Originally published as JCO Early Release 10.1200/JCO.2008.21.6465 on March 9 2009

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In Reply

Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX

Gronchi et al¹ address the rationale for extended resection for retroperitoneal sarcomas as well as the quality of the evidence provided in their recently published articles.^2,3 They provide an expanded rationale and concise summary of their assessment of the utility of retrospective data in planning treatment for individual patients.

Issues that warrant consideration in interpreting the data of Gronchi et al^2,3 include the limitations of the methodologies used, the issues of case selection, and the various forms of bias associated with the types of analyses performed in their reports. These issues were not optimally addressed in the discussion of either article, but were pointed out in detail in my accompanying editorial,⁴ so extensive further discussion of them is not warranted. Suffice it to say that the degree of bias introduced by selective use of this extended surgical procedure and the retrospective nature of these reports make a comparison of patients who underwent resection of retroperitoneal sarcomas plus uninvolved adjacent organs to patients who did not undergo resection of uninvolved adjacent organs inexact at best. Indeed, because of this bias (unavoidable in most retrospective studies), we cannot use the outcome data from these reports to justify much more than hypothesis generation and perhaps discussion with occasional patients who have relatively small, favorably located retroperitoneal sarcomas.

We also should give serious consideration to the message transmitted to general surgeons vis-à-vis what should be considered standard treatment for patients with retroperitoneal sarcomas. In the United States, as in many other countries, surgery for retroperitoneal sarcomas is performed mostly by general surgeons. Data from the United States and Europe for more common but similarly complex oncologic procedures (such as pancreaticoduodenectomy) demonstrate a clear relationship between the individual surgeon's (and institution's) case volume and the associated morbidity and mortality.^5–7 There is no reason to believe that this volume-outcome relationship does not also exist for multivisceral resection for retroperitoneal sarcoma. Thus, I believe that we should be extremely cautious in advocating resection of normal adjacent organs as part of surgical therapy for patients with this group of diseases. If resection of uninvolved adjacent organs is liberally pursued by well-intentioned but less experienced surgeons on the basis of these articles, the result is bound to be increased morbidity and mortality.

Gronchi et al¹ also suggest that distal pancreatectomy, splenectomy, and diaphragmatic resection can be performed in conjunction with retroperitoneal sarcoma resection without added morbidity and mortality. They provide no data on this, and many experienced surgeons will not agree with this assertion. Data on surgery for gastric cancer suggest that greater resection does in fact increase surgical risks. In randomized trials of extended lymphadenectomy for gastric cancer, extended lymphadenectomy necessitated resection of the usually uninvolved spleen and sometimes pancreas; an increased mortality rate was observed in the extended lymphadenectomy group and attributed to the splenectomy or distal pancreatectomy/splenectomy.^8,9 Thus, there are some data from randomized trials demonstrating that resection of uninvolved adjacent organs increases the risk for operative mortality. Moreover, the increased mortality rate associated with more aggressive surgical procedures may offset any potential therapeutic benefit. For these reasons, further study of extended resection for retroperitoneal sarcoma requires more careful assessment of the morbidity and mortality risks.

In summary, I do believe that we need to thoughtfully consider these data, the limitations resulting from selection bias, and the safety issues surrounding this procedure before recommending it as standard treatment outside the context of a clinical trial or outside the handful of high-volume centers for retroperitoneal sarcoma surgery.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Gronchi A, Bonvalot S, Le Cesne A, et al: Resection of uninvolved adjacent organs can be part of surgery for retroperitoneal soft tissue sarcoma. J Clin Oncol 27:2106–2107, 2009.[Free Full Text]

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.[Abstract/Free Full Text]

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.[Abstract/Free Full Text]

4. 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.[Free Full Text]

5. Birkmeyer JD, Siewers AE, Finlayson EV, et al: Hospital volume and surgical mortality in the United States. N Engl J Med 346:1128–1137, 2002.[Abstract/Free Full Text]

6. Birkmeyer JD, Dimick JB, Staiger DO, et al: Operative mortality and procedure volume as predictors of subsequent hospital performance. Ann Surg 243:411–417, 2006.[CrossRef][Medline]

7. van Heek NT, Kuhlmann KFD, Scholten RJ, et al: Hospital volume and mortality after pancreatic resection: A systematic review and an evaluation of intervention in the Netherlands. Ann Surg 242:781–788, 2005.[CrossRef][Medline]

8. Bonenkamp JJ, Hermans J, Sasako M, et al: Extended lymph-node dissection for gastric cancer. N Engl J Med 340:908–914, 1999.[Abstract/Free Full Text]

9. Cuschieri A, Weeden S, Fielding J, et al: Patient survival after D-1 and D-2 resections for gastric cancer: Long-term results of the MRC randomized surgical trial. Br J Cancer 79:1522–1530, 1999.[CrossRef][Medline]

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