Neoadjuvant chemotherapy for advanced stage endometrial cancer: A systematic review.

OBJECTIVE: While primary cytoreductive surgery (PCS) is considered the standard of care for women who present with stage IV endometrial cancer, neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) has emerged as an alternative treatment strategy. We summarized the literature and compared outcomes of PCS compared to NACT and ICS. METHODS: We conducted a systematic search on PubMed, Embase, Web of Science, and Scopus for articles published from January 1, 1990 to December 31, 2020. Key search terms included multiple descriptors of advanced disease status in combination with "endometrial cancer" and "neoadjuvant chemotherapy". Our review included studies that examined survival and surgical outcomes of patients with stage III or IV endometrial cancer treated with neoadjuvant chemotherapy followed by interval cytoreductive surgery versus those who received primary cytoreductive surgery. We excluded studies examining only patients with leiomyosarcomas, carcinosarcomas, and stromal sarcomas due to the biologic heterogeneity of these malignancies. RESULTS: The nine included studies encompassed 5,844 patients, of which 1,317 (22.5%) received NACT and 4,527 received PCS (77.5%). With the exception of a single study, all were retrospective observational studies or case series. Use of NACT in patients with stage IV EC increased from 16.0% in 2010 to 23.9% in 2015. Five studies analyzed median overall survival and all but one reported no significant difference between NACT + ICS vs. PCS. Optimal cytoreduction (<1 cm of residual disease) rates were similar across both treatment groups in three separate analyses, however pooled data suggest improved rates of optimal cytoreduction for NACT + ICS vs. PCS patients (81.9% vs. 51.5% respectively). Patients receiving NACT experienced significantly shorter hospital admissions and lower operative times compared to PCS counterparts. CONCLUSIONS: NACT followed by ICS reduces perioperative morbidity while offering similar overall survival.

Primary cytoreductive surgery for advanced stage endometrial cancer: a systematic review and meta-analysis.

OBJECTIVE: Endometrial cancer uncommonly presents at an advanced stage and little prospective evidence exists to guide the management thereof. We aimed to summarize the evidence about primary cytoreductive surgery in the treatment of advanced stage endometrial cancer. DATA SOURCES: MEDLINE, Embase, and Scopus databases were searched from inception to September 11, 2020, using search terms representing the themes "endometrial cancer," "advanced stage," and "primary cytoreductive surgery." STUDY ELIGIBILITY CRITERIA: We included full-text, English reports that included ≥10 patients undergoing primary cytoreductive surgery for advanced stage endometrial cancer and that reported on the outcomes of primary cytoreductive surgery and survival rates based on the residual disease burden. METHODS: Two reviewers independently screened the studies and with disagreements between the reviewers resolved by a third reviewer. Data were extracted using a standardized form. The percentage of cases reaching maximal (no gross residual disease) and optimal (<1 cm or <2 cm residual disease) cytoreduction were assessed by summing binomials proportions, and the association with survival was assessed using an inverse variance-weighted meta-analysis of logarithmic hazard ratios. RESULTS: From 1219 unique records identified, 34 studies were selected for inclusion. Studies consisted of single or multi-institutional cohorts of patients collected over a period of 6 to 24 years and included various mixes of histologies (endometrioid, serous, clear cell, and carcinosarcoma) and disease stages (III or IV). In a meta-analysis of the extent of residual disease after primary cytoreductive surgery, we found that 52.1% of cases reached no gross residual disease status (n=18 studies; 1329 patients) and 75% reached <1 cm residual disease status (n=27 studies; 2343 patients). The proportion of cytoreduction for both thresholds was lower for studies of stage IV vs stage III to IV disease (41.4% vs 69.8% for no gross residual disease; 63.2% vs 82.2% for <1 cm residual disease) but did not vary notably by histology. In a meta-analysis of the reported hazard ratios, submaximal (any gross residual disease vs no gross residual disease) and suboptimal (≥1 cm vs <1 cm) cytoreduction thresholds were associated with worse progression-free survival (submaximal hazard ratio, 2.16; 95% confidence interval, 1.45-3.21; I2=68%; suboptimal hazard ratio, 2.55; 95% confidence interval, 1.93-3.37; I2=63%) and overall survival rates (submaximal hazard ratio, 2.57; 95% confidence interval, 2.13-3.10; I2=1%; suboptimal hazard ratio, 2.62; 95% confidence interval, 2.20-3.11; I2=15%). Sensitivity analyses limited to high-quality studies demonstrated consistent results. CONCLUSION: Among cases of advanced stage endometrial cancer undergoing primary cytoreductive surgery, a significant proportion of patients are left with residual disease, which is associated with worse survival outcomes. Further investigations about the roles of neoadjuvant chemotherapy and primary cytoreductive surgery in prospective trials is warranted in this population.

Impact of quality of care on racial disparities in survival for endometrial cancer.

BACKGROUND: Black women experience poorer survival compared with white women across all endometrial cancer stages and histologies. The incidence of endometrial cancer is 30% lower in black women compared with white women, yet mortality is 80% higher in black women. Differences in adherence to evidence-based guidelines have been proposed to be major contributors to this disparity. OBJECTIVES: We examined whether adherence to evidence-based treatment recommendations for endometrial cancer could mitigate survival disparities between black and white women. STUDY DESIGN: The National Cancer Database was used to identify women with endometrial cancer treated from 2004 through 2016. We established 5 evidence-based quality metrics based on review of primary literature and accepted guidelines: surgical treatment within 6 weeks of diagnosis (Q1), use of minimally invasive surgery (stage I-IIIC; Q2), pelvic nodal assessment (high-risk tumors; Q3), adjuvant radiation (high intermediate risk; Q4), and systemic chemotherapy (stage III-IV; Q5). The rates of 30 and 90 day mortality and 5 year survival were compared between black and white women. To determine the influence of quality on outcomes, we compared outcomes among perfectly adherent black and white women with stage I and III endometrial cancer. RESULTS: We identified 310,208 women including 35,035 (11.3%) black women and 275,173 (88.3%) white women. Black women were less likely than white women to receive Q1 (65.8 vs 75.6%), Q2 (58.5 vs 72.9%), Q3 (71.3 vs 74.2%), and Q5 (72.7 vs 73.2%) (P < .05 for all). Adherence to each quality metrics was associated with improved survival. Among women with stage I disease, perfect adherence to the relative quality metrics was seen in 53.1% of white and 41.5% of black women. Among perfectly adherent stage I patients, outcomes in black women improved relative to unselected black women; however, they still experienced higher risk of 30 day (adjusted relative risk, 2.25; 95% confidence interval, 1.30-3.90), 90 day (adjusted relative risk, 1.84; 95% confidence interval, 1.23-2.76), and 5 year mortality (adjusted hazard ratio, 1.42; 95% confidence interval, 1.26-1.59) compared with similar white women. Among women with stage III tumors, perfect adherence to the relative quality metrics was seen in 56.6% of white and 44.1% of black women. Perfectly adherent black women with stage III disease had improved outcomes but remained at increased risk of 30 day (adjusted relative risk, 1.86; 95% confidence interval, 1.01-3.44) and 5 year mortality (adjusted hazard ratio, 1.35; 95% confidence interval, 1.22-1.50) compared with white women. CONCLUSION: Black women are less likely than white women with endometrial cancer to receive evidence-based care. However, receipt of evidence-based care mitigates but does not eliminate racial disparities in outcomes and black women remain at greater risk of death from endometrial cancer.