Minimally Invasive Radical Hysterectomy for Cervical Cancer: A Systematic Review and Meta-analysis.

OBJECTIVE: To compare recurrence rate, progression-free survival (PFS), and overall survival for early-stage cervical cancer after minimally invasive (MIS) vs abdominal radical hysterectomy. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Library databases. METHODS OF STUDY SELECTION: We identified studies from 1990 to 2020 that included women with stage I or higher cervical cancer treated with primary radical hysterectomy and compared recurrence and/or PFS and overall survival with MIS vs abdominal radical hysterectomy. (The review protocol was registered with the International Prospective Register of Systematic Reviews: CRD4202173600). TABULATION, INTEGRATION, AND RESULTS: We performed random-effects meta-analyses overall and by length of follow-up. Fifty articles on 40 cohort studies and 1 randomized controlled trial that included 22 593 women with cervical cancer met the inclusion criteria. Twenty percent of the studies had <36 months of follow-up, and 24% had more than 60 months of follow-up. The odds of PFS were worse for women undergoing MIS radical hysterectomy (odds ratio 1.54; 95% CI [confidence interval], 1.24-1.94; 14 studies). When limited to studies with longer follow-up, the odds of PFS were progressively worse with MIS radical hysterectomy (HR [hazard ratio] 1.48 for >36 months; 95% CI, 1.21-1.82; 10 studies; HR 1.69 for >48 months; 95% CI, 1.26-2.27; 5 studies; and HR 2.020 for >60 months; 95% CI, 1.36-3.001; 3 studies). For overall survival, the odds were not significantly different for MIS vs abdominal hysterectomy (odds ratio 0.94; 95% CI, 0.66-1.35; 14 studies) (HR 0.99 for >36 months; 95% CI, 0.66-1.48; 9 studies; HR 1.05 for >48 months; 95% CI, 0.57-1.94; 4 studies; and HR 1.35 for >60 months; 95% CI, 0.73-2.51; 3 studies). CONCLUSION: In our meta-analysis of 50 studies, MIS radical hysterectomy was associated with worse PFS than open radical hysterectomy for early-stage cervical cancer. The emergence of this finding with longer follow-up highlights the importance of long-term, high-quality studies to guide cancer and surgical treatments.

Basic social resource needs screening in the gynecologic oncology clinic: a quality improvement initiative.

BACKGROUND: Social determinants of health are known to contribute to disparities in health outcomes. Routine screening for basic social needs is not a part of standard care; however, the association of those needs with increased healthcare utilization and poor compliance with guideline-directed care is well established. OBJECTIVE: In this study, we aimed to assess the prevalence of basic social resource needs identified through a quality improvement initiative in a gynecologic oncology outpatient clinic. In addition, we aimed to identify clinical and demographic factors associated with having basic social resource needs. STUDY DESIGN: We performed a prospective cohort study of women presenting to a gynecologic oncology clinic at an urban academic institution who were screened for basic social resource needs as part of a quality improvement initiative from July 2017 to May 2018. The following 8 domains of resource needs were assessed: food insecurity, housing insecurity, utility needs, financial strain, transportation, childcare, household items, and difficulty reading hospital materials. Women with needs were referred to resources to address those needs. Demographic and clinical information were collected for each patient. The prevalence of needs and successful follow-up interventions were calculated. Patient factors independently associated with having at least 1 basic social resource need were identified using multivariable Poisson regression. RESULTS: A total of 752 women were screened in the study period, of whom 274 (36%) reported 1 or more basic social resource need, with a median of 1 (range, 1-7) need. Financial strain was the most commonly reported need (171 of 752, 23%), followed by transportation (119 of 752, 16%), difficulty reading hospital materials (54 of 752, 7%), housing insecurity (31 of 752, 4%), food insecurity (28 of 752, 4%), household items (22 of 752, 3%), childcare (15 of 752, 2%), and utility needs (13 of 752, 2%). On multivariable analysis, independent factors associated with having at least 1 basic social resource need were being single, divorced or widowed, nonwhite race, current smoker, nonprivate insurance, and a history of anxiety or depression. A total of 36 of 274 (13%) women who screened positive requested assistance and were referred to resources to address those needs. Of the 36 women, 25 (69%) successfully accessed a resource or felt equipped to address their needs, 9 (25%) could not be reached despite repeated attempts, and 2 (6%) declined assistance. CONCLUSION: Basic social resource needs are prevalent in women presenting to an urban academic gynecologic oncology clinic and can be identified and addressed through routine screening. To help mitigate ongoing disparities in this population, screening for and addressing basic social resource needs should be incorporated into routine comprehensive care in gynecologic oncology clinics.

NCCN Guidelines Insights: Cervical Cancer, Version 1.2020.

The NCCN Guidelines for Cervical Cancer provide recommendations for diagnostic workup, staging, and treatment of patients with the disease. These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to first- and second-line systemic therapy recommendations for patients with recurrent or metastatic disease, and emerging evidence on a new histopathologic classification system for HPV-related endocervical adenocarcinoma.

Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.

Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.

Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

Endometrial carcinoma is a malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus. Endometrial carcinoma is the most common gynecologic malignancy. Approximately two-thirds of endometrial carcinoma cases are diagnosed with disease confined to the uterus. The complete NCCN Guidelines for Uterine Neoplasms provide recommendations for the diagnosis, evaluation, and treatment of endometrial cancer and uterine sarcoma. This manuscript discusses guiding principles for the diagnosis, staging, and treatment of early-stage endometrial carcinoma as well as evidence for these recommendations.

Sentinel lymph node assessment in endometrial cancer: a systematic review and meta-analysis.

BACKGROUND: In the staging of endometrial cancer, controversy remains regarding the role of sentinel lymph node mapping compared with other nodal assessment strategies. OBJECTIVE: We conducted a systematic review to evaluate the diagnostic accuracy and clinical impact of sentinel lymph node mapping in the management of endometrial cancer. DATA SOURCES: We searched Medline, Embase, and the Cochrane Central Registry of Controlled trials for studies published in English before March 25, 2016 (PROSPERO CRD42016036503). STUDY ELIGIBILITY CRITERIA: Studies were included if they contained 10 or more women with endometrial cancer and reported on the detection rate, sensitivity, and/or impact on treatment or survival of sentinel lymph node mapping. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors independently reviewed abstracts and full-text articles for inclusion and assessed study quality. The detection rate, sensitivity, and factors associated with successful mapping (study size, body mass index, tumor histology and grade, injection site, dye type) were synthesized through random-effects meta-analyses and meta-regression. RESULTS: We identified 55 eligible studies, which included 4915 women. The overall detection rate of sentinel lymph node mapping was 81% (95% confidence interval, 77-84) with a 50% (95% confidence interval, 44-56) bilateral pelvic node detection rate and 17% (95% confidence interval, 11-23) paraaortic detection rate. There was no difference in detection rates by patient body mass index or tumor histology and grade. Use of indocyanine green increased the bilateral detection rate compared with blue dye. Additionally, cervical injection increased the bilateral sentinel lymph node detection rate but decreased the paraaortic detection rate compared with alternative injection techniques. Intraoperative sentinel lymph node frozen section increased the overall and bilateral detection rates. The sensitivity of sentinel node mapping to detect metastases was 96% (95% confidence interval, 91-98); ultrastaging did not improve sensitivity. Compared with women staged with complete lymphadenectomy, women staged with sentinel lymph node mapping were more likely to receive adjuvant treatment. CONCLUSION: Sentinel lymph node mapping is feasible and accurately predicts nodal status in women with endometrial cancer. The current data favors the use of cervical injection techniques with indocyanine green. Sentinel lymph mapping may be considered an alternative standard of care in the staging of women with endometrial cancer.

Vulvar Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is a rare gynecologic malignancy. Ninety percent of vulvar cancers are predominantly squamous cell carcinomas (SCCs), which can arise through human papilloma virus (HPV)-dependent and HPV-independent pathways. The NCCN Vulvar Cancer panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecological oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vulvar Cancer provide an evidence- and consensus-based approach for the management of patients with vulvar SCC. This manuscript discusses the recommendations outlined in the NCCN Guidelines for diagnosis, staging, treatment, and follow-up.

The Utility of Sentinel Lymph Node Mapping in High-Grade Endometrial Cancer.

OBJECTIVE: The aim of this study was to report the utility and false-negative rates of sentinel lymph node (SLN) mapping during surgical staging of women with high-grade, apparent uterine-confined endometrial cancer. METHODS: This was a single-institution study performed at a high-volume academic center. From December 2012 to December 2015, women with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, and carcinosarcoma) underwent SLN mapping via cervical injection followed by robot-assisted total laparoscopic hysterectomy and completion lymphadenectomy. Ultrastaging of SLNs was performed in patients with tumors with any degree of myoinvasion. Patient demographics, SLN test characteristics, treatment, and recurrence outcomes were prospectively evaluated for analysis. RESULTS: Fifty-two patients with high-grade histologic findings underwent SLN mapping followed by completion lymphadenectomy. The median patient age was 64 years, and median body mass index was 31.8 kg/m2. Most patients had either serous (46%) or grade 3 endometrioid histology (27%) on preoperative biopsy. Nine patients had nodal metastases, 7 of whom had metastases identified in SLNs. No low-volume nodal metastases were identified on ultrastaging. Two patients had false-negative SLN mapping (22%). After a median follow-up of 15.6 months, 14 recurrences (27%) were diagnosed; all were distant or multisite relapses. Sentinel lymph node mapping did not impact the choice of adjuvant therapy or recurrence risk in node-positive patients. CONCLUSIONS: Sentinel lymph node detection of metastases in patients with high-grade endometrial cancer is high, but false-negative results were encountered. More research is needed to determine whether SLN mapping can safely replace systemic lymphadenectomy in women with high-risk histologic findings.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent ovarian carcinoma: analysis of 30-day morbidity and mortality.

PURPOSE: The aim of this study was to evaluate morbidity and mortality associated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian, fallopian tube, and primary peritoneal cancer. METHODS: A retrospective review of patients undergoing cytoreductive surgery plus HIPEC from 1 January 2007 to 29 July 2013 at two academic medical centers was performed. Grade 3/4 complications (National Cancer Institute's Common Toxicity Criteria version 4.0) from day of surgery until 30 days postoperatively were recorded. RESULTS: Thirty-two patients were identified, with 27 cases of ovarian cancer, three primary peritoneal cancers, and two fallopian tube cancers. Indications included 24 at the time of cancer recurrence, six at interval surgical resection, and two in the consolidative setting. Hyperthermic chemotherapeutic regimens included carboplatin (n = 21), cisplatin (n = 4), oxaliplatin (n = 2), oxaliplatin + intravenous 5-fluorouracil (n = 1), doxorubicin (n = 1), and cisplatin + doxorubicin (n = 1). Infusion time ranged from 30 to 90 min, with a maximum temperature range of 41-43 °C. The combined grade 3/4 morbidity rate was 65.6 %, and the most frequent morbidities included grade 3 anemia (40.6 %), infection (15.6 %), and pleural effusion (12.5 %). Six patients required readmission (18.8 %), and two patients required reoperation (6.2 %). Full-thickness diaphragm resection/peritoneal stripping had a significant association with grade 3/4 pleural effusions (p = 0.0007). CONCLUSIONS: Cytoreductive surgery plus HIPEC is feasible in patients with ovarian cancer with 65.6 % grade 3/4 morbidity and no deaths. Balancing these complications with potential survival benefits is important in centers considering implementing HIPEC protocols.

Updates and emerging therapies for rare epithelial ovarian cancers: one size no longer fits all.

Epithelial ovarian carcinoma consists of not one, but several, entities. A number of subtypes exist, including high-grade and low-grade serous carcinomas, clear cell, endometrioid carcinoma and mucinous carcinoma. Historically, women with epithelial ovarian cancer have been treated similarly and "lumped" in the same cooperative group treatment trials, irrespective of their tumor subtype. Recently, however, differences in epidemiology, tumor biology, tumor marker expression and treatment responses have been elucidated among the histologic subtypes, with a clear distinction emerging between the Type I, lower grade tumors and Type 2, higher grade epithelial malignancies. A mounting body of research demonstrates that a "one-size-fits-all" treatment approach to epithelial ovarian tumors is no longer relevant, especially for the Type I subtypes. Indeed, with the exception of high-grade serous carcinoma, most other epithelial subtypes exhibit some degree of chemotherapy resistance, rendering treatment problematic, especially in the setting of advanced disease. This review summarizes the genetic, molecular, and clinical differences of the more rare, but clinically important, Type I epithelial ovarian tumors. Additionally, a critical appraisal of both historical and contemporary treatment approaches and the rationale for targeted therapies are emphasized.

Cervical Cancer, Version 2.2015.

The NCCN Guidelines for Cervical Cancer provide interdisciplinary recommendations for treating cervical cancer. These NCCN Guidelines Insights summarize the NCCN Cervical Cancer Panel's discussion and major guideline updates from 2014 and 2015. The recommended systemic therapy options for recurrent and metastatic cervical cancer were amended upon panel review of new survival data and the FDA's approval of bevacizumab for treating late-stage cervical cancer. This article outlines relevant data and provides insight into panel decisions regarding various combination regimens. Additionally, a new section was added to provide additional guidance on key principles of evaluation and surgical staging in cervical cancer. This article highlights 2 areas of active investigation and debate from this new section: sentinel lymph node mapping and fertility-sparing treatment approaches.

Uterine Sarcoma, Version 1.2016: Featured Updates to the NCCN Guidelines.

The NCCN Guidelines for Uterine Neoplasms provide interdisciplinary recommendations for treating endometrial carcinoma and uterine sarcomas. These NCCN Guidelines Insights summarize the NCCN Uterine Neoplasms Panel's 2016 discussions and major guideline updates for treating uterine sarcomas. During this most recent update, the panel updated the mesenchymal tumor classification to correspond with recent updates to the WHO tumor classification system. Additionally, the panel revised its systemic therapy recommendations to reflect new data and collective clinical experience. These NCCN Guidelines Insights elaborate on the rationale behind these recent changes.

Lifestyle and Weight Management Counseling in Uterine Cancer Survivors: A Study of the Uterine Cancer Action Network.

OBJECTIVE: The purpose of this study was to examine the experiences, attitudes, and preferences of uterine cancer survivors with regard to weight and lifestyle counseling. MATERIALS AND METHODS: Members of the US Uterine Cancer Action Network of the Foundation for Women's Cancer were invited to complete a 45-item, Web-based survey. Standard descriptive statistical methods and χ tests were used to analyze responses. RESULTS: One hundred eighty (28.3%) uterine cancer survivors completed the survey. Median age was 58 years, 85% were white, and median survivorship period was 4.4 years. Most had stage I-II disease (69%) and were overweight or obese (65%). Eighty-nine percent of respondents received care by a gynecologic oncologist. Increased respondent body mass index was associated with decreased exercise frequency (P = 0.016). Only 50% of respondents underwent any weight/lifestyle counseling, with those living in the West and Southwest reporting the highest rates (70.8% and 69.2%, P = 0.011). Most who received counseling felt that discussions were motivating, performed in a sensitive manner, and did not undermine the patient-physician relationship. Specific recommendations were rarely offered; there were no reported referrals to weight loss programs or bariatric specialists, and few (6%) reported referrals to nutritionists. Respondents (85%) preferred their gynecologic oncologist address weight using direct, face-to-face counseling with specific recommendations regarding interventions and referral to specialists. Finally, self-reported overweight respondents experienced greater success with weight loss compared to those reporting obesity or morbid obesity (30.8% vs 15.8% vs 12.5%, P = 0.011). CONCLUSIONS: Uterine cancer survivors reported high obesity, low activity rates, and a desire for substantive weight loss counseling from their gynecologic oncologists. Respondents suggested that current counseling practices are inadequate and incongruent with their needs. Further research to define optimal timing, interventional strategies, and specific recommendations for successful lifestyle changes in this population is warranted.

High-grade endometrial cancer: revisiting the impact of tumor size and location on outcomes.

OBJECTIVE: Research on tumor size (TS) and intracavitary tumor location in endometrial cancer has focused primarily on low-grade tumors. Data in patients with high-grade histology are limited. Our goal is to determine if TS or lower uterine segment (LUS) involvement, is associated with nodal disease and recurrence in women with high-grade endometrial cancer. METHODS: This is an IRB-approved, multi-institutional cohort study of patients with clinically early-stage, high-grade endometrial cancer who underwent comprehensive surgical staging. Records were reviewed for demographic, pathologic, and treatment data. Nodal involvement and recurrence as a function of TS and location were estimated with odds ratios and hazard ratios. RESULTS: From 2005 to 2012, 208 patients were identified. Of these, 188 patients had tumor location and 183 had TS reported. There were 75 endometrioid (36.1%), 35 serous (16.8%), 12 clear cell (5.8%), and 26 carcinosarcoma (12.5%) cases, and 60 (28.8%) undifferentiated or mixed histologies. There were 55 recurrences (median follow up 17.2 mo). LUS tumors were associated with pelvic and para-aortic nodal disease (OR 3.83, 95% CI 1.70-8.60, p<0.01, OR 5.13, 95% CI 1.96-13.45, p<0.01). TS ≥ 2 cm was associated with pelvic nodal disease (27.4% vs. 0%, p=0.01; OR 10.00, p=0.01). Neither TS nor LUS location was independently associated with recurrence. CONCLUSIONS: In high-grade endometrial cancers, tumor involvement of the LUS and TS>2 cm was associated with pelvic nodal disease, and LUS involvement was also significantly associated with para-aortic nodal disease. There was no association between LUS involvement or TS>2 cm and recurrence.

A comparison of colorimetric versus fluorometric sentinel lymph node mapping during robotic surgery for endometrial cancer.

OBJECTIVE: The study objective was to compare the ability to detect sentinel lymph nodes (SLNs) in women with endometrial cancer (EC) or complex atypical hyperplasia (CAH) using fluorometric imaging with indocyanine green (ICG) versus colorimetric imaging with isosulfan blue (ISB). METHODS: Women underwent SLN mapping, with either ISB or ICG, during robotic-assisted total laparoscopic hysterectomy (RA-TLH) from September 2012 to March 2014. SLNs were submitted for permanent pathologic analysis. Completion lymphadenectomy and ultrastaging were performed according to institutional protocols. RESULTS: RA-TLH and SLN mapping was performed in 71 women; 64 had EC (64) and 7 had CAH. Age, body mass index (BMI), stage and tumor characteristics were similar in the ICG versus the ISB cohorts. Overall, SLNs were identified bilaterally (62.0%), unilaterally (21.1%), or neither (16.9%), and in 103 of 142 hemi-pelvises (72.5%). The mean number of SLNs retrieved per hemipelvis was 2.23(SD 1.7). SLNs were identified in the hypogastric (76.8%), external iliac (14.2%), common iliac (4.5%) and paraaortic (4.5%) regions. ICG mapped bilaterally in 78.9% of women compared with 42.4% of those injected with ISB (p=0.02). Five women (7%) had positive lymph nodes, all identified by the SLN protocol (false negative rate: 0%). On multivariate analysis, BMI was negatively correlated with bilateral mapping success (p=0.02). When stratified by dye type, the association with BMI was only significant for ISB (p=0.03). CONCLUSIONS: Fluorescence imaging with ICG may be superior to colorimetric imaging with ISB in women undergoing SLN mapping for endometrial cancer. SLN mapping success is negatively associated with increasing patient BMI only when ISB is used.