Gynecologic cancer care in the first year of the COVID-19 pandemic.

OBJECTIVE: To analyze the impact of the early COVID-19 pandemic on the diagnosis and initiation of treatment for patients with gynecologic cancer. METHODS: Patients diagnosed with gynecologic cancer in the National Cancer Database during 2017-2020 were included. For the first aim, incidence rate ratios were calculated to compare gynecologic cancer diagnosis in the first year of the COVID-19 pandemic to the three years prior, and factors associated with a reduction in diagnosis were identified. For the second aim, patients who experienced an 8-week delay in cancer treatment were compared to those who did not. Multivariate logistic regression was used to identify factors associated with treatment delay. Propensity score analysis was utilized to compare the rate of cancer treatment delay in patients who were diagnosed with COVID-19 to those who were not. RESULTS: The incidence rate ratio of being diagnosed with gynecologic cancer in 2020 versus 2017-2019 was 0.90 (95%CI 0.90-0.91). Factors associated with increased risk of missed or delayed diagnosis in 2020 included cervical cancer, earlier cancer stage, younger age, lower levels of medical comorbidity, and lack of health insurance. In 2020, factors associated with treatment delay included COVID-19 diagnosis (aOR 1.50, 95%CI 1.35-1.67), in addition to race and ethnicity, insurance type, comorbidity, cancer stage, and primary site. The risk of treatment delay remained significantly elevated in patients diagnosed with COVID-19 after propensity-score matching. CONCLUSIONS: Gynecologic cancer diagnosis and timely provision of care were negatively impacted during the first year of the COVID-19 pandemic, with certain subgroups at elevated risk.

Home monitoring for clinically suspected obstructive sleep apnea in pregnancy.

STUDY OBJECTIVES: To determine if a home sleep apnea test (HSAT) using a type III portable monitor (PM), Nox-T3 (Nox Medical, Inc., Reykjavik, Iceland), detects obstructive sleep apnea in pregnant women. METHODS: Ninety-two pregnant women (34.5 ± 4.3 years; gestational age 25.4 ± 8.9 weeks; body mass index 29.9 ± 4.7 kg/m2) with suspected obstructive sleep apnea underwent HSAT with the Nox-T3 PM followed by overnight polysomnography (PSG) and PM recording simultaneously in the laboratory within 1 week. PMs were scored automatically and manually using a 3% criteria and compared with PSGs scored by following guidelines. RESULTS: Apnea-hypopnea indexes were 8.56 ± 10.42, 8.19 ± 13.79, and 8.71 ± 14.19 events/h on HSAT, in-laboratory PM recording, and PSG (P = .955), respectively. Bland-Altman analysis of the apnea-hypopnea index on PSG vs HSAT showed a mean difference (95% confidence interval) of -0.15 (-1.83, 1.53); limits of agreement (± 2 SD) were -16.26 to 16.56 events/h. Based on a threshold apnea-hypopnea index ≥ 5 events/h, HSAT had 91% sensitivity, 85% specificity, 84% positive-predictive value, and 92% negative-predictive value compared with PSG. When comparing the simultaneous recordings, closer agreement was observed. Automated vs manual analysis of PM showed no significant difference. CONCLUSIONS: A type III PM had an acceptable failure rate and high diagnostic performance operating as a reasonable alternative for in-laboratory PSG in pregnant women. CITATION: Wang J, Zhang C, Xu L, et al. Home monitoring for clinically suspected obstructive sleep apnea in pregnancy. J Clin Sleep Med. 2023;19(11):1951-1960.

Effect of continuous post-operative lidocaine infusion in an enhanced recovery program on opioid use following gynecologic oncology surgery.

OBJECTIVE: To determine the effectiveness of implementing an Enhanced Recovery After Surgery (ERAS) program, including continuous intraoperative and postoperative intravenous (IV) lidocaine infusion, on perioperative opioid use. METHODS: This was a single-institution retrospective pre- post- cohort study. Consecutive patients undergoing planned laparotomy for known or potential gynecologic malignancy were identified after implementation of an ERAS program and compared to a historical cohort. Opioid use was calculated as morphine milligram equivalents (MMEs). Cohorts were compared using bivariate tests. RESULTS: A total of 215 patients were included in the final analysis, 101 patients received surgery before ERAS implementation and 114 received surgery after. A reduction in total opioid use was observed in ERAS patients compared with historical controls (MME 26.5 [9.6-60.8] versus 194.5 [123.8-266.8], p<0.001). Length of stay (LOS) was reduced by 25% in the ERAS cohort (median 3 days, range 2-26, versus 4 days, range 2-18; p<0.001). Within the ERAS cohort, 64.9% received IV lidocaine for the planned 48 hours, and 5.6% had the infusion discontinued early. Within the ERAS cohort, patients who received IV lidocaine infusion used less opioids compared to those who did not (median 16.9, range 5.6-55.1, versus 46.2, range 23.2-76.1; p<0.002). CONCLUSION: An ERAS program including a continuous IV lidocaine infusion as the opioid-sparing analgesic strategy was noted to be safe and effective, leading to decreased opioid consumption and LOS compared with a historic cohort. Additionally, lidocaine infusion was noted to decrease opioid consumption even among patients already receiving other ERAS interventions.

Feasibility and Prediction of Adverse Events in a Postoperative Monitoring Program of Patient-Reported Outcomes and a Wearable Device Among Gynecologic Oncology Patients.

PURPOSE: The objective of this study was to test the feasibility of implementing a postoperative monitoring program for women with gynecologic cancers composed of patient-reported outcomes (PROs) and a wearable activity monitor. METHODS: We prospectively enrolled patients undergoing gynecologic cancer surgery to this single-arm study. Enrolled patients completed PROs (Patient-Reported Outcomes Measurement Information System physical function, sleep disturbance, anxiety, fatigue, and pain intensity) at baseline and one-week intervals for 4 weeks. They also wore a wearable accelerometer device that measured steps, heart rate, and intensity of physical activity. The primary outcome was feasibility. The secondary outcome was prediction of unscheduled contacts with the health care system on a given postoperative day. RESULTS: We enrolled 34 women. Three patients were unevaluable. The mean age was 58 years. The mean body mass index was 31 kg/m2; 17 patients were White (54.8%), 12 patients were Black (38.7%), and two patients (6.5%) were Asian. The overall wear time was 83.8%, and patients responded to 80.4% of the PRO instruments. Twenty-two patients (71%) had an unscheduled contact with the health care system postoperatively (median 1.5, 0.0-8.0). The day of an unscheduled health care utilization event was predicted with acceptable discrimination (area under the receiver operating characteristic curve 0.75; 95% CI, 0.67 to 0.81). PROs of fatigue and physical function were most predictive followed by wearable device outputs of lightly active minutes and average daily heart rate. CONCLUSION: Implementation of a postoperative monitoring program of patient-reported outcomes and a wearable device was feasible. The specific day of an unscheduled contact with the health care system was predicted with acceptable discrimination.

Successful management of stage IV epithelioid trophoblastic tumor using multimodality treatment: A case report.

Epithelioid trophoblastic tumor (ETT) is a rare variant of gestational trophoblastic neoplasia (GTN) that develops from chorionic-type intermediate trophoblast, is more resistant to chemotherapy than choriocarcinoma, and presents with metastatic disease in 25-35% of cases. We report a case of a 32-year-old who presented one week postpartum with severe abdominal pain and was found to have profound anemia and an elevated hCG level. CT scans and MRI revealed bleeding from hepatic masses, multiple hemorrhagic pulmonary nodules, a 7 cm uterine mass, and brain metastases. She underwent emergent hepatic embolization, was started on induction chemotherapy with weekly low-dose etoposide and cisplatin followed by a transition to etoposide, high-dose methotrexate, actinomycin D, etoposide, and cisplatin (HD EMA-EP), received stereotactic brain radiotherapy, and subsequently underwent minimally-invasive hysterectomy. She remains disease free over one year after the completion of treatment. An aggressive multimodal treatment approach employing etoposide/cisplatin-based chemotherapy as well as surgical procedures to control hemorrhage or excise resistant disease, and radiotherapy for brain metastases can result in successful treatment of stage IV ETT.

Placental site trophoblastic tumor: Successful treatment of 13 cases.

Placental site trophoblastic tumor (PSTT) is a rare variant of gestational trophoblastic neoplasia (GTN) that is characterized by slow growth resulting in mostly uterine-confined disease, low human chorionic gonadotropin (hCG) levels, and resistance to chemotherapy. Our objective was to update our center's experience with PSTT with respect to presentation, prognostic factors, treatment, and outcomes from 2003 to 2019. Thirteen women with PSTT were identified. Mean age was 32 years. The most frequent presenting symptom was abnormal uterine bleeding (69%). A uterine mass was noted in 62%. The diagnosis was usually established by endometrial biopsy or curettage (62%). Nonmolar pregnancy was the preceding gestation in 85%. Median time from last pregnancy to diagnosis was 13 months (range 0-240 months). Serum hCG levels at diagnosis ranged from 1 to 2606 mIU/mL (median 98 mIU/mL). Three women (23%) presented with metastatic disease. All 13 women underwent surgery: 12 had a hysterectomy, 1 had a fertility-sparing hysteroscopic resection, and 2 underwent pulmonary metastatectomy. Nine women (69%) also received chemotherapy for persistently elevated hCG levels after hysterectomy (2), high-risk factors (4), or metastatic disease (3). Overall survival was 100% with a median survival of 65 months (range 30-167 months). Survival for PSTT increased from 57% to 100%, including from 33% to 100% for metastatic disease, at our center from 1982 to 2003 to 2003-2017. Surgery is the most important component in the treatment of women with PSTT. Multidrug platinum/etoposide- chemotherapy should be used in women with metastatic disease and considered in women with nonmetastatic disease with high-risk features.

Perivascular epithelioid cell tumors (PEComa) in pregnancy with uterine rupture and ongoing abdominal gestation: A case report.

Perivascular epithelioid cell tumors (PEComa) represent a rare family of tumors characterized by distinct histology and immunohistochemistry characteristics. Approximately one-quarter of reported cases are gynecologic in origin and associated pregnancies are rare. We report a case of PEComa in pregnancy with initial undiagnosed presentation at 18 weeks of gestation and subsequent presentation and diagnosis at 30 weeks of gestation. Abdominal pain led to the use of magnetic resonance imaging, which raised concerns about placentation abnormality and abdominal pregnancy. Exploratory laparotomy was notable for a 10 cm by 15 cm posterior uterine defect through which the placenta and amniotic sac containing the fetus were extruded. Placenta-like tissue was noted to be invading through the anterior wall of the uterus, which led to concern regarding placenta percreta. A total abdominal hysterectomy and bilateral salpingectomy were then performed, given the complete loss of normal uterine architecture. Pathology returned with findings of placenta accreta and PEComa. Indolent uterine rupture in the setting of PEComa led to an ongoing viable abdominal pregnancy. Uterine PEComa can masquerade as a placenta and lead to obstetrical complications.

Cystoscopy at the Time of Hysterectomy for Benign Indications and Delayed Lower Genitourinary Tract Injury.

OBJECTIVE: To compare the rate of delayed 30-day lower genitourinary tract injury in women who underwent cystoscopy at the time of hysterectomy for benign indications to those who did not. METHODS: This was a retrospective cohort study of patients who underwent hysterectomy without a concomitant procedure for prolapse or incontinence for benign pathology with a general obstetrician-gynecologist (ob-gyn) recorded in the National Surgical Quality Improvement Program targeted hysterectomy file between 2015 and 2017. The primary outcome was a delayed lower genitourinary tract injury in the 30 days after hysterectomy. Secondary outcomes included urinary tract infection and operative time. The exposure of interest was cystoscopy at the time of hysterectomy. Stratified analysis was performed by route of surgery. Bivariable tests were used to examine associations. RESULTS: We identified 39,529 women who underwent hysterectomy for benign indications with a general ob-gyn. Surgical approach was open (26%), laparoscopic or robotic assisted laparoscopic (46%), and vaginal or vaginally assisted (28%). Overall, 25% of women underwent cystoscopy at the time of hysterectomy; cystoscopy was more commonly performed in laparoscopic or robotic (32%) and vaginal hysterectomy (25%) as compared with open hysterectomy (11%) (P<.001). There was no difference in delayed lower genitourinary tract injury between patients who underwent cystoscopy at time of hysterectomy compared with those who did not undergo cystoscopy (0.27% vs 0.24%, P=.64). Patients who underwent cystoscopy were more likely to be diagnosed with a urinary tract infection (2.6% vs 2.0%, RR 1.27 95% CI 1.09-1.47). Median operative time was increased by 17 minutes in cases where cystoscopy was performed (132 vs 115 minutes, P<.001). CONCLUSION: Cystoscopy at the time of hysterectomy for benign indications does not result in a lower rate of 30-day delayed lower genitourinary tract injury compared with no cystoscopy.

Examining Disparities in Route of Surgery and Postoperative Complications in Black Race and Hysterectomy.

OBJECTIVE: To estimate the associations among race, route of hysterectomy, and postoperative complications among women undergoing hysterectomy for benign indications. METHODS: A cohort study was performed. All patients undergoing hysterectomy for benign indications, recorded in the National Surgical Quality Improvement Program and its targeted hysterectomy file in 2015, were identified. The primary exposure was patient race. The primary outcome was route of hysterectomy and the secondary outcome was postoperative complication. Associations were examined using both bivariable tests and logistic regression. RESULTS: Of 15,136 women who underwent hysterectomy for benign indications, 75% were white and 25% were black. Black women were more likely to undergo an open hysterectomy than white women (50.1% vs 22.9%; odds ratio [OR] 3.36, 95% CI 3.11-3.64). Black women had larger uteri (median 262 g vs 123 g; 60.7% vs 25.6% with uterus greater than 250 g), more prior pelvic surgery (58.5% vs 53.2%), and higher body mass indices (32.7 vs 30.4). After adjusting for these and other clinical factors, black women remained more likely to undergo an open hysterectomy (adjusted OR 2.02, 95% CI 1.85-2.20). Black women experienced more major complications than white women (4.1% vs 2.3%; P<.001) and more minor complications (11.4% vs 6.7%; OR 1.78, P<.001). Again these disparities persisted with adjustment (major adjusted OR 1.56, 95% CI 1.25-1.95; minor adjusted OR 1.27, 95% CI 1.11-1.47). CONCLUSIONS: Black women undergo a higher proportion of open hysterectomy and experience more major and minor postoperative complications. These differences persisted even after adjusting for confounding medical, surgical, and gynecologic factors.

Discussing sarcoma risks during informed consent for nonhysterectomy management of fibroids: an unmet need.

There is no reliable way to distinguish symptomatic uterine fibroids from sarcoma without a surgical specimen. Many women with a uterine sarcoma are initially managed without hysterectomy under a presumed fibroid diagnosis, without understanding sarcoma risks. Currently many alternatives to hysterectomy, including medical and procedural interventions, for treatment of fibroids are promoted. The sarcoma incidence among women with presumed fibroids is 0.29% (1/340) to 0.05% (1/2000). Nonmetastatic leiomyosarcoma has a 63% 5-year survival rate whereas metastatic leiomyosarcoma has a 14% 5-year survival rate. In uterine sarcoma, we often cannot identify who has sarcoma before making a potentially cure-denying decision by delaying surgery. Therefore, women electing an alternative to hysterectomy for fibroids should undergo an informed consent process that specifically includes discussion of uterine sarcoma incidence and mortality. Alternatives to hysterectomy for presumed fibroids remain preferable treatment options for many women with symptomatic fibroids, so long as underlying sarcoma risks are adequately discussed. The challenge for obstetrician- gynecologists then is how to provide better informed consent and maintain the primacy of patient autonomy over our concern to "First, do no harm." Major threats to patient's autonomy are faced in the sarcoma risk discussion. How we should present sarcoma risk information to avoid being dismissive of sarcoma or frightening women toward hysterectomy is unstudied. Research is needed to determine how to provide sarcoma risk information with less bias during informed consent.

The selected biomarker analysis in 5 types of uterine smooth muscle tumors.

Uterine smooth muscle tumors (USMTs) consist of a group of histologically heterogeneous and clinically diverse diseases ranging from malignant leiomyosarcoma (LMS) to benign leiomyoma (ULM). The genetic alterations in LMS are complex, with some genetic alterations present in both LMS and other atypical histologic variants of USMT. In this study, we reviewed 119 USMTs with a diagnosis of LMS, smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, and cellular leiomyoma, as well as 46 ULMs and 60 myometrial controls. We selected 17 biomarkers highly relevant to LMS in 4 tumorigenic pathways including steroid hormone receptors (estrogen receptor [ER] and progesterone receptor [PR]), cell cycle/tumor suppressor genes, AKT pathway markers, and associated oncogenes. ER and PR expression was significantly lower in LMS than smooth muscle tumor of uncertain malignant potential, atypical leiomyomas/leiomyoma with bizarre nuclei, cellular leiomyoma, and ULM (P < .01). Sixty-five percent of LMSs showed complete loss of ER, and 75% of LMSs showed complete loss of PR. All cell cycle genes were differentially expressed in different types of tumor, but significant overlap was noted. More than 75% of LMSs had Ki-67 index greater than 33%, and only 5% in all other types of USMT. Expression of the selected oncogenes varied widely among different types of USMT. PR positivity and p53 had a borderline association with progression-free survival (P = .055 for PR and P = .0847 for p53). Furthermore, high PR expression was significantly associated with a longer overall survival (P = .0163, hazard ratio 0.198). Cell proliferative indices (Ki-67) and sex steroid hormone receptors were the most valuable markers in differentiating LMS from other USMT variants.

Survival After Primary Debulking Surgery Compared With Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: A National Cancer Database Study.

OBJECTIVE: The aim of this study was to compare overall survival (OS) of women with advanced ovarian cancer treated with primary debulking surgery (PDS) or neoadjuvant chemotherapy (NAC) using a large national cohort. METHODS: The 1998-2011 National Cancer Database was queried to identify women with stage III or IV ovarian cancer treated with multiagent chemotherapy and stage-appropriate surgery. Overall survival was estimated and compared using Kaplan-Meier analysis between women who received PDS followed by multiagent chemotherapy or NAC followed by interval surgery. Multivariable Cox proportional hazards regression model tested for associations of potential explanatory variables with OS. Analyzed confounders included age, composite comorbidity scores, stage, grade, histology, insurance status, income quartile, and race. RESULTS: Overall, 44,907 women (85.9%) underwent PDS, and 7348 women (14.1%) received NAC. Women who received NAC were older (64 vs 61 years, P < 0.001), had higher comorbidity scores (P < 0.001), and more often had stage IV disease (44.1% vs 26.1%, P < 0.001). Median OS was 41.1 (40.5-41.7) months among women who underwent PDS compared with 30.3 (29.3-31.1) months among women who received NAC (log-rank, P < 0.001). Among women with stage III disease, PDS was associated with increased OS compared with NAC (median OS, 44.9 [44.2-45.7] vs 31.4 [30.2-33.0] months; hazard ratio [95% confidence interval], 0.70 [0.66-0.76]; P < 0.001). Among women with stage IV disease, there was no OS difference between PDS and NAC cohorts (median OS, 31.2 [30.4-32.3] vs 28.4 [27.2-30.2] months; hazard ratio [95% confidence interval], 0.93 [0.85-1.02]; P = 0.12). CONCLUSIONS: Primary debulking surgery was associated with increased OS among women with stage III but not stage IV ovarian cancer in a nationally representative cohort with low NAC use. If this finding reflects treatment assignment bias, it suggests that providers often well select candidates for PDS rather than NAC, although median OS times remain low.

Transversus abdominis plane block with liposomal bupivacaine compared to oral opioids alone for acute postoperative pain after laparoscopic hysterectomy for early endometrial cancer: a cost-effectiveness analysis.

BACKGROUND: To determine the cost-effectiveness of transversus abdominis plane block with liposomal bupivacaine (TAP) compared to oral opioids alone for acute postoperative pain after laparoscopic hysterectomy for early endometrial cancer. METHODS: A cost-effectiveness analysis using a decision tree structure with a 30.5 day time-horizon was used to calculate incremental cost-effectiveness ratio (ICER) values per quality-adjusted life-year (QALY). Base-case costs, probabilities, and QALY values were identified from recently published all-payer national database studies, 2017 Medicare fee-schedules, randomized trials, institutional case series, or assumed, when published values were not available. One-way, two-way and multiple probabilistic sensitivity analyses were performed. RESULTS: The TAP strategy dominated the oral opioid-only strategy, with decreased costs and increased effectiveness. Specifically, the TAP strategy saved $235.90 under the base-case assumptions. Threshold analyses demonstrated that if the relative same-day discharge probability was ≥ 12% higher in the TAP group, then TAP was cost-saving over oral opioids-alone. Similarly, TAP was cost-saving whenever the costs saved by same-day discharge compared to admission were ≥ $1115.22. Cost-effectiveness of the TAP strategy was highly robust of a variety of sensitivity analyses. CONCLUSIONS: TAP with liposomal bupivacaine was robustly cost-effective at conventional willingness-to-pay thresholds. Further, TAP was cost-saving compared to opioids-only when the same-day discharge rate among TAP users was greater than among opioid-only users.

Prognosis and treatment of uterine leiomyosarcoma: A National Cancer Database study.

OBJECTIVE: To determine overall survival and factors associated with survival of women with uterine leiomyosarcoma. METHODS: We performed an observational cohort study of women with uterine leiomyosarcoma (n=7455) from the 1998-2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to investigate predictors of survival. Sensitivity and matched cohort analyses were performed to evaluate the roles of oophorectomy, lymphadenectomy, and chemotherapy in early leiomyosarcoma and chemotherapy in metastatic leiomyosarcoma. RESULTS: Median (interquartile range) age at diagnosis was 54 (48-63) years. Older age, higher comorbidity, black race, higher stage or grade, larger tumor size, lymph node involvement, metastasis at diagnosis, positive surgical margin, adjuvant chemotherapy, and brachytherapy were independently associated with decreased survival by unmatched cohort analyses. Private insurance was associated with increased survival. By matched cohort analyses, omitting oophorectomy was not associated with survival among women≤51years old at diagnosis (event time ratio (ETR) (95% CI) 1.06 (0.90-1.25), P=0.48). Omitting lymphadenectomy was not associated with survival (ETR (95% CI) 1.02 (0.94-1.10), P=0.60). Among women with stage I leiomyosarcoma, adjuvant chemotherapy was not associated with increased survival (ETR (95% CI) 0.91 (0.78-1.05), P=0.18). Chemotherapy was associated with increased survival of women with metastatic leiomyosarcoma (median survival (95% CI) 19.4 (16.4-23.0) versus 10.9 (7.7-14.3) months, ETR (95% CI) 1.66 (1.46-1.90), P<0.001). CONCLUSION: Early and complete resection is the best-evidenced treatment for uterine leiomyosarcoma. Oophorectomy and lymphadenectomy may be safely omitted for clinically uterus-confined leiomyosarcoma. Chemotherapy increases survival of women with metastatic leiomyosarcoma.

Applicability of the modified ACOG/SGO referral criteria for adnexal mass within a limited-resource setting.

OBJECTIVE: To evaluate the performance of the modified American Congress of Obstetricians and Gynecologists (ACOG)/Society of Gynecologic Oncology (SGO) referral guidelines in a high-risk limited-resource setting. METHODS: In a retrospective study, data were assessed for all women who underwent surgery for an adnexal mass at John H. Stroger Jr Hospital, Chicago, IL, USA, between July 2006 and July 2011. Sensitivity, specificity, and positive and negative predictive values were calculated both for actual practice referral patterns and for the modified ACOG/SGO guidelines. RESULTS: Among 542 study women, 176 (32.5%) were diagnosed with ovarian malignancy. The ACOG/SGO guidelines showed 81.3% sensitivity and 71.9% specificity for the prediction of malignancy at time of surgery, with positive and negative predictive values of 58.1% and 88.9%, respectively. Actual practice patterns demonstrated lower sensitivity (68.2%; P<0.001) but higher specificity (84.2%; P<0.001). CONCLUSION: As compared with practice patterns, the modified ACOG/SGO guidelines lacked sufficient specificity for referral and might not be applicable in high-risk, low-resource settings. For this population, screening should be based on stratifying patients into low-, intermediate-, and high-risk categories to allow limited resources to be focused on women at highest risk.

Association of Lymph Node Count and Overall Survival in Node-Negative Endometrial Cancers.

Purpose: To estimate whether the number of lymph nodes removed during surgery is associated with overall survival among women with endometrial cancer. Methods: We performed a retrospective cohort study of women with node-negative, stage I to IIIB endometrial cancer (n = 152,702) identified from the 1998-2011 National Cancer Database. Multivariable Cox proportional hazards regression tested for an association of lymph node count with survival. Restricted mean survival and relative hazard curves were plotted for survival as a function of number of removed lymph nodes. Results: Among women with node-negative endometrioid endometrial cancer, for each additional five lymph nodes removed, the hazard for death decreased: stage I, the hazard ratio (HR) was 0.95 (95% CI, 0.93 to 0.97; P < .001), stage II, HR was 0.90 (95% CI, 0.87 to 0.94; P < .001); and stage IIIA-B, HR was 0.92 (95% CI, 0.88 to 0.96; P < .001). When grouped by grade, each additional five lymph nodes removed was also associated with decreased hazard for death: grade 1, HR was 0.96 (95% CI, 0.93 to 0.99; P = .009); grade 2,HR was0.91 (95%CI, 0.89 to0.94; P <.001);and grade 3,HR was 0.95 (95%CI, 0.92 to 0.97; P <.001). Increased lymph node dissection was also associated with increased survival among women with node-negative stage II (HR, 0.92; 95% CI, 0.86 to 0.98; P = .01) or stage IIIA-B (HR, 0.94; 95% CI, 0.89 to 0.99; P = .025) uterine serous carcinoma, but not among women with carcinosarcoma or clear cell adeno-carcinoma. Five-year survival for women with one to four nodes removed and endometrioid or serous histology was 85% (95% CI, 84% to 85%) and 54% (95% CI, 50% to 59%), respectively. Five-year survival was significantly higher for women with ≥ 20 removed nodes and endometrioid (91%; 95% CI, 90% to 91%) or serous (72%; 95% CI, 68% to 76%) histology (P < .001). Conclusion: Increased lymph node count is associated with a 1% to 14% decreased hazard of death per each additional five lymph nodes removed and a 5% to 20% increased 5-year survival among women with pathologically node-negative endometrioid and serous endometrial cancers.

Survival Disparities by Hospital Volume Among American Women With Gynecologic Cancers.

PURPOSE: We describe survival disparities among women with uterine, ovarian, or cervical cancer by cancer-specific mean annual hospital volume. METHODS: National Cancer Database 1998-2011 uterine (n = 441,863), ovarian (n = 223,017), and cervical (n = 146,698) cancer data sets were used. Cancer-specific mean annual hospital volumes were calculated. Overall survival (OS) was plotted by hospital volume using restricted mean OS times from Cox regression. RESULTS: Uterine, ovarian, and cervical cancers were reported from 1,651, 1,633, and 1,600 hospitals, respectively. Median values of mean annual hospital volumes among hospitals were 8.6 (interquartile range [IQR], 2.6 to 20.8), 4.4 (IQR, 1.4 to 10.3), and 2.4 (IQR, 0.6 to 6.6) for uterine, ovarian, and cervical cancers, respectively. Increased hospital volume was associated with increased OS among women with stage III to IV high-grade serous ovarian cancer, stage II to IV squamous or adenocarcinoma cervical cancer, and stage I to IV endometrioid, clear cell, serous, or carcinosarcoma uterine cancers (all P < .03). Differential OS between women treated at higher- versus lower-volume cancer centers exceeded 5, 5, and 13 months among women with advanced endometrial, ovarian, or cervical cancer, respectively (all P < .001). Hospital volume was not associated with OS among patients with stage II to IV cervical cancer treated with brachytherapy ( P = .17). Use of adjuvant therapies decreased OS disparities by hospital volume among women with advanced ovarian or endometrial cancer. CONCLUSION: Increased delivery of brachytherapy for treatment of cervical cancer may decrease survival disparities by hospital volume. Standardization of adjuvant therapies may diminish survival disparities by hospital volume among women with advanced ovarian or endometrial cancer. In addition, survival of American women with gynecologic cancer may be increased by centralization of care.

Survival After Pelvic Exenteration for Cervical Cancer: A National Cancer Database Study.

OBJECTIVE: To determine overall survival (OS) and factors associated with OS after pelvic exenteration for cervical cancer. METHODS: Women with cervical cancer who underwent exenteration (n = 517) were identified from the 1998 to 2011 National Cancer Database. Kaplan-Meier and multivariate Cox proportional-hazards survival analyses were performed to test for associations of potential explanatory variables with OS. Analyzed confounders included age, insurance status, income, distance from home to treatment center, stage, exenteration type, surgical margin status, and treatment with adjuvant radiation and/or chemotherapy. RESULTS: Among the entire cohort with clinical follow-up (n = 313), median OS was 24 months. Stage (P = 2.5 × 10), lymph node status (P = 1.3 × 10), insurance status (P = 1.5 × 10), and histologic type (P = 0.04) were significantly associated with OS by the log-rank test. Unadjusted median OS was 24.2 and 61.8 months for women with squamous and adenocarcinoma histologies, respectively. By multivariate Cox regression, age, insurance status, stage, margin status, and adjuvant radiation were associated with OS. Histology was not independently associated with OS on multivariate regression. Among women with node-negative disease, median OS was 73.2 months. CONCLUSIONS: Exenteration may be curative for more than half of women with node-negative cervical cancer. Stage, insurance status, lymph node status, and surgical margin are independently associated with differential OS after exenteration.

Chemotherapy delay after primary debulking surgery for ovarian cancer.

OBJECTIVE: To determine the association of chemotherapy delay with overall survival (OS) and investigate predictors of delay among a population-representative American ovarian cancer cohort. METHODS: An observational retrospective cohort analysis of women with ovarian cancer who received National Comprehensive Cancer Network guideline-consistent care was performed with the 1998-2011 National Cancer Data Base. Chemotherapy delay was defined as initiation of multiagent chemotherapy >28days from primary debulking surgery. Associations of patient and disease characteristics with chemotherapy delay were tested with multivariate logistic regression. Survival analyses for women diagnosed from 2003 to 2006 approximated a 21-daycycle intravenous platinum-taxane chemotherapy cohort. Overall survival was estimated by Kaplan-Meier analyses and Cox proportional-hazards regressions, with sensitivity analyses using matched cohorts. RESULTS: 58.1% (26,149/45,001) of women experienced chemotherapy delay. Race, insurance status, cancer center type, and community median income were significantly associated with chemotherapy delay (P<0.001). Odds for chemotherapy delay were higher for older or sicker women, women with endometrioid or mucinous histology, lower stage or grade disease, and uninsured or low-income women (P<0.05). Chemotherapy delay >35days from surgery was associated with a 7% (95% confidence interval, 2-13%) increased hazard of death (P=0.01). Relative hazard of death was lowest between 25 and 29days after surgery but was not significantly different within the longer two-week interval from 21 to 35days. CONCLUSION: A survival benefit may be achieved by consistently starting chemotherapy between 21 and 35days from primary debulking surgery. Women at higher risk for chemotherapy delay may be targeted for close follow-up.