Follow-up Recommendations for Patients with Stage I-III Malignant Melanoma

Abstract & Commentary

Synopsis: There are more than 44,000 new cases of malignant melanoma diagnosed each year in the United States and more than 80% of these cases will be localized. A major clinical problem is the development of rational follow-up recommendations for this increasingly large group of patients. Investigators from the Yale Melanoma Unit retrospectively reviewed the records of patients who were seen and followed according to their surveillance protocol to determine the time interval between initial visit and recurrence and the most common method of detecting recurrences. The five-year survival rates for stages I, II, and III were 95%, 72%, and 52%, respectively. Seventy-nine percent of recurrences were detected within the first two years of follow-up. Based on this experience, the authors recommended a schedule for follow-up.

Source: Poo-Hwu WJ, et al. Cancer 1999;86: 2252-2258.

Patients in this study were followed by a multidisciplinary team of dermatologists, medical oncologists and plastic surgeons, according to a uniform protocol that combined frequent, comprehensive examinations with extensive patient education. Patients received instructions in performing self-examinations of the skin and a list of signs and symptoms of recurrence that should alert them to contact their physician. Pamphlets and videotapes were used to educate patients and family members regarding photoprotection. At each follow-up visit, a history, physical examination, complete blood count (CBC), and liver function tests including lactate dehydrogenase (LDH) were performed. Chest x-rays were obtained annually for stage I and II patients and every six months for stage III patients during the first five years of follow-up. Patients with stage III disease had a baseline computed tomography (CT) for complete staging examination. Follow-up CT scans were obtained only if there were abnormal findings initially that were not clearly indicative of metastatic disease.

The charts of 419 patients were reviewed, 46 of which were excluded primarily because patients had inadequate follow-up at Yale. Of the 373 patients whose charts were reviewed, 78 developed disease recurrence. Patient-reported symptoms resulted in detection of recurrence in 34 patients (44%), while the remaining 44 patients (56%) were diagnosed by procedures performed during a scheduled visit. Of the 44 physician-detected recurrences, 57% were identified by either history or physical examination; 18% were detected by chest x-ray and 23% were detected by CT or magnetic resonance imaging (MRI) scanning. The latter group, CT and MRI scans, were obtained because of abnormal findings on the baseline scans or suspicious findings on physical examination. There was only one patient (2%) in whom an abnormal laboratory result (elevated LDH) was the sole indicator for recurrent disease. The recurrences were evenly divided between distant and local regional metastases. Based on the hazard ratios for recurrence by stage, Poo-Hwu and colleagues recommend annual follow-up for patients with stage I disease and six months follow-up for the first two years for stage II with annual follow-up thereafter. For stage III, Poo-Hwu et al recommend follow-up every three months during the first year, every four months during the second year, every six months for years 3-5, and then annually thereafter.

COMMENT BY MICHAEL J. HAWKINS, MD

With the increasing incidence of early stage malignant melanoma, it is extremely important to develop rational, evidence-based follow-up programs. In patients with stage I disease, detection of second primaries or premalignant lesions is equally, if not more, important than screening for systemic recurrence. Annual follow-up with liver function tests including an LDH and chest x-ray seems sufficient for these patients. Close, ongoing surveillance for second primaries is best determined by the patient’s dermatologist and will depend upon the number of moles present and whether any of the moles exhibit atypical features. In this series, nine out of 493 patients with stage I disease developed recurrences, seven of which were physician detected. Thirty-five of 117 patients with stage II malignant melanoma developed recurrent disease. Detection in this group was equally divided between patient and physician. Since most recurrences occur within the first two years, Poo-Hwu et al recommend follow-up every six months with these patients. Many clinicians are uncomfortable with this interval, especially in young patients with deep primary lesions, and would tend to use the guidelines specified for stage III patients.

Clinical studies to date, however, have not shown a benefit for any follow-up protocol. This is in part due to the lack of effective therapies that can have a positive effect on survival once recurrence has occurred. Some patients who develop locoregional recurrence of their malignant melanoma will have long-term disease-free survivals following surgery with or without adjuvant systemic therapy. In this study, 60% of locoregional recurrences were detected by the patient. Single-arm studies of aggressive chemoimmunotherapy regimens have reported a 20% complete remission rate in patients with metastatic malignant melanoma.1 The usefulness of immunotherapy in this context is currently being evaluated in a large-scale randomized trial comparing chemotherapy alone vs. chemoimmunotherapy.2 Should effective systemic therapies become available and make early detection of systemic relapse desirable, follow-up programs would need to strongly consider the use of noncontrast CT scans of the chest instead of chest x-rays. However, trials of Interleukin-2 in metastatic renal cell carcinoma and Rituximab in non-Hodgkin’s lymphoma have demonstrated tumor responses in patients with large-volume disease and have not seen a clustering of responses in patients with smaller tumor burdens.3,4

References

1. Legha SS, et al. J Clin Oncol 1998;16:1752-1759.

2. Fisher RI, et al. Ann Intern Med 1988;108:518-523.

3. Maloney DG, et al. Blood 1997;90:2188-2195.

4. Study #’s: ECOG E3695, SWOG E3695, CALGB 509802.

In patients with stage I-III cutaneous malignant melanoma who develop disease recurrence, three-fourths of these recurrences will have occurred within what time from diagnosis?

a. 1 year

b. 2 years

c. 3 years

d. 5 years