Continued uncertainty regarding hyperthermic intraperitoneal chemotherapy in malignant peritoneal mesothelioma.

TO THE EDITOR: In a recent issue of Journal of Clinical Oncology, Yan et al report a multiyear, multi-institutional, nonrandomized retrospective experience with aggressive cytoreductive surgery (CRS) in the management of diffuse malignant peritoneal mesothelioma (DMPM), which, in the large majority of cases, included the delivery of hyperthermic intraperitoneal chemotherapy (HIPEC). The investigators conclude that “the data suggest that CRS combined with HIPEC achieved prolonged survival in selected patients with DMPM.” The data in this report supporting the role of HIPEC, in what is clearly impressive overall survival for patients in this specific setting, must be challenged. The investigators appear to base their claim for the utility of this procedure added to aggressive CRS on both a univariate and multivariate analysis that evaluated a variety of potentially relevant clinical factors. However, in this series, only 8% of the total patient population did not receive HIPEC. The investigators acknowledge that although the explanation for why HIPEC was withheld in a number of patients is not known, in at least seven, failure to use the technique was because the individuals were “hemodynamically unstable intraoperatively.” In fact, it is rational to suggest that a likely reason for failure to administer HIPEC in this nonrandomized experience of multiple institutions was the appropriate clinical judgment of the surgeons that these patients were not good candidates for the procedure because of a marginal performance status; relatively larger residual tumor volumes; or comorbidity that increased concerns for postoperative complications. Furthermore, it is reasonable to propose that such factors will be associated (and perhaps quite strongly) with a relative reduction in the survival of these individuals. It is important to note here a previously published randomized trial that compared aggressive CRS plus HIPEC versus no (or only palliative) surgery plus systemic chemotherapy in colorectal cancer. Unfortunately, this study failed to examine the essential question of the independent contribution of HIPEC versus a strategy of aggressive CRS alone in carefully selected patients (eg, relatively slowly growing diffuse intraperitoneal cancers). The current retrospective analysis of this approach in DMPM suffers from the same serious deficiency. Unless a randomized trial is conducted in this arena that specifically evaluates the role of combining HIPEC with aggressive CRS, it will remain unknown whether this expensive and potentially highly morbid procedure is of any added clinical value in the management of DMPM or other malignant disease processes principally confined to the peritoneal cavity. Unfortunately, a sophisticated statistical analysis of completely uncontrolled retrospective data simply cannot correct for the fundamental problem of distinguishing between the influence of a specific treatment strategy on an observed outcome (eg, survival) versus both appropriate physician judgment in the selection of such therapy and the inherent biology of the cancer in individual patients.