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Management of locally recurrent retroperitoneal sarcoma

Management of locally recurrent retroperitoneal sarcoma
Literature review current through: Jan 2024.
This topic last updated: Aug 09, 2022.

INTRODUCTION — Sarcomas are malignant tumors that arise from skeletal and extraskeletal connective tissues, including the peripheral nervous system. The majority of soft tissue sarcomas (STS) present in the extremities; however, many other sites can be affected, including the retroperitoneum.

This topic review will cover management of a locally recurrent retroperitoneal sarcoma (RPS). A general discussion of the diagnostic evaluation and staging of STS; the clinical features, evaluation, and initial treatment of RPS; local and systemic therapy for metastatic STS; and treatment of locally recurrent desmoid tumors (which may present in intra-abdominal and abdominal wall sites) are presented elsewhere:

(See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Introduction'.)

(See "Surgical treatment and other localized therapy for metastatic soft tissue sarcoma".)

(See "Overview of the initial treatment of metastatic soft tissue sarcoma".)

(See "Desmoid tumors: Epidemiology, molecular pathogenesis, clinical presentation, diagnosis, and local therapy", section on 'Management of recurrent disease'.)

FREQUENCY OF LOCAL RECURRENCE, TIME COURSE, AND RISK FACTORS — Surgical resection has traditionally been the only potentially curative treatment for localized RPS. In contrast to extremity soft tissue sarcoma (STS), for which the most common site of first recurrence (at least for intermediate- or high-grade tumors) is a distant site, the primary pattern of treatment failure after resection of RPS is local, although this also depends upon the histologic subtype. As an example, in one multicenter series of 1007 patients undergoing resection of a primary RPS, 408 patients developed recurrent disease during follow-up, including 219 patients (54 percent) with a local recurrence alone, 146 patients (36 percent) with distant metastases alone, and the remainder (10 percent) with both a local and distant recurrence [1]. (See "Initial management of retroperitoneal soft tissue sarcoma", section on 'Prognosis'.)

Locoregional recurrences can occur in the tumor bed, and they may also be multifocal or multicentric. In an analysis of 247 patients with well-differentiated/dedifferentiated liposarcoma arising in the retroperitoneum, 66 of 142 well-differentiated liposarcomas recurred locoregionally, and of these, 33 (50 percent) were unifocal and the remainder were multifocal (defined as the presence of two or more tumors in the retroperitoneum) [2]. Of the 33 multifocal recurrences, 11 (33 percent) were multicentric and outside field (defined as development of at least one tumor in a compartment remote from the index tumor). Patients with multifocal recurrent disease had an inferior survival rate compared with those with unifocal recurrent disease. Of the 105 patients with dedifferentiated liposarcomas, 48 recurred locoregionally, and one-half of these were unifocal recurrences. Of the 33 multifocal recurrences, seven were multicentric and outside field. Survival was not significantly worse for those with multifocal recurrent disease.

Several factors contribute to a high rate of local recurrence for RPS compared with extremity STS [3] (see "Initial management of retroperitoneal soft tissue sarcoma", section on 'Prognosis'):

RPS are typically large at the time of diagnosis and are anatomically situated such that a wide resection is often not achievable. (See "Surgical resection of retroperitoneal sarcoma", section on 'Determination of resectability'.)

The radiation tolerance of adjacent normal tissues (eg, liver [30 Gy], kidney [20 Gy], gastrointestinal tract [small bowel 50.4 Gy], and spinal cord [50 Gy]) is below the radiation dose levels for postoperative radiation therapy (RT), where doses of >60 Gy have typically been used for extremity sarcomas.

An important point is that local recurrences after complete resection of a primary RPS may be delayed [4,5]:

In several series, local control rates range from 41 to 55 percent at five years but are only 18 to 40 percent at 10 years [6-9].

In a report of 198 adult patients with RPS who were eligible for ≥5 years of follow-up, 40 percent of the 48 patients who were alive and disease free at five years recurred by 10 years [7].

Thus, long-term follow-up, even beyond 10 years, is mandatory following initial treatment of RPS. (See "Initial management of retroperitoneal soft tissue sarcoma", section on 'Prognosis'.)

Risk factors for local recurrence include tumor size, histologic subtype and grade, status of the surgical margins, and whether adjunctive RT was administered [1,5,10-12]. As examples:

In a single-institution prospective database of 675 patients treated surgically for primary nonmetastatic RPS from 1982 to 2010, the five-year cumulative incidence of local recurrence was 39 percent, and the independent factors for local recurrence were incomplete resection, tumor size, and histologic type [5]. The highest local recurrence rates were in liposarcomas of all subtypes (approximately 60 percent by 15 years), but early recurrences were especially pronounced with the dedifferentiated, round cell, and pleomorphic liposarcoma subtypes (the majority recurred within five years). Rates of local recurrence were lowest in leiomyosarcoma (approximately 22 percent) and solitary fibrous tumor (approximately 10 percent). Patients undergoing a macroscopically incomplete (R2) resection were 2.5 times more likely to have local progression compared with those with a complete or microscopically complete (R1/R0) resection.

The influence of histologic type on patterns of recurrence was further shown in a series of 1007 consecutive patients with localized primary RPS who underwent resection between January 2002 and December 2011 at eight international centers [12]. Local recurrence rates were highest (>30 percent) with liposarcoma (especially the dedifferentiated type) and undifferentiated pleomorphic sarcoma, and were lowest (<15 percent) with leiomyosarcoma and solitary fibrous tumor.

There are no randomized trials of surgery with and without postoperative (adjuvant) external beam RT. In retrospective series, the addition of postoperative RT reduced the risk of local recurrence and lengthened the recurrence-free interval. However, it has been more difficult to demonstrate a survival benefit.

The largest uncontrolled single-institution experience included 145 French patients who presented with a localized RPS [13]. The median tumor size was 15 cm (range 2 to 70 cm), 31 percent presented with neurovascular or bone involvement, 39 percent had grade 3 lesions, and 30 percent had liposarcoma subtype. Complete (macroscopic) excision had been carried out in 94, and 60 of these patients received postoperative RT (median dose 50 Gy). Among the patients who underwent complete excision, the five-year actuarial local recurrence-free survival was significantly greater for the 60 irradiated patients compared with the 34 who did not receive it (55 versus 23 percent).

PRETREATMENT ASSESSMENT — Our approach to the pretreatment assessment of recurrent RPS is consistent with the comprehensive guidelines from the Trans-Atlantic RPS Working Group (TARPSWG) [14].

Radiographic studies — Radiographic imaging is a key component of the evaluation of a patient with a suspected local recurrence of RPS. All relevant imaging studies performed prior to resection of the primary RPS should be obtained and reviewed, as should all subsequent imaging studies, including the initial postoperative baseline imaging to determine the initial disease stage and whether residual gross disease remained after the initial resection. (See "Clinical presentation and diagnosis of retroperitoneal soft tissue sarcoma", section on 'Imaging studies'.)

The current extent of local and distant disease should be determined using an oral and intravenous contrast-enhanced thin slice (2.5 to 5 mm [15]) multidetector row computed tomography (CT) scan of the abdomen and pelvis to evaluate the primary site, as well as a chest CT to rule out metastatic disease to the lungs. The lungs are the first site of metastasis in the majority of cases. Imaging obtained at the time of recurrence should be compared with all prior imaging to ascertain the extent and progression of recurrent disease, with attention to the pattern of relapse (locoregional versus peritoneal versus distant to other sites), whether there is evidence of invasion into adjacent organs/critical structures, and the rate of progression. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'MRI and CT' and "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Pattern of spread'.)

Although not required in most cases, magnetic resonance imaging (MRI) may be a useful ancillary modality in selected situations to define the extent of local invasion into adjacent organs/structures that is not clear on CT. Specifically, MRI may be helpful for patients with a serious contrast allergy or another contraindication to CT, and for operative planning for pelvic tumors that may abut/involve musculoskeletal structures (eg, vertebrae, psoas muscle) [14].

Positron emission tomography (PET) with fluorodeoxyglucose (FDG) may be useful in selected cases. Integrated PET/CT scanning can achieve whole body imaging and is widely considered to be more sensitive than CT for the detection of occult distant metastases in a variety of solid tumors. One reported benefit in soft tissue sarcomas (STS) as a group is to detect sites of extrapulmonary metastatic disease. However, the risk is so low with most STS (including RPS) that routine use of PET for this purpose is unlikely to change the therapeutic plan. However, imaging with PET/CT may have a role in patients with clinical suspicion of recurrent RPS if the results on cross-sectional imaging are difficult to interpret. As examples, PET/CT may help clarify the situation if the extent of active abdominal disease is difficult to evaluate. PET/CT may show peritoneal implants, help distinguish postsurgical change from tumor, and/or delineate multifocal lesions [14,16]. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Is there a role for PET/CT?'.)

Histopathology — The histopathology of the primary RPS should be reviewed by a pathologist specializing in the evaluation of soft tissue tumors, and molecular subtyping should be performed where appropriate. (See "Clinical presentation, histopathology, diagnostic evaluation, and staging of soft tissue sarcoma", section on 'Molecular diagnostics'.)

Percutaneous core biopsy confirmation of a suspected recurrence is often useful to provide a definitive diagnosis because a variety of other entities can be mistaken for recurrence of the original primary RPS, which might be treated differently (eg, desmoid fibromatosis, radiation-induced osteosarcoma, or an angiosarcoma in the resection bed of an original liposarcoma).

TREATMENT — Locally recurrent RPS is best managed by an experienced multidisciplinary team in a specialized referral center. Although the best chance for cure is at the time of primary presentation, some patients with locally recurrent disease have prolonged disease control, and this is most likely to be optimized when care is delivered by an expert multidisciplinary team.

Although surgical resection may be considered in patients with isolated metastases to the lung and liver, resection of locally recurrent tumor is generally not appropriate for patients who have synchronous distant metastatic disease [14]. Patients with metastatic disease are treated with systemic chemotherapy, which is discussed separately. (See "Surgical treatment and other localized therapy for metastatic soft tissue sarcoma" and "Overview of the initial treatment of metastatic soft tissue sarcoma".)

General approach — Although each case of recurrent RPS is unique and care must be individualized, the following represents our general approach to the patient:

The most significant predictor of outcome following local recurrence is surgical resectability. Where feasible, reresection should be attempted for an isolated local recurrence. Approximately 60 percent of such tumors are potentially resectable, and five-year survival rates after reresection may be as high as 50 percent. Patients most likely to benefit from resection are those with a longer disease-free interval, no history of tumor rupture at primary resection, low-grade tumors (especially well-differentiated liposarcomas), and unifocal rather than multifocal disease. Multifocal intra-abdominal disease is difficult to resect completely, will almost certainly recur again, and carries a poor prognosis, particularly with resection alone. Because the oncologic benefit of surgery is likely to be limited and the risk of morbidity substantial, a very careful approach to patient selection for surgical intervention is required [14]. The surgeon will need to weigh all factors, including the age and functional status of the patient, the tumor biology (ie, the strategy for a recurrent well-differentiated liposarcoma will be very different from that for a dedifferentiated liposarcoma or a leiomyosarcoma), the likelihood of achieving a complete resection, and the anticipated surgical morbidity. (See 'Surgical reresection' below.)

For patients who did not receive radiation therapy (RT) as part of initial therapy for their sarcoma, we suggest preoperative RT. Intraoperative RT (IORT) may also be an option. Postoperative RT is discouraged. (See 'Preoperative therapy' below and 'Postoperative therapy' below.)

Although not used in the United States, preoperative regional hyperthermia with systemic chemotherapy is another therapeutic option for locally recurrent tumors in parts of the world where it is available (mainly Europe), especially for previously irradiated patients. Whether this approach is superior to surgery, with or without RT, or chemoradiation is not clear. (See 'Prior radiation therapy' below.)

For patients with an unresectable recurrence (ie, due to involvement or encasement of critical structures such as aorta, superior mesenteric vessels, porta hepatis, or major nerve roots), the role of surgical debulking is unclear. Debulking surgery may be a reasonable option for some patients with low-grade (ie, well-differentiated) liposarcomas, although complete resection is preferred, if feasible. In most other situations, debulking surgery does not improve long-term survival, and it should not be attempted except for palliation of symptoms. Some RPS that is unresectable may be controlled long term with the use of high-dose charged-particle irradiation. However, availability of this technology is limited to a few specialized centers. (See 'Locally unresectable disease' below.)

Potentially resectable disease

Surgical reresection

Treatment approach — Where feasible, reresection should be considered for an isolated locally recurrent tumor. Approximately 60 percent of such tumors are potentially resectable, and five-year survival rates may be as high as 50 percent. Patients most likely to benefit from resection are those with a longer disease-free interval, no history of tumor rupture/piecemeal resection at primary resection, low-grade tumors (especially well-differentiated liposarcomas), and unifocal rather than multifocal disease. Surgery should not be undertaken for patients with a multifocal recurrence and those with a poor performance status (table 1).

The addition of IORT may improve the local control rate in patients undergoing an operation for recurrent RPS, although the available data are limited [17-19]. In one series of 32 such patients, 20 of whom had locally recurrent disease, patients received maximal tumor resection, IORT, and postoperative RT where feasible [17]. The local control rate was 54 percent for patients with recurrent disease. The most common posttreatment complications were gastrointestinal obstruction (18 percent) and fistula formation (9 percent). Wound complications occurred in 3 percent. Preoperative RT is an option to improve local control.

Some patients, particularly those with well-differentiated liposarcoma, may benefit from a period of initial observation followed by reimaging to select patients who are most likely to benefit from resection (ie, those who have a truly isolated local recurrence).

Reresection may also be feasible for selected patients with a second and third local recurrence. However, with each local recurrence, there is a greater need for more complex en bloc resections, and tumor resectability dramatically diminishes with each reoperation. In one series, resectability rates were 80 percent for primary tumors compared with 57, 33, and 14 percent for first, second, and third recurrences, respectively [20].

Data suggest that a surgical approach to recurrent RPS is safe, as the rates of postoperative morbidity and mortality are comparable to those seen with surgery for primary RPS. As an example, one study conducted by the Trans-Atlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG) evaluated 681 patients with a first local recurrence of RPS treated with resection. In this study, the 90-day postoperative mortality rate was 0.4 percent and the major complication rate was 16 percent. A transfusion requirement was predictive of major complications and worse overall survival (OS), but having a major complication was not associated with worse OS or a higher incidence of local recurrence or distant metastasis [21]. (See "Surgical resection of retroperitoneal sarcoma", section on 'Perioperative morbidity and mortality'.)

Survival outcomes and predictive nomograms — Five-year OS rates after complete resection of a recurrent RPS range from 19 to 57 percent [1,22-28]. However, even patients who undergo complete reresection have high rates of future local recurrence [22,24]. As an example, in a report of 24 patients who underwent complete reresection of a locally recurrent RPS at the University of Heidelberg between 1988 and 2002, 20 patients (83 percent) recurred locally [22].

The predictors of long-term outcome after reresection of a locally recurrent RPS are time interval to the local recurrence, completeness of resection, and histology. Long-term tumor control and survival rates are poorer for high-grade histologies [23,24,29-31], rapidly progressing tumors [32], those with short recurrence-free intervals [1,33], and those resected with a positive margin [1,22,24,33].

Data demonstrating a survival benefit in those treated with surgical reresection are as follows:

The most significant predictor of outcome following local recurrence is the resectability of the recurrent disease [1,11,25]. Approximately 60 percent of locally recurrent RPS are potentially resectable [22,33], and outcomes are significantly better in patients whose tumors are resected compared with those whose tumors are not resected [1,11]. As an example, in one multicenter series of 219 patients with locally recurrent RPS, the two-year OS rates for those undergoing resection versus no resection were 73 and 43 percent, respectively, while at five years, OS rates were 43 and 11 percent, respectively [1].

In a multi-institutional review of 1007 patients with primary RPS from the TARPSWG who were managed by extended resection, 408 patients experienced disease recurrence [1]. The initial site of recurrence was local only in 219 patients (54 percent), distant only for 146 patients (36 percent), and both local and distant in 43 patients (10 percent). Of the 219 patients who had a local recurrence alone, resection was performed in 105 (48 percent), and chemotherapy and radiotherapy were administered to 68 (31 percent) and 39 (18 percent) patients, respectively. The five-year OS rate after resection was 43 percent, compared with 11 percent for those who were not resected. The crude cumulative incidence of another recurrence after resection was 40 percent at two years and 58 percent at five years, underscoring the high-risk nature of these tumors.

Predictive nomogram for survival The TARPSWG also published a study with a novel nomogram predicting survival in patients undergoing resection of a locally recurrent RPS [34]. Covariates used in the TARPSWG nomogram to predict six-year DFS and OS included (figure 1):

Age at second surgery

Tumor multifocality, histology, and grade

Completeness of tumor resection at second surgery

Chemotherapy/radiotherapy at first surgery

Number of organs resected at first surgery

The nomogram was developed based on a study of 602 patients who underwent resection of a locally recurrent RPS, at a median follow-up of 119 months, the six-year disease-free survival (DFS) and OS rates were 19.2 and 54.1 percent, respectively. Recurrence patterns and survival probability were histology-specific, with liposarcoma subtypes having the highest six-year crude-cumulative-incidence (CCI) of a second local recurrence (60.2 to 70.9 percent) and leiomyosarcoma having a higher six-year CCI of distant metastasis (36.3 percent).

Preoperative therapy

No prior radiation therapy — For patients who have not previously received RT, management of a local recurrence should be the same as for a de novo RPS. Preoperative RT is preferred over postoperative RT. (See "Initial management of retroperitoneal soft tissue sarcoma", section on 'Toxicity'.)

There are no published guidelines for the RT fields to be employed in this situation. Some consideration should be given to treating both the area of recurrent disease as well as the site of the original tumor to a dose of 45 to 50.4 Gy at 1.8 to 2 Gy daily, although the target volume encompassing the area of original disease may need to be limited to the posterior abdominal wall tumor margin because of bowel that is often found in the prior resection cavity.

There is anecdotal experience with intensity-modulated RT (IMRT) to deliver an escalated dose of 57.5 Gy (similar to that reported in the setting of primary disease [35]) to the posterior margin of the recurrent disease if bowel can be excluded from the target volume.

Where available, preoperative chemotherapy with regional hyperthermia may also represent an alternative to preoperative RT.

Prior radiation therapy — Preoperative therapy options for patients who have received prior RT include chemotherapy alone or, where available, chemotherapy with regional hyperthermia.

Chemotherapy with regional hyperthermia – A potential benefit for regional hyperthermia in conjunction with preoperative chemotherapy was suggested in the European Organisation for Research and Treatment of Cancer (EORTC) trial 62961, which included patients with locally recurrent RPS [36]. Other data support the safety of this approach in patients with RPS, both in the neoadjuvant and adjuvant settings [37,38].

Chemotherapy alone – Although data are limited, neoadjuvant (preoperative) chemotherapy occasionally induces a radiographic response, which may impact surgical therapy in a few patients with chemosensitive histologies (ie, dedifferentiated liposarcoma, leiomyosarcoma, synovial sarcoma). Although responders tend to do better than nonresponders, whether this reflects an impact of chemotherapy, disease biology, or patient selection remains uncertain.

If this approach is chosen, the optimal regimen has not been established, and the choice is empiric. However, at least one trial conducted in patients with high-risk soft tissue sarcoma (STS) of the extremities or body wall showed that histotype-tailored chemotherapy did not provide a benefit over standard chemotherapy (an anthracycline plus ifosfamide) when used in the neoadjuvant setting [39]. (See "Adjuvant and neoadjuvant chemotherapy for soft tissue sarcoma of the extremities", section on 'Histotype-driven therapy'.)

Postoperative therapy — There is no proven role for postoperative therapy after complete resection of a recurrent RPS, and we suggest against this approach, especially if RT has been previously administered.

Locally unresectable disease — The goal of reresection of locally recurrent RPS is complete resection, which may not be feasible if there is evidence of involvement or encasement of critical structures such as the aorta, superior mesenteric vessels, porta hepatis, or major nerve roots.

Surgical debulking — Whether there is benefit from palliative "debulking" surgery in patients who have unresectable locally recurrent disease at the time of exploration is unclear. In patients with a primary or recurrent RPS that cannot be completely resected, surgical debulking is not associated with an improvement in long-term survival. Moreover, although short-term palliation of many symptoms associated with intra-abdominal sarcomas may be achieved, perioperative morbidity and mortality rates are high (29 and 12 percent in one series of 112 patients undergoing palliative surgery at Memorial Sloan Kettering Cancer Center [40]), and the opportunity to achieve sustained relief of gastrointestinal obstructive symptoms is limited. (See "Initial management of retroperitoneal soft tissue sarcoma", section on 'Palliative resection'.)

On the other hand, repeated debulking surgery may be a reasonable option for some patients with low-grade (ie, well-differentiated) liposarcomas, although complete resection is the preferred intent of surgery, if feasible [41].

Other possible treatments — Some unresectable RPS may be controlled long term with the use of high-dose charged-particle irradiation (carbon ions) [42]. This may require the surgical placement of a spacer to displace bowel away from the tumor to avoid bowel injury by high-dose radiation. Availability of this technology is limited to a few specialized centers.

If charged-particle irradiation is not available, palliative systemic therapy is another option. (See "Overview of the initial treatment of metastatic soft tissue sarcoma".)

Recommendations from expert groups — Consensus-based treatment recommendations for locally recurrent RPS are available from the National Comprehensive Cancer Network (NCCN) [43], the European Society for Medical Oncology (ESMO) [44], and the TARPSWG [14].

For patients with potentially resectable locally recurrent RPS other than gastrointestinal stromal tumors or desmoid tumors, NCCN guidelines [43] suggest surgery, with or without intraoperative radiation therapy (RT), or preoperative therapy (RT or chemotherapy). Following resection, in the event of a microscopically involved margin (R1 resection), an RT boost (10 to 16 Gy) could be considered if preoperative RT was given, intraoperative RT was not given, and normal tissue radiation constraints can still be achieved. For completely resected tumors, postoperative RT is not recommended.

ESMO guidelines recommend surgery on an individualized basis for patients with a local recurrence of RPS, especially those with well-differentiated liposarcoma and a long disease-free interval between the initial resection and subsequent recurrence, or for patients responding to medical therapies [44].

Consensus-based guidelines are also available from the international TARPSWG [14]:

For an isolated locoregional recurrence, especially if the prior resection was incomplete, the goal of resection should be curative, the extent as required to achieve a complete gross resection. Prior operative notes should be reviewed, if available. The intent of a given operation for locally recurrent RPS (eg, curative or palliative) should be defined upfront.

A macroscopically incomplete (R2) resection may be indicated for symptom control in highly selected patients, particularly well-differentiated liposarcoma; in contrast, R2 resection (ie, debulking surgery) is not indicated for other more aggressive histologies.

The oncologic benefit of surgery in patients with borderline resectable disease is likely to be limited, and the risk of morbidity may be substantial, and thus a very careful approach to patient selection is required. Multifocal intra-abdominal disease is difficult to resect completely, will almost certainly recur again, and carries a poor prognosis, particularly with resection alone. The role of surgery in these patients is limited to palliative intervention as dictated by symptoms (eg, intestinal obstruction, pain control) [45].

A history of prior piecemeal resection/tumor rupture indicates a strong potential for multifocal peritoneal recurrence, and attempted curative-intent resection is not appropriate.

Histopathologic subtypes should factor into the decision to pursue reresection because outcomes differ (eg, well-differentiated liposarcoma would be favored for reresection).

In general, patients with synchronous local and distant recurrence should not undergo resection of local disease; these patients should be offered systemic chemotherapy.

A period of observation and reimaging may help to select more favorable candidates for resection, particularly for asymptomatic well-differentiated liposarcomas. In such cases, a "strategic" delay until there is an increase in tumor size may be reasonable in order to space out the interval between resections.

For patients being considered for reresection, neoadjuvant therapy should be considered, ideally in the context of a clinical trial.

Cytotoxic and/or targeted systemic therapies may be of benefit to downsize recurrent disease to improve resectability (especially in cases of leiomyosarcoma, dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma, solitary fibrous tumor, and synovial sarcoma), and they may also facilitate assessment of tumor biopsy/natural history (especially when a high-grade RPS has recurred after a short disease-free interval, and when resection of locally recurrent disease is anticipated to be morbid).

Preoperative RT should be considered, particularly if no previous RT has been administered and the recurrence is isolated. However, its value in improving disease control has not been studied in the setting of recurrent disease, and toxicity may be magnified.

Intraoperative RT may be considered following resection of recurrent RPS, although the evidence of benefit is limited [46].

There is no proven role for postoperative systemic therapy or postoperative RT after complete resection of recurrent RPS and such treatments are not recommended.

After resection of RPS, patients should be followed with regular cross-sectional imaging, given the high risk for further relapse.

Links to additional society guidelines can be found elsewhere. (See 'Society guideline links' below.)

POSTTREATMENT FOLLOW-UP — There are no robust data evaluating different surveillance strategies following completion of treatment for locally recurrent retroperitoneal sarcoma (RPS). Our approach is in keeping with consensus-based guidelines from the National Comprehensive Cancer Network (NCCN) [43]:

For resected RPS, we recommend a physical examination with abdominal/pelvic imaging every three to six months for two to three years, then every six months for the next two years, then annually.

For retroperitoneal and visceral leiomyosarcomas and pleomorphic undifferentiated sarcomas (as compared with other histologies), we recommend imaging of the chest in addition to the abdomen and pelvis on a regular schedule. Some clinicians routinely perform surveillance chest imaging for all patients with large high-grade tumors, regardless of histology.

Given that late recurrences are not uncommon, long-term follow-up to at least 10 years is essential. (See "Initial management of retroperitoneal soft tissue sarcoma", section on 'Posttreatment follow-up'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Soft tissue sarcoma".)

SUMMARY AND RECOMMENDATIONS

Patterns of local recurrence – Surgical resection is the only potentially curative treatment for localized retroperitoneal sarcoma (RPS). However, in contrast to extremity soft tissue sarcomas (STS), the primary pattern of treatment failure after resection of RPS is local. Recurrences may be delayed beyond five years. Factors that determine the frequency of local recurrence include tumor size, histologic subtype and grade, status of the surgical margins, and whether adjunctive radiation therapy (RT) was administered. (See 'Frequency of local recurrence, time course, and risk factors' above.)

Pretreatment assessment – Radiographic imaging is a key component of the evaluation of a patient with a suspected local recurrence of RPS. The current extent of local and distant disease should be determined using an oral and intravenous contrast-enhanced CT scan of the abdomen and pelvis to evaluate the primary site, as well as a chest CT to rule out metastatic disease to the lungs. Imaging obtained at the time of recurrence should be compared with all relevant imaging studies performed prior to resection of the primary RPS and with the initial postoperative baseline imaging. (See 'Pretreatment assessment' above.)

Potentially resectable disease

Reresection – The most significant predictor of outcome following local recurrence is the resectability of the recurrent disease. Where feasible, reresection should be attempted for an isolated locally recurrent tumor; approximately 60 percent of such tumors are potentially resectable, and five-year survival rates may be as high as 50 percent. A surgical approach to recurrent RPS is safe, as the rates of postoperative morbidity and mortality are comparable to those seen with surgery for primary RPS. Patients most likely to benefit from resection are those with a longer disease-free interval, no history of tumor rupture at primary resection, low-grade tumors (especially well-differentiated liposarcomas), and unifocal rather than multifocal disease. (See 'Potentially resectable disease' above.)

Predictive nomograms – Nomograms to predict disease-free survival (DFS) and overall survival (OS) rates for patients undergoing surgery for first relapse of locally recurrent RPS can provide individualized, disease-relevant survival estimations and may prove helpful in clinical decision-making (figure 1). (See 'Survival outcomes and predictive nomograms' above.)

No prior radiation therapy – For patients who did not receive RT as part of initial therapy, we suggest preoperative RT (Grade 2C). Intraoperative RT may also be an option. Postoperative RT is discouraged. (See 'No prior radiation therapy' above.)

Prior radiation therapy – An option for patients who have received prior RT is preoperative systemic chemotherapy with or without regional hyperthermia. Although not used in the United States, preoperative regional hyperthermia with systemic chemotherapy is used for locally recurrent tumors in parts of the world where it is available (mainly Germany). Whether this approach is superior to surgery, with or without RT, or chemotherapy alone will require a randomized trial. (See 'Prior radiation therapy' above.)

Unresectable locally recurrent disease

For patients with unresectable locally recurrent disease, the role of surgical debulking is unclear. Repeated debulking surgery may be a reasonable option for some patients with low-grade liposarcomas, although complete resection is preferred, if feasible. For other patients, debulking surgery does not improve long-term survival, and it should not be attempted. (See 'Surgical debulking' above.)

Some unresectable RPS may be controlled long term with the use of high-dose charged-particle irradiation (carbon ions). However, availability of this technology is limited to a few specialized centers. Another option is palliative systemic chemotherapy. (See 'Locally unresectable disease' above.)

Posttreatment surveillance – Following treatment, patients should be followed with regular cross-sectional imaging, given the high risk for further relapse. Long-term follow-up beyond five years is warranted because of late relapses. (See 'Posttreatment follow-up' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Thomas F DeLaney, MD, who contributed to earlier versions of this topic review.

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Topic 115829 Version 14.0

References

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