Early Recurrence in Completely Resected IIIB and IIIC Melanoma Warrants Restaging Prior to Adjuvant Therapy

Abstract

PurposeTo evaluate the results of restaging completely resected stage IIIB/C melanoma prior to start of adjuvant therapy.Patients and MethodsOne hundred twenty patients with stage IIIB or IIIC (AJCC 2009) melanoma who underwent complete surgical resection were screened for inclusion in our trial investigating adjuvant dendritic cell therapy (NCT02993315). All patients underwent imaging to exclude local relapse or metastasis before entering the trial. The frequency of recurrent disease within 12 weeks after resection and the method of detection were investigated.ResultsSixty-nine (58%) stage IIIB and 51 (43%) stage IIIC melanoma patients were screened. Median age was 54 (range 27–79) years. Twenty-two (18%) of 120 patients with completely resected stage IIIB/C melanoma had evidence of early recurrent disease, despite exclusion thereof by prior imaging. Median interval between resection and detection of relapse was 7.4 (range 4.3–10.7) weeks. Recurrence was asymptomatic in 17 (77%) patients, but metastasis was noticed by the patient or physician in 5 (23%). Eight patients with local relapse received local treatment with curative intent, and one was treated with systemic therapy. The remaining patients had distant metastasis, 1 of whom underwent resection of a solitary liver metastasis while 12 patients received systemic treatment.ConclusionsPatients with completely resected stage IIIB/C melanoma have high risk of early recurrence before start of adjuvant therapy. Restaging should be considered for high-risk melanoma patients before start of adjuvant therapy.

The use of FDG‐PET/CT to detect early recurrence after resection of high‐risk stage III melanoma

“…In A study investigating recurrence before adjuvant therapy in a trial using adjuvant dendritic cell therapy, demonstrated a recurrence rate of 14% detected by FDG-PET/CT, which is very similar to ours. 24 The checkmate 238 study reported that 309 patients did not participate in the randomization between nivolumab and ipilimumab, of which we only know that they did not meet the inclusion criteria. 12 One might assume that in some patients, exclusion was caused by progression on rescreening before entering the trial.…”

Impact of Circulating and Tissue Biomarkers in Adjuvant and Neoadjuvant Therapy for High-Risk Melanoma: Ready for Prime Time?

“…Moreover, the comparison of tumor tissues obtained before and after surgery can reveal important information regarding potential biomarkers for response and resistance to treatment [ 20 ]. It is also important to underline that approximately 40% of patients with stage III melanoma will relapse within the first 3 years despite being treated with adjuvant therapy (either with targeted therapy or immunotherapy), and up to 25% of patients experience early relapse before even starting adjuvant treatment [ 22 ].…”

Time may Heal All Wounds, but While It Does, Melanoma Marches on

“…Bloemendal and colleagues are to be commended for reporting, in a rigorous fashion, the number of patients with surgically resected, high-risk, stage III metastatic melanoma who were screened prior to entering an adjuvant clinical trial. 3 The systematic precision of restaging before embarking on adjuvant therapy is proper clinical trial conduct; however, the real message from this work may be the high number of patients (18%) who were found to have disease within 7.5 weeks of their definitive surgical resection of stage III metastatic melanoma. This alarming number of patients who, on restaging, were found to have recurrent stage III or even stage IV disease highlights the need for a paradigm shift to neoadjuvant therapy for these high-risk patients.…”

“…This alarming number of patients who, on restaging, were found to have recurrent stage III or even stage IV disease highlights the need for a paradigm shift to neoadjuvant therapy for these high-risk patients. Instead of continuing with a surgery-first approach, we believe the work of Bloemendal et al 3 highlights the need to shift to a drug-first approach. We would encourage investigators to continue their thoughtful use of checkpoint hihibitors, BRAF and MEK inhibitors, and/or novel combinations in the neoadjuvant setting as opposed to the adjuvant setting for patients with high-risk stage III metastatic melanoma.…”

“…1,2 In the absence of effective systemic therapy, this has been the reality for the surgeon caring for these patients, despite knowing that some stage III metastatic melanoma patients are unlikely to benefit from aggressive surgical management. The study by Bloemendal et al 3 highlights this problem and seeks to characterize a group of patients at greatest risk for early recurrence. The authors present a group of 120 patients with stage IIIb (58%) and IIIc (43%) melanoma completely resected surgically and then screened within 10 weeks of surgery for inclusion in an adjuvant therapy trial.…”