Angelina E. Lim

Clinico-pathological characteristics and survival outcome associated with uterine leiomyosarcoma variants: epithelioid and myxoid types

Epithelioid and myxoid types represent uterine leiomyosarcoma variants, and their clinico-pathologic characteristics and survival outcomes have been under-studied because of their rarity. The objective of this study was to assess clinico-pathologic characteristics and survival associated with uterine leiomyosarcoma variants. This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. The study population included 7410 patients with uterine leiomyosarcoma, including conventional, epithelioid, and myxoid types, who had primary hysterectomy from 2010 to 2022. Demographic characteristics were assessed using descriptive analysis; overall survival was assessed using a multivariable Cox proportional hazards regression model. Epithelioid and myxoid types were reported in 478 (6.5%) and 327 (4.4%) patients, respectively. The proportion of the epithelioid variant increased from 5.5% in 2010-2014 to 7.8% in 2019-2022 (p = .005). The epithelioid type was associated with higher rates of lympho-vascular space invasion (33.1% vs 22.0%-23.7%) and nodal metastasis (6.9% vs 3.4%-3.6%), whereas the myxoid type was associated with a higher rate of stage I disease (64.5% vs 56.1%-58.7%) (all, p < .05). Compared with the conventional type, the epithelioid type was associated with improved overall survival (adjusted hazard ratio [aHR] 0.87, 95% confidence interval [CI] 0.75 to 0.99) including stage I (aHR 0.75, 95%CI 0.60 to 0.93) and stage III (aHR 0.59, 95% CI 0.39 to 0.91) disease; the myxoid type was also associated with improved overall survival (aHR 0.68, 95%CI 0.57 to 0.82) including stage I (aHR 0.62, 95% CI 0.47 to 0.82) and stage IV (aHR 0.60, 95% CI 0.41 to 0.88) disease. Across all three types, larger tumor size, lympho-vascular invasion, and higher stage were associated with decreased overall survival, with the survival impact of larger tumor size being more prominent in variants. For stage II to IV epithelioid type, adjuvant chemotherapy was associated with improved overall survival (aHR 0.43, 95% CI 0.29 to 0.64). The results of this cohort study suggest that uterine leiomyosarcoma variants (epithelioid and myxoid) exhibit distinct histopathologic characteristics and survival compared with the conventional type. These data also endorse the importance of accurate diagnosis, research inclusion criteria, and development of collaborative networks.

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

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. 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. 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). 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.