LACC Trial: Final Analysis on Overall Survival Comparing Open Versus Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The aim of this study was to compare overall survival between open and minimally invasive radical hysterectomy with participants followed for 4.5 years. The primary objective was to evaluate whether minimally invasive surgery was noninferior in disease-free survival (DFS) to abdominal radical hysterectomy. Secondary outcomes included overall survival. Sample size was based on DFS of 90% at 4.5 years and 7.2% noninferiority margin for minimally invasive surgery. A total of 631 patients were enrolled: 319 assigned to minimally invasive and 312 to open surgery. Of these, 289 (90.6%) patients underwent minimally invasive surgery and 274 (87.8%) patients open surgery. At 4.5 years, DFS was 85.0% in the minimally invasive group and 96% in the open group (difference of -11.1; 95% CI, -15.8 to -6.3; P = .95 for noninferiority). Minimally invasive surgery was associated with lower rate of DFS compared with open surgery (hazard ratio [HR], 3.91 [95% CI, 2.02 to 7.58]; P < .001). Rate of overall survival at 4.5 years was 90.6% versus 96.2% for the minimally invasive and open surgery groups, respectively (HR for death of any cause = 2.71 [95% CI, 1.32 to 5.59]; P = .007). Given higher recurrence rate and worse overall survival with minimally invasive surgery, an open approach should be standard of care.

Uterine transposition for fertility preservation in pelvic cancers.

OBJECTIVE: To review rates of uterine preservation and gonadal function, surgical outcomes, and pregnancy outcomes in patients undergoing surgical uterine transposition. METHODS: A structured search and analysis of the published literature on uterine transposition was conducted. Information on study type, sample size, patient characteristics, clinical indications, details of the surgical technique, trans-operative and post-operative results, success rates in preserving reproductive organ function and fertility were extracted. RESULTS: A total of 18 cases were reported to date. Patients' median age was 29 (range 3-38) years. Rectal cancers accounted for 9 (50%) cases of published cases of uterine transposition, followed by 6 (33%) cervical squamous cell carcinomas, 1 (6%) vaginal squamous cell carcinoma, 1 (6%) sacral yolk sac tumor, and 1 (6%) pelvic liposarcoma. The median time for uterine transposition to the upper abdomen was 150 (range 80-360) min, and 90 (range 80-310) min for organ reimplantation in the pelvis. Cervical ischemia occurred in 5 (27.8%) cases, being the most commonly reported complication. The median follow-up time was 25 months, and three patients achieved spontaneous pregnancies resulting in successful gestations, out of five patients who were reported as having tried. One patient experienced recurrence and succumbed to the tumor during treatment. CONCLUSIONS: Uterine transposition is a feasible and safe surgical approach that offers patients undergoing pelvic radiotherapy an option to preserve gonadal and uterine function, with the potential for spontaneous pregnancy.

Uterine transposition in a patient with vulvar cancer.

Objective: To report the first uterine transposition for fertility preservation in a patient with vulvar cancer.Case: A 26-year-old nulliparous patient with stage IIIB vulvar cancer, which was resected with adequate margins and bilateral inguinofemoral lymphadenectomy.Laparoscopic transposition of the uterus to the upper abdomen, outside of the scope of radiation was performed to preserve fertility and ovarian function. After the end of radiotherapy, the uterus was repositioned into the pelvis.Main Outcome Measure: Uterine and ovarian function preservation. Result: The patient recovered her menstrual cycles spontaneously 1 month after the reimplantation and exhibited normal variation in ovarian hormones.Twelve months after the surgery, the uterus was normal and there was no sign of recurrent disease. Conclusion: Uterine transposition might represent a valid option for fertility preservation in women who require pelvic radiotherapy. However, studies that assess its viability, effectiveness, and safety are required.

Uterine transposition for fertility and ovarian function preservation after radiotherapy.

OBJECTIVE: To evaluate the feasibility of uterine transposition as a method of preserving fertility and ovarian function after pelvic radiation. METHODS: This prospective multicenter observational study included patients with non-gynecologic pelvic cancers who underwent pelvic radiation as part of their cancer treatment between June 2017 and June 2019. For inclusion in the study, patients were required to have normal menstrual cycles and hormone levels (follicle-stimulating hormone, luteinizing hormone, and estrogen) before treatment. Uterine transposition to the upper abdomen was performed prior to irradiation. Clinical examinations and Doppler ultrasonography were used to evaluate the gonadal vasculature post-surgery. The uterus was repositioned into the pelvis 2-4 weeks after radiation therapy or at the time of rectosigmoid resection in patients with rectal cancer who had undergone neoadjuvant treatment. Cancer treatment and follow-up were performed according to standard guidelines. RESULTS: Eight patients (seven with rectal cancer and one with pelvic liposarcoma) underwent uterine transposition at a median age of 30.5 years (range 19-37). The uterus was successfully preserved in six patients, accompanied by normal menses, hormonal levels, and vaginal intercourse after treatment. One patient with rectal cancer died of carcinomatosis 4 months after uterine transposition. One patient presented with uterine necrosis 4 days after uterine transposition, and the uterus was removed; however, one ovary was preserved. Cervical ischemia was the most common post-surgical complication in three (37.5%) patients. Three patients attempted to conceive, and two (66%) were spontaneously successful and delivered healthy babies at 36 and 38 weeks by cesarean section without complications. CONCLUSIONS: Uterine transposition is a feasible procedure for preserving gonadal and uterine function in patients requiring pelvic radiotherapy for non-gynecological cancer, with the potential for achieving spontaneous pregnancy and successful delivery.

Does sentinel node mapping impact morbidity and quality of life in endometrial cancer?

OBJECTIVES: To evaluate the prevalence of post-operative complications and quality of life (QoL) related to sentinel lymph node (SLN) biopsy vs systematic lymphadenectomy in endometrial cancer. METHODS: A prospective cohort included women with early-stage endometrial carcinoma who underwent lymph node staging, grouped as follows: SLN group (sentinel lymph node only) and SLN+LND group (sentinel lymph node biopsy with addition of systematic lymphadenectomy). The patients had at least 12 months of follow-up, and QoL was assessed by European Organization for Research and Treatment of Cervical Cancer Quality of Life Questionnaire 30 (EORTC-QLQ-C30) and EORTC-QLQ-Cx24. Lymphedema was also assessed by clinical evaluation and perimetry. RESULTS: 152 patients were included: 113 (74.3%) in the SLN group and 39 (25.7%) in the SLN+LND group. Intra-operative surgical complications occurred in 2 (1.3%) cases, and all belonged to SLN+LND group. Patients undergoing SLN+LND had higher overall complication rates than those undergoing SLN alone (33.3% vs 14.2%; p=0.011), even after adjusting for confound factors (OR=3.45, 95% CI 1.40 to 8.47; p=0.007). The SLN+LND group had longer surgical time (p=0.001) and need for admission to the intensive care unit (p=0.001). Moreover, the incidence of lymphocele was found in eight cases in the SLN+LND group (0 vs 20.5%; p<0.001). There were no differences in lymphedema rate after clinical evaluation and perimetry. However, the lymphedema score was highest when lymphedema was reported by clinical examination at 6 months (30.1 vs 7.8; p<0.001) and at 12 months (36.3 vs 6.0; p<0.001). Regarding the overall assessment of QoL, there was no difference between groups at 12 months of follow-up. CONCLUSIONS: There was a higher overall rate of complications for the group undergoing systematic lymphadenectomy, as well as higher rates of lymphocele and lymphedema according to the symptom score. No difference was found in overall QoL between SLN and SLN+LND groups.

MILACC study: could undetected lymph node micrometastases have impacted recurrence rate in the LACC trial?

OBJECTIVE: The etiology of inferior oncologic outcomes associated with minimally invasive surgery for early-stage cervical cancer remains unknown. Manipulation of lymph nodes with previously unrecognized low-volume disease might explain this finding. We re-analyzed lymph nodes by pathologic ultrastaging in node-negative patients who recurred in the LACC (Laparoscopic Approach to Cervical Cancer) trial. METHODS: Included patients were drawn from the LACC trial database, had negative lymph nodes on routine pathologic evaluation, and recurred to the abdomen and/or pelvis. Patients without recurrence or without available lymph node tissue were excluded. Paraffin tissue blocks and slides from all lymph nodes removed by lymphadenectomy were re-analyzed per standard ultrastaging protocol aimed at the detection of micrometastases (>0.2 mm and ≤2 mm) and isolated tumor cells (clusters up to 0.2 mm or <200 cells). RESULTS: The study included 20 patients with median age of 42 (range 30-68) years. Most patients were randomized to minimally invasive surgery (90%), had squamous cell carcinoma (65%), FIGO 2009 stage 1B1 (95%), grade 2 (60%) disease, had no adjuvant treatment (75%), and had a single site of recurrence (55%), most commonly at the vaginal cuff (45%). Only one patient had pelvic sidewall recurrence in the absence of other disease sites. The median number of lymph nodes analyzed per patient was 18.5 (range 4-32) for a total of 412 lymph nodes. A total of 621 series and 1242 slides were reviewed centrally by the ultrastaging protocol. No metastatic disease of any size was found in any lymph node. CONCLUSIONS: There were no lymph node low-volume metastases among patients with initially negative lymph nodes who recurred in the LACC trial. Therefore, it is unlikely that manipulation of lymph nodes containing clinically undetected metastases is the underlying cause of the higher local recurrence risk in the minimally invasive arm of the LACC trial.

First live birth after uterine transposition.

OBJECTIVE: To our knowledge, to report the first case of live birth of a child after uterine transposition (UT), pelvic radiotherapy, and subsequent uterine repositioning. DESIGN: Case report. SETTING: Tertiary referral cancer hospital. PATIENT(S): A 28-year-old nulligravid woman with left iliac and thoracic synchronous myxoid low-grade liposarcoma, which was resected with close margins. INTERVENTION(S): The patient underwent UT before undergoing pelvic (60 Gy) and thoracic (60 Gy) radiation on October 25, 2018. After radiotherapy, her uterus was reimplanted in the pelvis on February 20, 2019. MAIN OUTCOME MEASURE(S): The patient became pregnant in June 2021 and experienced an uneventful pregnancy until 36 weeks, when the patient started preterm labor and had a cesarean section delivery on January 26, 2022. RESULT(S): A boy was delivered after a gestation period of 36 weeks and 2 days (2686 g and 46.5 cm), with Apgar scores of 5 and 9, respectively; both mother and child were discharged the following day. After 1 year of follow-ups, the infant maintained normal development and the patient showed no signs of recurrence. CONCLUSION(S): To our knowledge, this case of the first live birth after UT is a proof-of-concept for the viability of UT as a procedure to prevent infertility in patients requiring pelvic radiotherapy.

Recommendations for the treatment of vulvar cancer in settings with limited resources: Report from the International Gynecological Cancer Society consensus meeting.

Introduction: Due to scant literature and the absence of high-level evidence, the treatment of vulvar cancer is even more challenging in countries facing limited resources, where direct application of international guidelines is difficult. Recommendations from a panel of experts convened to address some of these challenges were developed. Methods: The panel met in Rio de Janeiro in September 2019 during the International Gynecological Cancer Society congress and was composed of specialists from countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East. The panel addressed 62 questions and provided recommendations for the management of early, locally advanced, recurrent, and/or metastatic vulvar cancer. Consensus was defined as at least 75% of the voting members selecting a particular recommendation, whereas a majority vote was considered when one option garnered between 50.0% and 74.9% of votes. Resource limitation was defined as any issues limiting access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or funding for the provision of contemporary medical care. Results: Consensus was reached for nine of 62 (14.5%) questions presented to the panel, whereas a majority vote was reached for 29 (46.7%) additional questions. For the remaining questions, there was considerable heterogeneity in the recommendations. Conclusion: The development of guidelines focusing on areas of the world facing more severe resource limitations may improve medical practice and patient care.

Recommendations for the prevention, screening, diagnosis, staging, and management of cervical cancer in areas with limited resources: Report from the International Gynecological Cancer Society consensus meeting.

Introduction: Nearly 85% of cervical cancer new cases are diagnosed in limited resources countries. Although several strategies have been proposed to reduce the disease burden, challenges remain to provide the best possible care. We report recommendations from an expert consensus meeting convened to address from prevention to management of cervical cancer in limited resources countries. Methods: The expert panel, composed by invited specialists from 38 developing countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East, convened in Rio de Janeiro in September 2019, during the Global Meeting of the International Gynecological Cancer Society (IGCS). Panel members considered the published scientific evidence and their practical experience on the topics, as well as the perceived cost-effectiveness of, and access to, the available interventions. The focus of the recommendations was on geographic regions rather than entire countries because medical practice varies considerably in the countries represented. Resource limitation was qualified as limited access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or overall funding for provision of state-of-the-art care. Consensus was defined as at least 75% of the voting members selecting a particular answer of the multiple-choice questionnaire, whereas the majority vote was considered as 50% to 74.9%. Results: Consensus was reached for 25 of the 121 (20.7%) questions, whereas for 54 (44.6%) questions there was one option garnering between 50% to 74.9% of votes (majority votes). For the remaining questions, considerable heterogeneity in responses was observed. Discussion: The implementation of international guidelines is challenging in countries with resource limitations or unique health-care landscapes. The development of guidelines by the health care providers in those regions is more reflective of the reality on the ground and may improve medical practice and patient care. However, challenges remain toward achieving that goal at political, economic, social, and medical levels.

Cancer risk-reducing surgery: Brazilian society of surgical oncology guideline part 1 (gynecology and breast).

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Fourteen questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reduction bilateral salpingo-oophorectomy, hysterectomy, and mastectomy, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO, and it should serve as an important reference for the management of families with cancer predisposition.

Brazilian Society of Surgical Oncology surgical standards for resectable colorectal cancer liver metastases.

The management of colorectal cancer liver metastasis (CRLM) has become complex because of the increasing availability of medical, radiological, and surgical treatment options applied either alone or in combination. However, resection remains the only evidence-based curative therapy. These Brazilian Society of Surgical Oncology surgical standards are intended to guide clinicians in the decision-making process for modern surgical management of CRLM within a multidisciplinary team in an evidence-based framework, focusing on resectable disease.

Cancer risk-reducing surgery: Brazilian Society of Surgical Oncology Guideline Part 2 (Gastrointestinal and thyroid).

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Eleven questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reducing colectomy, gastrectomy, and thyroidectomy, a major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO and it should serve as an important reference for the management of families with cancer predisposition.

Brazilian Society of Surgical Oncology guidelines for malignant bowel obstruction management.

BACKGROUND: Malignant bowel obstruction (MBO) is a frequent complication in advanced cancer patients and especially those with abdominal tumors. The clinical management of MBO requires a specific and individualized approach based on the disease prognosis. Surgery is recommended. Less invasive approaches such as endoscopic treatments should be considered when surgery is contraindicated. The priority of care for inoperable and consolidated MBO is to control the symptoms and promote the maximum level of comfort. OBJECTIVES: This study aimed to develop recommendations for the effective management of MBO. METHODS: A questionnaire was administered to all members of the Brazilian Society of Surgical Oncology, of whom 41 surgeons participated in the survey. A literature review of studies retrieved from the National Library of Medicine database was conducted on particular topics chosen by the participants. These topics addressed questions regarding the MBO management, to define the level of evidence and strength of each recommendation, and an adapted version of the Infectious Diseases Society of America Health Service rating system was used. RESULTS: Most aspects of the medical approach and management strategies reviewed were strongly recommended by the participants. CONCLUSIONS: Guidelines outlining the strategies for management MBO were developed based on the strongest evidence available in the literature.

Sentinel lymph node mapping versus sentinel lymph node mapping with systematic lymphadenectomy in endometrial cancer: an open-label, non-inferiority, randomized trial (ALICE trial).

BACKGROUND: Growing evidence suggest that sentinel lymph node (SLN) biopsy in endometrial cancer accurately detects lymph node metastasis. However, prospective randomized trials addressing the oncological outcomes of SLN biopsy in endometrial cancer without lymphadenectomy are lacking. PRIMARY OBJECTIVES: The present study aims to confirm that SLN biopsy without systematic node dissection does not negatively impact oncological outcomes. STUDY HYPOTHESIS: We hypothesized that there is no survival benefit in adding systematic lymphadenectomy to sentinel node mapping for endometrial cancer staging. Additionally, we aim to evaluate morbidity and impact in quality of life (QoL) after forgoing systematic lymphadenectomy. TRIAL DESIGN: This is a collaborative, multicenter, open-label, non-inferiority, randomized trial. After total hysterectomy, bilateral salpingo-oophorectomy and SLN biopsy, patients will be randomized (1:1) into: (a) no further lymph node dissection or (b) systematic pelvic and para-aortic lymphadenectomy. MAJOR INCLUSION AND EXCLUSION CRITERIA: Inclusion criteria are patients with high-grade histologies (endometrioid G3, serous, clear cell, and carcinosarcoma), endometrioid G1 or G2 with imaging concerning for myometrial invasion of ≥50% or cervical invasion, clinically suitable to undergo systematic lymphadenectomy. PRIMARY ENDPOINTS: The primary objective is to compare 3-year disease-free survival and the secondary objectives are 5-year overall survival, morbidity, incidence of lower limb lymphedema, and QoL after SLN mapping ± systematic lymphadenectomy in high-intermediate and high-risk endometrial cancer. SAMPLE SIZE: 178 participants will be randomized in this study with an estimated date for completing accrual of December 2024 and presenting results in 2027. TRIAL REGISTRATION NUMBER: NCT03366051.

Open vs minimally invasive radical trachelectomy in early-stage cervical cancer: International Radical Trachelectomy Assessment Study.

BACKGROUND: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. OBJECTIVE: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. STUDY DESIGN: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. RESULTS: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery. CONCLUSION: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.