A population-based cohort study found no significant overall survival (OS) benefit from the addition of concomitant chemotherapy to radiotherapy for patients with intermediate-risk cervical cancer. Chemotherapy was more likely to be administered to patients with larger tumour size and non-squamous cell histology.
Future research should aim to establish precise criteria for identifying patients who may truly benefit from adjuvant chemotherapy according to Dr. Núria Agustí of the Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center in Houston, TX, US and colleagues, who published the findings from the cohort study conducted at Commission on Cancer accredited centres across the US, using prospectively collected data from the National Cancer Database, on 13 March 2025 in the JAMA Oncology.
The standard treatment for early-stage cervical cancer (2018 International Federation of Gynecology and Obstetrics stage IA1 to IIA1) involves hysterectomy and surgical lymph node assessment. After surgery, adjuvant treatment is guided by risk factors for recurrence, such as lymphovascular space invasion, stromal invasion, and tumour size. Most guidelines recommend radiotherapy for patients with intermediate-risk factors that meet Sedlis criteria. While concurrent chemoradiotherapy is effective in high-risk disease (patients with positive lymph nodes, parametrial extension, and/or positive margins), its role in patients with intermediate-risk patients remains unclear.
The authors wrote in the background that retrospective studies assessing the benefit of chemotherapy in the intermediate-risk population have shown conflicting results. A recent systematic review found higher recurrence-free survival (RFS) in the chemoradiotherapy group compared with radiotherapy alone. However, included studies had substantial limitations. Thus, it is difficult to determine the true benefit of chemoradiotherapy for intermediate-risk patients.
Furthermore, in clinical practice, there is a substantial gap in knowledge about the factors associated with the use of chemotherapy for these patients. This contributes to variability in treatment approaches, with up to 60% of patients still receiving chemoradiotherapy despite the absence of a clear benefit.
Given this variability and the potential for overtreatment, de-escalation of adjuvant therapies, including the omission of concurrent chemotherapy, may optimise treatment outcomes and reduce patient morbidity. This study aimed to evaluate the oncological outcomes of adjuvant chemoradiotherapy in patients with intermediate-risk cervical cancer, as well as examine factors associated with variability in treatment recommendations following radical hysterectomy for early-stage cervical cancer. The primary outcome was time to death or last follow-up. Secondary objectives included identifying clinical factors associated with the use of chemoradiotherapy.
This study focused on patients with a diagnosis of 2018 International Federation of Gynecology and Obstetrics stage IB cervical carcinoma (squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma) of intermediate risk who were undergoing adjuvant radiotherapy treatment after radical hysterectomy from January 2010 through December 2020. Missing variables were multiple imputed, and propensity score matching 1:1 was performed to balance baseline characteristics. A Kaplan-Meier analysis and proportional hazard models were used to compare the hazard of death between the groups.
A total of 1116 patients (mean age 47 years) were identified, of whom 486 (43.5%) received concurrent chemoradiotherapy. Chemotherapy was administered more frequently among those with adenocarcinoma or adenosquamous histology compared with squamous cell carcinoma (risk ratio [RR] 1.26; 95% confidence interval [CI] 1.10-1.44) and those with tumours larger than 4 cm compared with tumours measuring 2-4 cm (RR 1.31; 95% CI 1.14-1.51).
Propensity score matching yielded a cohort of 868 patients with balanced covariates. Patients who received chemoradiotherapy had similar OS (5-year survival 87%) as those who received radiotherapy alone (5-year survival 87%; hazard ratio 0.85; 95% CI 0.59-1.23; p = 0.38). There were no significant differences in survival associated with chemotherapy receipt among subgroups defined by tumour size, histology, presence of lymphovascular space invasion, surgical approach, or receipt of adjuvant brachytherapy.
De-escalating adjuvant therapies, such as reducing concurrent chemotherapy, may be associated with non-inferior outcomes while minimising patient morbidity. Understanding the trends and factors associated with the prescription of chemotherapy is important for improving clinical practice.
The authors commented that the results of the GOG 263 study in patients with intermediate-risk cervical cancer are awaited. The study is recruiting 534 patients to compare RFS between chemoradiotherapy and radiotherapy alone in patients with stage I to IIA cervical cancer with intermediate-risk factors following radical hysterectomy. These results are expected to provide a guidance on the role of chemoradiotherapy in this population.
However, the sample size of this study may not be sufficient to provide conclusive evidence for OS. Given this limitation and the likelihood that future prospective trials may not reach the necessary sample size, large national databases, like the one used in this study, may become the most generalisable clinical data source of evidence.
Reference
Agustí N, Viveros-Carreño D, Wu C-F, et al. Adjuvant Chemoradiotherapy vs Radiotherapy Alone for Patients With Intermediate-Risk Cervical Cancer. JAMA Oncology; Published online 13 March 2025. doi:10.1001/jamaoncol.2025.0146