Objective: The optimal treatment of clinically early-stage cervical cancer with suspicious lymph nodes on pretreatment imaging is unclear. Therefore, we aimed to compare surgery (i.e., radical hysterectomy and pelvic lymphadenectomy±adjuvant therapy) with primary chemoradiotherapy as treatment strategies in this patient group regarding recurrence-free, overall survival and toxicity. Methods: Women diagnosed between 2009–2017 with the International Federation of Gynecology and Obstetrics (2009) stage IA–IIA and suspicious nodes based on radiologic assessment of pretreatment imaging were retrospectively selected from the Netherlands Cancer Registry. Cox proportional hazard was used to estimate survival and logistic regression for toxicity. Inverse probability weighting was used to correct for confounding.Grade ≥2 surgery-related (≤30 days) and grade ≥3 chemotherapy or radiotherapy-related (≤6 months) toxicity were collected. Missing data were imputed. Results: Of 330 patients included, 131 (40%) received surgery (followed by adjuvant therapy in 54%) and 199 (60%) chemoradiotherapy. Pathological nodal status was known in 100% of the surgery group and 32% (n=63) of the chemoradiotherapy group, of whom 43% (56/131) and 89% (56/63), respectively, had metastases. After adjustment for confounders, the recurrence-free survival (hazard ratio [HR]=0.67; 95% confidence interval [CI]=0.34–1.31) and overall survival (HR=0.75; 95% CI=0.38–1.47) were not significantly different between both groups, while surgery was associated with more toxicity (odds ratio=2.82; 95% CI=1.42– 5.60), mainly surgery-related. Conclusion In patients with clinically early-stage cervical cancer and suspicious nodes on imaging, surgery and primary chemoradiotherapy yielded comparable results in terms of survival, whereas surgery might be associated with more (surgery-related) short-term toxicity.

Objective: The modeled CA-125 ELIMination rate constant K (KELIM) has been validated as a marker of response to chemotherapy in >12,000 patients with advanced epithelial ovarian carcinoma (EOC) treated in first-line setting enrolled in >12 clinical trials. Patient KELIM is calculable online https://www.biomarker-kinetics.org/presentation. The objective was to investigate the prognostic value of KELIM in a large real-life national cancer registry with non-selected patients. Methods: We investigated 4,025 EOC patients from the Netherlands Cancer Registry treated with neoadjuvant chemotherapy (NACT) ± followed by interval debulking surgery (IDS).Patient KELIM values were calculated in patients with ≥ 3 CA-125 measurements during NACT. KELIM was standardized with a pre-specified cut-off and scored as unfavorable/ favorable (<1.0/≥1.0). KELIM’s prognostic value regarding radiological response, completeness of IDS, progression-free survival (PFS), and overall survival (OS) was assessed using univariate/multivariate analyses. Results: The data from 1,582 patients treated with heterogeneous chemotherapy regimens and sequences were assessable. KELIM was prognostic for radiological response and the likelihood of complete IDS after NACT (odds ratio=2.59; 95% confidence interval [CI]=2.04– 3.29). Moreover, KELIM was independently associated with PFS (hazard ratio [HR]=0.76;95% CI=0.66–0.87), and OS (HR=0.79; 95% CI=0.69–0.91). Combining KELIM with the completeness of the IDS resulted in 3 prognostic groups (satisfactory, intermediate, and poor) with significant OS differences, namely a good, intermediate, and poor survival respectively. Conclusion The value of KELIM, as a pragmatic indicator of response to chemotherapy, was maintained in a large real-life population-based cohort, highlighting its applicability in routine conditions.

Objective: The modeled CA-125 ELIMination rate constant K (KELIM) has been validated as a marker of response to chemotherapy in >12,000 patients with advanced epithelial ovarian carcinoma (EOC) treated in first-line setting enrolled in >12 clinical trials. Patient KELIM is calculable online https://www.biomarker-kinetics.org/presentation. The objective was to investigate the prognostic value of KELIM in a large real-life national cancer registry with non-selected patients. Methods: We investigated 4,025 EOC patients from the Netherlands Cancer Registry treated with neoadjuvant chemotherapy (NACT) ± followed by interval debulking surgery (IDS).Patient KELIM values were calculated in patients with ≥ 3 CA-125 measurements during NACT. KELIM was standardized with a pre-specified cut-off and scored as unfavorable/ favorable (<1.0/≥1.0). KELIM’s prognostic value regarding radiological response, completeness of IDS, progression-free survival (PFS), and overall survival (OS) was assessed using univariate/multivariate analyses. Results: The data from 1,582 patients treated with heterogeneous chemotherapy regimens and sequences were assessable. KELIM was prognostic for radiological response and the likelihood of complete IDS after NACT (odds ratio=2.59; 95% confidence interval [CI]=2.04– 3.29). Moreover, KELIM was independently associated with PFS (hazard ratio [HR]=0.76;95% CI=0.66–0.87), and OS (HR=0.79; 95% CI=0.69–0.91). Combining KELIM with the completeness of the IDS resulted in 3 prognostic groups (satisfactory, intermediate, and poor) with significant OS differences, namely a good, intermediate, and poor survival respectively. Conclusion The value of KELIM, as a pragmatic indicator of response to chemotherapy, was maintained in a large real-life population-based cohort, highlighting its applicability in routine conditions.

Objective: The modeled CA-125 ELIMination rate constant K (KELIM) has been validated as a marker of response to chemotherapy in >12,000 patients with advanced epithelial ovarian carcinoma (EOC) treated in first-line setting enrolled in >12 clinical trials. Patient KELIM is calculable online https://www.biomarker-kinetics.org/presentation. The objective was to investigate the prognostic value of KELIM in a large real-life national cancer registry with non-selected patients. Methods: We investigated 4,025 EOC patients from the Netherlands Cancer Registry treated with neoadjuvant chemotherapy (NACT) ± followed by interval debulking surgery (IDS).Patient KELIM values were calculated in patients with ≥ 3 CA-125 measurements during NACT. KELIM was standardized with a pre-specified cut-off and scored as unfavorable/ favorable (<1.0/≥1.0). KELIM’s prognostic value regarding radiological response, completeness of IDS, progression-free survival (PFS), and overall survival (OS) was assessed using univariate/multivariate analyses. Results: The data from 1,582 patients treated with heterogeneous chemotherapy regimens and sequences were assessable. KELIM was prognostic for radiological response and the likelihood of complete IDS after NACT (odds ratio=2.59; 95% confidence interval [CI]=2.04– 3.29). Moreover, KELIM was independently associated with PFS (hazard ratio [HR]=0.76;95% CI=0.66–0.87), and OS (HR=0.79; 95% CI=0.69–0.91). Combining KELIM with the completeness of the IDS resulted in 3 prognostic groups (satisfactory, intermediate, and poor) with significant OS differences, namely a good, intermediate, and poor survival respectively. Conclusion The value of KELIM, as a pragmatic indicator of response to chemotherapy, was maintained in a large real-life population-based cohort, highlighting its applicability in routine conditions.

Objective: Peritoneal metastases (PM) are a challenge in gynecological cancers, but its appearance has never been described in a population-based study. Therefore, we describe the incidence of PM and identify predictors that increase the probability of peritoneal spread. Methods: All ovarian, endometrial and cervical cancer patients diagnosed in the Netherlands between 1989 and 2015 were identified from the Netherlands Cancer Registry and stratified for PM. Crude and age-adjusted incidence over time was calculated. Independent predictors for PM were identified using uni- and multivariable analyses. Results: The 94,981 patients were diagnosed with ovarian, endometrial or cervical cancer and respectively 61%, 2% and 1% presented with PM. Predictors for PM in ovarian cancer were: age between 50 and 74 years (odds ratio [OR]=1.19; 95% confidence interval [CI]=1.08–1.32), other distant metastases (OR=1.25; 95% CI=1.10–1.41), poor differentiation grade (OR=2.00; 95% CI=1.73–2.32) and serous histology. Predictors in endometrial cancer were lymph node metastases (OR=2.32; 95% CI=1.65–3.26), other distant metastases (OR=1.38; 95% CI=1.08–1.77), high-grade tumors (OR=1.95; 95% CI=1.38–2.76) and clear cell (OR=1.49; 95% CI=1.04–2.13) or serous histology (OR=2.71; 95% CI=2.15–3.42). In cervical cancer, the risk is higher in adenocarcinoma than in squamous cell carcinoma (OR=4.92; 95% CI=3.11–7.79). Conclusion PM are frequently seen in patients with ovarian cancer. In endometrial and cervical cancer PM are rare. Histological subtype was the strongest predictive factor for PM in all 3 cancers. Better understanding of predictive factors for PM and thus the biological behavior is of paramount importance.