The impact of extranodal spread on overall and recurrence-free survival in patients with clinically early-stage cervical cancer, but with tumor positive pelvic lymph nodes after radical hysterectomy

Objective Extranodal spread is an adverse prognostic factor in several cancers. In clinically early-stage cervical cancer and positive lymph nodes after radical hysterectomy, extranodal spread is routinely registered in pathology reports, but it does not influence adjuvant treatment decisions. This nationwide study assessed the prognostic value of extranodal spread. Methods Patients diagnosed between 2009 and 2024 with clinical early-stage cervical cancer (TNM T1 to T2a2) and pathologically positive regional lymph nodes after radical hysterectomy were identified from the Netherlands Cancer Registry. Cox proportional-hazard models assessed differences in overall survival and recurrence-free survival. A Bayesian Cox model with informative prior was applied to complement overall survival analysis. Recurrence patterns were compared by extranodal spread status. Results Among 408 patients, 46 (11.3%) had extranodal spread. In multivariable frequentist analysis, extranodal spread was significantly associated with poorer recurrence-free survival (hazard ratio [HR] 1.97, 95% confidence interval [CI] 1.11-3.49), but not with overall survival (HR 1.37, CI 0.78-2.41). Bayesian analysis showed a significant difference in overall survival (HR 1.63, CI 1.14-2.27). Among patients with recurrence, the distribution of locoregional and distant recurrence patterns did not significantly differ between those with and without extranodal spread (p=0.09). Conclusion Extranodal spread is associated with poorer recurrence-free survival in clinically early-stage cervical cancer treated with radical hysterectomy. For overall survival, results were directionally consistent but dependent on the analytical approach, likely reflecting limited statistical power. These findings suggest a role for extranodal spread in risk stratification and follow-up, warranting further investigation before informing treatment decisions.