Introduction/Background The aims of this study were to analyze the pathological response, and survival outcomes of adenocarcinoma/adenosquamous (AC/ASC) versus squamous cell carcinoma (SCC) in patients with locally advanced cervical cancer (LACC) managed by chemoradiotherapy followed by radical surgery.

Methodology Retrospective, multicenter, observational study, including patients with SCC and AC/ACS LACC patients treated with preoperative CT/RT followed by tailored radical surgery (RS) between 06/2002 and 05/2017. Clinical-pathological characteristics were compared between patients with SCC versus AC/ASC. A 1:3 ratio propensity score (PS) matching was applied to remove the variables imbalance between the two groups.

Results After PS, 320 patients were included, of which 240 (75.0%) in the SCC group, and 80 (25.0%) in the AC/ASC group. Clinico-pathological and surgical baseline characteristics were balanced between the two study groups. Percentage of pathologic complete response was 47.5% in SCC patients versus 22.4% of AC/ASC ones (p<0.001). With a median follow-up of 51 months (range:1–199), there were 54/240 (22.5%) recurrences in SCC versus 28/80 (35.0%) in AC/ASC patients (p=0.027). AC/ASC patients experienced worse disease free (DFS), and overall survival (OS) compared to SCC patients (p=0.019, and p=0.048, respectively). In multivariate analysis, AC/ACS histotype, and FIGO stage were associated with worse DFS and OS.

Conclusion In LACC patients treated with CT/RT followed by RS, AC/ASC histology was associated with lower pathological complete response to CT/RT, and higher risk of recurrence and death compared with SCC patients. This highlights the need for specific therapeutic strategies based on molecular characterization to identify targets and develop novel treatments.