S-100B in the follow-up of patients with stage III and IV melanoma: pursuit of the Holy Grail
Keywords:Melanoma, S-100B marker, Follow-up, Recurrent disease
Background: Patients with stage III-IV melanoma are at considerable risk for disease recurrence. Early detection of recurrence is important to optimize immunotherapy administration and improving progression-free and overall survival. S-100B can be used as tumor marker to evaluate whether patients are at risk for developing disease recurrence or progression. It could be a promising tool to determine whether patients need to receive additional diagnostic procedures. However, implementation in routine clinical setting is limited. Hence, this study aimed to evaluate the value of S-100B as a decision tool for the need to perform an 18F-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT) to confirm disease recurrence or progression in stage III-IV melanoma patients.
Methods: Data of 51 stage III-IV melanoma patients, presenting for follow-up after surgery with curative intent, was retrospectively extracted from a single-center electronic patient record system. 18FDG-PET/CT was performed based on clinical signs or elevated S-100B levels. S-100B measurements were treated as independent data points.
Results: Fifteen out of 303 S-100B levels were elevated. Six elevated levels were causes by disease progression; 4/6 measurements were noted with concurrent clinical signs. Twenty-four events of disease progression were confirmed. The sensitivity and specificity of S-100B serum test were 25.0% [95% CI (9.8-46.7)] and 96.8% [95% CI (94.0-98.5)]. The positive predictive value (PPV) and negative predictive value (NPV) of S-100B were 40.0% [95% CI (20.6-63.2)] and 93.8% [95% CI (92.2-95.0)].
Conclusions: Elevated S-100B levels did not exclude nor indicate metastatic or recurrent disease in this study. Using S-100B in routine clinical setting does not seem to be of additional value.
Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472-92.
von Schuckmann LA, Hughes MCB, Ghiasvand R, Malt M, van der Pols JC, Beesley VL, et al. Risk of Melanoma Recurrence After Diagnosis of a High-Risk Primary Tumor. JAMA Dermatol. 2019;155(6):688-93.
Leiter U, Buettner PG, Eigentler TK, Forschner A, Meier F, Garbe C. Is detection of melanoma metastasis during surveillance in an early phase of development associated with a survival benefit? Melanoma Res. 2010;20(3):240-6.
Franklin C, Livingstone E, Roesch A, Schilling B, Schadendorf D. Immunotherapy in melanoma: Recent advances and future directions. Eur J Surg Oncol. 2017;43(3):604-11.
Belter B, Haase-Kohn C, Pietzsch J. Biomarkers in Malignant Melanoma: Recent Trends and Critical Perspective. In: Ward WH, Farma JM, editors. Cutaneous Melanoma: Etiology and Therapy. Brisbane (AU): Codon Publications. 2017;3.
Mocellin S, Zavagno G, Nitti D. The prognostic value of serum S100B in patients with cutaneous melanoma: A meta-analysis. Int J Cancer. 2008;123(10):2370-6.
Peric B, Zagar I, Novakovic S, Zgajnar J, Hocevar M. Role of serum S100B and PET-CT in follow-up of patients with cutaneous melanoma. BMC Cancer. 2011;11:328.
Aukema TS, Olmos RA, Korse CM, Kroon BB, Wouters MW, Vogel WV, et al. Utility of FDG PET/CT and brain MRI in melanoma patients with increased serum S-100B level during follow-up. Ann Surg Oncol. 2010;17(6):1657-61.
Wieder HA, Tekin G, Rosenbaum-Krumme S, Klode J, Altenbernd J, Bockisch A, Nagarajah J. 18FDG-PET to assess recurrence and long term survival in patients with malignant melanoma. Nuklearmedizin. 2013;52(5):198-203.
Integraal Kankercentrum Nederland, IKNL, Netherlands Comprehensive Cancer Organisation. The dutch medical guideline - melanoma. Available at: https://iknl.nl/en/about-iknl. Accessed on 24 July 2021.
Xing Y, Bronstein Y, Ross MI, Askew RL, Lee JE, Gershenwald JE, et al. Contemporary diagnostic imaging modalities for the staging and surveillance of melanoma patients: A meta-analysis. J Natl Cancer Inst. 2011;103(2):129-42.
D Deckers EA, Wevers KP, Muller Kobold AC, Damude S, Vrielink OM, van Ginkel RJ, et al. S-100B as an extra selection tool for FDG PET/CT scanning in follow-up of AJCC stage III melanoma patients. J Surg Oncol. 2019;120(6):1031-7.
Madu MF, Timmerman P, Wouters, Michel WJM, van der Hiel B, van der Hage, Jos A, van Akkooi, Alexander CJ. PET/CT surveillance detects asymptomatic recurrences in stage IIIB and IIIC melanoma patients: A prospective cohort study. Melanoma Res. 2017;27(3).
Lewin J, Sayers L, Kee D, Walpole I, Sanelli A, Te Marvelde L, 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.
Kurtz J, Beasley GM, Agnese D. Surveillance strategies in the follow-up of melanoma patients: Too much or not enough? J Surg Res. 2017;214:32-7.
Freeman M, Laks S. Surveillance imaging for metastasis in high-risk melanoma: Importance in individualized patient care and survivorship. Melanoma management. 2019;6(1):MMT12.
Kruijff S, Hoekstra HJ. The current status of S-100B as a biomarker in melanoma. Eur J Surg Oncol. 2012;38(4):281-5.
Wevers KP, Kruijff S, Speijers MJ, Bastiaannet E, Muller Kobold AC, Hoekstra HJ. S-100B: A stronger prognostic biomarker than LDH in stage IIIB-C melanoma. Ann Surg Oncol. 2013;20(8):2772-9.
Bouwhuis MG, Suciu S, Kruit W. Prognostic value of serial blood S100B determinations in stage IIB-III melanoma patients: A corollary study to EORTC trial 18952. Eur J Cancer. 2011;47(3):361-8.
Damude S, Wevers KP, Murali R, Kruijff S, Hoekstra HJ, Bastiaannet E. A prediction tool incorporating the biomarker S-100B for patient selection for completion lymph node dissection in stage III melanoma. Eur J Surg Oncol. 2017;43(9):1753-9.
Andrés R, Mayordomo JI, Zaballos P, Rodino J, Isla D, Escudero P, Elosegui L, Filipovich E, Saenz A, Polo E, Tres A. Prognostic value of serum S-100B in malignant melanoma. Tumori. 2004;90(6):607-10.
Smit LH, Korse CM, Hart AA. Normal values of serum S-100B predict prolonged survival for stage IV melanoma patients. Eur J Cancer. 2005;41(3):386-92.