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
- 1Netherlands Comprehensive Cancer Organisation
Abstract
ObjectiveExtranodal 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.
MethodsPatients 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.
ResultsAmong 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).
ConclusionExtranodal 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.
DisclosuresThe authors have no conflicts of interest to disclose.
Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSExtranodal spread is an established adverse prognostic factor in several malignancies. In clinically early-stage cervical cancer treated with radical hysterectomy, extranodal spread is routinely reported when lymph nodes are positive, although it does not currently influence adjuvant treatment decisions.
What this study addsIn this nationwide cohort of patients with clinically early-stage cervical cancer treated with radical hysterectomy, extranodal spread was associated with poorer recurrence-free survival. For overall survival, estimates consistently suggested worse outcomes in patients with extranodal spread, although statistical significance depended on the analytical approach.
How this study might affect research, practice or policyThese findings suggest that extranodal spread may be a clinically relevant prognostic marker in clinically early-stage cervical cancer and could contribute to improved risk stratification, follow-up strategies, and future evaluation of adjuvant treatment guidelines.
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BibTeX
@misc{ven2026impact,
title = {{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}},
author = {R. G. F. M. van der Ven and H. H. Wenzel and M. A. van der Aa and C. H. Mom and N. B. Thuijs and J. van der Velden},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.26362042},
url = {https://www.medrxiv.org/content/10.64898/2026.09.02.26362042v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - 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
AU - R. G. F. M. van der Ven
AU - H. H. Wenzel
AU - M. A. van der Aa
AU - C. H. Mom
AU - N. B. Thuijs
AU - J. van der Velden
PY - 2026
DA - 2026/09/02
PB - medRxiv
DO - 10.64898/2026.09.02.26362042
UR - https://www.medrxiv.org/content/10.64898/2026.09.02.26362042v1
AB - ObjectiveExtranodal 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. MethodsPatients 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. ResultsAmong 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). ConclusionExtranodal 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. DisclosuresThe authors have no conflicts of interest to disclose. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSExtranodal spread is an established adverse prognostic factor in several malignancies. In clinically early-stage cervical cancer treated with radical hysterectomy, extranodal spread is routinely reported when lymph nodes are positive, although it does not currently influence adjuvant treatment decisions. What this study addsIn this nationwide cohort of patients with clinically early-stage cervical cancer treated with radical hysterectomy, extranodal spread was associated with poorer recurrence-free survival. For overall survival, estimates consistently suggested worse outcomes in patients with extranodal spread, although statistical significance depended on the analytical approach. How this study might affect research, practice or policyThese findings suggest that extranodal spread may be a clinically relevant prognostic marker in clinically early-stage cervical cancer and could contribute to improved risk stratification, follow-up strategies, and future evaluation of adjuvant treatment guidelines.
ER -