Surgical resection is the primary treatment for RPS.
Results of Large Series and Prognostic Factors
Table 27-1 summarizes five large surgical series of RPS, including two reports from MKSCC (New York, the United States), one report from the Insituto Nazionale Tumori (Milan, Italy), a multi-institution report from France, and a two-institution report from the Insituto Nazionale Tumori and Institut Gustave Rousssy (Villejuif, France).2-4,30 All these series include only patients who presented with primary tumors. The median size of tumors was up to 18 cm. Complete gross resection rates ranged from 75% to 93%, and contiguous organs resection was required in 58% to 77% of cases. The proportion of tumors resected with a negative microscopic varied between 47% and 59%. Of note, the negative microscopic margin rate may be misleading given the ability to detect a positive microscopic margin depends highly on (1) whether the surgeon orients the specimen for the pathologists and identifies the location or locations of the closest margin and (2) how extensively the pathologist examines these often very large specimens.
Selected Surgical Series
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Selected Surgical Series
|Institution/Group ||MSKCC ||MSKCC ||INT ||Multi-institution ||INT and IGR |
| ||New York ||New York ||Milan ||France ||Milan and Villejuif |
|Time period ||1982–1997 ||1982–2010 ||1985–2007 ||1985–2005 ||2000–2008 |
|Year published ||1998 ||2104a ||2009 ||2009 ||2010 |
|Median follow-up (month) ||28 ||52 ||58 ||53 ||37 |
|Number of patients ||231 ||675 ||288 ||382 ||249 |
|Mean or median age ||NR ||60 ||55 ||57 ||55 |
|Primary tumors ||100% ||100% ||67% ||100% ||100% |
|Mean or median size ||>10 cm ||17 cm ||16 ||18 ||17 |
|Intermediate- or high-grade ||60% ||64% ||71% ||64% ||67% |
|Complete gross resection ||80% ||85% ||89% ||75% ||93% |
|Contiguous organ resection ||77% ||58% ||71% ||67% ||NR |
|Negative microscopic margin ||59% ||50% ||NR ||47% ||NR |
|Mortality ||4% ||3.4% ||NR ||3% ||3% |
|Adjuvant radiation ||NR ||14% ||31% ||32% ||36% |
|Adjuvant chemotherapy ||NR ||16% ||32% ||17% ||37% |
|5-year local recurrence ||41% ||39% ||29%–48% ||49% ||22% |
|5-year distant recurrence ||21% ||24% ||13%–22% ||34% ||24% |
|5-year overall survival ||54% ||59% ||51%–60% ||57% ||65% |
As noted earlier, the primary problem with RPS is local recurrence, and patients who ultimately succumb to RPS more commonly die of local recurrence than distant metastasis. The estimated 5-year local recurrence rates in the five largest reported series varied between 29% to 49%, but these can vary significantly depending on length of follow-up and rates may be significantly higher in smaller series. The median time to local recurrence after RPS resection is about 22 months31 but well-differentiated liposarcomas can recur beyond 5 and 10 years after surgical resection. Five-year distant recurrence rates varied between 13% to 24% and 5-year overall survival rates ranged from 51% to 65%.
Some series have examined prognostic factors for both local and distant recurrence. Some surgical series have examined prognostic factors for local recurrence and found histologic subtype, grade, radiation, and type of surgery to be prognostic factors.2-4,32 Only one study2 found margin to be prognostic while another study did not.4 Prognostic factors for distant recurrence and overall survival prognostic factors (found in one or more studies) included histologic subtype, grade, complete gross resection, and radiation therapy.2-4,32-34
Extent of Primary Surgery
For tumors where complete gross resection is possible, leaving a negative microscopic margin around the entire tumor can be challenging. The EORTC-Soft Tissue and Bone Sarcoma Group recently described a standardized surgical approach to RPS.35 The anterior surface of these tumors is often covered by peritoneum and organs, which can be resected with relatively low morbidity (e.g., colon, tail of pancreas, spleen, and kidney) enabling a negative anterior margin. In other instances, the anterior margin may be the head of the pancreas and duodenum, and performance of a pancreaticoduodenectomy may significantly increase morbidity. Laterally, the peritoneum and the transversalis fascia can generally be left on the tumor as margin. Medially, tumors can generally be dissected of the aorta and inferior vena cava, leaving adjacent areolar tissue on the tumor as margin. The posterior margin of these tumors often abuts retroperitoneal fat and the psoas musculature, where obtaining negative margins requires visualization and sharp dissection due to the lack of anatomic dissection planes. Thus, tumors should be dissected circumferentially from anterior to posterior to allow visualization and sharp dissection rather than working on the posterior aspect of the tumor through a limited hole. Resection of major vessels, nerves, and bone is generally not necessary unless there is direct invasion. Major arteries can usually be dissected free leaving adventitia on the tumor, major nerves can be dissected free leaving epineurium on tumor, and bone can be dissected free leaving periosteum on tumor.
The aggressiveness of RPS surgery, particularly in the resection of adjacent organs and tissues, has been a topic of significant debate. Gronchi et al from the Istituto Nazionale del Tumor in Milan retrospectively examined 288 patients with primary RPS surgically resected between 1985 and 2007.3 Prior to 2002, adjacent organs were generally only resected if there was direct involvement by tumor. From 2002 onward, a more aggressive policy was instituted with resection of adjacent organs and tissues. Radiation was delivered in about 30% of patients. Five-year actuarial local recurrence was 48% in the less aggressive surgery group and 29% in the more aggressive surgery group. Thus the authors argued that a policy of liberal en block resection of adjacent organs and tissues may improve local control. A multicenter retrospective review of 382 RPS patients in France divided patients by surgical procedure into compartmental resection of contiguous organs (32%), resection of only involved organs (35%), simple complete resection (17%), and re-excision of tumor bed (6%).2 Incomplete gross resection (e.g., R2 resection) occurred in 65 of patients. Thirty-two percent of patients received radiation therapy and 37% received chemotherapy. The study found that compartmental resection of contiguous organs was associated on multivariate analysis with a 3.29-fold lower rate of local recurrence compared to only complete gross tumor resection. Morbidity occurred in 22% of patients, with about 5% of patients requiring reoperation and 3% dying of complications. In response to these Milan and French studies, an editorial to these studies argued that aggressive resection was predominately limited to the kidney, colon, and psoas that may be associated with less morbidity than resection of major vessels, and the pancreas or diaphragm that may also be involved by tumor.36 The editorial concluded: "Until better safety data and more convincing outcome data are available, we should not use the retrospective data from these studies, given the myriad of interpretative issues and the presence of various forms of bias, to change the surgical approach to patients with retroperitoneal sarcomas."36
Bonvalot et al subsequently published a pooled series from two high-volume institutions.37 In the pooled data of 249 patients, 5-year overall survival was 65% and local recurrence-free survival was 78%. Further analysis demonstrated that resection of greater than three organs was associated with increasing morbidity, 12% of patients required reoperation postoperatively for complications, and 3% of patients suffered postoperative mortality. The authors again advocated for the use of aggressive surgical resection based on the high rate of complete resection and favorable recurrence and survival data. This article was accompanied by an editorial that again pointed out the possible flawed concept of resecting only selected contiguous organs and vital structures and the difficulty in interpreting retrospective analyses.38 Thus, there remains no consensus on the appropriate resection for RPS and no prospective trials to guide surgical practice. Certainly for surgeries requiring extensive organ resection or multiple surgeons from different specialties, the operation would ideally be treated at a high-volume sarcoma center. Of note, several articles on major vascular resections, liver resections, pancreaticoduodenctomies, and other aggressive strategies for primary RPS have been published.39-41
Debulking Surgery and Surgery for Local Recurrence
Surgeons should be wary of attempting surgery if complete surgical resection cannot be performed. In some series, incomplete resection has resulted in the same overall survival as patients undergoing biopsy alone.4,42,43 However, there may be some role for debulking unresectable RPS in very selected circumstances such as for very slow-growing tumors (e.g., well-differentiated liposarcomas) or for the relief of symptoms. MSKCC studied 55 patients with unresectable liposarcomas and found increased survival (26 vs. 4 months) in patients receiving partial resection compared to biopsy alone.44 The majority of benefit for partial resection was seen in patients with primary disease, and patients undergoing partial resection of local recurrence showed significantly decreased survival compared to after partial resection of primary disease (17 vs. 46 months). Several studies have shown that approximately 75% of patients report symptomatic improvement after palliative surgery.44-46 This improvement, however, can be short-lived. One study showed 71% of patients had symptomatic improvement at 30 days but this fell to 54% by 100 days.46 Also in this study, palliative operations had a morbidity rate of 29% and mortality rate of 12%. Thus, selection of patients and surgical judgment is critical as these operations are often extensive and may not provide prolonged alleviation of symptoms.
Surgical resection of locally recurrent RPS is generally significantly more difficult than resection for primary disease, and the risk of another local recurrence is even higher than that for primary disease. In studies specifically addressing resection of locally recurrent RPS, rates of complete resection ranged between 44% and 60% and complete resection was significantly associated with increased survival.31,43,45 Reported 5-year overall survival after complete resection is between 30% and 46% compared to 27% or less in unresectable patients. Park et al examined 105 patients who had local recurrence of RP sarcoma.47 After a median follow-up of 65 months, local recurrence size, primary histologic subtype and grade, and local recurrence growth rate were independent predictors of disease-specific survival. Local recurrence growth rate for the first local recurrence was defined as the tumor size divided by the time from primary resection to local recurrence. Patients with a local recurrence growth rate <1 cm per month had improved survival following resection of the local recurrence.