Steerable DROP-IN radioguidance during minimal-invasive non-robotic cervical and endometrial sentinel lymph node surgery.

PURPOSE: The recently introduced tethered DROP-IN gamma probe has revolutionized the way robotic radioguided surgery is performed, fully exploiting the nature of steerable robotic instruments. Given this success, the current first-in-human study investigates if the DROP-IN can also provide benefit in combination with steerable non-robotic instruments during conventional laparoscopic surgery, showing equivalence or even benefit over a traditional rigid gamma probe. METHODS: The evaluation was performed in ten patients during laparoscopic cervical (n = 4) and endometrial (n = 6) cancer sentinel lymph node (SLN) procedures. Surgical guidance was provided using the hybrid, or bi-modal, SLN tracer ICG-99mTc-nanocolloid. SLN detection was compared between the traditional rigid laparoscopic gamma probe, the combination of a DROP-IN gamma probe and a steerable laparoscopic instrument (LaproFlex), and fluorescence imaging. RESULTS: The gynecologists experienced an enlarged freedom of movement when using the DROP-IN + LaproFlex combination compared to the rigid laparoscopic probe, making it possible to better isolate the SLN signal from background signals. This did not translate into a change in the SLN find rate yet. In both cervical and endometrial cancer combined, the rigid probe and DROP-IN + LaproFlex combination provided an equivalent detection rate of 96%, while fluorescence provided 85%. CONCLUSION: We have successfully demonstrated the in-human use of steerable DROP-IN radioguidance during laparoscopic cervical and endometrial cancer SLN procedures, expanding the utility beyond robotic procedures. Indicating an improved surgical experience, these findings encourage further investigation and consideration on a path towards routine clinical practice and improved patient outcome. TRIAL REGISTRATION: HCB/2021/0777 and NCT04492995; https://clinicaltrials.gov/study/NCT04492995.

Key issues in diagnostic accuracy of sentinel lymph node biopsy in early-stage ovarian cancer: systematic review and meta-analysis.

OBJECTIVE: Sentinel lymph node (SLN) mapping may reduce the morbidity of lymphadenectomy while maintaining diagnostic accuracy. Nevertheless, SLN mapping in epithelial ovarian cancer is still under investigation. This systematic review and meta-analysis aimed to assess the detection rate and diagnostic accuracy of SLN mapping for each field (pelvic and para-aortic), and to evaluate the tracers and doses used. METHODS: A systematic search was conducted in PubMed, Cochrane Library, Scopus, and Web of Science. Patients with clinical stages I-II ovarian cancer undergoing SLN biopsy (index test) and a systematic pelvic and para-aortic lymphadenectomy (reference standard) were included. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. A meta-analysis was performed to assess SLN mapping detection rates and diagnostic accuracy for each field (pelvic and para-aortic) and by subgroups (type of tracer and dosage). RESULTS: 239 patients from four studies were included. The SLN detection rate was 59.5% (95% CI 50.2 to 68.1%) and 64.4% (95% CI 58.2 to 70.2%) for the pelvic and para-aortic fields, respectively. The use of technetium-99 (99mTc), alone or in combination, compared with the use of indocyanine green alone, was associated with a higher detection rate in both the pelvic (66.6%; 95% CI 53.3 to 78.3%; p=0.1211) and para-aortic (87.1%; 95% CI 76.9 to 93.9%, p=0.0000013) fields. The use of 0.2-0.5 mL of indocyanine green was associated with higher pelvic (68%; 95% CI 53.3 to 80.4%, p=0.1057) and para-aortic (88.3%, 95% CI 77.4 to 95.2%, p=0.0000018) detection rates compared with a 2 mL indocyanine green injection. Diagnostic accuracy, sensitivity, specificity, and negative predictive value of SLN for lymph node metastasis were: 100% each for the pelvic field and 98.1%, 85.7%, 100%, and 97.8%, respectively, for the para-aortic field. CONCLUSION: The use of 99mTc in combination with a low volume injection (0.2-0.5 mL) of indocyanine green increased SLN detection rates. In apparent early stage epithelial ovarian cancer, SLN is a feasible technique with a high diagnostic accuracy. TRIAL REGISTRATION: PROSPERO CRD42024544812.

Multimodal prehabilitation improves functional capacity in patients with advanced ovarian cancer undergoing cytoreductive surgery.

OBJECTIVE: Prehabilitation, defined as the preparatory intervention to increase patient preparedness in the lead-up to surgery, has shown a decrease in post-operative complications in various types of surgery. However, there is limited evidence in advanced ovarian cancer surgery. This study aimed to evaluate the benefits of multimodal prehabilitation in advanced ovarian cancer patients in terms of improving physical functioning, body composition, and psychological well-being during the pre-operative period. METHODS: This single-center, ambispective study included patients with advanced ovarian cancer eligible for primary or interval cytoreductive surgery. Participants attended a multimodal prehabilitation program comprising medical optimization, supervised exercise training, nutritional counseling and supplementation, and psychological support. Functional capacity, nutritional status, and psychological well-being were assessed before the start of the program and before surgery. RESULTS: 62 patients were referred for the multimodal prehabilitation program from July 2019 to May 2023. Median adherence to the training program reached 75% (IQR 58-87%). 35 patients (59%) were evaluated pre-operatively. Patients attended a median of 8 (IQR 6-12) supervised exercise training sessions with no differences between those who underwent primary or interval cytoreductive surgery (p=0.80). A significant improvement was observed in functional capacity according to the 6 min walk test (mean 33.1 m, 95% CI 10.5 to 55.5) as well as in the 30 s sit-to-stand test (+3.3 repetitions, 95% CI 1.8 to 4.8), with both being above the minimal clinically important difference of 14 m and two repetitions, respectively. Patients also reported a significant decrease in depression, anxiety, and total scores of the Hospital Anxiety and Depression Scale. CONCLUSIONS: Multimodal prehabilitation in patients with advanced ovarian cancer undergoing cytoreductive surgery improves pre-operative physical functioning and decreases emotional distress. Further controlled studies with a larger sample size are warranted to corroborate improvement in functional capacity, body composition, and psychological well-being through prehabilitation programs.

Attitudes toward uterus transplantation. An option for motherhood?

INTRODUCTION: Uterus transplantation is a novel surgical procedure that allows women with absolute uterine factor infertility to carry a pregnancy and give birth. While previous studies have explored the attitudes of women with absolute uterine factor infertility toward uterus transplantation, none have surveyed and compare their views with other groups of interest (Morris syndrome women, relatives of Morris syndrome and Rokitansky syndrome women, infertile women and women of childbearing age) in the same sociocultural setting. The objective of this study was to evaluate attitudes and insights regarding uterus transplantation among women with Rokitansky syndrome and other groups of interest. MATERIAL AND METHODS: We designed a cross-sectional study including five groups of women: women with Rokitansky syndrome, women with Morris syndrome, relatives of women with Morris and Rokitansky syndrome, infertile women, and childbearing-age women. We conducted an online survey through the REDCap platform. The link was distributed by mail, telephone and in hospital outpatient visits. Baseline demographic information was assessed and information regarding motherhood preferences, attitude toward uterus transplantation, preferred uterus graft and perception of risk of the procedure was collected. RESULTS: We obtained a total of 200 responses, with a mean participant age of 34.5 years (±9.8). Overall, 17.5% (n = 35) were women with Rokitansky syndrome, 5.5% (n = 11) Morris syndrome women, 21.5% (n = 43) infertile women, 26.5% (n = 53) relatives of Morris and Rokitansky syndrome women and 29% (n = 58) childbearing-age women. 71.5% of women with Rokitansky syndrome would undergo uterus transplantations ahead of adoption and surrogacy with no statistically significant differences found between groups. Overall, more than one-half (58%) would prefer deceased over living donor. CONCLUSIONS: The results of this survey indicate that uterus transplantation is desired by most women who would benefit from the procedure, including those with either Morris syndrome or absolute uterine factor infertility. This was also the preferred option for motherhood if absolute uterine factor infertility was diagnosed among surveyed infertility patients or women of childbearing age with no known reproductive difficulties. Overall, most respondents indicated a deceased donor was preferable to a living donor and that patients may not be sufficiently aware of potential risks of uterus transplantation, highlighting the importance of adequate counseling by medical providers.

Mapping sentinel lymph nodes in early-stage ovarian cancer (MELISA) trial - a further step towards lymphadenectomy replacement.

OBJECTIVE: Sistematic pelvic and para-aortic lymphadenectomy is part of the staging surgery for early-stage epithelial ovarian cancer, with no therapeutic value. The Mapping Sentinel Lymph Nodes In Early-Stage Ovarian Cancer (MELISA) trial prospectively assessed the SLN detection rate and the diagnostic accuracy of the SLN mapping technique in patients with early-stage epithelial ovarian cancer. METHODS: This prospective, single-arm study included patients diagnosed with early-stage epithelial ovarian cancer (FIGO stages I and II), via either primary surgery or re-staging surgery. SLN mapping was performed by injecting 0.2 mL of 37-mBq 99mTc-nanocoloid albumin and 2 mL of 2.5 mg/mL indocyanine green into the infundibulopelvic and utero-ovarian ligaments. After removal of SLNs, a complete systematic pelvic and para-aortic lymphadenectomy was performed. SLN Ultrastaging analysis was applied. The primary outcome was the overall SLN detection rate, either with one or both tracers. Secondary outcomes were the diagnostic accuracy of detecting lymph node metastases and factors that may influence SLN detection. RESULTS: Thirty patients were included. SLNs were identified in 27 patients (90%). Detection rates in primary and re-staging surgery were 89% and 92%, respectively. Para-aortic drainage was the predominant lymphatic spread, observed in 26 of 27 patients. Ultrastaging pathologic reports listed 1 SLN with macrometastasis, 1 with micrometastasis, and 5 with isolated tumor cells; the sensitivity of SLN mapping was 100%, with a false-negative rate of 0%. Univariate analysis showed a nonsignificant higher proportion of patients with uterine fibroids, adenomyosis, and endometriosis (100%, 67%, 67%, respectively) in patients in whom SLNs were not detected. CONCLUSION: SLN mapping has a high detection rate (90%) and is an accurate technique for detecting lymph node involvement in early-stage epithelial ovarian cancer. SLN mapping is a potential alternative to systematic lymphadenectomy to reduce associated morbidity, but further research is needed to evaluate the impact of SLN mapping on oncologic outcomes and its cost-effectiveness.

Impact of gynecological cancers on health-related quality of life: historical context, measurement instruments, and current knowledge.

Gynecologic cancers, comprising 14.4% of newly diagnosed cancer cases in women globally, are substantial causes of both mortality and morbidity, with a profound impact on the quality of life (QoL) of survivors. Over the past few decades, advancements in interdisciplinary and interprofessional care have contributed to an increase in the average life expectancy of gynecological cancer patients. However, the disease and its treatments have a profound impact on patients, leading to physical changes and psychological consequences, including psychosocial and psychosexual effects, which negatively affect their QoL.The primary objective of management strategies is to minimize harm while improving survival rates and enhancing QoL during the survivorship stage. QoL measures play a crucial role in enhancing our comprehension of how cancer and its treatments affect individuals. Consequently, various measurement instruments, such as the EORTC QLQ 30, PROMIS-29, FACT-G, and QOL-CS, have been developed to assess health-related quality of life (HRQoL). Pre- and post-treatment HRQoL measurements have been shown to be predictive factors for post-operative complications and prognostic factors for overall survival and progression-free survival in gynecological oncology patients. Patient-reported outcomes related to HRQoL are essential tools for measuring patient outcomes and enabling patient-centered clinical decision-making.This article focuses on HRQoL, providing a historical context, summarizing measurement instruments, and discussing the current understanding of the impact of gynecological cancers on HRQoL.

Sentinel lymph node detection in early-stage ovarian cancer: a systematic review and meta-analysis.

BACKGROUND: A systematic pelvic and para-aortic lymphadenectomy remains the surgical standard management of early-stage epithelial ovarian cancer. Sentinel lymph node mapping is being investigated as an alternative procedure; however, data reporting sentinel lymph node performance are heterogeneous and limited. OBJECTIVE: This study aimed to evaluate the detection rate and diagnostic accuracy of sentinel lymph node mapping in patients with early-stage ovarian cancer. METHODS: A systematic search was conducted in Medline (through PubMed), Embase, Scopus, and the Cochrane Library. We included patients with clinical stage I-II ovarian cancer undergoing a sentinel lymph node biopsy and a pelvic and para-aortic lymphadenectomy as a reference standard. We conducted a meta-analysis for the detection rates and measures of diagnostic accuracy and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with identifying number CRD42022351497. RESULTS: After duplicate removal, we identified 540 studies, 18 were assessed for eligibility, and nine studies including 113 patients were analyzed. The pooled detection rates were 93.3% per patient (95% CI 77.8% to 100%; I2=74.3%, p<0.0001), and the sentinel lymph node technique correctly identified 11 of 12 patients with lymph node metastases, with a negative predictive value per patient of 100% (95% CI 97.6% to 100%; I2=0%). The combination of indocyanine green and 99mTc-albumin nanocolloid had the best detection rate (100% (95% CI 94% to 100%; I2=0%)) when injected into the utero-ovarian and infundibulo-pelvic ligaments. CONCLUSION: Sentinel lymph node biopsy in early-stage ovarian cancer showed a high detection rate and negative predictive value. The utero-ovarian and infundibulo-pelvic injection using the indocyanine green and technetium-99 combination could increase sentinel lymph node detection rates. However, given the limited quality of evidence and the small number of reports, results from ongoing trials are awaited before its implementation in routine clinical practice.

Oncological outcomes among young women with non-epithelial ovarian cancer: the YOC-Care study (Young Ovarian Cancer - Care).

OBJECTIVE: To determine oncological outcomes and associated prognostic factors in women younger than 45 years diagnosed with non-epithelial ovarian cancer. METHODS: A retrospective, multicenter Spanish study was performed including women with non-epithelial ovarian cancer younger than 45 years between January 2010 and December 2019. All types of treatments and stages at diagnosis with at least 12 months of follow-up were collected. Women with missing data, epithelial cancers, borderline or Krukenberg tumors, and benign histology, as well as patients with previous or concomitant cancer, were excluded. RESULTS: A total of 150 patients were included in this study. The mean±SD age was 31.45±7.45 years. Histology subtypes were divided into germ cell (n=104, 69.3%), sex-cord (n=41, 27.3%), and other stromal tumors (n=5, 3.3%). Median follow-up time was 58.6 (range: 31.10-81.91) months. Nineteen (12.6%) patients presented with recurrent disease with a median time to recurrence of 19 (range: 6-76) months. Progression-free survival and overall survival did not significantly differ among histology subtypes (p=0.09 and 0.26, respectively) and International Federation of Gynecology and Obstetrics (FIGO) stage (I-II vs III-IV) with p=0.08 and p=0.67, respectively. Univariate analysis identified sex-cord histology with the lowest progression-free survival. Multivariate analysis showed that body mass index (BMI) (HR=1.01; 95% CI 1.00 to 1.01) and sex-cord histology (HR=3.6; 95% CI 1.17 to 10.9) remained important independent prognostic factors for progression-free survival. Independent prognostic factors for overall survival were BMI (HR=1.01; 95% CI 1.00 to 1.01) and residual disease (HR=7.16; 95% CI 1.39 to 36.97). CONCLUSIONS: Our study showed that BMI, residual disease, and sex-cord histology were prognostic factors associated with worse oncological outcomes in women younger than 45 years diagnosed with non-epithelial ovarian cancers. Even though the identification of prognostic factors is relevant to identify high-risk patients and guide adjuvant treatment, larger studies with international collaboration are essential to clarify oncological risk factors in this rare disease.

Prognostic factors in young women with epithelial ovarian cancer: the Young Ovarian Cancer-Care (YOC-Care) study.

OBJECTIVE: To determine oncological outcomes and to identify prognostic factors in women aged <45 years with epithelial ovarian cancer. METHODS: A multicenter retrospective study was performed of patients treated for epithelial ovarian cancer aged <45 years between January 2010 and December 2019. RESULTS: A total of 998 patients with epithelial ovarian cancer from 55 different institutions in Spain were collected. The median age of the study population was 40.8 years (range 35.6-43.4). The grouped International Federation of Gynecology and Obstetrics (FIGO) stage distribution was 508 (50.9%) patients in initial stages (I and II) and 490 (49.1%) with advanced stages (III and IV). Three hundred and twenty-five (32.6%) patients presented with recurrent disease after a median follow-up of 33.1 months (range 16.1-66.4). The type of staging surgery (incomplete vs complete), type of initial treatment modality (primary cytoreduction vs interval surgery), and amount of residual disease were all significantly associated with overall survival. Tumor rupture was noted in 288 (27.9%) cases, but it was not associated with oncologic outcomes (p=0.11 for overall survival). In the multivariate analysis, the response based on radiological findings (HR 3.24, 95% CI 2.14 to 4.91 for partial response; HR 6.93, 95% CI 4.79 to 10.04 for progression), neoadjuvant chemotherapy (HR 1.42, 95% CI 1.04 to 1.94), and FIGO stage (HR 1.68, 95% CI 1.40 to 2.02) were identified as independent prognostic factors associated with worse oncologic outcomes (p<0.001). CONCLUSION: The partial and progression radiology-based response after chemotherapy, neoadjuvant chemotherapy, and advanced FIGO stage are independent prognostic factors associated with worse oncological outcomes in women aged <45 years with epithelial ovarian cancer.

PARa-aOrtic LymphAdenectomy in locally advanced cervical cancer (PAROLA trial): a GINECO, ENGOT, and GCIG study.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) fails to detect approximately 25% of aortic lymph node metastasis in patients with PET/CT stage IIIC1 cervical cancer. Surgical staging could lead to treatment modification and to improved para-aortic and distant control. PRIMARY OBJECTIVES: To demonstrate if chemoradiation with tailored external beam radiation field based on surgical staging and pathologic examination of the para-aortic lymph node is associated with improved 3-year disease-free survival compared with patients staged with PET/CT staging only. STUDY HYPOTHESIS: Surgical staging followed by tailored chemoradiation will improve disease-free survival while avoiding unnecessary prophylactic extended-field chemoradiation in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC1 cervical cancer. TRIAL DESIGN: This is an international multicenter, randomized, phase III study. Eligible patients will be randomized 1:1 between PET/CT staging followed by chemoradiation (control arm), or surgical staging followed by tailored chemo-radiation (experimental arm). Randomization will be stratified by tumor stage according to TNM classification, center, and adjuvant treatment. MAJOR INCLUSION/EXCLUSION CRITERIA: Main inclusion criteria are histologically proven PET/CT FIGO stage IIIC1 cervical cancer. Main exclusion criteria include unequivocal positive common iliac or para-aortic lymph node at pre-therapeutic imaging PET/CT. PRIMARY ENDPOINTS: The primary endpoint is disease-free survival defined as the time from randomization until first relapse (local, regional, or distant), or death from any cause. SAMPLE SIZE: 510 eligible patients ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The estimated date for completing accrual will be Q2 2027. The estimated date for presenting results will be Q4 2030. TRIAL REGISTRATION NUMBER: NCT05581121.

Simple radiologic assessment of visceral obesity and prediction of surgical morbidity in endometrial cancer patients undergoing laparoscopic aortic lymphadenectomy: A reliability and accuracy study.

AIM: To evaluate the reliability of sagittal abdominal diameter (SAD)-a surrogate of visceral obesity-in magnetic resonance imaging, and its accuracy to predict the surgical morbidity of aortic lymphadenectomy. METHODS: We conducted a multicenter reliability (phase 1) and accuracy (phase 2) cohort study in three Spanish referral hospitals. We retrospectively analyzed data from the STELLA-2 randomized controlled trial that included high-risk endometrial cancer patients undergoing minimally invasive surgical staging. Patients were classified into subgroups: conventional versus robotic-assisted laparoscopy, and transperitoneal versus extraperitoneal technique. In the first phase, we measured the agreement of three SAD measurements (at the umbilicus, renal vein, and inferior mesenteric artery) and selected the most reliable one. In phase 2, we evaluated the diagnostic accuracy of SAD to predict surgical morbidity. Surgical morbidity was the main outcome measure, it was defined by a core outcome set including variables related to blood loss, operative time, surgical complications, and para-aortic lymphadenectomy difficulty. RESULTS: In phase 1, all measurements showed good inter-rater and intra-rater agreement. Umbilical SAD (u-SAD) was the most reliable one. In phase 2, we included 136 patients. u-SAD had a good diagnostic accuracy to predict surgical morbidity in patients undergoing transperitoneal laparoscopic lymphadenectomy (0.73 in ROC curve). It performed better than body mass index and other anthropometric measurements. We calculated a cut-off point of 246 mm (sensitivity: 0.56, specificity: 0.80). CONCLUSIONS: u-SAD is a simple, reliable, and potentially useful measurement to predict surgical morbidity in endometrial cancer patients undergoing minimally invasive surgical staging, especially when facing transperitoneal aortic lymphadenectomy.

Evaluation of patients with advanced epithelial ovarian cancer before primary treatment: correlation between tumour burden assessed by [18F]FDG PET/CT volumetric parameters and tumour markers HE4 and CA125.

OBJECTIVES: Accurate assessment of disease extent is required to select the best primary treatment for advanced epithelial ovarian cancer patients. Estimation of tumour burden is challenging and it is usually performed by means of a surgical procedure. Imaging techniques and tumour markers can help to estimate tumour burden non-invasively. 2-[18F]FDG PET/CT allows the evaluation of the whole-body disease. This study aimed to correlate HE4 and CA125 serum concentrations with tumour burden evaluated by volumetric 2-[18F]FDG PET/CT parameters in advanced high-grade epithelial ovarian cancer. METHODS: We included 66 patients who underwent 2-[18F]FDG PET/CT and serum tumour markers determination before primary treatment. Volumes of interest were delimited in every pathological uptake. Whole-body metabolic tumour volume (wb_MTV) and total lesion glycolysis (wb_TLG) were calculated summing up every VOI's MTV value. SUVmax thresholds were set at 40% (MTV40 and TLG40) and 50% (MTV50 and TLG50). In addition, four VOI subgroups were defined: peritoneal carcinomatosis, retroperitoneal nodes, supradiaphragmatic nodes, and distant metastases. MTV and TLG were calculated for each group by adding up the corresponding MTV values. TLG was calculated likewise. RESULTS: wb_MTV and wb_TLG were found to be significantly correlated with serum CA125 and HE4 concentrations. The strongest correlation was observed between HE4 and wb_MTV40 (r = 0.62, p < 0.001). Pearson's correlation coefficients between peritoneal carcinomatosis MTV40 and tumour markers were 0.61 (p < 0.0001) and 0.29 (p = 0.02) for HE4 and CA125 respectively. None of these tumour markers showed a positive correlation with tumour load outside the abdominal cavity assessed by volumetric parameters. CONCLUSION: HE4 performs better than CA125 to predict metabolic tumour burden in high-grade epithelial ovarian cancer before primary treatment. 2-[18F]FDG PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution. These results support the usefulness of HE4 and PET/CT to improve the stratification of these patients in clinical practice. KEY POINTS: • In patients with high-grade advanced ovarian epithelial carcinoma, both CA125 and HE4 correlate to whole-body tumour burden assessed by PET/CT before primary treatment. • HE4 estimates peritoneal disease much better than CA125. • PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution.

A multimodal prehabilitation program for the reduction of post-operative complications after surgery in advanced ovarian cancer under an ERAS pathway: a randomized multicenter trial (SOPHIE).

BACKGROUND: Multimodal prehabilitation programs that combine exercise training, nutritional support, and optimize psychological status have demonstrated efficacy in reducing post-operative complications in non-gynecological abdominal surgeries; however, the benefit in advanced ovarian cancer is unclear. PRIMARY OBJECTIVE: To compare the post-operative complications of a multimodal prehabilitation program in patients undergoing cytoreductive surgery for advanced ovarian cancer with standard pre-operative care. STUDY HYPOTHESIS: Multimodal prehabilitation reduces post-operative complications in patients undergoing cytoreductive surgery for advanced ovarian cancer and subsequently reduces the length of hospital stay and time to initiation of adjuvant therapy. TRIAL DESIGN: This prospective, multi-institutional, randomized clinical trial will randomize candidates for surgery to either the standard of care or multimodal prehabilitation consisting of (1) 2- or 3-weekly supervised high-intensity resistance training sessions and promotion of physical activity through a mobile phone application; (2) respiratory physiotherapy; (3) nutrition counseling with supplementation as needed; and (4) weekly psychological and cognitive behavioral sessions. Baseline, pre-operative and 1 month post-operative data will be collected. An independent blinded evaluator will collect intra- and post-operative surgical data. MAJOR INCLUSION/EXCLUSION CRITERIA: Women with advanced ovarian cancer International Federation of Gynecology and Obstetrics (2014) stage III or IV scheduled to undergo primary debulking surgery, interval debulking surgery,or secondary or tertiary cytoreductive surgery will be included. Women are eligible if they are able to undergo a minimum of 2 weeks of prehabilitation prior to surgery. Patients with <75% adherence to the total program will be excluded. PRIMARY ENDPOINT: Post-operative complications in patients with advanced ovarian cancer undergoing cytoreductive surgery according to the Comprehensive Complication Index. SAMPLE SIZE: 146 patients will be included, 73 in each group. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual should be completed in December 2024 with results reported soon thereafter. TRIAL REGISTRATION NUMBER: NCT04862325.

Oncological safety of hysteroscopy in endometrial cancer.

OBJECTIVE: It has been suggested that the manipulation of neoplastic tissue during hysteroscopy may lead to dissemination of tumor cells into the peritoneal cavity and worsen prognosis and overall survival. The goal of this study was to assess the oncological safety comparing hysteroscopy to Pipelle blind biopsy in the presurgical diagnosis of patients with endometrial cancer. METHODS: We performed a retrospective multicentric study among patients who had received primary surgical treatment for endometrial cancer. A multivariate statistical analysis model was used to compare relapse and survival rates in patients who had been evaluated preoperatively either by hysteroscopy or Pipelle biopsy. The relapse rate, disease-free survival, and overall survival were assessed as the main outcomes. The histological type, tumor size, myometrial invasion, International Federation of Gynecology and Obstetrics (FIGO) stage, surgical approach, use of a uterine manipulator, and adjuvant treatment were also included in the analysis. RESULTS: A total of 1731 women from 15 centers were included: 1044 in the hysteroscopy group and 687 in the Pipelle sampling group. 225 patients relapsed during the 10 year follow-up period: 139 (13.3%) in the hysteroscopy group and 86 (12.4%) in the Pipelle sampling group. There is no evidence of an association between the use of hysteroscopy as a diagnostic method and relapse rate (HR 1.24, 95% CI 0.92 to 1.66; p=0.16), lower disease-free survival (HR 1.23, 95% CI 0.92 to 1.66; p=0.15), or overall survival (HR 0.95, 95% CI 0.70 to 1.29; p=0.76). CONCLUSION: Hysteroscopy is a safe diagnostic method for patients with endometrial cancer with no impact on oncological outcomes when compared with sampling by Pipelle.

Laparoscopic Debulking of Enlarged Pelvic Nodes during Surgical Para-aortic Staging in Locally Advanced Cervical Cancer: A Retrospective Comparative Cohort Study.

STUDY OBJECTIVE: To evaluate laparoscopic pelvic lymph node debulking during extraperitoneal aortic lymphadenectomy in diagnosis, therapeutic planning, and prognosis of patients with locally advanced cervical cancer and enlarged lymph nodes on imaging before chemoradiotherapy. DESIGN: Retrospective, multicenter, comparative cohort study. SETTING: The study was carried out at 11 hospitals with specialized gynecologic oncology units in Spain. PATIENTS: Total of 381 women with locally advanced cervical cancer and International Federation of Gynecology and Obstetrics 2018 stage IIIC 1r (radiologic) and higher who received primary treatment with chemoradiotherapy. INTERVENTIONS: Patients underwent pelvic lymph node debulking and para-aortic lymphadenectomy (group 1), only para-aortic lymphadenectomy (group 2), or no lymph node surgical staging (group 3). On the basis of pelvic node histology, group 1 was subdivided as negative (group 1A) or positive (group 1B). MEASUREMENTS AND MAIN RESULTS: False positives and negatives of imaging tests, disease-free survival, overall survival, and postoperative complications were evaluated. In group 1, pelvic lymph node involvement was 43.3% (71 of 164), and aortic involvement was 24.4% (40 of 164). In group 2, aortic nodes were positive in 29.7% (33 of 111). Disease-free survival and overall survival were similar in the 3 groups (p = .95) and in groups 1A and 1B (p = .25). No differences were found between groups 1 and 2 in intraoperative (3.7% vs 2.7%, p = .744), early postoperative (8.0% vs 6.3%, p = .776), or late postoperative complications (6.1% vs 2.7%, p = .252). Fewer early and late complications were attributed to radiotherapy in group 1A than in the others (p = .022). CONCLUSION: Laparoscopic pelvic lymph node debulking during para-aortic staging surgery in patients with locally advanced cervical cancer with suspicious nodes allows for the confirmation of metastatic lymph nodes without affecting survival or increasing surgical complications. This information improves the selection of patients requiring boost irradiation, thus avoiding overtreatment of patients with negative nodes.

Postreatment squamous cell carcinoma antigen as a survival prognostic factor in patients with locally advanced cervical cancer. A Spanish multicenter study. The SEGO Spain-GOG group.

OBJECTIVE: To evaluate the clinical value of postreatment plasmatic levels of the squamous cell carcinoma antigen (SCC-Ag) as a survival independent prognostic factor in patients with LACC. METHODS: Retrospective, multicenter study including LACC patients (FIGO 2009 stages IB2, IIA2-IVA) managed at the Gynecology Oncological Units corresponding to eight reference hospitals in Spain between 2000 and 2016. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off values of postreatment SCC-Ag levels in prediction of survival. Survival curves were calculated by using the Kaplan-Meier method and were compared with the log-rank test. Cox models were used to analyze different factors in terms of their prognosis predictive value. RESULTS: The study included 447 patients with a median follow-up time of 53 months (IQR 26-101) and median pre- and postreatment SCC-Ag levels of 3.4 ng/ml (IQR 1.2-11) and 0.8 ng/ml (IQR 0.5-1.2), respectively. The cut-off level of pretreatment SCC-Ag was 11.75 ng/ml (sensibility 37.5%; specificity 80.5%) and that of postreatment SCC-Ag was 1.24 ng/ml (sensibility 34.6%; specificity 83.1%). In a multivariate Cox regression analysis, factors that were independent predictors of OS were: FIGO stage (HR 2.12; 95%CI 1.18-3.8; p = 0.011), paraaortic lymph node involvement (HR 3.56; 95%CI 2.04-6.2; p < 0.0001), postreatment SCC-Ag level ≥ 1.2 ng/ml (HR 1.95; 95%CI 1.11-3.44; p = 0.02) and incomplete response to treatment (HR 4.5; 95%CI 2.5-8.11; p < 0.0001). CONCLUSION: Postreatment plasmatic SCC-Ag level ≥ 1.2 ng/ml was an independent risk factor for the survival of patients with LACC. Further factors influencing survival included: paraaortic lymph node involvement, advanced disease and poor response to concomitant chemoradiotherapy.

Surgical complications comparing extraperitoneal vs transperitoneal laparoscopic aortic staging in early stage ovarian and endometrial cancer.

OBJECTIVE: To determine whether the extraperitoneal approach for paraaortic staging lymphadenectomy results in a lower rate of surgical complications compared to the transperitoneal approach, without compromising oncological outcomes. METHODS: Prospective randomized multicenter study of patients with early endometrial or ovarian cancer undergoing paraaortic lymphadenectomy in 2010-2019. Patients were randomized to minimally invasive surgery (laparoscopy or robotic-assisted) using an extraperitoneal or a transperitoneal approach. The primary end point measure was a composite outcome that included developing one or more of the following surgical complications: bleeding during paraaortic lymphadenectomy ≥500 mL, any intraoperative complication related to paraaortic lymphadenectomy, severe postoperative complication (Dindo ≥ IIIA), impossibility to complete the procedure, or conversion to laparotomy. RESULTS: There were 103 patients in the extraperitoneal group and 100 in the transperitoneal group. Differences in the composite outcome (transperitoneal 26.0% vs, extraperitoneal 18.4%; P = 0.195) were not found. Differences in the operative time, conversion to laparotomy, intraoperative bleeding, or survival were not observed. A higher number of lymph nodes were retrieved through the extraperitoneal approached (median, interquartile range [IQR] 12 [7-17] vs, 14 [10-19]: P = 0.026). Older age and greater body mass index (BMI) or waist-to-hip ratio (WHR) increased the risk for surgical complications independently of the laparoscopic approach. CONCLUSIONS: The extraperitoneal approach did not show differences regarding surgical and oncological parameters compared with the transperitoneal approach, although the number of aortic nodes retrieved was higher. The decision to use one or another laparoscopic route is a matter of the surgeon preference. Trial registration ClinicalTrials.gov.identifier: NCT02676726.

M-TRAP: Safety and performance of metastatic tumor cell trap device in advanced ovarian cancer patients.

OBJECTIVE: Despite radical surgery and chemotherapy, most patients with ovarian cancer die due to disease progression. M-Trap is an implantable medical device designed to capture peritoneal disseminated tumor cells with the aim to focalize the disease. This trial analyzed the safety and performance of the device. METHODS: This first-in-human prospective, multi-center, non-blinded, single-arm study enrolled 23 women with high-grade serous advanced ovarian cancer. After primary or interval debulking surgery, 3 M-Trap devices were placed in the peritoneum of the abdominal cavity. 18-months post-implantation or at disease progression, devices were initially removed by laparoscopy. The primary safety endpoint was freedom from device and procedure-related major adverse events (MAEs) through 6-months post-implantation compared to an historical control. The primary performance endpoint was histopathologic evidence of tumor cells capture. RESULTS: Only one major adverse event was attributable to the device. 18 women were free of device and procedure related MAEs (78.3%). However, the primary safety endpoint was not achieved (p = 0.131), primarily attributable to the greater surgical complexity of the M-Trap patient population. 62% of recurrent patients demonstrated tumor cell capture in at least one device with a minimal tumor cell infiltration. No other long-term device-related adverse events were reported. The secondary performance endpoint demonstrated a lack of disease focalization. CONCLUSIONS: The M-Trap technology failed to meet its primary safety objective, although when adjusted for surgical complexity, the study approved it. Likewise, the devices did not demonstrate the anticipated benefits in terms of tumor cell capture and disease focalization in recurrent ovarian cancer.

Impact of uterine manipulator on oncological outcome in endometrial cancer surgery.

BACKGROUND: There are limited data available to indicate whether oncological outcomes might be influenced by the uterine manipulator, which is used at the time of hysterectomy for minimally invasive surgery in patients with endometrial cancer. The current evidence derives from retrospective studies with limited sample sizes. Without substantial evidence to support its use, surgeons are required to make decisions about its use based only on their personal choice and surgical experience. OBJECTIVE: To evaluate the use of the uterine manipulator on oncological outcomes after minimally invasive surgery, for apparent early-stage endometrial cancer. STUDY DESIGN: We performed a retrospective multicentric study to assess the oncological safety of uterine manipulator use in patients with apparent early-stage endometrial cancer, treated with minimally invasive surgery. The type of manipulator, surgical staging, histology, lymphovascular space invasion, International Federation of Gynecology and Obstetrics stage, adjuvant treatment, recurrence, and pattern of recurrence were evaluated. The primary objective was to determine the relapse rate. The secondary objective was to determine recurrence-free survival, overall survival, and the pattern of recurrence. RESULTS: A total of 2661 women from 15 centers were included; 1756 patients underwent hysterectomy with a uterine manipulator and 905 without it. Both groups were balanced with respect to histology, tumor grade, myometrial invasion, International Federation of Gynecology and Obstetrics stage, and adjuvant therapy. The rate of recurrence was 11.69% in the uterine manipulator group and 7.4% in the no-manipulator group (P<.001). The use of the uterine manipulator was associated with a higher risk of recurrence (hazard ratio, 2.31; 95% confidence interval, 1.27-4.20; P=.006). The use of uterine manipulator in uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics [FIGO] I-II) was associated with lower disease-free survival (hazard ratio, 1.74; 95% confidence interval, 0.57-0.97; P=.027) and higher risk of death (hazard ratio, 1.74; 95% confidence interval, 1.07-2.83; P=.026). No differences were found regarding the pattern of recurrence between both groups (chi-square statistic, 1.74; P=.63). CONCLUSION: In this study, the use of a uterine manipulator was associated with a worse oncological outcome in patients with uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics I-II) who underwent minimally invasive surgery. Prospective trials are essential to confirm these results.

Robot-assisted Extraperitoneal Para-aortic Lymphadenectomy Is Associated with Fewer Surgical Complications: A Post Hoc Analysis of the STELLA-2 Randomized Trial.

STUDY OBJECTIVE: To evaluate if extraperitoneal para-aortic lymphadenectomy (PALND) using a robot-assisted approach was associated with fewer complications than all other approaches (conventional laparoscopic transperitoneal or extraperitoneal and robot-assisted transperitoneal) without compromising lymph node yield, operative time, or length of stay. DESIGN: Post hoc analysis of the prospective randomized open-label multicenter trial (STELLA-2). SETTING: Three academic referral hospitals. PATIENTS: Two hundred and three eligible patients from the STELLA-2 trial were included. INTERVENTIONS: The patients were randomized to extraperitoneal or transperitoneal PALND using a minimally invasive approach (either laparoscopic or robot-assisted) for surgical staging of endometrial or ovarian cancer. The minimally invasive approaches were not subjected to randomization. MEASUREMENTS AND MAIN RESULTS: The primary end point was evaluated through a composite variable that included at least 1 of the following events: blood loss ≥500 mL during PALND, any intraoperative complication related to PALND, severe postoperative complication (Clavien-Dindo ≥grade IIIA), impossibility of completing the procedure, or conversion to laparotomy. Of the 203 patients analyzed, 68 were assigned to the extraperitoneal laparoscopic group (X-L), 62 to the transperitoneal laparoscopic group (T-L), 35 to the extraperitoneal robotic group (X-R), and 38 to the transperitoneal robotic group (T-R). A reduced trend in complications was observed in the extraperitoneal robot-assisted arm when considering the primary end point (X-L: 25.0%, T-L: 24.2%, X-R: 5.7%, T-R: 28.9%; p = .073). In a multivariable analysis, age (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.00-1.09), body mass index (OR 1.09; 95% CI, 1.03-1.16), and waist-to-hip ratio (OR 1.66; 95% CI, 1.12-2.47) were found to independently increase the risk of PALND complications, whereas the extraperitoneal robotic approach (OR 0.13; 95% CI, 0.02-0.64) was an independent protective factor for complication occurrence. CONCLUSION: Robot-assisted extraperitoneal PALND is associated with fewer surgical complications, without compromising lymph node retrieval, operative time, or length of stay. Robot-enhanced 3D visualization, surgeon ergonomics, or hemostatic precision could explain our results.