Patterns and Timing of Initial Relapse in Pathologic Stage II Melanoma Patients

Abstract

Purpose Pathologic stage II melanoma patients have variable outcomes when divided by sub-stage. We hypothesized that an understanding of the patterns of initial relapse by sub-stage will better inform follow-up guidelines. Methods We performed a retrospective review of 738 adult patients with pathologic stage II cutaneous melanoma treated at Memorial Sloan Kettering Cancer Center between 1993 and 2013. Clinical records were reviewed to determine time, location, and method of detection of initial relapse. Results At a median follow-up of 52 months, 219 patients relapsed. Relapses were detected more frequently in higher sub-stages. Initial relapses were most commonly local/in-transit for IIA and IIB, and systemic for IIC. Lung and brain were the most frequent sites of systemic relapse. Patient-detection was the most common method of relapse detection (59%) in all sub-stages. The 5-year cumulative incidence for patient-detected relapse was 13.6% for IIA, 18.9% for IIB, and 23.3% for IIC, and for image-detected relapse was 3.4%, 7.9% and 16.6%, respectively. The 5-year cumulative incidence for physician-detected relapse was less than 10% across all sub-stages and leveled off at three years for stage IIA and IIB and two years for stage IIC. Conclusion Relapses were most frequently patient-detected in all stage II sub-stages, highlighting the importance of patient education and self-examination. The highest yield for routine imaging is in stage IIC patients during the first four years. Physician examination is unlikely to detect relapses beyond three years for stage IIA and IIB, and beyond two years for stage IIC patients.

Follow‐up of the melanoma patient

“…In a 2017 retrospective analysis of 466 patients, Park et al detected the proportion of recurrences to be systemic in 48% of stage II, 68% of stage III, and 77% of resected stage IV patients. This trend continues into substage, with stage IIA and IIC patients having reported systemic recurrence rates of 34% and 52%, respectively . In the 2010 study by Romano et al, as substage increased from IIIA to IIIB to IIIC, the proportion of local and in‐transit recurrence as the site of first relapse progressively decreased at 32%, 30%, and 22%, respectively.…”

“…Studies grouping stage I and II melanoma patients have estimated 1 and 10‐year recurrence rates at approximately 9% and 23%, respectively, with increasing risk dependent on substage . When stratified by American Joint Committee on Cancer (AJCC) substage, a large retrospective study at Memorial Sloan Kettering Cancer Center found the 5‐year risk of recurrence for stage IIA, IIB, and IIC to be 21.6%, 35.1%, and 45.3%, respectively . Substratification of stage III patients in a large retrospective analysis reported overall 5‐year risk of recurrence for stages IIIA, IIIB, and IIIC to be approximately 48%, 71%, and 85%, respectively …”

“…Regarding timing, over half of relapses occur within 1 year of diagnosis, and the significant majority occur within 3 years (Table ) . Risk of recurrence for all melanoma patients approaches zero, but relapses after 10 years are well documented.…”

“…Regional lymph node metastasis as the site of first recurrence may increase in frequency in the post‐Multicenter Selective Lymphadenectomy Trial (MSLT) II era given the anticipated decrease in CLND . The most common sites of nonbrain systemic recurrence are the liver and lungs …”

“…The overall majority of recurrences are detected by the treated melanoma patient or the patient's family . This can be a product of either patient education with routine self‐examination, or through symptoms prompting presentation to the patient's treatment team.…”