| Lymphedema in Patients With MelanomaLymphedema in Patients With Melanoma Janice N. Cormier, MD, MPH
Department of Surgical Oncology
University of Texas M.D. Anderson Cancer Center
Houston, TX
jcormier@mdanderson.org Latunya Davidson
Department of Surgical Oncology
University of Texas M.D. Anderson Cancer Center
Houston, TX Wendy J. Evans
Sinclair School of Nursing and Ellis Fischel Cancer Center
University of Missouri-Columbia
Columbia, MO Jane M. Armer
Sinclair School of Nursing and Ellis Fischel Cancer Center
University of Missouri-Columbia
Columbia, MO Melanoma is a growing public health problem with an estimated 132,000 cases diagnosed annually worldwide (World Health Organization, 2004). It is the sixth most common malignancy among Americans (American Cancer Society, 2004) and accounts for more than 79% of all skin cancer-related deaths (Geller & Annas, 2003; Trask et al., 2001). Fortunately, the majority of patients diagnosed with melanoma present with early-stage disease that is cured by surgical excision alone. For others, presenting with regional or distant metastatic disease, the prognosis is not as favorable. The most critical factors for determining the prognosis of patients with melanoma are primary tumor thickness and the status of regional lymph nodes. Both of these elements are incorporated into the American Joint Committee on Cancer staging system for melanoma (American Joint Committee on Cancer, 2002). Surgical Treatment
The most important information for determining surgical treatment of melanoma is the thickness (Breslow thickness), which is measured in millimeters and is determined by pathologic examination of a biopsy of the primary tumor. Current surgical guidelines (National Comprehensive Cancer Network, 2004) include a wide local excision (WLE) of the primary tumor. Regional lymph nodes are the most common first site of melanoma metastases. Over the last decade, sentinel lymph node (SLN) biopsy has emerged as a reliable technique for identifying micrometastatic disease in clinically negative regional lymph node basins. SLN biopsy is a highly accurate, minimally invasive surgical procedure based on the theory that lymphatic metastases associated with melanoma follow an orderly progression through lymph channels from the primary tumor to a particular lymph node (designated the “sentinel” lymph node) before spreading into other regional (“nonsentinel”) lymph nodes (Reintgen et al., 1994). Current guidelines outlined by the National Comprehensive Cancer Network for the treatment of patients with melanoma recommend SLN biopsy for all patients with primary melanomas greater than 1 mm thickness and subsets of patients with high-risk thin (< 1 mm) melanomas (Ak, Stokkel, Bergman, & Pauwels, 2000). In patients with an SLN that tests negative for presence of cancer, no further surgical therapy is recommended. In patients with metastases identified in the SLN, a complete lymph node dissection is performed. This combination of surgical treatments, a WLE of a primary tumor along with SLN biopsy and possible subsequent complete lymph node dissection, results in multiple sites of lymphatic disruption. Unlike axillary (“armpit”) node dissection for patients with breast cancer, which includes dissection of level I and II lymph nodes, axillary node dissection for patients with melanoma of the upper extremity or trunk includes the routine dissection of level I, II, and III lymph nodes. Level III lymph nodes are the highest axillary nodes (apical). A standard lymph node dissection for patients with lower extremity or truncal melanomas draining to the inguinal region includes the removal of lymph nodes located in the inguinofemoral (groin) region. In addition, subsets of patients with melanoma with bulky nodal disease undergo an additional deep pelvic dissection. The surgical treatment of melanoma results in varying degrees of lymphatic disruption resulting in a lifetime risk for developing lymphedema. It is postulated that lymphedema may occur more frequently in patients with melanoma because of: (1) multiple surgical sites (e.g., primary tumor excision on an extremity in conjunction with lymph node biopsy or dissection), (2) extent of nodal dissections, and (3) anatomic sites, particularly the lower extremity, which may be at increased risk due to physiologic reasons. Review of the Literature
The data estimating the incidence of lymphedema in patients with melanoma are far from complete. We have systematically reviewed the literature and found a total of 25 studies performed between 1972 and 2004 pertaining to melanoma and lymphedema. Of these 25 studies, 12 (48%) were retrospective, 10 (40%) prospective, 2 (8%) clinical trials, and 1 (4%) a case series. As with the reported incidence of postsurgical lymphedema for patients with breast cancer (Passik & McDonald, 1998; Petrek & Heelan, 1998), the reported incidence of lymphedema in patients with melanoma varies widely, with reported rates ranging from 2% to 67%. The disparity likely relates to the heterogeneity of the reports, which will be discussed below. Measurement Methods
Volume measurement using water displacement historically has been regarded as the most sensitive and accurate measure; however, clinicians rarely use this cumbersome approach (Petlund, 1991; Tierney, Aslam, Rennie, & Grace, 1996). Two of the 25 studies used water displacement alone (James, 1982) or in combination with circumference measurements (Baas et al., 1992). Circumference measurements were utilized in five of the studies (Holmes et al., 1977; Karakousis, Heiser, & Moore, 1983; Lawton, Rasque, & Ariyan, 2002; Papachristou & Fortner, 1977; Urist, Maddox, Kennedy, & Balch, 1983). The remaining 15 studies reported on lymphedema in patients with melanoma using clinical definitions with no objective measurement criteria. Lymphedema Classification
In one study in which significant lymphedema was defined as greater than 1 inch difference (measured at the ankle or midcalf) between the affected and unaffected limb, lymphedema was reported in 80% of patients five years after surgery (Papachristou & Fortner, 1977). Two other studies reported rates of 21%–26% when 2–4 cm (Urist et al., 1983) or 3–4.5 cm (Karakousis et al., 1983) differences were used as criteria. Surgical Procedures
In 235 patients who underwent SLN biopsy in the axillary or inguinofemoral region, only 5 patients (2%) were reported to have lymphedema on an average of six weeks after surgery (range of 2–10 weeks) (Wrone et al., 200). Three studies reported lymphedema in 20%–45% of patients undergoing inguinofemoral dissections, with no difference noted between superficial dissections alone or in combination with deep pelvic dissections (Baas et al., 1992; Karakousis & Driscoll, 1994; Stevens et al., 2000). Postoperative wound complications often are associated with extensive nodal dissections, particularly in the inguinal region. Seven studies reported postoperative wound complications, including cellulitis in 6%–33% of patients (Baas et al., 1992; Ingvar, Erichsen, & Jonsson, 1984; Karakousis & Driscoll, 1994; Lawton et al., 2002; Serpell, Carne, & Bailey, 2003; Strobbe, Jonk, Hart, Nieweg, & Kroon, 1999; Urist et al., 1983). Anatomic Variation—Upper Versus Lower Extremity
It is difficult to make direct comparisons of rates of lymphedema at various anatomic sites among studies given the heterogeneity of the reports. Of the studies that examined lymphedema associated with axillary versus inguinofemoral nodal dissections, similar trends were noted. The reported range of upper extremity lymphedema was 5%–8% (Shaw & Koea, 1992; Urist et al., 1983) compared to 14%–29% for lower extremity lymphedema (Lawton et al., 2002; Serpell et al., 2003). It appears from these reports that the incidence of lower extremity lymphedema may be twice as high as upper extremity lymphedema. Time Horizon
It has been noted that breast cancer lymphedema studies with the shortest follow-up (12 months) report the lowest incidence (6%) (Petrek & Heelan, 1998), whereas studies with the longest follow-up have the highest incidence. Similar trends are noted in this review, with the lowest lymphedema rates (upper and lower extremity) noted in studies that examined patients six months postoperatively (Wrone et al., 2000), whereas the highest incidence (67%, lower extremity lymphedema) had the longest follow-up (20 years) (Papachristou & Fortner, 1977). High rates (44%) also were noted when lymphedema was defined as swelling lasting more than six months (Beitch & Balch, 1992). Discussion
All people diagnosed with melanoma are at a lifetime risk of developing lymphedema because of the extensive lymphatic disruption associated with surgical treatment. Lymphedema and its sequelae are much-understudied morbidities associated with cancer treatment, particularly in patients with melanoma. In patients with breast cancer, lymphedema has been described as an overlooked, underdiagnosed, and undertreated condition, which, other than tumor recurrence, is the most feared effect of treatment (Disa & Petrek (2001)). The same likely can be said of melanoma and lymphedema. Lymphedema is a significant problem. In addition to the symptoms and risks, the associated challenges also may lead to post-treatment psychosocial distress. Although researchers have documented the psychological sequelae of breast cancer treatment (Tobin, Lacey, Meyer, & Mortimer, 1993), we know little about such issues in patients with melanoma, especially those that may involve lymphedema of the lower extremity. A conclusion by Maunsell, Brisson, and Deschenes (1993) still stands: “The impact of lymphedema problems on patient quality of life has not been quantitatively assessed.” This research has been hampered by the traditional view that quality of life is less important than the eradication of cancer and detection of recurrence. Unfortunately, lack of attention to lymphedema by health professionals has not only meant that many people go undiagnosed and fail to receive basic preventive information (Maunsell et al.), but this lack of attention also has hindered the development of effective psychosocial and physiological therapeutic interventions. Early detection and intervention hold the greatest promise of reducing this widespread condition (Petrek, Pressman, & Smith, 2000; Rockson, 1998). The range of findings in the literature reflects inconsistent criteria for defining lymphedema, small studies, retrospective analyses, and short follow-up. 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