Delayed publication of clinical trials in gynecologic oncology.

OBJECTIVES: Delays in clinical trial publication can hinder timely implementation of evidence-based practices. We sought to determine publication rates and time to publication for clinical trials addressing gynecologic malignancies. METHODS: All clinical trials addressing gynecologic cancers in the ClinicalTrials.gov registry with a primary completion date between 1/1/2018 and 1/1/2020 were identified. The primary outcome was publication rate. All included studies had been completed for at least 3 years. Secondary outcomes were time to publication and associations between publication rate and sponsor, cancer type, and the number and location of primary study sites. RESULTS: Of the 290 trials included, 161 (55.5%) had a peer-reviewed publication for the primary outcome within at least 3 years after completion. Of these, 123 had positive results (76.4%) and 38 were negative (23.6%). The average duration from primary completion to manuscript publication was 23.6 months (SD 13.9; median 21.4, IQR 15.1-32.4). Only 73 had results posted on the ClinicalTrials.gov registry (25.2%). Studies with positive findings had a significantly faster time to publication than those with negative results (22.0 mo vs 29.0 mo, p = 0.009). There was no significant difference between publication rate and funding source, cancer type, or location and number of primary sites. CONCLUSIONS: Timely publication of clinical trials addressing gynecologic cancers remains an issue. Studies with positive findings were published faster than those with negative results, but the average publication time was still almost 2 years from trial completion. Further efforts should be made to identify and address barriers to clinical trial publication.

The RECOURSE Study: Long-term Oncologic Outcomes Associated With Robotically Assisted Minimally Invasive Procedures for Endometrial, Cervical, Colorectal, Lung, or Prostate Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess long-term outcomes with robotic versus laparoscopic/thoracoscopic and open surgery for colorectal, urologic, endometrial, cervical, and thoracic cancers. BACKGROUND: Minimally invasive surgery provides perioperative benefits and similar oncological outcomes compared with open surgery. Recent robotic surgery data have questioned long-term benefits. METHODS: A systematic review and meta-analysis of cancer outcomes based on surgical approach was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines using Pubmed, Scopus, and Embase. Hazard ratios for recurrence, disease-free survival (DFS), and overall survival (OS) were extracted/estimated using a hierarchical decision tree and pooled in RevMan 5.4 using inverse-variance fixed-effect (heterogeneity nonsignificant) or random effect models. RESULTS: Of 31,204 references, 199 were included (7 randomized, 23 database, 15 prospective, 154 retrospective studies)-157,876 robotic, 68,007 laparoscopic/thoracoscopic, and 234,649 open cases. Cervical cancer: OS and DFS were similar between robotic and laparoscopic [1.01 (0.56, 1.80), P =0.98] or open [1.18 (0.99, 1.41), P =0.06] surgery; 2 papers reported less recurrence with open surgery [2.30 (1.32, 4.01), P =0.003]. Endometrial cancer: the only significant result favored robotic over open surgery [OS; 0.77 (0.71, 0.83), P <0.001]. Lobectomy: DFS favored robotic over thoracoscopic surgery [0.74 (0.59, 0.93), P =0.009]; OS favored robotic over open surgery [0.93 (0.87, 1.00), P =0.04]. Prostatectomy: recurrence was less with robotic versus laparoscopic surgery [0.77 (0.68, 0.87), P <0.0001]; OS favored robotic over open surgery [0.78 (0.72, 0.85), P <0.0001]. Low-anterior resection: OS significantly favored robotic over laparoscopic [0.76 (0.63, 0.91), P =0.004] and open surgery [0.83 (0.74, 0.93), P =0.001]. CONCLUSIONS: Long-term outcomes were similar for robotic versus laparoscopic/thoracoscopic and open surgery, with no safety signal or indication requiring further research (PROSPERO Reg#CRD42021240519).

Modeling of minimal systems based on ATP-Zn coordination for chemically fueled self-assembly.

Following nature's example, there is currently strong interest in using adenosine 5'-triphosphate (ATP) as a fuel for the self-assembly of functional materials with transient/non-equilibrium behaviours. These hold great promise for applications, e.g. in catalysis and drug delivery. In a recent seminal work [Maiti et al., Nat. Chem., 2016, 8, 725], binding of ATP to the metallosurfactant zinc hexadecyl-1,4,7-triazacyclononane ([ZnC16 TACN]2+) was exploited to produce ATP-fueled transient vesicles. Crucial to the complex formation is the ability of ATP to bind to the metal ion. As a first step to unveil the key elements underlying this process, we investigate the interaction of ATP with Zn2+ and with methyl-1,4,7-triazacyclononane ([ZnCH3 TACN]2+), using all-atom molecular dynamics simulations. The free energy landscape of the complex formation is sampled using well-tempered metadynamics with three collective variables, corresponding to the coordination numbers of Zn2+ with the oxygen atoms of the three phosphate groups. We find that the structure of the ternary complex is controlled by direct triphosphate coordination to zinc, with a minor role played by the interactions between ATP and CH3 TACN which, however, may be important for the build-up of supramolecular assemblies.

Sentinel lymph node biopsy in high-grade endometrial cancer: a systematic review and meta-analysis of performance characteristics.

OBJECTIVE: A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280). DATA SOURCES: We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. ClinicalTrials.gov was searched to identify ongoing registered clinical trials. STUDY ELIGIBILITY CRITERIA: We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data. METHODS: We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44-82.5 years) and the study-level median body mass index was 28.6 kg/m2 (range, 19.4-43.7 kg/m2). The pooled detection rates were 91% per patient (95% confidence interval, 85%-95%; I2=59%) and 64% bilaterally (95% confidence interval, 53%-73%; I2=69%). The overall node positivity rate was 26% (95% confidence interval, 19%-34%; I2=44%). Of the 87 patients with positive node results, a sentinel lymph node biopsy correctly identified 80, yielding a pooled sensitivity of 92% per patient (95% confidence interval, 84%-96%; I2=0%), a false negative rate of 8% (95% confidence interval, 4%-16%; I2=0%), and a negative predictive value of 97% (95% confidence interval, 95%-99%; I2=0%). CONCLUSION: Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer.

Development of a surgical competency assessment tool for sentinel lymph node dissection by minimally invasive surgery for endometrial cancer.

INTRODUCTION: Sentinel lymph node dissection is widely used in the staging of endometrial cancer. Variation in surgical techniques potentially impacts diagnostic accuracy and oncologic outcomes, and poses barriers to the comparison of outcomes across institutions or clinical trial sites. Standardization of surgical technique and surgical quality assessment tools are critical to the conduct of clinical trials. By identifying mandatory and prohibited steps of sentinel lymph node (SLN) dissection in endometrial cancer, the purpose of this study was to develop and validate a competency assessment tool for use in surgical quality assurance. METHODS: A Delphi methodology was applied, included 35 expert gynecological oncology surgeons from 16 countries. Interviews identified key steps and tasks which were rated mandatory, optional, or prohibited using questionnaires. Using the surgical steps for which consensus was achieved, a competency assessment tool was developed and subjected to assessments of validity and reliability. RESULTS: Seventy percent consensus agreement standardized the specific mandatory, optional, and prohibited steps of SLN dissection for endometrial cancer and informed the development of a competency assessment tool. Consensus agreement identified 21 mandatory and three prohibited steps to complete a SLN dissection. The competency assessment tool was used to rate surgical quality in three preselected videos, demonstrating clear separation in the rating of the skill level displayed with mean skills summary scores differing significantly between the three videos (F score=89.4; P<0.001). Internal consistency of the items was high (Cronbach α=0.88). CONCLUSION: Specific mandatory and prohibited steps of SLN dissection in endometrial cancer have been identified and validated based on consensus among a large number of international experts. A competency assessment tool is now available and can be used for surgeon selection in clinical trials and for ongoing, prospective quality assurance in routine clinical care.

Controversies in Sentinel Lymph Node Biopsy for Gynecologic Malignancies.

OBJECTIVE: Sentinel lymph node (SLN) biopsy represents an evolution in the advancement of minimally invasive surgical techniques for gynecologic cancers. Prospective and retrospective studies have consistently shown its accuracy in the detection of lymph node metastases for endometrial and cervical cancers. However, consistent with any emerging surgical technique in the early phases of adoption, new questions have arisen regarding its application and impact. This paper served as a scoping review to identify the key controversies that have arisen in the field of SLN biopsy for endometrial and cervical cancers. DATA SOURCES: Several key controversies were identified, and PubMed, the Cochrane Library (cochranelibrary.com) advanced search function, and the National Comprehensive Cancer Network guidelines were searched for supporting evidence. These included search terms such as "the accuracy of SLN biopsy for high grade endometrial cancer or cervical cancers >2-cm," "cost effectiveness of SLN biopsy for gynecologic cancers," "clinical significance of low volume metastases in endometrial cancer," "morbidity of SLN biopsy for endometrial and cervical cancer," and "impact on cancer survival of SLN biopsy for endometrial and cervical cancer." METHODS OF STUDY SELECTION: Studies were selected for review if they included significant numbers of patients, were level I evidence, or were prospective trials. Where this level of evidence failed to exist, seminal observational series that were published in high-quality journals were included. TABULATION, INTEGRATION, AND RESULTS: Similar studies were listed and subcategorized and cross-compared, excluding those that included repeated analyses of the same patient populations. The relevant clinical trials or observational studies were clustered and reviewed for each chosen controversy. Adequate evidence supports the accuracy of SLN biopsy in the staging of high-grade endometrial cancer and cervical cancer, and it seems to be a cost-effective strategy for invasive endometrial cancer. Conclusive evidence was lacking with respect to the oncologic outcomes related to SLN biopsy, the impact on patient morbidity, and whether clinicians should treat isolated tumor cells in SLNs with adjuvant therapy. CONCLUSION: SLN biopsy is an accepted staging strategy for cervical and endometrial cancer surgery; however, controversies remain in how it can be applied with the most safety and efficacy. These ultimately need to be resolved with further clinical trials and observations of larger series of patients.

When to Operate, Hesitate and Reintegrate: Society of Gynecologic Oncology Surgical Considerations during the COVID-19 Pandemic.

The COVID-19 pandemic has challenged our ability to provide timely surgical care for our patients. In response, the U.S. Surgeon General, the American College of Srugeons, and other surgical professional societies recommended postponing elective surgical procedures and proceeding cautiously with cancer procedures that may require significant hospital resources and expose vulnerable patients to the virus. These challenges have particularly distressing for women with a gynecologic cancer diagnosis and their providers. Currently, circumstances vary greatly by region and by hospital, depending on COVID-19 prevalence, case mix, hospital type, and available resources. Therefore, COVID-19-related modifications to surgical practice guidelines must be individualized. Special consideration is necessary to evaluate the appropriateness of procedural interventions, recognizing the significant resources and personnel they require. Additionally, the pandemic may occur in waves, with patient demand for surgery ebbing and flowing accordingly. Hospitals, cancer centers and providers must prepare themselves to meet this demand. The purpose of this white paper is to highlight all phases of gynecologic cancer surgical care during the COVID-19 pandemic and to illustrate when it is best to operate, to hestitate, and reintegrate surgery. Triage and prioritization of surgical cases, preoperative COVID-19 testing, peri-operative safety principles, and preparations for the post-COVID-19 peak and surgical reintegration are reviewed.

Defining the learning curve for successful staging with sentinel lymph node biopsy for endometrial cancer among surgeons at an academic institution.

BACKGROUND: Sentinel lymph node (SLN) biopsy is increasingly used in endometrial cancer staging; however, success of the technique is variable, and the learning curve needs to be better understood. Success is defined as identification of a SLN specimen containing nodal tissue in bilateral hemi-pelvises. OBJECTIVE: To assess the learning curve of surgeons at an academic institution in performing successful SLN mapping and biopsy during robotic staging for endometrial cancer. METHODS: After institutional review board approval, patients who underwent staging with robotic SLN mapping using indocyanine green at a single academic program between July 2012 and December 2017 were identified. Demographic, pathologic, and surgical data were retrospectively collected from the medical records. Descriptive and comparative statistics were performed. Surgeon rates of successful bilateral SLN mapping and removal of lymphoid-containing SLN specimens were compared. A logistic model was used to analyze the probability of successful SLN mapping and removal of lymph node-containing tissue with increasing number of procedures performed. RESULTS: Three hundred and seventeen patients met the eligibility criteria. Most had early-stage, low-grade endometrial cancer. A total of 194 (61%) patients had successful bilateral mapping. Among seven surgeons, a plateau in rates of successful bilateral mapping was achieved after 40 cases. No linear correlation was seen between the number of surgeries performed and the rate of removal of lymph node-containing tissue among surgeons. Each additional 10 procedures performed was associated with a 5% and an 11% increase in the odds of successful SLN mapping and removal of lymph node-containing tissue, respectively. DISCUSSION: The successful removal of lymph node-containing specimens appears to be a surgeon-specific phenomenon. The plateau of the learning curve for successful bilateral mapping seems to be reached at around 40 cases. These first 40 cases offer a time for auditing of individual rates of SLN mapping and removal to identify surgeons who may benefit from procedure-specific remediation.

Extent of lymphadenectomy and postoperative major complications among women with endometrial cancer treated with minimally invasive surgery.

BACKGROUND: In patients with endometrial cancer, sentinel lymphadenectomy is used to accurately prognosticate extent of disease, and has been proposed as a method to decrease the incidence of medical and surgical complications associated with more extensive lymphadenectomy. It is unknown whether patients who undergo traditional lymphadenectomy experience major postoperative complications at the same rates as those who undergo sentinel lymphadenectomy or those who do not undergo lymphadenectomy. OBJECTIVE: The aim of this study was to compare the incidence of major postoperative complications among endometrial cancer patients undergoing total laparoscopic hysterectomy with traditional lymphadenectomy vs sentinel or no lymphadenectomy. MATERIALS AND METHODS: Patients with endometrial cancer who underwent total laparoscopic hysterectomy recorded in the National Surgical Quality Improvement Program (NSQIP) database between 2015 and 2016 were identified using Current Procedural Terminology (CPT) and International Classification of Diseases (ICD) codes. Primary exposure was extent of lymphadenectomy. The primary outcome was major postoperative complications as defined by the Clavien-Dindo scale. Associations were examined with bivariable tests and multivariable logistic regression. RESULTS: A total of 3282 women with endometrial cancer who underwent total laparoscopic hysterectomy were identified; of these, 2049 (62.4%) did not undergo lymphadenectomy, 1089 (33.2%) underwent traditional lymphadenectomy, and 144 (4.4%) underwent sentinel lymphadenectomy. Traditional lymphadenectomy had the highest rate of major complications (3.6%) compared with sentinel lymphadenectomy (2.0%) and no lymphadenectomy (2.0%) (P = .03). Patients who underwent traditional lymphadenectomy also had the longest operating room times and procedures that were most surgically complex (171 minutes, 30.6 relative value units [RVU]) compared with patients who underwent sentinel lymphadenectomy (166 minutes, 24.9 RVU) or no lymphadenectomy (141 minutes, 15.0 RVU) (all P < .001). Patients who underwent traditional lymphadenectomy had nearly twice the odds of a major complication (adjusted odds ratio [aOR], 1.8; 95% confidence interval [CI], 1.2-2.9) and need for readmission (aOR, 2.2; 95% CI, 1.5-3.4) compared to those who underwent sentinel or no lymphadenectomy. The incidence of readmission after traditional lymphadenectomy was higher (4.6%) than after sentinel lymphadenectomy (1.4%) and no lymphadenectomy (2.2%) (P < 0.001). CONCLUSION: Sentinel lymphadenectomy among patients undergoing total laparoscopic hysterectomy for endometrial cancer was associated with a decreased incidence of major postoperative complications and need for readmission when compared with traditional lymphadenectomy.

Current state of sentinel lymph nodes for women with endometrial cancer.

Sentinel lymph node (SLN) biopsy has been investigated as an alternative to conventional pelvic and para-aorticlymphadenectomy for the surgical staging of endometrial cancer. Clinical trials have established the accuracy of sentinel nodes in the detecting metastatic disease. Novel advancements in tracers from the historically favored blue dyes and radio labeled colloids to near infrared imaging of fluorescent dyes has improved the ability to detect sentinel nodes and increased options for surgeons. The uterine cervix has been shown to be a feasible and accurate injection site for tracer, though the potential for under-evaluation of the para-aortic nodes remains a controversy, particularly for high-risk cancers. Additionally, sentinel node evaluation provides qualitatively different information than traditional staging techniques by identifying lymph nodes outside of traditional sampling locations and through the identification of very low volume meta static disease implants, such as isolated tumor cells. It is unclear how this altered staging information should be interpreted, guide the prescription of adjuvant therapy and its impact on long term clinical outcomes such as recurrence and survival. In this review we will discuss the evidence that has supported the use of the SLN technique in the staging of endometrial cancer, the options for surgical technique and the implications of managing the results of staging pathology.

Benign hysterectomy performed by gynecologic oncologists: Is selection bias altering our ability to measure surgical quality?

OBJECTIVE: To compare the characteristics of women undergoing hysterectomy for benign disease with either a benign gynecologist or a gynecologic oncologist and to assess for differences in complication rates with and without risk adjustment. METHODS: Patients undergoing benign hysterectomy recorded in the National Surgical Quality Improvement Program (NSQIP) targeted hysterectomy file in 2015 were identified. The primary outcome was any postoperative complication. Stratified analysis was performed by route of surgery. Bivariable tests and modified Poisson regression were used to adjust for confounding by procedure type and patient characteristics. RESULTS: We identified 17,639 patients who underwent hysterectomy for benign pathology, primary surgeon was a benign gynecologist (82%) or gynecologic oncologist (18%). Patients who underwent surgery with gynecologic oncologists were older (51yo v 46yo), had a higher mean BMI (32 v 30), and a higher prevalence of prior abdominal surgery (29% v 25%, p < 0.001), diabetes (10.6% v 7.0%), hypertension (34% v 25%) and higher ASA and Charlson comorbidity scores (p < 0.001, for all). For laparoscopy, surgery with a gynecologic oncologist was associated with a decreased risk of complication (RR 0.80, 95% CI 0.66-0.98). For laparotomy, surgery with a gynecologic oncologist was associated with an increased risk of complication (RR 1.18 95% CI 1.01-1.38), however, this was no longer the case with risk adjustment (aRR 0.90, 95% CI 0.76-1.07). CONCLUSIONS: Patients operated on by gynecologic oncologists have a higher prevalence of risk factors for complication compared to those operated on by benign gynecologists even with a benign indication for surgery. Quality measurement should account for this selection bias.

A comparison of sentinel lymph node biopsy to lymphadenectomy for endometrial cancer staging (FIRES trial): a multicentre, prospective, cohort study.

BACKGROUND: Sentinel-lymph-node mapping has been advocated as an alternative staging technique for endometrial cancer. The aim of this study was to measure the sensitivity and negative predictive value of sentinel-lymph-node mapping compared with the gold standard of complete lymphadenectomy in detecting metastatic disease for endometrial cancer. METHODS: In the FIRES multicentre, prospective, cohort study patients with clinical stage 1 endometrial cancer of all histologies and grades undergoing robotic staging were eligible for study inclusion. Patients received a standardised cervical injection of indocyanine green and sentinel-lymph-node mapping followed by pelvic lymphadenectomy with or without para-aortic lymphadenectomy. 18 surgeons from ten centres (tertiary academic and community non-academic) in the USA participated in the trial. Negative sentinel lymph nodes (by haematoxylin and eosin staining on sections) were ultra-staged with immunohistochemistry for cytokeratin. The primary endpoint, sensitivity of the sentinel-lymph-node-based detection of metastatic disease, was defined as the proportion of patients with node-positive disease with successful sentinel-lymph-node mapping who had metastatic disease correctly identified in the sentinel lymph node. Patients who had mapping of at least one sentinel lymph node were included in the primary analysis (per protocol). All patients who received study intervention (injection of dye), regardless of mapping result, were included as part of the assessment of mapping and in the safety analysis in an intention-to-treat manner. The trial was registered with ClinicalTrials.gov, number NCT01673022 and is completed and closed. FINDINGS: Between Aug 1, 2012, and Oct 20, 2015, 385 patients were enrolled. Sentinel-lymph-node mapping with complete pelvic lymphadenectomy was done in 340 patients and para-aortic lymphadenectomy was done in 196 (58%) of these patients. 293 (86%) patients had successful mapping of at least one sentinel lymph node. 41 (12%) patients had positive nodes, 36 of whom had at least one mapped sentinel lymph node. Nodal metastases were identified in the sentinel lymph nodes of 35 (97%) of these 36 patients, yielding a sensitivity to detect node-positive disease of 97·2% (95% CI 85·0-100), and a negative predictive value of 99·6% (97·9-100). The most common grade 3-4 adverse events or serious adverse events were postoperative neurological disorders (4 patients) and postoperative respiratory distress or failure (4 patients). 22 patients had serious adverse events, with one related to the study intervention: a ureteral injury incurred during sentinel-lymph-node dissection. INTERPRETATION: Sentinel lymph nodes identified with indocyanine green have a high degree of diagnostic accuracy in detecting endometrial cancer metastases and can safely replace lymphadenectomy in the staging of endometrial cancer. Sentinel lymph node biopsy will not identify metastases in 3% of patients with node-positive disease, but has the potential to expose fewer patients to the morbidity of a complete lymphadenectomy. FUNDING: Indiana University Health, Indiana University Health Simon Cancer Center, and the Indiana University Department of Obstetrics and Gynecology.

Surgical readmission and survival in women with ovarian cancer: Are short-term quality metrics incentivizing decreased long-term survival?

OBJECTIVES: To determine the association between treatment with neoadjuvant chemotherapy (NACT) or primary debulking surgery (PDS) and readmission after surgical hospitalization as well as overall survival among women with stage IIIC epithelial ovarian cancer (EOC). METHODS: We identified incident cases of stage IIIC EOC treated with both chemotherapy and surgery in the National Cancer Database (NCDB) from 2006 to 2012. 30-day readmissions were categorized as planned or unplanned. Log binomial models were used to estimate risk ratios and 95% confidence intervals. Survival analysis was performed using cox proportional hazards models. RESULTS: We identified 20,853 women with stage IIIC EOC. 15.6% (n=3242) were treated with NACT and 11.6% (n=2427) were readmitted within 30days of surgery, 59% (n=1421) were unplanned. NACT was associated with a 48% reduction in the risk of any readmission (aRR 0.52 95%CI 0.45-0.60) compared to PDS with adjustment for age, race, insurance, histology, year of diagnosis, and Charlson co-morbidity index score. However, in the same population, receipt of neoadjuvant chemotherapy was also associated with a 33% increase in the rate of death (HR 1.33 95%CI 1.29-1.40) with adjustment for the same factors. CONCLUSIONS: Among women with stage IIIC EOC, NACT is associated with both decreased rates of readmission and decreased survival compared to PDS. While selection bias may account for some of the observed differences in survival, the current focus on short-term hospital-wide quality metrics, such as postoperative readmission, in the ovarian cancer population, may be creating incentives inconsistent with long-term goals.

Variation in neoadjuvant chemotherapy utilization for epithelial ovarian cancer at high volume hospitals in the United States and associated survival.

OBJECTIVE: To estimate variation in the use of neoadjuvant chemotherapy by high volume hospitals and to determine the association between hospital utilization of neoadjuvant chemotherapy and survival. METHODS: We identified incident cases of stage IIIC or IV epithelial ovarian cancer in the National Cancer Database from 2006 to 2012. Inclusion criteria were treatment at a high volume hospital (>20 cases/year) and treatment with both chemotherapy and surgery. A logistic regression model was used to predict receipt of neoadjuvant chemotherapy based on case-mix predictors (age, comorbidities, stage etc). Hospitals were categorized by the observed-to-expected ratio for neoadjuvant chemotherapy use as low, average, or high utilization hospitals. Survival analysis was performed. RESULTS: We identified 11,574 patients treated at 55 high volume hospitals. Neoadjuvant chemotherapy was used for 21.6% (n=2494) of patients and use varied widely by hospital, from 5%-55%. High utilization hospitals (n=1910, 10 hospitals) had a median neoadjuvant chemotherapy rate of 39% (range 23-55%), while low utilization hospitals (n=2671, 14 hospitals) had a median rate of 10% (range 5-17%). For all ovarian cancer patients adjusting for clinical and socio-demographic factors, treatment at a hospital with average or high neoadjuvant chemotherapy utilization was associated with a decreased rate of death compared to treatment at a low utilization hospital (HR 0.90 95% CI 0.83-0.97 and HR 0.85 95% CI 0.75-0.95). CONCLUSIONS: Wide variation exists in the utilization of neoadjuvant chemotherapy to treat stage IIIC and IV epithelial ovarian cancer even among high volume hospitals. Patients treated at hospitals with low rates of neoadjuvant chemotherapy utilization experience decreased survival.

Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations.

The emphasis in contemporary medical oncology has been "precision" or "personalized" medicine, terms that imply a strategy to improve efficacy through targeted therapies. Similar attempts at precision are occurring in surgical oncology. Sentinel lymph node (SLN) mapping has recently been introduced into the surgical staging of endometrial cancer with the goal to reduce morbidity associated with comprehensive lymphadenectomy, yet obtain prognostic information from lymph node status. The Society of Gynecologic Oncology's (SGO) Clinical Practice Committee and SLN Working Group reviewed the current literature for preparation of this document. Literature-based recommendations for the inclusion of SLN assessment in the treatment of patients with endometrial cancer are presented. This article examines.

Sentinel Lymph Node Biopsy in Endometrial Cancer: a New Standard of Care?

OPINION STATEMENT: Lymph node status is one of the most important factors in determining prognosis and the need for adjuvant treatment in endometrial cancer (EMCA). Unfortunately, full lymphadenectomy bears significant surgical and postoperative risks. The majority of patients with clinical stage I disease will not have metastatic disease; thus, a full lymphadenectomy only increases morbidity in this population of patients. The use of the sentinel lymph node (SLN) biopsy has emerged as an alternative to complete lymphadenectomy in EMCA. By removing the highest yield lymph nodes, the SLN biopsy has the same diagnostic ability as lymphadenectomy while minimizing morbidity. The sensitivity of sentinel lymph node identification with robotic fluorescence imaging for detecting metastatic endometrial and cervical cancer (FIRES) trial published this year is the largest prospective, multi-institution trial investigating the accuracy of the SLN biopsy for endometrial and cervical cancer. Results of this trial found an excellent sensitivity (97.2%) and false negative rate (3%) with the technique. The conclusions from the FIRES trial and those of a recent meta-analysis are that SLN biopsy has an acceptable diagnostic accuracy in detecting lymphatic metastases, and can replace lymphadenectomy for this diagnostic purpose. There remains controversy surrounding the SLN biopsy in high-risk disease and the use of adjuvant therapy in the setting of low volume disease detected with ultrastaging. Current data suggests that the technique is accurate in high-risk disease and that the increased detection of metastasis helps guide adjuvant therapy such that oncologic outcomes are likely not affected by forgoing a full lymphadenectomy. Further prospective study is needed to investigate the impact of low volume metastatic disease on oncologic outcomes and the need for adjuvant therapy in these patients.

Controversies in the Surgical Management of Gynecologic Cancer: Balancing the Decision to Operate or Hesitate.

Cancer outcomes are largely measured in terms of disease-free survival or overall survival, which is highly dependent on timely diagnosis and access to treatment methods available within the country's existing health care system. Although cancer survival rates have markedly led in the past few decades, any improvement in the 5-year survival of gynecologic cancers has been modest, as in the case of ovarian and cervical cancers, or has declined, as in the case of endometrial cancer. The lack of effective screening options contributes to many women presenting with advanced-stage disease and the need for radical approaches to treatment. Although treatment for early-stage disease can lead to a cure, advanced-stage disease is fraught with a high potential for morbidity and mortality, and recent clinical trials have aimed to assess the noninferiority of minimally invasive options versus aggressive surgical approaches. Of particular interest is fertility-sparing treatments for endometrial and cervical cancers, which have recently been on the rise among younger women. Balancing morbidity with the risk of mortality, and loss of fertility and quality of life requires a targeted patient-centered approach to treatment. This is an ongoing area of intense research and sometimes may challenge current treatment paradigms. In this two-part review, we present an overview of current approaches to gynecologic cancer treatment and the need to de-escalate radical surgical approaches and preserve fertility. We also review the intricacies of ovarian and advanced endometrial cancer treatment, exploring the nuances in surgical debulking timing and its impact on outcomes.