Intensive imaging in melanoma remains controversial because its survival impact is unknown. We investigated the impact of imaging intensity on the rates of asymptomatic surveillance-detected recurrence (ASDR) and subsequent treatment outcomes in patients with access to immune checkpoint inhibitors (ICIs) and targeted therapy (TT).
Patients with resected malignant melanoma undergoing imaging surveillance at a single center between 2006 and 2016 were identified. Surveillance and recurrence characteristics (imaging, symptom, treatment, and survival data) were retrospectively collected. Univariate (t test, Chi square test) and multivariate Cox regression analyses were conducted.
Of 353 high-risk melanoma patients (stage IIB, 24%; IIC, 19%; IIIA, 27%; IIIB, 16%; IIIC, 14%), 71 (45%) had ASDR and 88 (55%) had symptomatic recurrence (SR). Shorter imaging intervals identified more ASDR (57%, 0–6 months; 34%, 6–12 months; 33%, > 12 months; p = 0.03). ASDR had better prognostic factors than SR [fewer than three metastatic sites (43 vs. 21%, p = 0.003), normal lactate dehydrogenase (LDH; 53 vs. 38%, p = 0.09), brain metastases (11 vs. 40%, p < 0.001)] and received more systemic treatment (72 vs. 49%, p = 0.003; ICIs 55 vs. 31%, p = 0.002; TT 8 vs. 13%, p = 0.41). ASDR had better survival outcomes on ICI treatment (2-year OS, 56 vs. 31%, p < 0.001). Median OS from surveillance start was 39.6 vs. 22.8 months (p < 0.001). ASDR was independently associated with survival (hazard ratio 0.47, 95% confidence interval 0.29–0.78, p = 0.003), adjusting for stage, sex, age, disease burden, LDH, era of recurrence, brain metastases, and ICI/TT treatment.
These real-world data support further study on intensified imaging surveillance protocols for high-risk resected melanoma, as ASDR was associated with superior survival outcomes from ICI therapy.
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Balch CM, Gershenwald JE, Soong S, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6200–6.
Trotter SC, Sroa N, Winkelmann RR, et al. A global review of melanoma follow-up guidelines. J Clin Aesthet Dermatol. 2013;6(9):8–26.
Cromwell KD, Ross MI, Xing Y, et al. Variability in melanoma post-treatment surveillance practices by country and physician specialty: a systematic review. Melanoma Res. 2012;22(5):1–21.
Podlipnik S, Carrera C, Sanchez M, et al. Performance of diagnostic tests in an intensive follow-up protocol for patients with American Joint Committee on Cancer (AJCC) Stage IIB, IIC, and III localized primary melanoma: a prospective cohort study. J Am Acad Dermatol. 2016;75(3):516–24.
Romano E, Scordo M, Dusza SW, et al. Site and timing of first relapse in stage III melanoma patients: implications for follow-up guidelines. J Clin Oncol. 2010;28(18):3042–7.
Meyers MO, Yeh JJ, Frank J, et al. Method of detection of initial recurrence of stage II/III cutaneous melanoma: analysis of the utility of follow-up staging. Ann Surg Oncol. 2009;16:941–7.
Moore DK, Zhou Q, Panageas KS, et al. Methods of detection of first recurrence in patients with stage I/II primary cutaneous melanoma after sentinel lymph node biopsy. Ann Surg Oncol. 2008;15(16):2206–14.
National Comprehensive Cancer Network®. NCCN Guidelines Version 1.2017 Melanoma. Plymouth Meeting, PA: National Comprehensive Cancer Network, Inc.; 2016.
Rajagopal S, Souter LH, Baetz T, et al. Program in evidence-based care, cancer care Ontario (CCO) guideline 8–7: follow up of patients with cutaneous melanoma who were treated with curative intent. Toronto, ON: Cancer Care Ontario; 2015.
Garbe C, Paul A, Kohler-Spath H, et al. Prospective evaluation of a follow-up schedule in cutaneous melanoma patients: recommendations for an effective follow-up strategy. J Clin Oncol. 2003;21(3):520–9.
Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.
Topalian SL, Hodi FS, Brahmer JR, et al. Safety, Activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.
Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2017;377:1345–56.
Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017;390:1853–62.
Long GV, Grob J-J, Nathan P, et al. Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials. Lancet Oncol. 2016;17(12):1743–54.
Nishino M, Giobbie-Hurder A, Ramaiya NH, Hodi FS. Response assessment in metastatic melanoma treated with ipilimumab and bevacizumab: CT tumor size and density as markers for response and outcome. J Immunother Cancer. 2014;2:40.
Eggermont AMM, Chiarion-Sileni VC, Grob J-J, et al. Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med. 2016;375(19):1845–55.
Weber J, Mandala M, Del Vecchio M, et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377:1824–35.
Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377:1813–23.
Eggermont AMM, Blank CU, Mandala M, et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med. 2018;378:1789–801.
Swetter SM. Commentary: improved patient outcomes remain elusive after intensive imaging surveillance for high-risk melanoma. J Am Acad Dermatol. 2016;75(3):525–7.
Koskivuo I, Kemppainen J, Giordano S, et al. Whole body PET/CT in the follow-up of asymptomatic patients with stage IIB-IIIB cutaneous melanoma. Acta Oncol. 2016;55(11):1355–9.
Faries M, Thompson JF, Cochran AJ, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med. 2017;276:2211–22.
Leiter U, Stadler R, Mauch C, et al. Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-DLT): a multicenter, randomized, phase 3 trial. Lancet Oncol. 2016;17(6):757–67.
Park TS, Phan GQ, Yang JC, et al. Routine Computer tomography imaging for the detection of recurrences in high-risk melanoma patients. Ann Surg Oncol. 2017;24(4):947–51.
Lewin J, Sayers L, Kee D, et al. Surveillance imaging with FDG-PET/CT in the post-operative follow-up of stage 3 melanoma. Ann Oncol. 2018;29(7):1569–74.
Sweeny CJ, Chen Y-H, Carducci M, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737–46.
James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163–77.
Long GV, Atkinson V, Menzies AM, et al. A randomized phase II study of nivolumab or nivolumab combined with ipilimumab in patients (pts) with melanoma brain metastases (mets): the anti-PD1 brain collaboration (ABC). J Clin Oncol. 2017;35(15):9508.
Kirkwood JM, Long GV, Trefzer U, et al. BREAK-MB: a phase II study assessing overall intracranial response rates (OIRR) to dabrafenib (GSK2118436) in patients (pts) with BRAF V600E/k mutation-positive melanoma with brain metastases (mets). J Clin Oncol. 2012;30(Suppl 15):8501.
Tawbi HA, Forsyth PA, Algazi A, et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med. 2018;379:722–30.
Pflugfelder A, Kochs C, Blum A, et al. Malignant melanoma S3-guideline “diagnosis, therapy and follow-up of melanoma”. J Dtsch Dermatol Ges. 2013;11(Suppl 6):1–116.
Guillot B, Dalac S, Denis MG, et al. French updated recommendations in stage I to III melanoma treatment and management. J Eur Acad Dermatol Venereol. 2017;31(4):594–602.
Dummer R, Hauschild A, Lindenblatt N, et al. Cutaenous melanoma: ESMO clinical practice guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2015;26(Suppl 5):v126–32.
NICE. Melanoma: assessment and management. NICE 2018. Available at: https://www.nice.org.uk/guidance/ng14/chapter/1-Recommendations#follow-up-after-treatment-for-melanoma-2. Accessed 31 July 2018.
American Academy of Dermatology (AAD). Melanoma: staging workup and followup recommendations. American Academy of Dermatology Association. 2018. Available at: https://www.aad.org/practicecenter/quality/clinical-guidelines/melanoma/staging-workup-and-followup. Accessed 31 July 2018.
Babour A, Millward M, Morton R, Saw R. Cancer Guidelines Wiki: investigations and follow-up for melanoma patients. Cancer Council Australia (CCA); 2018. Available at: https://wiki.cancer.org.au/australia/Guidelines:Investigations_and_Follow-up_for_Melanoma_Patients. Accessed 31 July 2018.
BC Cancer Agency: Management: 6.4 Follow-up. Provincial Health Services Authority. 2018. Available at: http://www.bccancer.bc.ca/health-professionals/clinical-resources/cancer-management-guidelines/skin/melanoma#Follow-up. Accessed 31 July 2018.
Podlipnik S, Moreno-Ramírez D, Carrera C, et al. Cost-effectiveness analysis of imaging strategy for an intensive follow-up of patients with AJCC stage IIB, IIC and III malignant melanoma. Br J Dermatol. 2018;180(5):1190–7.
Knackstedt RW, Knackstedt T, Gastman B. Gene expression profiling in melanoma: past results and future potential. Future Oncol. 2019;15(7):791–800.
The Cancer Genome Atlas Network. Genomic classification of cutaneous melanoma. Cell. 2015;161(7):1681–96.
Haydu LE, Lo SN, McQuade JL, Amaria RN, Wargo J, Ross MI, et al. Cumulative incidence and predictors of CNS metastasis for patients with American joint committee on cancer 8th edition stage III melanoma. J Clin Oncol. Epub 28 Jan 2020 (JCO1901508).
All authors read and approved the manuscript. This manuscript has not previously been published and is not currently under consideration for publication in any other journal. Michael Ong has been a consultant to and received honoraria from Bristol-Myers Squibb, Merck, AstraZeneca, and Roche/Genentech. Carolyn Nessim has received honoraria from Merck, EMD Serono and Novartis, and has been on an advisory board for Novartis. Xinni Song has been a consultant to and received honoraria from Bristol-Myers Squibb and Merck. Dominick Bossé has been a consultant to Bristol-Myers Squibb, Pfizer and AbbVie, and has received honoraria from AstraZeneca, Ipsen, Amgen and Janssen. Andrea Marie Ibrahim, Melanie Le May, and Horia Marginean declare they have no competing interests.
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Ibrahim, A.M., Le May, M., Bossé, D. et al. Imaging Intensity and Survival Outcomes in High-Risk Resected Melanoma Treated by Systemic Therapy at Recurrence. Ann Surg Oncol 27, 3683–3691 (2020). https://doi.org/10.1245/s10434-020-08407-8