BRAF V600E status may facilitate decision-making on active surveillance of low-risk papillary thyroid microcarcinoma

[Introduction]: Conservative active surveillance has been proposed for low-risk papillary thyroid microcarcinoma (PTMC), defined as ≤1.0 cm and lacking clinical aggressive features, but controversy exists with accepting it as not all such PTMCs are uniformly destined for benign prognosis. This study investigated whether BRAF V600E status could further risk stratify PTMC, particularly low-risk PTMC, and can thus help with more accurate case selection for conservative management.
[Methods]: This international multicenter study included 743 patients treated with total thyroidectomy for PTMC (584 women and 159 men), with a median age of 49 years (interquartile range [IQR], 39–59 years) and a median follow-up time of 53 months (IQR, 25–93 months).
[Results]: On overall analyses of all PTMCs, tumour recurrences were 6.4% (32/502) versus 10.8% (26/241) in BRAF mutation-negative versus BRAF mutation-positive patients (P = 0.041), with a hazard ratio (HR) of 2.44 (95% CI (confidence interval), 1.15–5.20) after multivariate adjustment for confounding clinical factors. On the analyses of low-risk PTMC, recurrences were 1.3% (5/383) versus 4.3% (6/139) in BRAF mutation-negative versus BRAF mutation-positive patients, with an HR of 6.65 (95% CI, 1.80–24.65) after adjustment for confounding clinical factors. BRAF mutation was associated with a significant decline in the Kaplan–Meier recurrence-free survival curve in low-risk PTMC.
[Conclusions]: BRAF V600E differentiates the recurrence risk of PTMC, particularly low-risk PTMC. Given the robust negative predictive value, conservative active surveillance of BRAF mutation-negative low-risk PTMC is reasonable whereas the increased recurrence risk and other well-known adverse effects of BRAF V600E make the feasibility of long-term conservative surveillance uncertain for BRAF mutation-positive PTMC.
This study was supported partly by US National Institutes of Health (NIH) Grant Nos. R01CA215142 and R01CA189224 (M.X.) and by the following additional funding at the individual participating centres: Polish National Center of Research and Development MILESTONE (Molecular Diagnostics and Imaging in Individualized Therapy for Breast, Thyroid and Prostate Cancer) Project Grant No. STRATEGMED2/267398/4/NCBR/2015 (A.C., B.J.); grants from the Menzies Health Institute, Griffith University, Queensland Cancer Council, and Queensland Smart State Fellowship in Australia (A.K.L.); Ministry of Economy and Competitiveness (MINECO) and Fondo Europeo de Desarrollo Regional (FEDER) Grant No. SAF2016-75531-R, Instituto de Salud Carlos III Grant No. PI14/01980, Asociación Española Contra el Cáncer Foundation Grant No. GCB14142311CRES, and TIRONET2-CM Grant No. B2017/BMD-3724 TIRONET2-CM in Spain (P.S., G.R.-E.); Institute of Endocrinology Grant Nos. AZV 16-32665A and MH CZ-DRO 00023761 in the Czech Republic (B.B., V.S.); grants from the New South Wales Cancer Institute (C.J.O.) and Cancer Council of New South Wales (R.C.-B.) in Australia; National Institute on Aging, NIH, Grant No. 5R03AG042334-02 (L.Y.); grants from the Ministero della Istruzione Universitaria e Ricerca Scientifica, the Associazione Italiana per la Ricerca sul Cancro, the Istituto Toscano Tumori, and the Ministero della Salute in Italy (D.V. and R.E.).