Optimal use of radiotherapy in the definitive treatment of non-bulky IB-IIA cervical cancer: A population-based long-term survival analysis.

Young‐Jun Lim ,Han Na Lee

doi:10.1371/journal.pone.0253649

Abstract

PurposeAlthough current clinical guidelines recommend surgery or radiotherapy for non-bulky IB-IIA cervical cancer, clinical data supporting the curative role of radiotherapy in the early-stage disease are insufficient. We evaluated the prognostic implications of definitive radiotherapy and determined its optimal use in clinical practice.MethodsPatients with non-bulky (<4 cm) IB-IIA cervical cancer who underwent hysterectomy or primary radiotherapy between 1988 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Based on the use of brachytherapy and/or chemotherapy, the primary radiotherapy group was classified into three cohorts: hysterectomy vs. radiotherapy overall, with/without brachytherapy and/or chemotherapy (cohort A); radiotherapy and brachytherapy with/without chemotherapy (patients with external beam radiation alone were excluded, cohort B); radiotherapy with brachytherapy and chemotherapy (patients who did not receive chemotherapy were additionally excluded, cohort C). Disease-specific survival (DSS) after hysterectomy was compared to that after primary radiotherapy in each cohort.ResultsAmong the 9,391 initially identified patients, 1,762, 1,244, and 750 patients were classified into cohorts A, B, and C, respectively, after propensity score matching. In cohort A, DSS after primary radiotherapy was inferior to that after hysterectomy (P = 0.001). In cohort B, a trend toward differential survival in favor of hysterectomy was observed with marginal significance (P = 0.061). However, in cohort C, DSS after primary radiotherapy was not significantly different to that after hysterectomy (P = 0.127). According to hazard rate function plots, patients receiving external beam radiation alone had an increased short-term risk of disease-specific mortality, whereas patients without evidence of chemotherapy had a distinct late risk surge at approximately 15 years of follow-up.ConclusionOptimizing radiotherapy methods with brachytherapy and the use of chemotherapy should be considered for the long-term curative efficacy of primary radiotherapy for non-bulky IB-IIA cervical cancer. Further studies are warranted to corroborate our results.

Highlights

According to the Global Cancer Observatory 2020 report, cervical cancer is the fourth most commonly diagnosed cancer in women worldwide [1]
Optimizing radiotherapy methods with brachytherapy and the use of chemotherapy should be considered for the long-term curative efficacy of primary radiotherapy for non-bulky IBIIA cervical cancer
The eligibility criteria were as follows: 1) age 18 years; 2) year of diagnosis between 1988 and 2015; 3) no distant metastasis at initial diagnosis; 4) Stage IB1, IB2, or IIA1 tumors according to the revised staging system of the International Federation of Gynecology and Obstetrics (FIGO); 5) primary tumor size 4 cm; 6) histology of squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma; 7) cancer-directed treatment with surgery or primary RT; 8) no previous history of a cancer diagnosis

Summary

Introduction

According to the Global Cancer Observatory 2020 report, cervical cancer is the fourth most commonly diagnosed cancer in women worldwide [1]. The incidence rates of cervical cancer have declined, the malignancy remains a challenging problem in lower-middle-income countries [2]. In the updated cancer statistics in the United States, an estimated 13,800 new cases will be diagnosed with carcinoma of the uterine cervix, while 4,290 patients will die of this malignancy [3]. Localized early-stage disease accounts for approximately 44% of cervical cancer cases, and a 5-year survival rate of 92% has been reported in a subset of patients [4]. The National Comprehensive Cancer Network guidelines recommend choosing between radical hysterectomy and primary radiotherapy (RT) for non-bulky IB1, IB2, and IIA1 tumors [6]. Owing to insufficient high-level evidence, it is uncertain whether these findings are applicable to clinical practice

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