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Originally published as JCO Early Release 10.1200/JCO.2008.21.5467 on March 9 2009 © 2009 American Society of Clinical Oncology.
Resection of Uninvolved Adjacent Organs Can Be Part of Surgery for Retroperitoneal Soft Tissue SarcomaIstituto Nazionale Tumori, Milan, Italy
Institute Gustave Roussy, Villejuif, Paris, France
Istituto Nazionale Tumori, Milan, Italy To the Editor: We thank Dr Pisters for his thoughtful comments1 on our two retrospective case series analyses about wide surgery in retroperitoneal sarcomas.2–3 He concludes that we should not change our clinical practice until prospective evidence is provided. He stresses the retrospective nature of evidence we provided in regard to both efficacy and safety. He also challenges in principle the notion that our surgery in reality amounted to wide surgery. We believe the two points are interconnected with a view to our clinical practice. In other words, if some evidence, although not necessarily a randomized clinical trial, were available in favor of a truly wide surgery of retroperitoneal sarcomas, one might conclude, in the end, that retroperitoneal sarcomas should, or at least could, be treated the same way we ordinarily treat limb and other sarcomas. In fact, there is no logical reason to believe that a limb sarcoma should be treated with wide surgery, while the same disease, with the same histology, should not because it arises from a different primary site. Conversely, we understand that if both the quality of evidence and the rationale for wide surgery are perceived to be weak, one should definitely claim for more evidence. Of course, we are talking about a rare tumor (indeed retroperitoneal sarcomas are made up of two major histological types), amounting to 10% of soft tissue sarcomas, which are 1% of cancers. We understand that the discussion is open, and we will briefly touch both issues—the rationale and the quality of evidence. In adult soft tissue sarcoma of all primary sites, we know that local control is mainly related to quality of surgery. This has to do with the ability to remove the tumor with a cuff of normal tissue all around. In retroperitoneal sarcomas, normal tissues around are viscera more than muscles. Some of them, including the kidney, the colon, and the psoas, can be safely removed with limited morbidity. The editorial1 points out that other organs may lie close to the tumor that cannot be resected without substantial morbidity. This is true, although this is not necessarily the case for all of them. In fact, the spleen, the left pancreas, and the diaphragm can be resected, if needed, without adding substantial morbidity. More importantly, we have learned from limb sarcoma surgery the concept of limited marginality—a resection with a planned-in-advance positive margin over a critical structure, but negative for the rest, is definitely better than a simply marginal resection all around the tumor.4 In other words, even if the tumor lies close to the duodenum/head of the pancreas or to large blood vessels, an aggressive resection all around, with a positive margin over these critical structures, might be better than limiting the resection overall just because of one critical spot. It is true that this kind of surgery can never reach the same quality of margins as in limb sarcomas, but it can approximate it, and this was shown in limb sarcomas to be of value. In addition, the variety of presentations is such that in some patients the quality of margins will be better, in others it will be worse, but this should not prevent the former from receiving an attempt of wide surgery. In brief, the kind of surgery we advocate coincides with a more liberal approach to resection of uninvolved close organs, within an individualized surgical planning weighing the quality of margins and the expected morbidity. We understand how difficult it is to translate all this into standard practice (clearly this surgery should be performed at a high volume center3), but in the end this is the difficulty of diseases like sarcomas, which, in addition to being rare, are complex (ie, heterogenous). Our two case series analyses were retrospective, indeed, and thus carry with them all the biases of retrospective evidence. First, selection biases are certainly in place. However, they are two different studies with different biases, to a certain extent. For example, in the Villejuif series3 relapses were not included, whereas they were in the Milan series.2 In addition, the follow-up is longer in the Villejuif series. Indeed, only first relapses were included in the Milan series, and results were similar in the two groups, of primary and relapsing patients, while the follow-up was however in the range of the median time to relapse for these tumors. By the way, even low-grade retroperitoneal liposarcomas tend to relapse and dedifferentiate when treated suboptimally. At that point, the risk of death is significantly increased,5–6 so that, to be fair, a watch-and-wait policy is almost never used for these tumors, with the obvious exceptions of unfit patients. A low-grade liposarcoma as presented in Figure 2 of the editorial is exactly one that may benefit from an aggressive frontline approach,1 we would say. Likewise, we agree of course that safety data were limited, again due to their retrospective nature. However, in the face of a disease that we should not forget is fatal, we did not see any major differences in morbidity in the two groups and mortality was exactly in the same range as previous studies. Again, the editorial1 observes that survival differences were not seen in both series according to the different extent of surgery. Fairly, it also adds that we lack such clear-cut, prospective demonstrations of survival benefits also in regard to the local treatment of limb sarcomas. Of course, survival does not depend only on local control in high grade tumors, while it requires a long follow-up in low-intermediate–grade ones. In any case, the benefit of a longer local disease control cannot be underestimated, in terms of quality of life and costs. In other words, if the number of local recurrences on a reasonable time interval were actually cut by a half, as we retrospectively saw in our series, the advantage would be substantial. In other words, we are dealing with a rare subgroup of tumors (retroperitoneal sarcomas) within a relatively rare group (adult soft tissue sarcomas). Two main histological subtypes (well-differentiated/dedifferentiated liposarcoma and leiomyosarcoma) are represented in retroperitoneal sarcomas, and about 50 in adult soft tissue sarcomas. The task of studying these tumors by means of prospective randomized trials is challenging, especially when subgroups need to be considered. The incidence of retroperitoneal sarcomas is less than 0.5 incidences per 100,000 pe ryr. We may discuss how standard treatment can be defined in rare tumors, particularly very rare ones. Clearly, we must take most profit from any evidence we have in our hands, by fairly balancing it by consensus within the medical community. Then, we must go the patient's bedside. We will have been left with a degree of uncertainty, and our task is to share it with our patient. A shared decision making in conditions of uncertainty will be the result. We believe that the evidence we provided adds to the information we can fairly provide to our patients with retroperitoneal sarcomas. We agree with Dr Pisters1 that it is definitely not enough to set a standard, but it is enough, we believe, to share with our patients the option of more extensive surgery. Is this much different from what we do with many patients with soft tissue sarcoma being offered adjuvant chemotherapy? AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Pisters PW: Resection of some–but not all–clinically uninvolved adjacent viscera as part of surgery for retroperitoneal soft tissue sarcomas. J Clin Oncol 27:6–8, 2009. 2. Gronchi A, Lo Vullo S, Fiore M, et al: Aggressive surgical policies in a retrospectively reviewed single-institution case series of retroperitoneal soft tissue sarcoma patients. J Clin Oncol 27:24–30, 2009. 3. Bonvalot S, Rivoire M, Castaing M, et al: Primary retroperitoneal sarcomas: A multivariate analysis of surgical factors associated with local control. J Clin Oncol 27:31–37, 2009. 4. Gerrand CH, Wunder JS, Kandel RA, et al: Classification of positive margins after resection of soft-tissue sarcoma of the limb predicts the risk of local recurrence. J Bone Joint Surg Br 83:1149–1155, 2001.[CrossRef][Medline] 5. Mussi C, Collini P, Miceli R, et al: Prognostic impact of dedifferentiation in retroperitoneal liposarcoma: A series of patients surgically treated at a single institution. Cancer 113:1657–1665, 2008.[CrossRef][Medline] 6. Fabre-Guillevin E, Coindre JM, De Saint Aubain Somerhausen N, et al: Retroperitoneal liposarcomas: Follow-up analysis of dedifferentiation after clinicopathologic reexamination of 86 liposarcomas and malignant fibrous histiocitomas. Cancer 106:2725–2732, 2006.[CrossRef][Medline]
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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