Extended Surgery for Retroperitoneal Sarcoma: Too Much Surgery for Some and Not Enough for Others?

Recently controversy has emerged regarding the extent of resection that constitutes optimal surgical management of retroperitoneal soft-tissue sarcoma. Unequivocally, anatomic site does influence survival in the sarcoma disease cohort. Indeed, overall survival is approximately 60% in extremity locations but only 40% in the retroperitoneum, demarcated at different time intervals in the various series. The constraints of retroperitoneal anatomy are also suggested by the approximately 50% preponderance of well-differentiated liposarcoma histologic subtypes in this location. The well-differentiated liposarcomas, effectively devoid of metastatic potential, kill via relentless serial episodes of local recurrence, leading to entrapment of critical organs in either unresectable tumor or indivisible scar tissue. Hence the pithy remark attributed to surgical oncologist Murray F. Brennan, from Memorial Sloan-Kettering Cancer Center: “The best sarcoma operation is the one before the one you’re doing.”

The crux of this debate is the contention that contiguous organ resection for retroperitoneal sarcoma should be standard practice for all such patients because margin-negative resection offers the best chance of cure. Others maintain that surgery for retroperitoneal sarcoma requires balancing the availability of resectable anatomy with the natural history of the specific sarcoma subtype for which surgery is contemplated. At the outset, it is important to note that these two positions are neither mutually exclusive nor diametrically opposed. Indeed, there are circumstances in which contiguous-organ resectors back away from such an approach, whereas those favoring more limited resection generally apply this strategy only for patients bearing well-differentiated liposarcoma. The challenge ahead lies in clarifying these specific exceptions so that gaps between proponents and opponents are resolved, to the benefit of patients everywhere.

Not all retroperitoneal sarcomas behave alike. At one end of the indolence-virulence continuum are the pushing, rare-to-metastasize, well-differentiated liposarcomas, and at the other end are the non–vascular-origin leiomyosarcomas, with their remarkable propensity for nearly synchronous dissemination, especially to the liver. Should these lesions be subject to the same extirpative strategies? Our interest in this dilemma stemmed from an initial desire to optimize the AJCC/UICC (American Joint Committee on Cancer /International Union Against Cancer) retroperitoneal sarcoma staging system. The vast majority of resectable retroperitoneal sarcomas are T2, N0, M0, G1-3 lesions, meaning that grade alone carries preponderant prognostic significance for such lesions. Compounding the problem, Kaplan-Meier plots for grade 2 vs grade 3 T2, N0, M0 retroperitoneal sarcomas are virtually superimposable, implying that there are actually only two prognostically relevant AJCC/UICC retroperitoneal sarcoma categories: T2N0M0G1 and T2N0M0G2-3. We hoped to improve on this situation by introducing histologic subtype as an additional prognostic consideration for retroperitoneal sarcoma. We analyzed a large cohort of patients who received surgical therapy for retroperitoneal sarcoma at The University of Texas MD Anderson Cancer Center, demonstrating that overall survival and disease-free survival were significantly better in patients with well-differentiated liposarcoma, followed by other histological subtypes and then dedifferentiated liposarcoma.[1] This finding was ultimately utilized as the basis for a single-institution retroperitoneal sarcoma staging nomogram,[2] recently modified using combined MD Anderson/University of California at Los Angeles/Instituto Tumori Milano datasets, and independently verified using an additional large dataset from the Institute Gustave Roussy, Paris, France.[3]

These critical differences in the natural history of retroperitoneal well-differentiated liposarcoma suggest that a routine policy of contiguous organ resection to achieve negative margins may be appropriate for some (but not all) retroperitoneal sarcoma subtypes. Lacking metastatic potential, the well-differentiated liposarcomas may merit a more conservative, organ-sparing approach. In fact, a policy of carefully timed, conservative surgical interventions may be optimal, provided that the tumor is in a relatively innocuous anatomic location and its rate of growth is demonstrably slow. Indeed, the high rate of multifocal local recurrence (57%) and multifocal, multicentric recurrences (12%; ie, multifocal recurrences distant from previous retroperitoneal surgical sites) in a large set of previously untreated, unifocal, well-differentiated liposarcoma patients initially resected at MD Anderson suggests that predicting the specific site(s) of recurrence for retroperitoneal well-differentiated liposarcoma is problematic (manuscript submitted). This reality, and the unfortunate fact that 41% of the resected contiguous organs in the recently published Italian series were not involved by tumor,[4] suggest that a blind policy of extended resection for retroperitoneal sarcoma will be too much surgery for some and, unfortunately, not enough surgery for others.

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

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REFERENCES

1. Anaya DA, Lahat G, Wang X, et al. Establishing prognosis in retroperitoneal sarcoma: a new histology-based paradigm. Ann Surg Oncol. 2009;16:667-75.

2. Anaya DA, Lahat G, Wang X, et al. Postoperative nomogram for survival in patients with retroperitoneal sarcoma treated with curative intent. Ann Oncol. 2009;249:1014-22.

3. Gronchi A, Miceli R, Shurell E, et al. Outcome prediction in primary resected retroperitoneal soft tissue sarcoma: histology-specific overall survival and disease-free survival nomograms built on major sarcoma center data sets. J Clin Oncol. 2013;31:1649-55.

4. Gronchi A, Miceli R, Colombo C, et al. Frontline extended surgery is associated with improved survival in retroperitoneal low-intermediate grade soft tissue sarcomas. Ann Oncol. 2012;23:1067-73.