Postoperative management of FIGO 2018 stage IIA1 cervical squamous cell carcinoma with only one intermediate-risk factor: Is radiotherapy needed?

OBJECTIVE: To investigate whether postoperative radiotherapy is required for FIGO 2018 stage IIA1 cervical squamous cell carcinoma patients with only one intermediate-risk factor. METHODS: This was a multicenter retrospective study. The selected patients were classified into no postoperative adjuvant therapy and postoperative radiotherapy groups. The 5-year overall survival (OS) and disease-free survival (DFS) rates were compared. RESULTS: In total, 159 patients with no postoperative adjuvant therapy and 179 patients with postoperative radiotherapy were included, with the former group showing a lower OS but no difference in DFS. No postoperative adjuvant therapy was an independent risk factor for patient mortality. Patients were also stratified by tumor diameter: 56 patients had a tumor diameter ≤2 cm, comprising 32 patients with postoperative radiotherapy and 24 patients without (no between-group difference was found); 272 patients had a tumor diameter >2 cm, comprising 122 patients with postoperative radiotherapy and 150 patients without, with the former group showing a higher OS, and no postoperative adjuvant therapy was an independent risk factor for patient mortality. CONCLUSION: For FIGO 2018 stage IIA1 cervical squamous cell carcinoma patients with only one intermediate-risk factor and a tumor diameter >2 cm, postoperative radiotherapy is likely beneficial to improve prognosis.

Analysis of clinical efficacy of radiotherapy alone and concurrent chemoradiotherapy in cervical cancer patients with intermediate risk factors after surgery / 中华放射肿瘤学杂志

Objective:To retrospectively analyze the differences of survival, recurrence, acute side effects and prognostic factors between early stage (stage ⅠB-ⅡA) cervical cancer patients with intermediate risk factors receiving postoperative concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone.Methods:Clinical data of 211 patients with intermediate risk factors after early stage cervical cancer surgery admitted to Department of Radiation Oncology of General Hospital of Ningxia Medical University from January 2016 to December 2018, were retrospectively analyzed. Among them, 91 cases were assigned in the RT group and 120 cases in CCRT group. The 3- and 5-year overall survival (OS), progression-free survival (PFS), recurrence and acute side effects were compared between two groups by Chi-square test. Univariate analysis of OS and PFS was performed by Kaplan-Meier method and log-rank test was performed. Multivariate prognostic analysis was conducted by using Cox model. Results:The 3- and 5-year OS of 211 patients were 95.0% and 93.8%, respectively. The 3- and 5-year PFS were 86.8% and 83.2%, respectively. The OS of CCRT and RT group were 93.9%, 96.5% (3-year), 91.8%, 96.5% (5-year) respectively ( χ2=1.763, P=0.184), and the PFS were 84.4%, 89.9% (3-year), 79.3%, 88.3% (5-year) ( χ2=2.619 ,P=0.106), with no difference between the two groups. The total recurrence rate was 15.64%, and there was no significant difference in the recurrence rate and recurrence area between two groups ( χ2=2.623 ,P=0.105; χ2=6.745 ,P=0.080). Locoregional recurrence and lung metastasis were the main patterns of failure. Multivariate prognostic analysis showed that pathological type might significantly affect the OS ( χ2=3.849, P=0.05), and depth of invasion significantly affected the PFS ( χ2=4.095, P=0.043). The incidence of acute gastrointestinal side effect and bone marrow suppression in the CCRT group was significantly higher than that in the RT group ( χ2=56.425, 27.833; both P<0.001). Conclusions:Patients with intermediate risk factors after early cervical cancer surgery obtain high efficacy after radiotherapy. The main patterns of failure are locoregional recurrence and lung metastasis. The pathological type may be an independent prognostic factor of OS and the depth of invasion is an independent prognostic factor of PFS. Compared with RT, CCRT increases the risk of acute gastrointestinal side effects and myelosuppression, which can be tolerated. There is no significant difference in the clinical efficacy between RT and CCRT, which remains to be validated by large sample size studies.

Risk Stratification of Early-Stage Cervical Cancer with Intermediate-Risk Factors: Model Development and Validation Based on Machine Learning Algorithm.

BACKGROUND: Adjuvant therapy for patients with cervical cancer (CC) with intermediate-risk factors remains controversial. The objectives of the present study are to assess the prognoses of patients with early-stage CC with pathological intermediate-risk factors and to provide a reference for adjuvant therapy choice. MATERIALS AND METHODS: This retrospective study included 481 patients with stage IB-IIA CC. Cox proportional hazards regression analysis, machine learning (ML) algorithms, Kaplan-Meier analysis, and the area under the receiver operating characteristic curve (AUC) were used to develop and validate prediction models for disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 35 (7.3%) patients experienced recurrence, and 20 (4.2%) patients died. Two prediction models were built for DFS and OS using clinical information, including age, lymphovascular space invasion, stromal invasion, tumor size, and adjuvant treatment. Patients were divided into high-risk or low-risk groups according to the risk score cutoff value. The Kaplan-Meier analysis showed significant differences in DFS (p = .001) and OS (p = .011) between the two risk groups. In the traditional Sedlis criteria groups, there were no significant differences in DFS or OS (p > .05). In the ML-based validation, the best AUCs of DFS at 2 and 5 years were 0.69/0.69, and the best AUCs of OS at 2 and 5 years were 0.88/0.63. CONCLUSION: Two prognostic assessment models were successfully established, and risk grouping stratified the prognostic risk of patients with CC with pathological intermediate-risk factors. Evaluation of long-term survival will be needed to corroborate these findings. IMPLICATIONS FOR PRACTICE: The Sedlis criteria are intermediate-risk factors used to guide postoperative adjuvant treatment in patients with cervical cancer. However, for patients meeting the Sedlis criteria, the choice of adjuvant therapy remains controversial. This study developed two prognostic models based on pathological intermediate-risk factors. According to the risk score obtained by the prediction model, patients can be further divided into groups with high or low risk of recurrence and death. The prognostic models developed in this study can be used in clinical practice to stratify prognostic risk and provide more individualized adjuvant therapy choices to patients with early-stage cervical cancer.

Cervical Cancer with Intermediate Risk Factors: Is there a Role for Adjuvant Radiotherapy? A Systematic Review and a Meta-Analysis.

BACKGROUND: The yield of adjuvant radiotherapy in cervical cancer patients with intermediate risk factors is controversial. The objective of our meta-analysis was to shed light on this important issue. MATERIAL AND METHODS: Search was conducted in several databases. By independent screening of titles and abstracts, 2 investigators selected original researches examining the effect of adjuvant radiation treatment on overall survival and progression-free survival in cervical cancer patients with intermediate risk factors. RESULTS: Of the 5 articles included, a total of 591 patients with intermediate risk factors were encompassed. Statistical significance was noted in favor of radiation therapy in a subgroup of patients with 2 or more intermediate factors in terms of recurrence (OR 0.46 [95% CI 0.28-0.74, p = 0.001]) and overall survival (OR 1.86 [95% CI 1.03-3.36, p = 0.04]). After adding patients with one risk factor, radiation exerted a non-significant effect on recurrence rate, overall survival, disease-free survival, and 5-year cancer-specific survival, while increasing the rate of gastrointestinal side effects (2.4 vs. 0%, p = 0.0156). CONCLUSIONS: Adjuvant radiation therapy decreases the risk for recurrence and increases the overall survival in patients with 2 intermediate risk factors. These benefits were not shown after adding patients with one risk factor.

Lymphadenectomy alone is a feasible option in managing incidentally-detected early-stage cervical cancer after simple hysterectomy without intermediate-risk factors: An application of the concept of less radical surgery.

AIM: To assess the feasibility of less radical surgery in patients with incidentally-detected cervical cancer at simple hysterectomy. PATIENTS AND METHODS: High-risk factors (HFs) were evaluated in 104 patients who underwent radical hysterectomy and lymphadenectomy for the treatment of stage IA1-IB1 cervical cancer according to intermediate-risk factors (IFs). RESULTS: Thirty-three patients without IFs had no HFs. As the number of IFs increased, the number of HFs increased (p=0.009). Multivariate analysis revealed that lymph node metastasis was the only independent risk factor for parametrial involvement (hazard ratio, 31.3; 95% confidence interval, 1.6-599.4; p=0.022). An absence of IFs was associated with a longer progression-free survival than the presence of IFs in the subgroup analysis of favorable histologies (p=0.044). CONCLUSION: HFs could be excluded in stage IA1-IB1 cervical cancer without IFs. Omitting parametrectomy seems a feasible option for selected patients with incidentally-detected early-stage cervical cancer at simple hysterectomy, without IFs.