Optimal adjuvant therapy for early-stage cervical cancer (ESCC) with intermediate-risk factors: A target trial emulation of GOG-0263 based on the NCDB.

5539 Background: Optimal adjuvant therapy for early-stage cervical cancer (ESCC) patients with intermediate-risk factors remains uncertain, specifically whether the addition of concurrent chemotherapy (CRT) to radiation therapy (RT) confers a survival benefit. The GOG-0263 randomized phase III trial compared adjuvant RT vs CRT in patients with FIGO Stage I-IIA cervical cancer who had undergone radical hysterectomy. We sought to emulate this trial using real-world data from the National Cancer Database (NCDB) to evaluate the benefit of CRT versus RT on overall survival (OS) in intermediate risk ESCC. Methods: Using the NCDB, we conducted a target trial emulation of GOG-0263 for patients diagnosed from 2004-2020 with pathologic T1-T2a2 N0 M0 cervical cancer who underwent radical hysterectomy. Eligible patients had intermediate risk factors, defined as tumor size ≥ 2 cm with lymph-vascular invasion (LVI) or tumor size ≥ 4 cm. OS, defined from the date of definitive surgery, was compared between patients who received adjuvant RT alone versus adjuvant CRT. Kaplan-Meier methods and Cox proportional hazards models, along with an inverse probability treatment weighting (IPTW) schema, were implemented to assess the treatment effect. Subgroup and sensitivity analyses were conducted to identify specific disease characteristics that maximize the benefit of CRT and to evaluate the impact of potential immortal time bias. Results: Among 1,171 eligible patients, 537 (45.9%) received CRT and 634 (54.1%) received RT alone, with median ages of 44 years (IQR: 36-55) and 46 years (IQR: 39-57) and median follow-up times of 7.5 years (IQR: 4.8-10.5) and 6.6 years (IQR: 4.2-9.9), respectively. There was no significant difference in OS between CRT and RT in unadjusted (HR 0.94; 95% CI, 0.71–1.25), adjusted (HR 0.89; 95% CI, 0.67–1.18), or weighted analyses (HR 0.88; 95% CI, 0.66–1.17). Five-year OS was similar between groups (86.4% vs. 86.6%). No subgroup demonstrated a significant survival benefit from CRT. Conclusions: In this real-world emulation of GOG-0263, addition of concurrent chemotherapy to adjuvant RT was not associated with improved OS for intermediate-risk ESCC. These findings support emerging trial evidence and supplement the conclusion of the GOG-0263 trial. The indication of this study suggests that chemotherapy may be safely omitted in this population under a doctor’s careful discretion, thereby potentially reducing treatment-related toxicity and preserving patients’ quality of life without compromising survival. These findings highlight the need for improved risk stratification and patient selection to identify those most likely to benefit from treatment intensification with concurrent chemotherapy in addition to adjuvant RT.