The MELFO Study: A Multicenter, Prospective, Randomized Clinical Trial on the Effects of a Reduced Stage-Adjusted Follow-Up Schedule on Cutaneous Melanoma IB–IIC Patients—Results After 3 Years

Abstract

Background This study compares well-being, recurrences, and deaths of early-stage cutaneous melanoma patients in follow-up, as recommended in the Dutch guideline, with that of patients in a stage-adjusted reduced follow-up schedule, 3 years after diagnosis, as well as costs. Methods Overall, 180 eligible pathological American Joint Committee on Cancer (AJCC) stage IB–IIC, sentinel node staged, melanoma patients (response rate = 87%, 48% male, median age 57 years), randomized into a conventional (CSG, n = 93) or experimental (ESG, n = 87) follow-up schedule group, completed patient-reported outcome measures (PROMs) at diagnosis (T1): State-Trait Anxiety Inventory–State version (STAI-S), Cancer Worry Scale (CWS), Impact of Event Scale (IES), and RAND-36 (Mental and Physical Component scales [PCS/MCS]). Three years later (T3), 110 patients (CSG, n = 56; ESG, n = 54) completed PROMs, while 42 declined (23%). Results Repeated measures analyses of variance (ANOVAs) showed a significant group effect on the IES (p = 0.001) in favor of the ESG, and on the RAND-36 PCS (p = 0.02) favoring the CSG. Mean IES and CWS scores decreased significantly over time, while those on the RAND-36 MCS and PCS increased. Effect sizes were small. Twenty-five patients developed a recurrence or second primary melanoma, of whom 13 patients died within 3 years. Cox proportional hazards models showed no differences between groups in recurrence-free survival (hazard ratio [HR] 0.71 [0.32–1.58]; p = 0.400) and disease-free survival (HR 1.24 [0.42–3.71]; p = 0.690). Costs per patient after 3 years (computed for 77.3% of patients) were 39% lower in the ESG. Conclusion These results seemingly support the notion that a stage-adjusted reduced follow-up schedule forms an appropriate, safe, and cost-effective alternative for pathological AJCC stage IB–IIC melanoma patients to the follow-up regimen as advised in the current melanoma guideline.

The MelFo Study UK: Effects of a Reduced-Frequency, Stage-Adjusted Follow-Up Schedule for Cutaneous Melanoma 1B to 2C Patients After 3-Years

“…These results mirror the findings of the Dutch group, which recently reported very similar results in 2019. 18 As in the Dutch study, our data indicated that the large majority of patients were satisfied with their follow-up regimen regardless of the schedule. The data suggest that patients undergo a period of adjustment during the first 12 months of the follow-up period after treatment before they settle into the follow-up routine.…”

“…The interim results of this phase 3 RCT at 3 years, undertaken in a native English-speaking cohort, appear to have validated the findings of our Dutch colleagues who undertook this study in the Netherlands using the same protocol. 18 The UK MelFO study seems to support the notion that a reduced stage-adjusted follow-up schedule is an appropriate and safe approach for AJCC stages 1B to 2C melanoma patients after staging with sentinel biopsy in terms of QoL, patient satisfaction, and disease safety at 3 years. We anticipate reporting the final outcome of the study at the end of 2020, with the data from the Netherlands and the UK combined to ensure adequate power to detect any difference in recurrence rates, thereby dispelling any lingering concerns about patient safety with a reduced follow-up regimen.…”

“…The current 3-year results show that the number of recurrences and second primary melanomas as well as the time until detection for the patients with AJCC stages 1B to 2C disease was independent of the assigned follow-up schedule, which is consistent with the Dutch 3-year MelFO results. 18 Almost half of recurrences (16/33) were detected within the first 12 months. Consistent with previous literature, this shows that the highest proportion of melanoma recurrences and second primaries is detected during the first year of follow-up evaluation and that the proportion declines in the following years.…”

“…The MELanoma FOllow-up (MelFO) study is an international phase 3 randomized controlled trial (RCT), and the 3-year interim data were reported recently from the Netherlands. 18 This clinical trial aimed to provide an evidence basis for the follow-up evaluation of cutaneous melanoma patients with no evidence of sentinel node metastasis. The primary end points of this trial are related to quality of life (QoL), cancer worry, and stress-related symptoms.…”

ASO Author Reflections: Stage-Adjusted Reduced Follow-Up of Melanoma Patients is Justified and Cost Effective, Until Biomarkers to Predict Prognosis Have Been Identified

“…The current randomized controlled MELFO study compared two groups of stage Ib-IIc melanoma patients, 3 years after diagnosis. 5 The first group received follow-up as advised in the guideline, while the second group received a stage-adjusted, less frequent follow-up schedule. Patients' QoL, anxiety, satisfaction regarding follow-up, and disease-free and overall survival were comparable, but a 39% cost reduction was found in those who were less frequently followed-up.…”