Chemoradiotherapy for anal cancer: are we as good as we think?

Definitive chemoradiotherapy (CRT) is the standard treatment for anal squamous cell carcinoma (ASCC). Data regarding treatment outcome according to TNM classification is scarce. Here, we review data of randomized trials and retrospective cohorts suggesting a poor 3‑year disease-free survival (DFS; or progression-free survival, PFS) of approximately 60%, or even lower, in patients with locally advanced T3-4 and/or N+ disease, while patients with T1-2N0 ASCC have 3‑year DFS/PFS rates exceeding 80%. These results are in line with our data in a cohort of 210 patients with ASCC treated with definitive 5‑fluorouracil/mitomycin C‑based CRT to a total dose of 50.4 Gy plus a boost of 3.6-10.8 Gy. The implications of these findings and the current trials testing radiotherapy dose escalation/de-escalation strategies are reported. Finally, we will discuss the strong rationale for testing immune checkpoint blockade (ICB) with CRT in clinical trials to improve results, especially in patients with advanced ASCC.