicin. At this dose, there was 18% grade 3–4 nausea. (Pisters PW et al., JCO 2003)

Summarize the outcomes of the retrospective study by the French Federation Cancer Sarcoma Group regarding adj RT for retroperitoneal sarcoma.

The French Federation Cancer Sarcoma Group retrospectively reviewed 145 pts with localized nonmetastatic retroperitoneal sarcoma. 65% underwent GTR, and 41% had adj RT. 5-yr OS was 46%. 5-yr LRC was 55% with adj RT vs. 23% with surgery alone. (Stoeckle E et al., Cancer 2001). These results should be interpreted cautiously, as selection bias may have favored the RT arm in this study and adj RT is associated with significant RT-related morbidity.

In the preop radiotherapy management of retroperitoneal sarcoma, does the whole tumor volume need to be treated? What prospective study studied this question?

This is uncertain. Bossi A et al. was a prospective trial enrolling 18 pts with retroperitoneal sarcoma. (IJROBP 2007) Pts were treated with neoadj IMRT limited to the postabdominal wall, and planning was compared to standard RT fields. All pts successfully completed RT and surgery. There were 2 LRs, 1 within the high-dose region and 1 marginal recurrence that would not have been covered by the standard CTV. The authors concluded that limiting the CTV to the postabdominal wall is feasible.

Is there a benefit of IMRT over 3D-CRT for the preop management of retroperitoneal sarcoma?

Yes. The Emory retrospective review compared 3D-CRT with IMRT for 10 pts with retroperitoneal sarcoma and showed improved tumor coverage with better sparing of organs at risk with IMRT. (Koshy M et al., Sarcoma 2003)