Role of surgery to the primary tumor in metastatic anaplastic thyroid carcinoma: pooled analysis and SEER-based study

Abstract

Purpose Anaplastic thyroid carcinoma (ATC) is an orphan disease with a fatal outcome. Surgery to the primary tumor in metastatic ATC is controversial. Determination of specific surgical techniques may help facilitate local control and, hence, beneficial overall and disease-specific survival. Methods Using individualized patient data derived from our systematic review of literature and our single center study (n = 123), conducting a Surveillance, Epidemiology, and End Results register (SEER)-based study (n = 617) we evaluated surgery, its combination with systemic and local therapies in metastatic ATC. Results Pooled cohort study showed surgery (p < 0.001), RT ≥ 30 Gy (p < 0.001), ChT (p < 0.001) and multimodal treatment (p = 0.014) to result in improved OS univariately. In the multivariate analysis, surgery (1.997 [1.162–3.433], p = 0.012) and RT ≥ 30 Gy (1.877 [1.232–2.843], p = 0.012) were independent predictors for OS. In SEER-based study of patients undergoing any tumor-directed treatment (n = 445) total thyroidectomy (p = 0.031), administration of ChT (p = 0.007), RT (p < 0.001), combination of surgery and RT ± ChT (p < 0.001) and multimodal treatment (p < 0.001) correlated with an improved DSS univariately. On the multivariate analysis, debulking surgery was an independent predictor for a worse outcome (HR 0.535, 95%CI 0.332–0.862, p = 0.010), whereas RT administration correlated with a longer DSS (HR 2.316, 95%CI 1.362–3.939, p = 0.002). Among operated patients from SEER register total thyroidectomy (p = 0.031), ChT (p = 0.007), RT (p < 0.001), combination of surgery and RT ± ChT (p < 0.001) and multimodal treatment (p < 0.001) correlated with an improved DSS in the univariate analysis, whereas debulking surgery was inversely correlated with the DSS (p < 0.001). On the multivariate analysis, debulking surgery was an independent predictor for a worse DSS (HR 0.535, 95%CI 0.332–0.862, p = 0.010), whilst RT administration correlated with a longer DSS (HR 2.316, 95%CI 1.362–3.939, p = 0.002). Conclusions Surgery to the primary tumor with the aim of R0/R1 resection, but not debulking, is associated with a significant OS and DSS benefit even in systemically metastasized disease.

First effectiveness data of lenvatinib and pembrolizumab as first-line therapy in advanced anaplastic thyroid cancer: a retrospective cohort study

“…As local radiotherapy in ATC is regularly administered at the time of diagnosis, using lenvatinib and pembrolizumab as systemic first-line therapy might potentially come with a higher risk to develop a fistula than using it later. Still, in a large retrospective analysis EBRT has recently been associated with improved disease-specific survival in ATC [ 27 ]. In ATC, local tumor aggressiveness drives complications and mortality.…”

Update on current diagnosis and management of anaplastic thyroid carcinoma

“…Surgery constitutes the cornerstone of treatment despite the existing debate. It may range from palliative debulking intervention to more radical resections, including total or near total thyroidectomy and extended lymphadenectomy, including the central and lateral lymph node level either unilaterally or bilaterally[ 6 , 8 , 36 , 53 , 61 ]. The above curative surgery may be performed in some patients with earlier disease and may provide, accompanied by adjuvant chemotherapy, occasional long survival over 5 years[ 18 , 19 ].…”

“…The above curative surgery may be performed in some patients with earlier disease and may provide, accompanied by adjuvant chemotherapy, occasional long survival over 5 years[ 18 , 19 ]. By multivariate analysis in a systematic review and meta-analysis, surgery and radiotherapy were found to be independent factors predicting increased overall survival[ 36 ]. Complete surgical excision followed by adjuvant therapy is the optimal opportunity for cure[ 4 , 47 ].…”

“…Tumor removal increases the benefits of the treatment. In combination with radiation, new chemotherapy and novel gene targeted therapy can achieve locoregional disease control and improve survival and quality of life[ 36 , 41 , 53 , 65 , 67 ]. The guidelines of the National Comprehensive Cancer Network and ATA recommend surgical resection by lobectomy or near total thyroidectomy with wide lymphadenectomy in stage IVA and IVB, even in stage IVC when an R0 or at least R1 intervention could be achieved in locally resectable tumors[ 36 , 43 , 68 - 70 ].…”

“…In combination with radiation, new chemotherapy and novel gene targeted therapy can achieve locoregional disease control and improve survival and quality of life[ 36 , 41 , 53 , 65 , 67 ]. The guidelines of the National Comprehensive Cancer Network and ATA recommend surgical resection by lobectomy or near total thyroidectomy with wide lymphadenectomy in stage IVA and IVB, even in stage IVC when an R0 or at least R1 intervention could be achieved in locally resectable tumors[ 36 , 43 , 68 - 70 ]. However, many locally unresectable cases may respond to neoadjuvant external beam radiation, chemotherapy or even targeted therapy (dabrafenib and trametinib) for BRAF gene mutation, thus becoming resectable and ensuring surgical excision[ 43 ].…”