Identifying the possible candidate population for adjuvant radiotherapy de-escalation for intermediate-risk cervical cancer.

Objective: To explore whether there is a possible candidate population for treatment de-escalation with active surveillance without adjuvant radiotherapy for patients with stage IB cervical cancer meeting the intermediate-risk criteria.

Methods: This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database in the United States. The study population included 1133 patients with node-negative, parametria-free, surgical margin-uninvolved, stage IB intermediate-risk cervical cancer (tumor size 2-4 cm with lymphovascular space invasion, or tumor size of >4 cm regardless of lymphovascular space invasion) who had primary radical hysterectomy and lymph node evaluation from 2010 to 2022. Exposure was adjuvant radiotherapy status: external beam radiotherapy with or without chemotherapy (n = 642) or active surveillance without radiotherapy (n = 491). The main outcome measure was overall survival, assessed in a propensity score inverse probability of treatment weighting cohort.

Results: At the whole-cohort level, hazard ratio (HR) for all-cause mortality comparing adjuvant radiotherapy de-escalation to adjuvant radiotherapy was 1.31 (95% confidence interval [CI] 0.92 to 1.86, p = .13). When stratified by histology type, adjuvant radiotherapy de-escalation was associated with increased all-cause mortality risk in squamous cell carcinoma (HR 1.55, 95% CI 1.02 to 2.34, p = .038) but not in adenocarcinoma or adenosquamous carcinoma (HR, 0.90; 95% CI 0.46 to 1.75, p = .75). When stratified by tumor differentiation, adjuvant radiotherapy de-escalation was associated with increased all-cause mortality risk in poorly-differentiated tumors (HR, 2.11; 95% CI 1.29 to 3.42, p =.003) but not in well- to moderately-differentiated tumors (HR, 0.83; 95% CI 0.50 to 1.37, p = .47).

Conclusion: The results of this cohort study in the United States suggest that overall survival benefits of adjuvant radiotherapy for study-defined intermediate-risk stage IB cervical cancer may vary based on histology type and tumor differentiation. Specifically, patients with squamous cell carcinoma or poorly-differentiated tumors benefited from receiving adjuvant radiotherapy, while those with adenocarcinoma/adenosquamous carcinoma or well- to moderately-differentiated tumors did not. Whether there may be candidates for treatment de-escalation in intermediate-risk cervical cancer warrants further investigation with a prospective design.