Matthew W. Lee

Relative survival of large cell to small cell neuroendocrine carcinoma of the uterine cervix.

This retrospective study compared clinico-pathological characteristics and survival of large cell to small cell neuroendocrine carcinomas of the uterine cervix identified in the Commission-on-Cancer's National Cancer Database from 2004 to 2022 (n = 2051). Large cell neuroendocrine carcinoma, reported in 16.3%, was more likely to be T1 classification (37.1% vs 29.5%) and have smaller cervical tumor (median size, 47 and 59 mm) but less likely to be T3 classification (15.6% vs 22.4%) and N1 classification (36.8% vs 45.1%) than small cell neuroendocrine carcinoma (all, p < .05). In propensity score inverse probability of treatment weighting, large cell neuroendocrine carcinoma had overall survival comparable to small cell neuroendocrine carcinoma (5-year rates, 33.8% vs 30.9%, hazard ratio 1.02, 95% confidence interval 0.86 to 1.20). This survival association was consistent across stage I, II, III, and IV diseases. In the secondary cohort of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program, cause-specific survival from cervical cancer was similar between large cell and small cell neuroendocrine carcinomas (5-year rates, 36.1% vs 39.1%, hazard ratio 1.25, 95% confidence interval 0.88 to 1.76). In conclusion, these data suggest that large cell neuroendocrine carcinoma represents less than 20% of neuroendocrine carcinomas of the uterine cervix, and although tumor characteristics appear to be less aggressive, oncologic outcomes are dismal and similar to small cell neuroendocrine carcinoma.

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.

Assessment of overall survival in reproductive-age patients with 2023 International Federation of Gynecology and Obstetrics stage IA1 grade 1 endometrioid endometrial cancer

This study aimed to assess the overall survival of reproductive-age patients with non-myoinvasive stage IA1 grade 1 endometrioid endometrial cancer. This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. The study population included 21,248 patients with grade 1 endometrioid endometrial cancer with the 2023 International Federation of Gynecology and Obstetrics stage IA1 (tumor with no myoinvasion; n = 6249), IA2 (tumor with inner-half myoinvasion; n = 11,113), and IB (tumor with outer-half myoinvasion; n = 3886), who had primary hysterectomy from 2010 to 2015. The main outcome measures were 5- and 10-year overall survival rates according to patient age (<40, 40-49, and ≥50 years) and cancer stage (IA1, IA2, and IB) stratifications. Stage IA1 was the most frequent sub-stage until age 45 years. The median follow-up was 8.3 (interquartile range; 6.8-10.0) years. Among patients aged <40 years, the 5- and 10-year overall survival rates were 100% and 98.7% (95% confidence interval [CI] 94.7 to 99.7) for stage IA1, 97.6% (95% Cl 94.7 to 98.9) and 94.4% (95% CI 88.1 to 97.4) for stage IA2, and 100% and 95.2% (95% CI 82.3 to 98.8) for stage IB, respectively (p-overall = .009). Among patients aged 40 to 49 years, the 5- and 10-year overall survival rates were 99.3% (95% CI 98.4 to 99.7) and 96.5% (95% CI 94.4 to 97.8) for stage IA1, 98.1% (95% Cl 96.9 to 98.8) and 94.4% (95% CI 92.1 to 96.0) for stage IA2 and 96.0% (95% CI 90.6 to 98.3) and 86.5% (95% CI 77.5 to 92.0) for stage IB, respectively (p-overall < .001). Among patients aged ≥50 years, the 5- and 10-year overall survival rates were 96.2% (95% CI 85.6 to 96.7) and 88.5% (95% CI 87.3 to 89.6) for stage IA1, 94.9% (95% CI 94.4 to 95.3) and 85.7% (95% CI 84.8 to 86.6) for stage IA2, and 92.1% (95% CI 91.2 to 93.0) and 78.0% (95% CI 76.3 to 79.6) for stage IB, respectively (p-overall < .001). This cohort study found that reproductive-age patients, particularly, adolescent and young adults, with non-myoinvasive stage IA1 grade 1 endometrioid endometrial cancer have favorable prognosis. These data may be used as the benchmark setting the foundation for future investigation on fertility-sparing options.

International Federation of Gynecology and Obstetrics 2023 stage IIIB2 endometrial cancer with pelvic peritoneal metastasis: assessment of adjuvant therapy effect on survival

The 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging schema classifies pelvic peritoneum only metastasis as stage IIIB2 disease. In this retrospective cohort study of 193 patients with FIGO 2023 stage IIIB2 endometrial cancer who underwent primary hysterectomy from 2006 to 2015 identified in the Commission-on-Cancer's National Cancer Database, systemic chemotherapy without external beam radiotherapy was the most frequent adjuvant therapy type (48.7%), followed by combination systemic chemotherapy and external beam radiotherapy (42.0%) and external beam radiotherapy without systemic chemotherapy (9.3%). After controlling for patient age, race and ethnicity, co-morbidity, and histology, combination systemic chemotherapy and external beam radiotherapy was associated with 40% reduction of all-cause mortality compared with systemic chemotherapy without external beam radiotherapy (5-year rates: 63.1% vs 45.7%, adjusted-hazard ratio 0.60, 95% confidence interval 0.40-0.92). This reduction of all-cause mortality for combination systemic chemotherapy and external beam radiotherapy compared with systemic chemotherapy without external beam radiotherapy increased to 55% among non-endometrioid histology (5-year overall survival rates: 52.0% vs 33.4%, adjusted-hazard ratio 0.45, 95% confidence interval 0.23-0.88). In conclusion, the results of this investigation suggest that, despite peritoneal disease spread, multi-modal treatment with combination systemic and local therapies may improve survival in FIGO 2023 stage IIIB2 endometrial cancer, especially in non-endometrioid histology.

Estimating high-grade serous fallopian tubal carcinoma in the era of tubal hypothesis

In the era of the serous tubal intraepithelial carcinoma hypothesis, investigation continues as to what proportions of high-grade serous tubo-ovarian carcinomas originate in the distal fallopian tube versus in the ovary. In this retrospective cohort study of 118,619 patients with high-grade serous tubo-ovarian carcinoma identified in the Commission-on-Cancer's National Cancer Database from 2004 to 2021, a diagnosis shift from high-grade serous ovarian carcinoma to high-grade serous fallopian tubal carcinoma occurred from 2004 to 2018 that the proportional distribution of high-grade serous fallopian tubal carcinoma increased 6.1-fold from 4.5% in 2004 to 27.6% in 2018 (p-trend < .001). This rapid diagnosis shift from high-grade serous ovarian carcinoma to high-grade serous fallopian tubal carcinoma reached a plateau at 2018, followed by steady proportional distribution of high-grade serous fallopian tubal carcinoma among the high-grade serous tubo-ovarian carcinomas for 4 consecutive years (27.6% in 2018 to 28.0% in 2021, p-trend = .801). The average rate of tubal carcinomas during this post-plateau period was 27.7%. In conclusion, the diagnosis shift in the primary site of high-grade serous tubo-ovarian carcinoma from the ovary to the fallopian tube may have ended in the late 2010s. After the implementation of College of American Pathologists diagnosis criteria, 1 in 3 to 4 high-grade serous tubo-ovarian carcinomas were classified as of fallopian tube origin.