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EDITORIALS |
From the Division of Surgical Oncology, University of Louisville, James Graham Brown Cancer Center, Louisville, Kentucky.
Correspondence: Address correspondence to: Kelly M. McMasters, MD, PhD, Division of Surgical Oncology, University of Louisville, James Graham Brown Cancer Center, 315 East Broadway, Room 308, Louisville, KY 40202; Fax: 502-629-3393; E-mail: kelly.mcmasters{at}nortonhealthcare.org
In-transit melanoma of the extremity can pose a terrible local disease control problem. Isolated limb perfusion (ILP), originally developed by Creech et al.1 in the 1950s, is capable of inducing a complete response in a substantial fraction of patients. Often this complete response is durable, perhaps even curative. Although enthusiasm for ILP has waxed and waned over the ensuing decades, and adjuvant ILP for primary melanomas has fallen out of favor,2 there can be no question that ILP plays an important role in local disease control of patients with extremity in-transit disease.
In this issue, Noorda et al.3 report their retrospective experience with 218 therapeutic ILP procedures in 202 patients. Fifty-three of these patients were 75 years of age or older. Response rates, toxicity, complications, and long-term morbidity were similar comparing patients <75 years of age with those over 75. Hospital stay was somewhat longer in older patients as would be expected. Interestingly, 56% of the older patients and 58% of the younger patients achieved complete response to ILP, and of those who achieved complete response, roughly half achieved durable long-term locoregional disease control. If one considers long-term limb-specific disease-free survival as the measure of success for this procedure, approximately one quarter of the patients had unequivocal benefit from the operation.
The article by Noorda et al.3 clearly demonstrates that older patients can undergo ILP safely and can enjoy the same degree of benefit as younger patients. This is encouraging, especially when we are faced with very difficult decisions about aggressive operation for advanced locoregional disease in melanoma patients who are elderly with other medical problems. The clear message is that for patients who need ILP, age should not be a contraindication.
However, the bigger question arises: who really needs ILP? Although the patients in the study by Noorda et al.3 were reported to have significant locoregional disease, the extent of the disease is rather poorly defined except for the M. D. Anderson staging classification, which gives us little real insight into the nature of the in-transit disease. For example, a patient with a single satellite lesion or local recurrence, which might be easily treated with simple surgical excision, could be included. Although ILP may be beneficial for patients who present with minimal in-transit metastasis or local recurrence, the population of patients who have significant risk to warrant this procedure remains poorly defined. The fact that 19% and 28% of the older and younger age groups, respectively, experienced significant grade III/IV limb toxicity underscores the fact that ILP remains a major operation with a risk of major complications, including limb loss in rare instances.
It has certainly been our experience that many patients who have minimal disease can forego ILP in favor of local excision, intralesional therapy with interferon or Calmette-Guérin Bacille or other local therapies. Many patients can be maintained for a long time with local treatment only. Furthermore, because patients with in-transit disease are at high risk for systemic metastasis, they may benefit from systemic treatment with biochemotherapy, high-dose interleukin-2, temozolomide-containing regimens, or other agents. It is clear that skin and subcutaneous metastases respond much better to systemic therapy than visceral metastases. Patients with a complete response, or a good partial response to systemic treatment, combined with surgical resection, may never need ILP for local disease control. We have been impressed with the fact that, at least at our center, uncontrolled in-transit disease requiring ILP is relatively uncommon. One could certainly argue that ILP as primary therapy for in-transit disease may have advantages over these other types of therapy. However, whether ILP is used as front-line therapy or as backup therapy, given the fact that the majority of patients with in-transit disease will suffer locoregional recurrence, it is useful to have additional modalities at our disposal.
Further study is certainly necessary to define the population of patients in which ILP is best indicated. Because many patients can be managed with less invasive procedures, ILP can be reserved truly for local disease control in the extremity when other measures fail. For patients who present with more advanced regional disease, ILP plays an important role, with a long-standing track record for local disease control. The important experience from Noorda et al.3 indicates that, when ILP is necessary, age should not be a concern in deciding whether or not to perform the procedure. Whether or not tumor necrosis factor should be included in melphalan-based ILP remains a subject of some controversy and is undergoing further study at the present time in the American College of Surgeons Oncology Group trial Z0020.
Received for publication October 15, 2002. Accepted for publication October 16, 2002.
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