Clinicopathological features and prognosis of anaplastic and poorly differentiated thyroid carcinoma: Insights on treatment strategies from a 28-year real-world study spanning the immunotherapy era.

e18145 Background: Anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid carcinoma (PDTC) are rare and aggressive thyroid cancers, with limited data on their clinicopathological features and survival outcomes. This study aimed to characterize the real-world features of ATC and PDTC and identify prognostic factors, with an emphasis on evaluating therapeutic strategies. Methods: This retrospective study analyzed 92 ATC and 89 PDTC patients diagnosed at a tertiary institution between 1997 and 2025. Demographic, clinical, pathological, molecular, and treatment data were collected, including combined positive score (CPS), treatments (surgery, radiotherapy, chemotherapy, targeted therapies [TT], immunotherapy [IO]), and follow-up information. Overall survival (OS) was estimated using the Kaplan-Meier method and compared via the log-rank test. Prognostic factors were evaluated using univariate and multivariate Cox regression models. Results: The median OS for ATC and PDTC was 15 months and 62 months, respectively. ATC patients were older at diagnosis (p<0.001), presented with more advanced local disease (p=0.002), and exhibited fewer distant metastases (p=0.033) compared to PDTC patients. The ATC group showed higher gene mutation rates (p=0.009), more CPS-positive cases (CPS>1, p=0.035), and received more intensive treatments, including higher rates of IO (p=0.006), TT+IO (p=0.015), and multimodal therapy (≥3 modalities, p=0.001). Univariate and multivariate Cox regression analyses identified age, TP53 mutation, TT+IO, and multimodal treatment as significant prognostic factors for ATC. Multimodal treatment significantly improved survival in ATC (p=0.003), with surgery combined with TT+IO yielding better outcomes for metastatic ATC (p=0.019). TP53 mutation and co-mutation (≥3 mutations) were associated with significantly worse survival (p=0.003 and p=0.008). Metastatic PDTC patients benefited from IO-based multimodal therapies (p=0.031). Additionally, both ATC and PDTC showed improved survival post-2018, coinciding with the introduction of immunotherapy (p=0.017 and p=0.045). Conclusions: ATC and PDTC exhibit distinct clinicopathological features and survival outcomes. Multimodal treatment significantly benefits ATC patients, while TT+IO offers promising survival advantages for metastatic ATC. IO-based multimodal therapy shows potential efficacy for metastatic PDTC. These findings support a disease-specific, IO-based multimodal strategy, which warrants prospective validation and extended follow-up.