Understanding the patient experience in nonsurgical management of endometrial cancer and complex atypical hyperplasia due to obesity: A qualitative analysis.

Objectives: Patients with class 3 obesity (BMI ≥ 40) and significant medical comorbidities with complex atypical hyperplasia (CAH) and early-stage endometrial cancer (EC) present challenges in standard surgical management. Progestin therapy is an alternative used for patient-centered reasons, including the desire for uterine preservation or because surgery is not a safe option. Our objective was to gain insights into the patient experience when undergoing this treatment approach. Methods: We identified and recruited patients who received oral or IUD progesterone in the last 5 years for EC or CAH. We conducted semi-structured phone interviews regarding patients' experience with non-surgical management as well as decision-making factors to start progesterone and weight loss. Interviews were audio-recorded and transcriptions were analyzed for common themes. Results: A total of 20 interviews were performed. We enrolled nine patients with CAH, eight with grade 1 EC, and three with grade 2 EC. The majority of patients (18/20) were managed with IUD. We identified the following 5 common themes support in diagnostic workup and long-term outcomes, autonomy in care, thoroughness in counseling, emotional impact of diagnosis, and perception of obesity as a defining identity. Conclusion: The themes identified in the present study highlight the challenges and the stigma these patients face. It also demonstrates areas of opportunity in their counseling and care, which will help to build a more effective therapeutic relationship and ultimately lead to greater adherence in care.

Surgical training of gynecologic oncology fellows: Long-term trends and implications for future education.

OBJECTIVES: The surgical training of gynecologic oncology (GO) fellows is critical to providing excellent care to women with gynecologic cancers. We sought to evaluate changes in techniques and surgical volumes over an 18-year period among established GO fellowships across the US. METHODS: We emailed surveys to 30 GO programs that had trained fellows for at least 18 years. Surveys requested the number of surgical cases performed by a fellow for seventeen surgical procedures over each of five-time intervals. A One-Way Analysis of Variance was conducted for each procedure, averaged across institutions, to examine whether each procedure significantly changed over the 18-year span. RESULTS: 14 GO programs responded and were included in the analysis using SPSS. We observed a significant increase in the use of minimally invasive (MIS) procedures (robotic hysterectomy (p < .001), MIS pelvic (p = .001) and MIS paraaortic lymphadenectomy (p = .008). There was a concurrent significant decrease in corresponding "open" procedures. There was a significant decrease in all paraaortic lymphadenectomies. Complex procedures (such as bowel resection) remained stable. However, there was a wide variation in the number of cases reported with extremely small numbers for some critical procedures. CONCLUSIONS: The experience of GO fellows has shifted toward increased use of MIS. While these trends in care are appropriate, they do not diminish the need in many patients for complex open procedures. These findings should help spur the development of innovative training to maintain the ability to provide these core, specialty-defining procedures safely.

Cost-effectiveness analysis of margin-controlled surgery for vulvar Paget's disease.

Objectives: To determine the cost of two surgical treatment approaches for vulvar Paget's disease and model the cost-effectiveness considering differences in recurrence and reoperation over time. Methods: We assessed cost-effectiveness between excision guided by Mohs micrographic surgery (MMS-E) and traditional wide local excision (WLE). We examined billing data from patients with vulvar Paget's disease who underwent MMS-E (cases, n = 24, 2018-2022) or WLE (controls, n = 64, 1990-2020). We created typical treatment bundles incorporating physician-administered services and facility costs standardized to Medicare reimbursements in 2022 United States Dollars (USD). The primary measure of effectiveness was disease-free years of life. A secondary analysis estimated quality-adjusted life years (QALY). A Markov model simulated treatment pathways over a 10-year time horizon. Transition probabilities were based on institutional recurrence rates (3-year RR 6.7 % for MMS-E vs 34.1 % for WLE). We used a willingness-to-pay threshold of 100,000 USD per QALY. Results: The cost of a single surgical episode was 34,664 USD for MMS-E and 14,969 USD for WLE. In the setting of lower recurrence rates with MMS-E, the incremental cost was 12,789 USD per disease-free year gained. A secondary analysis incorporating QALY showed an incremental cost of 72,820 USD per QALY. Conclusions: MMS-E appears to be a cost-effective treatment for vulvar Paget's disease compared to historic standard of care. Our ability to estimate quality of life gained by avoiding disease recurrence was limited by scant data for this rare condition; thus, future studies incorporating health utility values are needed to facilitate a more comprehensive analysis.

Genome-wide association analyses of ovarian cancer patients undergoing primary debulking surgery identify candidate genes for residual disease.

Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10-8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

Relationship between frailty and nutrition: Refining predictors of mortality after primary cytoreductive surgery for ovarian cancer.

OBJECTIVE: We aimed to examine the interplay between frailty and nutritional status on 90-day mortality after primary cytoreductive surgery (PCS) for ovarian cancer (OC). METHODS: Patients with OC who underwent PCS from 1/2/2006-4/30/2018 at a single institution were identified. Frailty index (FI) includes 30 items and is calculated summing across all the item scores and dividing by the total; frailty was defined as FI ≥0.15. Nutritional status was considered impaired when preoperative serum albumin was <3.5 g/dL. Logistic regression was used to analyze the association between FI (continuous) and albumin status (binary) and 90-day postoperative mortality. RESULTS: A total of 533 patients (mean age, 64.4 years) were included, the majority were stage IIIC disease and serous histology. Albumin was <3.5 g/dL in 87 patients (16.3%) and 113 patients (21.2%) were considered frail. Median FI was 0.07 (IQR 0.03, 0.13). Postoperative 90-day mortality occurred in 24 patients (4.5%). Mortality within 90 days was higher amongst patients with low albumin (12/87, 13.8%), regardless of frailty status (13.8% [9/65] non-frail and 13.6% [3/22] frail patients). Ninety-day mortality in patients with normal albumin (n = 446) was over twice as likely in frail versus non-frail patients (5.5% [5/91] vs. 2.0% [7/355], respectively, p = 0.08). A model to assess 90-day mortality that included both FI and low albumin significantly improved the overall discrimination compared to low albumin alone (AUC 0.76 vs. 0.68 p = 0.03). CONCLUSION: Our findings suggest that frailty and nutrition are both related to 90-day mortality. Preoperative interventions to improve functional and nutritional characteristics are needed.

Practice patterns and complications of hysterectomy for invasive cervical cancer after the Laparoscopic Approach to Cervical Cancer trial.

BACKGROUND: After the publication of the Laparoscopic Approach to Cervical Cancer trial, the standard surgical approach for early-stage cervical cancer is open radical hysterectomy. Only limited data were available regarding whether the change to open abdominal hysterectomy observed after the Laparoscopic Approach to Cervical Cancer trial led to an increase in postoperative complication rates as a consequence of the decrease in the use of the minimally invasive approach. OBJECTIVE: This study aimed to analyze whether there was a correlation between the publication of the Laparoscopic Approach to Cervical Cancer trial and an increase in the 30-day complications associated with surgical treatment of invasive cervical cancer. STUDY DESIGN: Data from the American College of Surgeons National Surgical Quality Improvement Program were used to compare the results in the pre-Laparoscopic Approach to Cervical Cancer period (January 2016 to December 2017) vs the results in the post-Laparoscopic Approach to Cervical Cancer period (January 2019 to December 2020). The rates of each surgical approach (open abdominal or minimally invasive) hysterectomy for invasive cervical cancer during the 2 periods were assessed. Subsequently, 30-day major complication, minor complication, unplanned hospital readmission, and intra- or postoperative transfusion rates before and after the publication of the Laparoscopic Approach to Cervical Cancer trial were compared. RESULTS: Overall, 3024 patients undergoing either open abdominal hysterectomy or minimally invasive hysterectomy for invasive cervical cancer were included in the study. Of the patients, 1515 (50.1%) were treated in the pre-Laparoscopic Approach to Cervical Cancer period, and 1509 (49.9%) were treated in the post-Laparoscopic Approach to Cervical Cancer period. The rate of minimally invasive approaches decreased significantly from 75.6% (1145/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 41.1% (620/1509) in the post-Laparoscopic Approach to Cervical Cancer period, whereas the rate of open abdominal approach increased from 24.4% (370/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 58.9% (889/1509) in the post-Laparoscopic Approach to Cervical Cancer period (P<.001). The overall 30-day major complications remained stable between the pre-Laparoscopic Approach to Cervical Cancer period (85/1515 [5.6%]) and the post-Laparoscopic Approach to Cervical Cancer period (74/1509 [4.9%]) (adjusted odds ratio, 0.85; 95% confidence interval, 0.61-1.17). The overall 30-day minor complications were similar in the pre-Laparoscopic Approach to Cervical Cancer period (103/1515 [6.8%]) vs the post-Laparoscopic Approach to Cervical Cancer period (120/1509 [8.0%]) (adjusted odds ratio, 1.17; 95% confidence interval, 0.89-1.55). The unplanned hospital readmission rate remained stable during the pre-Laparoscopic Approach to Cervical Cancer period (7.9% per 30 person-days) and during the post-Laparoscopic Approach to Cervical Cancer period (6.3% per 30 person-days) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.58-1.04)]. The intra- and postoperative transfusion rates increased significantly from 3.8% (58/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 6.7% (101/1509) in the post-Laparoscopic Approach to Cervical Cancer period (adjusted odds ratio, 1.79; 95% confidence interval, 1.27-2.53). CONCLUSION: This study observed a significant shift in the surgical approach for invasive cervical cancer after the publication of the Laparoscopic Approach to Cervical Cancer trial, with a reduction in the minimally invasive abdominal approach and an increase in the open abdominal approach. The change in surgical approach was not associated with an increase in the rate of 30-day major or minor complications and unplanned hospital readmission, although it was associated with an increase in the transfusion rate.

Nonsurgical management of early-stage endometrial cancer due to obesity: a survey of the practice patterns of current Society of Gynecologic Oncology members.

Objective: Nonsurgical management for endometrial cancer in patients with class 3 obesity (BMI ≥ 40 kg/m2) is a challenging scenario given lack of consensus on patient selection and treatment options. Our objective was to evaluate trends in practice patterns and physician opinions in the Society of Gynecologic Oncology (SGO) on nonsurgical management of endometrial cancer and complex atypical hyperplasia due to obesity. Methods: An online survey was sent to all gynecologic oncologist members of the SGO with questions centered on decision-making for nonsurgical approaches for patients with class 3 obesity patients. Fisher's exact tests were used to assess the associations between offering nonsurgical management and geographic region, practice type, and time in practice. Results: 255 (19.8 %) members from 6 geographic regions responded, of which 183 (71.8 %) offered primary nonsurgical management of endometrial cancer to patients with class 3 obesity and 72 (28.2 %) do not. The choice to offer initial nonsurgical management did not vary based on geographic region, time in practice or practice type. When asked to select BMI cutoff, the majority (65.2 %) started to offer nonsurgical management was BMI 60-64 kg/m2. Progesterone intrauterine device was the preferred treatment (68.3 %, 125/183). Of those who offered nonsurgical management, 97.3 % (178/183) recommended resampling in 3-6 months. Conclusion: Primary nonsurgical management of endometrial cancer in patients with class 3 obesity is offered by most gynecologic oncologists in SGO. However, almost one-third of gynecologic oncologists indicated they do not offer nonsurgical management for endometrial cancer for obesity alone. Additional data are needed to determine the safety of both approaches in these complex patients.

Dose-dense neoadjuvant chemotherapy before radical surgery in cervical cancer: a retrospective cohort study and systematic literature review.

OBJECTIVE: To evaluate the role of dose-dense neoadjuvant chemotherapy followed by radical hysterectomy in reducing adjuvant radiotherapy in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB1-IB2/IIA1 cervical cancer with disrupted stromal ring and as an alternative to concurrent chemoradiotherapy in FIGO 2018 stages IB3/IIA2. METHODS: This was a retrospective cohort study including patients with FIGO 2018 stage IB1-IIA2 cervical cancer undergoing dose-dense neoadjuvant chemotherapy at the European Institute of Oncology in Milan, Italy between July 2014 and December 2022. Weekly carboplatin (AUC2 or AUC2.7) plus paclitaxel (80 or 60 mg/m2, respectively) was administered for six to nine cycles. Radiological response was assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria. The optimal pathological response was defined as residual tumor ≤3 mm. Kaplan-Meier curves were used to estimate survival rates. A systematic literature review on dose-dense neoadjuvant chemotherapy before surgery for cervical cancer was also performed. RESULTS: A total of 63 patients with a median age of 42.8 years (IQR 35.3-47.9) were included: 39.7% stage IB-IB2/IIA1 and 60.3% stage IB3/IIA2. The radiological response was as follows: 81% objective response rate (17.5% complete and 63.5% partial), 17.5% stable disease, and 1.6% progressive disease. The operability rate was 92.1%. The optimal pathological response rate was 27.6%. Adjuvant radiotherapy was administered in 25.8% of cases. The median follow-up for patients who underwent radical hysterectomy was 49.7 months (IQR 16.8-67.7). The 5-year progression-free survival and overall survival were 79% (95% CI 0.63 to 0.88) and 92% (95% CI 0.80 to 0.97), respectively. Fifteen studies including 697 patients met the eligibility criteria for the systematic review. The objective response rate, operability rate, and adjuvant radiotherapy rate across studies ranged between 52.6% and 100%, 64% and 100%, and 4% and 70.6%, respectively. CONCLUSIONS: Dose-dense neoadjuvant chemotherapy before radical surgery could be a valid strategy to avoid radiotherapy in stage IB1-IIA2 cervical cancer, especially in young patients desiring to preserve overall quality of life. Prospective research is warranted to provide robust, high-quality evidence.

Mohs surgery for female genital Paget's disease: a prospective observational trial.

BACKGROUND: Extramammary Paget's disease recurs often after traditional surgical excision. Margin-controlled surgery improves the recurrence rate for male genital disease but is less studied for female anatomy. OBJECTIVE: This study aimed to compare surgical and oncologic outcomes of margin-controlled surgery vs traditional surgical excision for female genital Paget's disease. STUDY DESIGN: We conducted a prospective observational trial of patients with vulvar or perianal Paget's disease treated with surgical excision guided by Mohs micrographic surgery between 2018 and 2022. The multidisciplinary protocol consisted of office-based scouting biopsies and modified Mohs surgery followed by surgical excision with wound closure under general anesthesia. Modified Mohs surgery cleared peripheral disease margins using a moat technique with cytokeratin 7 staining. Medial disease margins (the clitoris, urethra, vagina, and anus) were assessed using a hybrid of Mohs surgery and intraoperative frozen sections. Surgical and oncologic outcomes were compared with the outcomes of a retrospective cohort of patients who underwent traditional surgical excision. The primary outcome was 3-year recurrence-free survival. RESULTS: Three-year recurrence-free survival was 93.3% for Mohs-guided excision (n=24; 95% confidence interval, 81.5%-100.0%) compared to 65.9% for traditional excision (n=63; 95% confidence interval, 54.2%-80.0%) (P=.04). The maximum diameter of the excisional specimen was similar between groups (median, 11.3 vs 9.5 cm; P=.17), but complex reconstructive procedures were more common with the Mohs-guided approach (66.7% vs 30.2%; P<.01). Peripheral margin clearance was universally achieved with modified Mohs surgery, but positive medial margins were noted in 9 patients. Reasons included intentional organ sparing and poor performance of intraoperative hematoxylin and eosin frozen sections without cytokeratin 7. Grade 3 or higher postoperative complications were rare (0.0% for Mohs-guided excision vs 2.4% for traditional excision; P=.99). CONCLUSION: Margin control with modified Mohs surgery significantly improved short-term recurrence-free survival after surgical excision for female genital Paget's disease. Use on medial anatomic structures (the clitoris, urethra, vagina, and anus) is challenging, and further optimization is needed for margin control in these areas. Mohs-guided surgical excision requires specialized, collaborative care and may be best accomplished at designated referral centers.

Systemic therapy de-escalation in advanced ovarian cancer: a new era on the horizon?

Poly(ADP-ribose) polymerase inhibitors (PARPi) have sculpted the current landscape of advanced ovarian cancer treatment. With the advent of targeted maintenance therapies, improved survival rates have led to a timely interest in exploring de-intensified strategies with the goal of improving quality of life without compromising oncologic outcomes. The emerging concept of systemic treatment de-escalation would represent a new frontier in personalizing therapy in ovarian cancer. PARPi are so effective that properly selected patients treated with these agents might require less chemotherapy to achieve the same oncologic outcomes. The fundamental key is to limit de-escalation to a narrow subpopulation with favorable prognostic factors, such as patients with BRCA-mutated and/or homologous recombination-deficient tumors without macroscopic residual disease after surgery or other high-risk clinical factors. Potential de-escalation strategies include shifting PARPi in the neoadjuvant setting, de-escalating adjuvant chemotherapy after primary debulking surgery, reducing PARPi maintenance therapy duration, starting PARPi directly after interval debulking surgery, omitting maintenance therapy, and continuing PARPi beyond oligoprogression (if combined with locoregional treatment). Several ongoing trials are currently investigating the feasibility and safety of de-escalating approaches in ovarian cancer and the results are eagerly awaited. This review aims to discuss the current trends, drawbacks, and future perspectives regarding systemic treatment de-escalation in advanced ovarian cancer.

Muscle loss during cancer therapy is associated with poor outcomes in advanced ovarian cancer.

Data evaluating change in body composition during treatment of advanced cancer are limited. Here we evaluated computed tomography (CT)-based changes in muscle mass during treatment for advanced ovarian cancer (OC) and association with outcomes. We analyzed the preoperative and posttreatment skeletal muscle index (SMI), skeletal muscle area normalized for height of 109 patients with advanced OC who underwent primary surgery and platinum-based chemotherapy from 2006 to 2016. Based on an SMI less than 39 cm2/m2, 54.1% of patients were never sarcopenic, 24.8% were sarcopenic on both CT scans, and 21.1% were newly sarcopenic upon treatment completion. Patients who lost muscle during treatment had the worst survival of the 3 groups identified: median survival 2.6 years vs 4.6 years if sarcopenic on both CT scans and 4.8 years if never sarcopenic. Loss of muscle portends a poor prognosis among patients with OC. Additional research is needed to better understand and best mitigate these changes.

Cross-sectional survey of surgical practices among gynecologic oncologists in the United States.

OBJECTIVE: We sought to document current surgical practices among gynecologic oncologists in the United States. METHODS: In March/April 2020, we conducted a cross-sectional survey among members of the Society of Gynecologic Oncology to identify gynecologic oncology practice trends in the United States. The survey collected demographic data and queried participants on types of surgical procedures performed and chemotherapy use. Univariant and multivariant analyses were used to evaluate the association between surgeon practice type, region of practice, working with gynecologic oncology fellows, time in practice, and dominant surgical modality of practice on performance of specific procedures. RESULTS: Among 1199 gynecologic oncology surgeons who were emailed the survey, 724 completed the survey (60.4% response rate). Of these respondents, 170 (23.5%) were within 6 years of fellowship graduation, 368 (50.8%) identified as female; and 479 (66.2%) worked in an academic setting. Surgeons who worked with gynecologic oncology fellows were more likely to perform bowel surgery, upper abdominal surgery, complex upper abdominal surgery, and prescribe chemotherapy. Surgeons who were ≥ 13 years out from fellowship graduation were more likely to perform bowel surgery and complex abdominal surgery and less likely to prescribe chemotherapy and perform sentinel lymph node dissections (P < 0.05). CONCLUSIONS: These findings highlight the variation in surgical procedures performed by gynecologic oncologists in the United States. These data support that there are practice variations that would benefit from further investigation.

Comparison of the Contracted Accordion, Expanded Accordion, and Clavien-Dindo complication grading scales after ovarian cancer cytoreduction.

OBJECTIVE: To compare the ability of current complication reporting scales (Contracted Accordion Scale, Expanded Accordion Scale, Clavien-Dindo Scale) to reflect the severity of patient outcomes after cytoreductive surgery for ovarian cancer. METHODS: We included all patients undergoing primary debulking surgery for stage IIIC/IV ovarian cancer from 2006 to 2016 at two expert centers for ovarian cancer. Complications within 30 days of surgery were graded according to three scales. Outcomes included length of stay, mortality (90-day), and delayed initiation of chemotherapy (>42 days after surgery). Correlations were assessed using the Spearman rank correlation, and comparisons between groups were evaluated using the Wilcoxon rank-sum test and the χ2 test. RESULTS: Among the 892 patients, 185 (20.7%) patients had a grade 3 or higher complication per all scales. Patients with grade 3 or higher complications (compared with those with none, grade 1 or grade 2) had longer length of stay, higher 90-day mortality, and delayed initiation of chemotherapy. The expanded scales (Expanded Accordion Scale and Clavien Dindo Scale) provided a more refined characterization of outcome compared with the Contracted Accordion Scale. However, mortality was actually found to be as high as 25.0% for grade 5 complications using the Expanded Accordion Scale. Patients with organ failure or requiring an invasive procedure had significantly worse outcomes than those without either complication, highlighting the importance of separating these events. CONCLUSIONS: All three scales demonstrated general correlation with important outcomes after ovarian cancer surgery. However, the expanded scales (Clavien Dindo Scale and Expanded Accordion Scale) used important events commonly encountered after cytoreductive surgery, provided a more refined view of the severity of complications, and should be used in reporting outcomes in ovarian cancer.

Validation of a risk-based algorithm to reduce poor operative outcomes after complex surgery for ovarian cancer.

OBJECTIVE: We developed an algorithm that identifies patients at high risk of morbidity/mortality after cytoreductive surgery for advanced ovarian cancer. We have previously shown that the Mayo triage algorithm reduces operative mortality internally, followed by validation using an external low complexity national dataset. However, validation in a higher complexity surgical setting is required before widespread acceptance of this approach, and this was the goal of our study. METHODS: We included patients who underwent debulking surgery (including primary or interval debulking surgery) for stage IIIC/IV ovarian cancer between October 2011 and November 2019 (SCORPION trial patients until May 2016 and non-trial patients thereafter) at Fondazione Policlinico A Gemelli, Italy. Using the algorithm, we classified patients as either high-risk or triage-appropriate and compared 30-day grade 3+ complications and 90-day mortality using a χ2 test or Fisher's exact test. RESULTS: A total of 625 patients were included. The mean age was 58.7±11.4 years, 73.6% (n=460) were stage IIIC, and 63.0% (n=394) underwent primary debulking surgery. Surgical complexity was intermediate or high in 82.6% (n=516) of patients (95.7% (n=377) for primary surgery and 60.2% (n=139) for interval surgery), and 20.3% (n=127) were classified as high-risk. When compared with triage-appropriate patients, high-risk patients had (1) a threefold higher rate of 90-day mortality (6.3% vs 2.0%, p=0.02); (2) a higher likelihood of 90-day mortality following a grade 3+ complication (25.9% vs 10.0%, p=0.05); and (3) comparable rates of grade 3+ complications (21.3% vs 16.1%, p=0.17). CONCLUSION: The evidence-based triage algorithm identifies patients at high risk of morbidity/mortality after cytoreductive surgery. Triage high-risk patients are poor candidates for surgery when complex surgery is required. This algorithm has been validated in heterogeneous settings (internal, national, and international) and degree of surgical complexity. Risk-based decision making should be standard of care when planning surgery for patients with advanced ovarian cancer, whether primary or interval surgery.

Into the future: A pilot study combining imaging with molecular profiling to predict resectability in ovarian cancer.

OBJECTIVE: We sought to determine the predictive value of combining tumor molecular subtype and computerized tomography (CT) imaging for surgical outcomes after primary cytoreductive surgery in advanced stage high-grade serous ovarian cancer (HGSOC) patients. METHODS: We identified 129 HGSOC patients who underwent pre-operative CT imaging and post-operative tumor mRNA profiling. A continuous CT-score indicative of overall disease burden was defined based on six imaging measurements of anatomic involvement. Molecular subtypes were derived from mRNA profiling of chemo-naïve tumors and classified as mesenchymal (MES) subtype (36%) or non-MES subtype (64%). Fischer exact tests and multivariate logistic regression examined residual disease and surgical complexity. RESULTS: Women with higher CT-scores were more likely to have MES subtype tumors (p = 0.014). MES subtypes and a high CT-score were independently predictive of macroscopic disease and high surgical complexity. In multivariate models adjusting for age, stage and American Society of Anesthesiologists (ASA) score, patients with a MES subtype and high CT-score had significantly elevated risk of macroscopic disease (OR = 26.7, 95% CI = [6.42, 187]) and were more likely to undergo high complexity surgery (OR = 9.53, 95% CI = [2.76, 40.6], compared to patients with non-MES tumor and low CT-score. CONCLUSION: Preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women unlikely to have resectable disease and likely to require high complexity surgery. Along with other clinical factors, these may refine predictive scores for resection and assist treatment planning. Investigating methods for pre-surgical molecular subtyping is an important next step.

Quality is more important than quantity: pre-operative sarcopenia is associated with poor survival in advanced ovarian cancer.

BACKGROUND: Sarcopenia is prevalent among older patients with cancer and is associated with poor outcomes. OBJECTIVE: To explore the relationship between muscle mass, quality, and patient age with overall survival after surgery for advanced ovarian cancer. METHODS: Patients with advanced stage (IIIC/IV) ovarian cancer who underwent primary cytoreductive surgery between January 2006 and July 2016 were included. Body composition measures were calculated from pre-operative CT imaging: skeletal muscle index (skeletal muscle index=skeletal muscle area normalized for height), skeletal muscle density, and skeletal muscle gauge (product of skeletal muscle index and skeletal muscle density). Each measure was transformed to a z-score and evaluated for association with risk of death using Cox proportional hazards models. Recursive partitioning was used to classify patients into homogeneous subgroups considering age and skeletal muscle gauge as predictors of overall survival. RESULTS: The study included 429 patients (mean age 64.2 years). Increased age moderately correlated with decreased skeletal muscle gauge (r=-0.45). Decreasing skeletal muscle density and skeletal muscle gauge were significantly associated with increased risk of death; HR (95% CI) per 1-unit decrease in z-score of 1.24 (1.10 to 1.39) for skeletal muscle density and 1.27 (1.12 to 1.44) for skeletal muscle gauge. Associations were diluted after adjusting for age (1.13 (1.00 to 1.29) skeletal muscle density and 1.14 (0.99 to 1.30) skeletal muscle gauge). Recursive partitioning identified three subgroups: <60 years old, ≥60 years old with skeletal muscle gauge ≥937.3, and ≥60 years old with skeletal muscle gauge <937.3; median overall survival was 5.8, 3.3, and 2.3 years, respectively (p<0.001). CONCLUSIONS: Skeletal muscle gauge, a novel sarcopenia measure incorporating quantity and quality, was associated with poorer survival in patients with advanced ovarian cancer, particularly among patients older than 60. Expanding our knowledge of how sarcopenia relates to solid tumor outcomes among high-risk patients can modify our treatment approach.

Cervical versus Utero-Ovarian Ligament Injection of the Tracer for the Pelvic Sentinel Lymph Node Mapping in Gynecologic Oncology: A Prospective Observational Study.

OBJECTIVE: In gynecologic oncology, the consolidated injection site for the pelvic sentinel lymph node mapping is the cervix. However, in apparent early-stage ovarian cancer, current trials map the pelvic area injecting the tracers in the utero-ovarian ligament. A different injection site is proposed based on a possible different lymphatic ovarian drainage through the utero-ovarian ligament and uterus and consequently a different pelvic sentinel lymph node mapping than the cervix; however, this was never proven. On that basis, this study aimed to investigate whether injecting the tracer in the utero-ovarian ligament map the same or a different pelvic sentinel lymph node than the cervix. DESIGN: A prospective observational study was conducted. METHODS: All consecutive women undergoing primary surgery for gynecologic malignancy with planned pelvic sentinel lymph node mapping were enrolled. The cervical injection was performed at 3 and 9 o'clock injecting indocyanine green. Bilateral utero-ovarian ligament injection was performed by injecting methylene blue. The probability of detecting the same sentinel lymph node (concordance rate) and the probability of detecting a different sentinel lymph node (discordance rate) in each hemipelvis were compared using McNemar's exact test. RESULTS: Out of 36 hemipelvis (18 patients), the overall detection rate with cervical indocyanine green injection was 86.1% (31/36) versus 52.8% (19/36) with utero-ovarian ligament methylene blue injection (p = 0.0004). Indocyanine green and methylene blue identified the same sentinel lymph node in all hemipelvis when sentinel lymph node mapping was obtained by both dyes (19/19; concordance rate 100%). No different or additional sentinel lymph nodes were identified by one of the two dyes (0/19; discordance rate 0%). The probability of detecting the same pelvic sentinel lymph node by the two injection sites was significantly higher than the probability of detecting a different pelvic sentinel lymph node (p < 0.0001). LIMITATIONS: The use of two different dyes with known different sentinel lymph node mapping performance impedes to evaluate differences in detection rate attributable to the two injection sites, limiting the comparison only in hemipelvis in which both dyes identified a sentinel lymph node. CONCLUSIONS: The cervix and utero-ovarian ligament are two sites for the tracer injection that have a higher probability of detecting the same than a different pelvic sentinel lymph node. Given the higher technical challenge in performing the utero-ovarian ligament injection, these results suggest that the injection of the tracer into the cervix could be a more reliable alternative for the pelvic sentinel lymph node mapping in ovarian cancer.

Ten years of live surgical broadcast at Charité-MAYO conferences (2010-2019): a systematic evaluation of the surgical outcome.

OBJECTIVE: The international Charité-MAYO Conference aims to promote international dialog on diagnostics, management, scientific breakthroughs, and state-of-the-art surgical procedures in gynecology and gynecologic oncology and senology. Live surgeries are a fundamental tool of interdisciplinary and international exchange of experts in their respective fields. Currently, there is a controversial and emotional debate about the true value, risks, and safety of live surgical broadcasts. The aim of the current study is to analyze peri-operative risks in patients who were operated live during the Charité-MAYO Conferences. METHODS: Live surgeries were performed by the core Charité team consisting of gynecologic oncologic surgeons, breast and plastic surgeons, partly in collaboration with visiting gynecologic oncologic surgeons. We performed a retrospective analysis of live surgeries performed during seven Charité-MAYO Conferences from 2010 to 2019 held in Berlin, Germany. Patients' files and tumor databases were analyzed as required and patients were contacted to update their long-term follow-up. RESULTS: Sixty-nine patients who were operated live were included. The types of surgery were as follows: urogynecologic procedures (n=13), breast surgery (n=21), and gynecologic oncology surgery for ovarian, uterine, vulvar or cervical cancer (n=35). Peri-operative complications were assessed according to the Clavien-Dindo classification. Despite a high rate of complete resection and the high frequency of multivisceral procedures, the rate of peri-operative complications was within the range published in the literature. Time of surgery and length of intensive unit care and hospital stay did not differ from data acquired at the home institution. CONCLUSIONS: Based on our analysis, live surgeries appear to be safe when performed within a multidisciplinary setting without an increase in surgical morbidity and mortality compared with historical controls and without compromise of patients' outcome. This is the first analysis of its kind to set the basis for patient information and consent for this type of surgeries.

Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease.

IMPORTANCE: Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms. OBJECTIVE: To develop recommendations for the care of adults with EMPD. EVIDENCE REVIEW: A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD. FINDINGS: The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years. CONCLUSIONS AND RELEVANCE: Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.

Ultrastaging of 'negative' pelvic lymph nodes in patients with low- and intermediate-risk endometrioid endometrial cancer who developed non-vaginal recurrences.

OBJECTIVE: Evidence on micrometastases and isolated tumor cells as factors associated with non-vaginal recurrence in low- and intermediate-risk endometrial cancer is limited. The goal of our study was to investigate risk factors for non-vaginal recurrence in low- and intermediate-risk endometrial cancer. METHODS: Records of all patients with endometrial cancer surgically managed at the Mayo Clinic before sentinel lymph node implementation (1999-2008) were reviewed. We identified all patients with endometrioid low-risk (International Federation of Gynecology and Obstetrics (FIGO) stage I, grade 1 or 2 with myometrial invasion <50% and negative peritoneal cytology) or intermediate-risk (FIGO stage I, grade 1 or 2 with myometrial invasion ≥50% or grade 3 with myometrial invasion <50% and negative peritoneal cytology) endometrial cancer at definitive pathology after pelvic and para-aortic lymph node assessment. All pelvic lymph nodes of patients with non-vaginal recurrence (any recurrence excluding isolated vaginal cuff recurrences) underwent ultrastaging. RESULTS: Among 1303 women, we identified 321 patients with low-risk (n=236) or intermediate-risk (n=85) endometrial cancer (median age 65.4 years; 266 (82.9%) stage IA; 55 (17.1%) stage IB). Of the total of 321, 13 patients developed non-vaginal recurrence (Kaplan-Meier rate 4.7% by 60 months; 95% CI 2.1% to 7.2%): 11 hematogenous/peritoneal and two para-aortic and distant lymphatic. Myometrial invasion and lymphovascular space invasion were univariately associated with non-vaginal recurrence. In these patients, the original hematoxylin/eosin slides review confirmed all 646 pelvic and para-aortic removed lymph nodes as negative. The ultrastaging of 463 pelvic lymph nodes did not identify any occult metastases (prevalence 0%; 95% CI 0% to 22.8% considering 13 patients; 95% CI 0% to 0.8% considering 463 pelvic lymph nodes). CONCLUSION: There were no occult metastases in pelvic lymph nodes of patients with low- or intermediate-risk endometrial cancer with non-vaginal recurrence. Myometrial invasion and lymphovascular space invasion appear to be associated with non-vaginal recurrence.