Risks and benefits of sentinel lymph node evaluation in the management of endometrial intraepithelial neoplasia.

INTRODUCTION: Endometroid intraepithelial neoplasia (EIN) is a premalignant lesion to endometrial cancer. Increasing number of gynecologic oncologists are performing sentinel lymph node (SLN) evaluation during hysterectomy for EIN to ensure complete staging if there is cancer on the final specimen. However, there are no clear guidelines and the benefits and risks to performing SLN evaluation for EIN patients are unclear. AREAS COVERED: This narrative review examines the advantages and disadvantages of SLN evaluation for EIN patients and provides an algorithm to assist clinicians in selectively applying the procedure for maximal patient benefit. Relevant articles up to March 2024 were obtained from a PubMed search on SLN use with endometrial pathology. EXPERT OPINION: Sentinel lymph node evaluation for patients with EIN is safe, feasible, and particularly important for the approximately 10% of patients with high-risk endometrial carcinoma on final pathology. However, as most diagnosed carcinomas are low-risk, SLN evaluation would have limited oncologic benefit. While SLN assessment may overtreat most patients with EIN, a significant minority of patients will be improperly staged. We propose an algorithm highlighting the importance of maximal preoperative endometrial sampling and stratifying patients via risk factors to selectively identify those who would benefit most from SLN evaluation.

Endometroid intraepithelial neoplasia (EIN) is a premalignant lesion to endometrial cancer, the most common gynecologic cancer in the United States. The definitive treatment for EIN is hysterectomy. An increasing number of gynecologic oncologists are performing sentinel lymph node (SLN) assessment during surgery for EIN since 30­40% of patients with EIN will have underlying carcinoma. For those patients, lymph node evaluation is important for cancer staging, especially if high-risk or advanced stage disease is found on the pathologic specimen. The SLN procedure cannot be performed post-hysterectomy, so an improperly staged patient may require a second operation for lymphadenectomy; this has a greater chance of morbidity compared to an SLN biopsy. However, an SLN evaluation still confers perioperative risk and comes at an additional monetary cost, especially when most patients diagnosed with endometrial cancer after EIN will ultimately have low-risk, stage IA disease. We propose an algorithm for clinicians to help determine which patients with EIN would best benefit from the SLN procedure; this includes maximizing preoperative endometrial sampling and considering selective criterion with risk factors for concurrent endometrial carcinoma including age, endometrial thickness, obesity, and molecular classification.

Cesarean hysterectomy for placenta accreta spectrum: 3-2-1 approach.

Given the high risk of complications associated with cesarean hysterectomy for placenta accreta spectrum (PAS), any surgical approach and technique can yield utility in reducing the surgical morbidity. Here, we propose the 3-2-1 approach as a schema to be implemented in the proper setting for the surgical management of a PAS cesarean hysterectomy. The 3-2-1 approach begins with the surgical dissection of three anatomical landmarks that ultimately facilitate a safe surgical site for the ligation and transection of the uterine vessels. First-step is identification of the three anatomical landmarks which are (i) posterior lower uterine segment peritoneum de-serosalization, (ii) identification of the ureters laterally, and (iii) anterior bladder dissection. Posterior-to-anterior progression avoids encountering dense adhesions and hypervascularity in the anterior lower uterine segment early in the surgery. Further, allows better mobilization of the uterus to identify the anatomical landmarks laterally and anteriorly. Second-step is to deploy the 2-hand technique where the surgeon places one hand anteriorly and the other hand posteriorly in the lower uterine segment below the placental bed. The surgeon brings both hands together with flexed fingers perpendicular to the uterine tissue and gently elevates the uterus and placenta out of the pelvis and ensures safe anatomical distance to surrounding structures. Third-step is the consideration of a supracervical hysterectomy. In summary, this 3-2-1 approach to reflect the anatomy of enlarged lower uterine segment in PAS is a stepwise schema that can aid surgeons in the completion of a cesarean hysterectomy, with the goal to improve surgical outcomes.

An absence of translated consent forms limits oncologic clinical trial enrollment for limited English proficiency participants.

OBJECTIVES: A lack of diversity amongst participants in cancer clinical trials has raised scrutiny over the past decade. Patients with limited English proficiency (LEP) are further excluded. One modifiable reason for low LEP participation is a lack of non-English consent forms. METHODS: We queried the clinical trials registry database at an academic hospital serving a predominantly Spanish-speaking patient population. Clinical trials related to gynecology oncology were evaluated for the availability of fully translated Spanish consent forms, the racial and ethnic identification of enrolled patients, and the number of signed Spanish consents. Enrolment data was compared before and after 2019, when institutional financial support for document translation was withdrawn. RESULTS: Sixteen gynecologic oncology clinical trials were opened between 2014 and 2022, with 10 trials enrolling 128 patients. Eight trials opened prior to 2019, all with fully translated consent forms. Seven of these trials enrolled 99 participants, 70% of whom identified as Hispanic and 60% who signed a Spanish consent. Eight trials opened after 2019 and one had a fully translated consent form. Three of the trials enrolled 29 participants, with 10% of subjects identifying as Hispanic and none signing a Spanish consent form. CONCLUSIONS: There was a decrease in fully translated clinical trial consent forms for gynecologic oncology studies following the loss of subsidized translation services in our single institution with a predominantly LEP population. This correlated with a decrease in enrollment of Hispanic subjects. To increase enrollment of diverse participants, including those with LEP, simple actions such as fully translating consent forms would help maintain equity in research conduct and improve clinical outcomes through trial involvement.

OvaPrint-A Cell-free DNA Methylation Liquid Biopsy for the Risk Assessment of High-grade Serous Ovarian Cancer.

PURPOSE: High-grade serous ovarian carcinoma (HGSOC) is the most lethal epithelial ovarian cancer (EOC) and is often diagnosed at late stage. In women with a known pelvic mass, surgery followed by pathologic assessment is the most reliable way to diagnose EOC and there are still no effective screening tools in asymptomatic women. In the current study, we developed a cell-free DNA (cfDNA) methylation liquid biopsy for the risk assessment of early-stage HGSOC. EXPERIMENTAL DESIGN: We performed reduced representation bisulfite sequencing to identify differentially methylated regions (DMR) between HGSOC and normal ovarian and fallopian tube tissue. Next, we performed hybridization probe capture for 1,677 DMRs and constructed a classifier (OvaPrint) on an independent set of cfDNA samples to discriminate HGSOC from benign masses. We also analyzed a series of non-HGSOC EOC, including low-grade and borderline samples to assess the generalizability of OvaPrint. A total of 372 samples (tissue n = 59, plasma n = 313) were analyzed in this study. RESULTS: OvaPrint achieved a positive predictive value of 95% and a negative predictive value of 88% for discriminating HGSOC from benign masses, surpassing other commercial tests. OvaPrint was less sensitive for non-HGSOC EOC, albeit it may have potential utility for identifying low-grade and borderline tumors with higher malignant potential. CONCLUSIONS: OvaPrint is a highly sensitive and specific test that can be used for the risk assessment of HGSOC in symptomatic women. Prospective studies are warranted to validate OvaPrint for HGSOC and further develop it for non-HGSOC EOC histotypes in both symptomatic and asymptomatic women with adnexal masses.

Malignant peritoneal cytology in endometrial cancer: a contemporary review.

INTRODUCTION: In endometrial cancer, malignant peritoneal cytology (MPC) refers to the presence of tumor cells in the peritoneal cytologic specimen obtained at hysterectomy. MPC was once a component of uterine cancer staging criteria, but it is no longer included in the current revision. Multiple societies and organizations, however, continue to recommend peritoneal cytologic testing at the time of hysterectomy for endometrial cancer. AREAS COVERED: This contemporary review provides a clinical summary of recent studies evaluating MPC, including risk factors and prognosis. Compared to prior studies showing a lack of impact on oncologic outcome, recent studies have larger sample sizes, use stricter inclusion criteria, and perform histology/cancer stage-specific analyses to balance risk factors and provide explicit interpretations for oncologic outcomes related to MPC. These newer data provide evidence that MPC does have a prognostic impact. EXPERT OPINION: Three key domains related to MPC are followings: First, recognition of MPC as a prognostic factor for endometrial cancer irrespective to stage (early and advanced) and histology (endometrioid and non-endometrioid) is necessary. Second, peritoneal cytologic testing at the beginning of each staging surgery is recommended. Last, incorporation of peritoneal cytology status in adjuvant treatment algorithms is useful and merits further development.

The Invisible Hand of Industry.

Over the last decades, federal funding for medical research has decreased, while industry funding has increased. The majority of clinical trials are now industry funded. Involvement of industry raises documented concerns of reporting and publication bias, data suppression, and conclusions that may more favorably align with funder motivations rather than study results. However, industry involvement may also lead to scientific innovation, efficiency, and a more rapid timeline to bring new developments to patients. Through a careful review of a manuscript, the reader can understand the nature of industry involvement and interpret the results in this context.

Hormonal therapy or chemotherapy for early-stage, low-grade endometrial cancer with malignant peritoneal cytology: A comparative effectiveness study.

OBJECTIVE: To examine trends, characteristics, and outcomes related to hormonal therapy (HT) or chemotherapy (CT) use for early-stage, low-grade endometrial cancer with malignant peritoneal cytology (MPC). METHODS: This is a comparative effectiveness study querying the National Cancer Database from 2010 to 2017. Study population was 2730 women with stage I grade 1-2 endometrioid endometrial cancer who had MPC at primary hysterectomy. Patients were stratified based on postoperative therapy as: CT (n = 348, 12.7%), HT (n = 112, 4.1%), and neither two (n = 2270, 83.2%). Outcome measures included (i) trends and characteristics related to adjuvant therapy, assessed with a multivariable logistic regression model, and (ii) overall survival (OS) assessed with a multivariable Cox proportional hazards regression model. RESULTS: The number of women who received HT (2.7% to 4.5%) or no adjuvant systemic therapy (81.8% to 84.4%) increased while CT use decreased (15.5% to 11.1%)(P = 0.04). In a multivariable analysis, HT use was associated with older age, more recent year of diagnosis, grade 1 lesions, treatment at academic/research facilities, performance of minimally invasive surgery, no lympho-vascular space invasion, and absence of radiotherapy compared to CT use (P < 0.05). Neither HT (adjusted-hazard ratio [aHR] 0.61, 95% confidence interval [CI] 0.27-1.40) nor CT (aHR 1.33, 95% CI 0.92-1.93) were associated with OS compared to no adjuvant systemic therapy. In the low-risk group (stage IA, grade 1-2 tumors, and no lympho-vascular space invasion; n = 1453), 69 (4.7%) women received HT and 117 (8.1%) received CT. OS was similar across the three groups (P = 0.89). CONCLUSION: There was an increasing utilization of HT and decreasing utilization of CT as adjuvant therapy for early-stage, low-grade endometrial cancer with MPC. These two adjuvant therapies were not associated with short-term OS compared to neither two.