Survival trends and prognostic factors of metastatic cervical cancer: a population-based cohort study

Metastatic cervical cancer (mCC) remains a highly lethal disease. While clinical trials support the addition of targeted therapy and immunotherapy to chemotherapy, real-world survival trends are less well characterized. This study aimed to evaluate real-world overall survival trends and prognostic factors in mCC patients over the past two decades, in the context of evolving targeted and immunotherapeutic treatments.

We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database to evaluate overall survival (OS) trends and prognostic factors among mCC patients diagnosed between 1998 and 2019. Based on major therapeutic milestones, patients were grouped into three calendar cohorts: 1998-2003 (pre-bevacizumab chemotherapy era), 2004-2013 (chemotherapy plus molecular-targeted therapy era), and 2014-2019 (chemotherapy plus immuno-molecular targeted therapy era, after pembrolizumab approval). Kaplan-Meier and Cox regression analyses were used to assess OS and identify independent prognostic variables.

Among 1,866 patients with distant mCC [corresponding to International Federation of Gynecology and Obstetrics (FIGO) stage IVB], 53.5% were aged ≥55 years and 67.1% had squamous cell carcinoma (SCC). Median OS increased from 11 months in 1998-2003 to 14 months in 2014-2019 (P=0.04), while the mortality rate declined from 91.6% in 1998-2003 to 75.9% in 2014-2019 (P<0.001). Among patients with SCC, median OS increased from 13 months in 1998-2003 to 16 months in 2014-2019 (P=0.006), whereas no significant survival improvement was observed among those with non-SCC histologies (P=0.48). Multivariable analysis identified SCC histology [hazard ratio (HR) =0.764, 95% confidence interval (CI): 0.670-0.871], lymphadenectomy (HR =0.730, 95% CI: 0.602-0.886), radiotherapy (HR =0.696, 95% CI: 0.619-0.783), and chemotherapy (HR =0.508, 95% CI: 0.452-0.571) were independently associated with improved survival. While age ≥55 years (HR =1.158, 95% CI: 1.045-1.284), Black race (HR =1.339, 95% CI: 1.108-1.620), absence of surgery (HR =2.160, 95% CI: 1.788-2.610), and local surgery alone (HR =1.501, 95% CI: 1.129-1.995) were associated with worse outcomes.

Survival for mCC has improved in the past two decades, possibly because of the advances of local therapy and systemic therapy. However, outcomes remain poor for patients with non-SCC histologies, older patients, and Black patients, highlighting the need for individualized, multimodal treatment approaches and better access to emerging therapies.