ESGE/ESGO/SERGS consensus statement on surgical steps in minimally invasive surgery in gynecologic oncology: transperitoneal and extraperitioneal approach for paraaortic lymphadenectomy.

INTRODUCTION: Assessment of retroperitoneal nodes is an important part of the surgical staging of gynecologic cancers. Although pelvic and paraaortic lymphadenectomy have been widely described by different authors, there is little consensus on the description of the different surgical steps for each procedure. An Intergroup Committee on Onco-Gyn Minimally Invasive Surgery has been established with members of the European Society for Gynecological Endoscopy (ESGE), European Society of Gynaecological Oncology (ESGO) and the Society of European Robotic Gynaecological Surgery (SERGS). The Intergroup Committee has various objectives: writing down a surgical description of the technique, which will be assessed by a group of experts following a formal consensus method and developing a specific Objective Structured Assessment of Technical Skills (OSATS) scale for each procedure. METHODS: A hierarchical task analysis was conducted by a working group of eight experts from the three societies in order to identify the surgical steps of transperitoneal and extraperitoneal approach in paraaortic lymphadenectomy. The selection of the definitive surgical steps was confirmed by a group of 19 experts from the different societies, following a formal consensus method. Two rounds of Delphi panel rating were considered necessary for achieving an agreement. The consensus agreement identified 29 surgical steps in transperitoneal and 17 surgical steps in extraperitoneal approach to complete a paraaortic lymphadenectomy. Once the description of the procedure and the consensus were established, an Objective specific Scale for the Assessment of Technical Skills for Paraaortic lymphadenectomy (PA-OSATS) in the transperitoneal and extraperitoneal approach was developed. RESULTS: In the first round of rating we found that 28 steps out of 29 in the transperitoneal approach and 13 out of 17 in the extraperitoneal approach did not reach a strong degree of agreement. They were reformulated based on comments made by the experts, and submitted to a second round of rating and this finally achieved an agreement. CONCLUSION: We defined a list of surgical steps in transperitoneal and extraperitoneal approach in paraaortic lymphadenectomy and a specific PA-OSATS scale for these procedures. This tool will be useful for teaching, assessing and standardizing this surgical procedure.

Cervical cancer: a new era.

Cervical cancer is a major global health issue, ranking as the fourth most common cancer in women worldwide. Depending on stage, histology, and patient factors, the standard management of cervical cancer is a combination of treatment approaches, including (fertility- or non-fertility-sparing) surgery, radiotherapy, platinum-based chemotherapy, and novel systemic therapies such as bevacizumab, immune checkpoint inhibitors, and antibody-drug conjugates. While ambitious global initiatives seek to eliminate cervical cancer as a public health problem, the management of cervical cancer continues to evolve with major advances in imaging modalities, surgical approaches, identification of histopathological risk factors, radiotherapy techniques, and biomarker-driven personalized therapies. In particular, the introduction of immune checkpoint inhibitors has dramatically altered the treatment of cervical cancer, leading to significant survival benefits in both locally advanced and metastatic/recurrent settings. As the landscape of cervical cancer therapies continues to evolve, the aim of the present review is to provide a comprehensive discussion of the current state and the latest practice-changing updates in cervical cancer.

Endometrial cancer with positive sentinel lymph nodes: pathologic characteristics of metastases as predictors of extent of lymphatic dissemination and prognosis.

OBJECTIVES: To assess predictors of extensive lymph node dissemination and non-vaginal recurrence in patients with endometrial cancer with positive sentinel lymph nodes (SLNs). METHODS: Patients with endometrial cancer who underwent primary surgery with SLN mapping and had at least one positive node between October 2013 and May 2019 were included. Positive SLNs were reviewed, and cases were classified according to the location of the metastasis (extracapsular vs intracapsular), and the size of the largest SLN metastasis (isolated tumor cells, micrometastasis, macrometastasis). Associations were assessed based on fitting logistic regression models and Cox proportional hazards models. RESULTS: A total of 103 patients met the inclusion criteria: including 36 (34.9%) with isolated tumor cells, 27 (26.2%) with micrometastasis, and 40 (38.8%) with macrometastasis. Notably, 71.4% of patients exhibiting extracapsular SLN metastases had multiple positive SLNs (p=0.008). Extracapsular invasion (adjusted odds ratio (aOR) 5.81, 95% CI 1.4 to 23.6) and age (aOR=1.8, 95% CI 1.1 to 3.0) emerged as independent predictors of multiple positive SLNs. Among the 38 patients who underwent a backup pelvic lymphadenectomy, 18 (47.4%) presented with positive pelvic non-SLNs, a phenomenon more prevalent in patients with macrometastasis (p=0.004).Independent predictors of non-vaginal recurrence included SLN macrometastasis (adjusted hazard ratio (aHR) 3.3, 95% CI 1.3 to 8.3), non-endometrioid histology (aHR=3.7, 95% CI 1.5 to 9.3), and cervical stromal invasion (aHR=5.5, 95% CI 2.0 to 14.9). Among the 34 patients with isolated tumor cells and endometrioid histology, 3 (9%) experienced a recurrence, all of whom had not received any adjuvant chemotherapy or external beam radiotherapy. CONCLUSION: Patients with positive SLN macrometastasis are independently associated with extensive lymphatic dissemination and distant recurrences. The risk of multiple positive SLNs increases with the extracapsular location of the SLN metastasis and with age. Independent uterine pathologic predictors of non-vaginal recurrence are non-endometrioid histology and cervical stromal invasion.

Role of immunotherapy for lymph node positive vulvar melanoma: utilization and outcomes.

OBJECTIVE: To investigate the utilization and outcomes of adjuvant immunotherapy for patients with vulvar melanoma and inguinal lymph node metastases. METHODS: The National Cancer Database was accessed and patients with vulvar melanoma diagnosed between 2004 and 2015 who did not have distant metastases, underwent inguinal lymphadenectomy, had positive lymph nodes, and at least 1 month of follow-up were identified. Administration of immunotherapy was evaluated and clinicopathological characteristics were compared. Median overall survival was compared with the log-rank test. Stratified analysis based on clinical status of lymph nodes was performed. A Cox model was constructed to evaluate survival after controlling for confounders. RESULTS: A total of 300 patients were identified; the rate of immunotherapy use was 25% (75 patients). Patients who received immunotherapy were younger (median 58 vs 70 years, p<0.001); however, the two groups were comparable in terms of clinical lymph node status, rate of positive tumor margins, presence of tumor ulceration, tumor size, Breslow thickness, and performance of comprehensive lymphadenectomy. There was no overall survival difference between patients who did (median 31.08 months) and did not (median 22.77 months) receive immunotherapy (p=0.18). Following stratification by clinical lymph node status, immunotherapy did not improve overall survival of patients with clinically negative (median 35.35 vs 33.22, p=0.75) or positive lymph nodes (median 23.33 vs 16.99, p=0.64). After controlling for confounders, administration of immunotherapy was not associated with better overall survival (HR 0.81, 95% CI 0.57 to 1.14). CONCLUSIONS: In this study approximately one in four patients received adjuvant immunotherapy. Immunotherapy was not associated with improved overall survival.

Survival after sentinel node biopsy alone in early-stage cervical cancer: a systematic review.

OBJECTIVE: To assess the oncologic outcomes of sentinel lymph node biopsy alone as part of surgical management in patients with early-stage cervical cancer. METHODS: A systematic search of the literature was performed following the PRISMA checklist. MEDLINE (through PubMed), EMBASE, and Scopus databases were searched from June 1991 to May 2023. Studies of women with early-stage cervical cancer International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IIA, of any age or histology, and articles only in English language were included. After the removal of duplicates, only articles including sentinel node mapping alone compared with full pelvic lymphadenectomy were retained. RESULTS: Four studies with a total of 2226 patients were included. Among these, 354 (15.9%) underwent sentinel lymph node biopsy alone. A total of 2210 (99.2%) patients had FIGO 2009 stage I disease and 1514 (68%) patients had squamous cell carcinoma. Median body mass index was 25.5 kg/m2 (range 23.5-27). Lymph vascular space invasion was present in 633 patients (34%) who underwent full lymphadenectomy and in 78 patients (22%) who underwent sentinel node biopsy alone. The results of the survival analysis showed that there was no significant difference in the 3-year progression-free survival rates of patients who underwent either sentinel biopsy alone or lymphadenectomy. Three-year recurrence-free survival was 93.1% (95% CI 28.3% to 64.7%) for patients who underwent sentinel node biopsy alone and 92.5% (95% CI 39.0% to 53.4%) for patients who underwent sentinel node biopsy and lymphadenectomy (p=0.773). CONCLUSIONS: In patients with early-stage cervical cancer, performing sentinel lymph node biopsy alone compared with pelvic lymphadenectomy does not appear to independently confer a higher risk or recurrence.

Sentinel lymph node sampling versus full lymphadenectomy in endometrial cancer: a SEER database analysis.

OBJECTIVE: To assess the long term outcomes and prognosis of sentinel lymph node sampling compared with full lymph node dissection in endometrial cancer patients. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database for information on women diagnosed with endometrial cancer from 2010 to 2019. We conducted a comparison including overall survival between patients who had undergone sentinel lymph node sampling only and patients who had undergone formal lymph node dissection. Propensity score matching was performed according to the patient's age, type of endometrial cancer, grade and stage of disease, and adjuvant therapy. Subgroup analyses were performed according to type and grade of endometrial cancer. RESULTS: 41411 endometrial cancer patients were identified through the database. After matching, 6019 patients each were included in the sentinel lymph node and lymph node dissection groups. Median (interquartile range (IQR)) follow-up time was 16 (7-31) months in both groups. One year survival rates were longer in the sentinel lymph node group compared with the lymph node dissection group (hazard ratio (HR) 1.61 (95% confidence interval (CI) 1.17 to 2.21); p=0.004). Subgroups analysis according to grade of disease showed that 1 year survival rates were longer in the sentinel lymph node group in patients with endometrioid-type grade 1-2 endometrial cancer (HR 1.70 (95% CI 1.31 to 2.56); p=0.01), while no difference in survival was found between the sentinel lymph node and lymph node dissection groups in the subgroup of patients with high grade endometrial cancer (HR 1.40 (95%CI 0.94 to 2.24); p=0.17). In patients with low grade endometrial cancer included in the sentinel lymph node group, only 7% had lymph nodes positive for malignancy compared with 17% in the high grade group. CONCLUSION: Survival rates were not compromised in endometrial cancer patients undergoing sentinel lymph node sampling versus full lymph node dissection for all grades of disease.

Prophylactic complex physiotherapy in gynecologic cancer survivors: patient-reported outcomes based on a lymphedema questionnaire.

OBJECTIVE: Lower extremity lymphedema secondary to cancer treatment impacts quality of life for gynecological cancer survivors. Complex decongestive physiotherapy is applied when lymphedema is diagnosed, but prophylactic physiotherapy is not yet a standard of care. The aim of this study is to evaluate prophylactic complex physiotherapy in patients with gynecological cancer and its effects on patient-reported symptoms based on the Gynecologic Cancer Lymphedema Questionnaire. METHODS: The data of patients diagnosed with gynecological cancers who underwent lymphadenectomy from July 2021 to June 2022 was evaluated. All patients were referred to the physiotherapy unit before adjuvant treatment. Patients who accepted prophylactic physiotherapy were informed and massage and exercise training were implemented, whereas patients who declined were solely informed. Bilateral lower extremity circumferences were measured at 1, 3, 6, and 12 months at the levels of 10 cm, 30 cm, and 50 cm above the heels. A translated form of the Gynecologic Cancer Lymphedema Questionnaire was administered to all patients at the last visit. RESULTS: A total of 100 patients were included in the study. Patients were diagnosed with endometrial (50%), ovarian (32%), cervical (16%), and vulvar (2%) cancer. Overall, 70% underwent systematic pelvic±para-aortic lymphadenectomy whereas sentinel lymph node mapping was performed in 30%. Lymphedema was seen in 5% (n=3) of the prophylactic physiotherapy positive group and in 60% (n=24) of the physiotherapy negative group. The median score was 3 (range 1-5) in the physiotherapy positive group and 16 (range 9-20) in the physiotherapy negative group. In patients diagnosed with lymphedema in the physiotherapy negative group, systematic lymphadenectomy was performed in 91.7% (n=22) and a higher number of lymph nodes was extracted (median 45.5; p=0.002). CONCLUSION: Prophylactic complex physiotherapy is associated with lower rates of lymphedema and better patient-reported symptom scores according to the Gynecologic Cancer Lymphedema Questionnaire.

Sentinel lymph node biopsy alone in the management of early cervical carcinoma.

OBJECTIVE: Sentinel lymph node (SLN) biopsy aims to assess lymph node status with reduced surgical morbidity. The aim of the study was to determine the accuracy and safety of SLN biopsy in the management of early cervical carcinoma using a double technique (technetium-99m (Tc-99m) nanocolloid and methylene blue dye injection). METHODS: This was a 10-year study from January 2009 to January 2019 that recruited 103 consecutive women undergoing surgery for early cervical carcinoma, FIGO 2009 stage IA1 (grade 3, and grade 2 with lymphovascular space invasion) to IB1 (<2 cm), at the West Kent Gynaecological Oncology Centre, Maidstone, UK. All patients were given the choice of pelvic node dissection and SLN mapping or SLN only. All patients elected to undergo SLN only. In total 97 patients had SLN mapping performed laparoscopically. We used the combined method (Tc-99m nanocolloid and/or methylene blue dye). All SLN routinely underwent ultrastaging. RESULTS: At least one SLN was detected in all 103 patients, using at least one of the combined methods (Tc-99m nanocolloid or blue dye). Bilaterally SLN were removed in 85/103 women with an 83% bilateral detection rate. The median SLN count was 2.3 (range 1-6) nodes. Of 103 patients, 7 (6.7%) patients had lymph node involvement. There were no pelvic or para-aortic lymph node recurrences with a median follow-up of 53 (range 8-120) months. The specificity and negative predictive value of a negative SLN was 100%. None of our 103 patients reported lower extremity lymphedema. CONCLUSION: In carefully selected patients with early cervical carcinoma, SLN biopsy alone appears to be a safe method for lymph node assessment of women undergoing surgical staging. Ultrastaging is an essential part of histologic examination of SLN.

Trans-inguinal pelvic lymphadenectomy in vulvar cancer patients: TRIPLE pilot study.

OBJECTIVE: The goal of this study was to assess the feasibility and safety of a retrograde extraperitoneal trans-inguinal novel approach to pelvic lymphadenectomy in vulvar cancer patients. The secondary objectives were to assess complications (early and late) and oncological outcomes. METHODS: In this pilot study, all patients referred to our institution from November 2019 to May 2021 were evaluated. The inclusion criteria were patients diagnosed with primary/recurrent vulvar cancer and who were candidates for concomitant groin and pelvic lymph node dissection. A consecutive sampling was planned during the study period. After conventional inguino-femoral lymph nodal dissection, ipsilateral extraperitoneal trans-inguinal pelvic lymphadenectomy (TRIPLE) was performed through a groin incision. Clinical data, type of treatment, perioperative complications, and follow-up were evaluated. RESULTS: 13 patients (8 primary, 5 recurrent vulvar cancer) underwent 16 TRIPLE procedures (10 unilateral, 3 bilateral). The median age was 69 years (range 58-93 years); 8 patients had comorbidities (61.5%). Up front locoregional radiotherapy was previously performed in two cases (15.4%). The pathology report showed metastatic lymph nodes in 20 (87%) groins and 11 (68.8%) pelvic sites; the mean number of removed and metastatic pelvic lymph nodes was 12.1 (range 5-33) and 2.9 (range 0-18), respectively. No intra-operative site-specific complications occurred. One (5.9%) post-operative site-specific complication was reported (pelvic abscess, grade 2), which was treated with antibiotics. One patient died due to concomitant pneumonia. No unilateral pelvic lymph node recurrence occurred during follow-up (median 13 months, range 2-43 months); 3 patients (23.1%) had distant site recurrence (median disease-free survival 9 months). CONCLUSIONS: TRIPLE seems to be a feasible and safe technique, providing adequate lymph node dissection. Despite being a high-risk and fragile population, morbidity was similar to previously reported data for conventional mini-invasive approaches. Prospective larger comparative series are necessary.

Endometrial stripe thickness: a preoperative marker to identify patients with endometrial intraepithelial neoplasia who may benefit from sentinel lymph node mapping and biopsy.

OBJECTIVES: The goal of our study was to identify preoperative factors in patients with endometrial intraepithelial neoplasia that are associated with concurrent endometrial cancer to select patients who may benefit from sentinel lymph node (SLN) assessment at the time of hysterectomy. METHODS: Retrospective single institution cohort study of patients with a preoperative diagnosis of endometrial intraepithelial neoplasia who underwent hysterectomy with or without staging from January 2010 to July 2020. Modified Poisson regression was used to calculate risk ratios (RR) and 95% confidence intervals (CI). RESULTS: Of 378 patients with a preoperative diagnosis of endometrial intraepithelial neoplasia, 275 (73%) had endometrial intraepithelial neoplasia and 103 (27%) had invasive cancer on final pathology. Age (p=0.003), race (p=0.02), and hypertension (p=0.02) were significantly associated with concurrent endometrial cancer. The median preoperative endometrial stripe was significantly greater in the endometrial cancer group (14 mm (range 10-19)) than in the endometrial intraepithelial neoplasia group (11 mm (range 8-16); p=0.002). A preoperative endometrial stripe ≥20 mm was associated with double the risk of endometrial cancer on final pathology (crude RR 2.0, 95% CI 1.3 to 2.9) and preoperative endometrial stripe ≥15 mm was 2.5 times more likely to be associated with high risk Mayo criteria on final pathology (crude RR 2.5, 95% CI 1.2 to 5.2). Of those with concurrent endometrial cancer, 5% were stage IB, 29% had tumors >2 cm, and 1% had grade 3 histology. Only 3% of all patients underwent lymph node evaluation. CONCLUSIONS: In a large cohort of patients with a preoperative diagnosis of endometrial intraepithelial neoplasia, less than a third had invasive cancer and even fewer had pathologic features considered high risk for nodal metastasis, arguing against the use of routine SLN dissection in these patients. Endometrial stripe ≥15 mm may be a useful preoperative marker to identify patients at higher risk for concurrent endometrial cancer and may be an important criterion for use of selective SLN dissection in carefully selected patients with endometrial intraepithelial neoplasia.

Uterine serous carcinoma: key advances and novel treatment approaches.

The incidence and mortality rates from endometrial cancer continue to increase worldwide, while rates in most other cancers have either plateaued or declined considerably. Uterine serous carcinoma represents a fraction of all endometrial malignancies each year, yet this histology is responsible for nearly 40% of all endometrial cancer-related deaths. These deaths disproportionately affect black women, who have higher rates of advanced disease at diagnosis. Molecular genetic analyses reveal major alterations including TP53 mutation, PIK3CA mutation/amplification, ERBB2 amplification, CCNE1 amplification, FBXW7 mutation/deletion, PPP2R1A mutation, and somatic mutations involving homologous recombination genes. Clinical risk factors for uterine serous carcinoma include advancing age, a history of breast cancer, tamoxifen usage, and the hereditary breast-ovarian cancer syndrome. Surgery remains the cornerstone of treatment. Recent advances in our understanding of uterine serous carcinoma molecular drivers have led to development of targeted therapeutics that promise improved outcomes for patients. Overexpression or amplification of HER2 in uterine serous carcinoma carries a poor prognosis; yet this actionable target has led to the incorporation of several anti-HER2 therapies, including trastuzumab which, when added to conventional chemotherapy, is associated with improved survival for women with advanced and recurrent HER2-positive disease. The combination of pembrolizumab and lenvatinib is also a promising targeted treatment strategy for women with uterine serous carcinoma, with a recent phase II study suggesting a 50% response rate in women with recurrent disease. Several trials examining additional targeted agents are ongoing. Despite years of stalled progress, meaningful, tailored treatment options are emerging for patients with this uncommon and biologically aggressive endometrial cancer subtype.

Risk factors for lymphedema and method of assessment in endometrial cancer: a prospective longitudinal multicenter study.

OBJECTIVE: The aim of the study was to determine risk factors for lymphedema of the lower limbs, assessed by four methods, 1 year after surgery for endometrial cancer. METHODS: A prospective longitudinal multicenter study was conducted in 14 Swedish hospitals. 235 women with endometrial cancer were included; 116 underwent surgery including lymphadenectomy, and 119 had surgery without lymphadenectomy. Lymphedema was assessed preoperatively and 1 year postoperatively objectively by systematic circumferential measurements of the legs, enabling volume estimation addressed as (1) crude volume and (2) body mass index-standardized volume, or (3) clinical grading, and (4) subjectively by patient-reported perception of leg swelling. In volume estimation, lymphedema was defined as a volume increase ≥10%. Risk factors were analyzed using forward stepwise logistic regression models and presented as adjusted odds ratio (aOR) and 95% confidence interval (95% CI). RESULTS: Risk factors varied substantially, depending on the method of determining lymphedema. Lymphadenectomy was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 14.42, 95% CI 3.49 to 59.62), clinical grading (aOR 2.11, 95% CI 1.04 to 4.29), and patient-perceived swelling (aOR 2.51, 95% CI 1.33 to 4.73), but not when evaluated by crude volume. Adjuvant radiotherapy was only a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 15.02, 95% CI 2.34 to 96.57). Aging was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 1.07, 95% CI 1.00 to 1.15) and patient-perceived swelling (aOR 1.06, 95% CI 1.02 to 1.10), but not when assessed by crude volume or clinical grading. Increase in body mass index was a risk factor for lymphedema when estimated by crude volume (aOR 1.92, 95% CI 1.36 to 2.71) and patient-perceived swelling (aOR 1.36, 95% CI 1.11 to 1.66), but not by body mass index-standardized volume or clinical grading. The extent of lymphadenectomy was strongly predictive for the development of lymphedema when assessed by body mass index-standardized volume and patient-perceived swelling, but not by crude volume or clinical grading. CONCLUSION: Apparent risk factors for lymphedema differed considerably depending on the method used to determine lymphedema. This highlights the need for a 'gold standard' method when addressing lymphedema for determining risk factors.

Reduced lymphedema after sentinel lymph node biopsy versus lymphadenectomy for endometrial cancer.

OBJECTIVE: Endometrial cancer surgical staging includes lymph node assessment which can lead to lower extremity lymphedema. The aim of this study was to estimate prevalence after sentinel lymph node biopsy versus lymphadenectomy. METHODS: Consecutive patients who underwent minimally invasive surgery at the Mayo Clinic, Rochester, Minnesota, USA, between January 2009 and June 2016 for newly diagnosed endometrial cancer were mailed our validated 13 item lower extremity lymphedema screening questionnaire. We also ascertained via questionnaire whether the patient was ever diagnosed with lower extremity lymphedema. RESULTS: Among 378 patients included in the analysis, 127 (33.5%) had sentinel lymph node biopsy with or without side specific lymphadenectomy (sentinel lymph node cohort) and 251 (66.4%) underwent bilateral lymphadenectomy prior to sentinel lymph node biopsy implementation at our institution or as 'backup' after sentinel lymph node mapping (lymphadenectomy cohort). The prevalence of lower extremity lymphedema was 41.5% (157/378), with 69 patients (18.3%) self-reporting a lower extremity lymphedema diagnosis after their endometrial cancer surgery at a median of 54.3 months (interquartile range 31.2-70.1 months), and an additional 88 patients (23.3%) identified by the screening questionnaire. The prevalence of lower extremity lymphedema was significantly higher in the lymphadenectomy cohort compared with the sentinel lymph node group (49.4% (124/251) vs 26.0% (33/127); p<0.001). When the cohorts were restricted to patients surgically managed after the introduction of sentinel lymph node, the prevalence of lower extremity lymphedema was still significantly higher in the lymphadenectomy cohort compared with the sentinel lymph node cohort (39.0% (41/105) vs 26.0% (33/127); p=0.03). In a multivariable analysis adjusted for body mass index, receipt of adjuvant external beam radiation, diabetes, congestive heart failure, and International Federation of Gynecology and Obstetrics grade, the adjusted odds ratio for the association between type of nodal sampling (lymphadenectomy cohort vs sentinel lymph node cohort) and lower extremity lymphedema was 2.75 (95% confidence interval 1.69 to 4.47, p<0.001). CONCLUSIONS: Sentinel lymph node biopsy was associated with a decreased risk of post-treatment lymphedema compared with lymphadenectomy in patients who underwent surgical staging for endometrial carcinoma.

Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators.

INTRODUCTION: Comprehensive updated information on cervical cancer surgical treatment in Europe is scarce. OBJECTIVE: To evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database. METHODS: The SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified. RESULTS: The mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m2 (SD 4.9). A total of 423 (36.6%) patients had a previous cone biopsy. Tumor size (clinical examination) <2 cm was observed in 667 (57.7%) patients. The most frequent histology type was squamous carcinoma (794 (68.7%) patients), and positive lymph nodes were found in 143 (12.4%) patients. A total of 633 (54.8%) patients were operated by open abdominal surgery. Intra-operative complications occurred in 108 (9.3%) patients, and post-operative complications during the first month occurred in 249 (21.5%) patients, with bladder dysfunction as the most frequent event (119 (10.3%) patients). Clavien-Dindo grade III or higher complication occurred in 56 (4.8%) patients. A total of 510 (44.1%) patients received adjuvant therapy. After a median follow-up of 58 months (range 0-84), the 5-year disease-free survival was 88.3%, and the overall survival was 94.9%. In our population, 10 of the 11 surgical-related quality indicators currently recommended by ESGO were fully fulfilled 5 years before its implementation. CONCLUSIONS: In this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

Conization and lymph node evaluation as a fertility-sparing treatment for early stage cervical cancer.

INTRODUCTION: To evaluate oncological and obstetrical outcomes of early stage cervical cancer patients who underwent conservative management to retain childbearing potential. METHODS: Data of women (aged <40 years) who underwent fertility sparing treatment for International Federation of Gynecology and Obstetrics (FIGO) stage IA1 with lymphovascular invasion (LVSI) and IB1 cervical cancer were prospectively collected. All patients underwent cervical conization/s and laparoscopic nodal evaluation (pelvic lymphadenectomy/sentinel node mapping). Oncological and obstetrical outcomes were assessed. RESULTS: Overall, 39 patients met inclusion criteria; 36 (92.3%) women were nulliparous. There were: 3 (7.7%) IA1-LVSI+; 11 (28.2%) IA2; and 25 (64.1%) IB1 cervical cancers, according to 2018 FIGO stage classification. Histological types were 22 (56.4%) squamous carcinoma and 17 (43.6%) adenocarcinoma. Pelvic lymphadenectomy was performed in 29 (74.4%) patients, while 10 (25.6%) patients had only sentinel node mapping. In 4 (10.3%) patients conservative treatment was discontinued due to nodal involvement and 2 (5.1%) patients requested definitive treatment (hysterectomy) after a negative lymph node evaluation. Among 33 (84.6%) patients who retained their childbearing potential, 17 (51.5%) had a second conization. 2 (6.1%) patients relapsed and underwent definitive treatment. After a median follow-up of 51 months (range 1-184) no deaths were reported. 22 (70.9%) patients attempted to conceive. There were 13 natural pregnancies among 12 (54.5%) women who got pregnant. Live birth rate was 76.9%: 9 (69.2%) term and 1 (7.7%) preterm (at 32 weeks) deliveries. 2 (15.4%) miscarriages (first and second trimester) and 1 (7.7%) termination of pregnancy for medical reasons were recorded. CONCLUSION: Conization plus laparoscopic nodal evaluation may be a safe and feasible conservative option in the setting of fertility-sparing treatment for early-stage cervical cancer patients.

Novel preoperative predictive score to evaluate lymphovascular space involvement in endometrial cancer: an aid to the sentinel lymph node algorithm.

INTRODUCTION: Sentinel lymph node (SLN) dissection has been recognized as a valid tool for staging in patients with endometrial cancer. Several factors are predictors of recurrence and survival in endometrial cancer, including positive lymphovascular space invasion. The aim of this study is to formulate a pre-operative score that, in the event of no-SLN identification, may give an estimate of the true probability of lymphovascular space invasion and guide management. METHODOLOGY: This was a multi-institutional retrospective study conducted from January 2007 to December 2017. We included all patients with any grade endometrial tumor with a complete pathological description of the surgical specimen and with a minimum follow-up of 12 months. All patients underwent a class A hysterectomy according to Querleu and Morrow and bilateral salpingo-oophorectomy. Lymphadenectomy was performed based on patient risk of node metastases. In order to verify the predictive capacity of the parameters associated with lymphovascular space invasion status, grading, abnormal CA125 (>35 units/ml), myometrial invasion, and tumor size, a synthetic score was calculated. The score was introduced in the receiver operating characteristic curve model in which the binary classifier was represented by the lymphovascular space invasion status. The ideal cut-off was calculated with the determination of the Youden index. Sensitivity and negative predictive value of lymphovascular space invasion score was calculated in patients with lymph node metastasis. RESULTS: Six hundred and fourteen patients were included in the study. The average age and BMI of patients were 64.8 (range 33-88) years and 30.1 (range 17-64) respectively. Of the 284 patients who underwent lymphadenectomy, 231 (81.3%) patients had no lymph node metastases, 33 (11.6%) patients had metastatic pelvic lymph nodes, 12 (4.2%) patients had metastatic aortic lymph nodes, and eight (2.8%) patients had both pelvic and aortic metastatic lymph nodes. Lymphovascular space invasion was associated with deep myometrial infiltration (P<0.001), G3 grading (P<0.001), tumor size ≥25 mm (P=0.012), abnormal CA125 (P<0.001), recurrence (P<0.001), overall survival (P<0.001), and disease-free survival (P<0.01). Of all patients with lymphovascular space invasion, 79% had an lymphovascular space invasion score ≥5. The score ranged from a minimum score of 1 to a maximum of 7. The score shows 78.9% sensitivity (95% CI 0.6971 to 0.8594), 65.3% specificity (95% CI 0.611 to 0.693), 29.4% positive predictive value (95% CI 0.241 to 0.353), and 94.4% negative predictive value (95% CI 0.916 to 0.964). CONCLUSION: We found that when lymphovascular space invasion score ≤4, there is a very low possibility of finding lymph nodal involvement. The preoperative lymphovascular space invasion score could complement the SLN algorithm to avoid unnecessary lymphadenectomies.

Impact of sentinel lymph node frozen section evaluation to avoid combined treatment in early-stage cervical cancer.

BACKGROUND: The need for radical surgery followed by adjuvant chemoradiation may be reduced by abandoning radical surgery in patients in whom lymph node involvement is detected intra-operatively. OBJECTIVES: To analyze, in a retrospective cohort study, the efficacy of the algorithm using intra-operative pathological assessment of sentinel lymph nodes. METHODS: A retrospective single-institution study was carried out, which analyzed data from all consecutive patients with cervical cancer who were referred for primary surgical treatment between May 2005 and December 2015. Inclusion criteria were as follows: (1) TNM stage T1a1 with lymphovascular space invasion, T1a2, T1b, T2a, and selected T2b with incipient parametrial invasion; (2) adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma; (3) no evidence of enlarged suspicious nodes or distant metastases on pre-operative imaging; (4) primary surgery with curative intent; (5) successful detection of sentinel lymph node, at least, unilaterally. All patients had at least one sentinel lymph node detected and submitted for frozen section evaluation. When sentinel lymph node involvement was detected intra-operatively, the cervical procedure was abandoned and the patient was referred for definitive chemoradiation. Radical surgery was completed in patients with intra-operative negative sentinel lymph nodes. The reliability of intra-operative sentinel lymph node assessment was evaluated by calculating the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio. RESULTS: The study included a total of 309 patients. Sentinel lymph nodes were detected bilaterally in 86% of the patients. Lymph node positivity was detected intra-operatively in 18 (6%) patients in whom the cervical procedure was abandoned. Adjuvant radiotherapy after completed radical surgery was given to 29 (9%) patients, including 20 patients with macrometastases (8) or micrometastases (12) reported from the final histology, eight patients with positive parametria (all ≤3 mm), and one patient with a positive vaginal resection margin. The sensitivity, specificity, positive predictive value, and negative predictive value for the intra-operative detection of lymph node positivity (macrometastases or micrometastases) was 47% (95% CI 31% to 64%), 100%, 100%, and 93% (95% CI 90% to 96%), respectively. A total of 18 (6%) patients were spared combined treatment owing to the intra-operative sentinel lymph node triage; 29 patients (9%) received combined treatment with both radical surgery and adjuvant radiotherapy CONCLUSIONS: Of 47 patients with high-risk prognostic risk factors (lymph node, parametria, or surgical margin involvement), combined treatment was successfully avoided in 18 (38%). Despite an effort to triage the patients intra-operatively, 9% received a combination of cervical procedure and adjuvant chemoradiation, mostly owing to the low sensitivity of the frozen section in the detection of micrometastases and macrometastases.

Sentinel lymph node mapping in endometrial cancer: performance of hysteroscopic injection of tracers.

OBJECTIVE: To report on the performance of hysteroscopic injection of tracers (indocyanine green (ICG) and technetium-99m (Tc-99m)) for sentinel lymph node (SLN) mapping in endometrial cancer. METHODS: Single-center retrospective evaluation of consecutive patients who underwent SLN mapping following hysteroscopic peritumoral injection of tracer. Detection rate (overall/bilateral/aortic) diagnostic accuracy, and oncologic outcomes were evaluated. RESULTS: A total of 221 procedures met the inclusion criteria. Mean patient age was 60 (range 28-84) years and mean body mass index was 26.9 (range 15-47) kg/m2 . In 164 cases (70.9%) mapping was performed laparoscopically. The overall detection rate of the technique was 94.1% (208/221 patients). Bilateral pelvic mapping was found in 62.5% of cases with at least one SLN detected and was more frequent using ICG than with Tc-99m (73.8% vs 53.3%; p<0.001). In 47.6% of cases SLNs mapped in both pelvic and aortic nodes, and in five cases (2.4%) only in the aortic area. In eight patients (3.8%) SLNs were found in aberrant (parametrial/presacral) areas. Mean number of detected SLNs was 3.7 (range 1-8). In 51.9% of cases at least one node other than SLNs was removed. Twenty-six patients (12.5%) had nodal involvement: 12 (46.2%) macrometastases, six (23.1%) micrometastases, and eight (30.7%) isolated tumor cells. In 12 cases (46.8%) the aortic area was involved. Overall, 6/221 (2.7%) patients had isolated para-aortic nodes. Three false-negative results were found, all in the Tc-99m group. All had isolated aortic metastases. Overall sensitivity was 88.5% (95% CI 71.7 to 100.0) and overall negative predictive value was 96.5% (95% CI 86.8 to 100.0). There were 10 (4.8%) recurrences: five abdominal/distant, four vaginal, and one nodal (in the aortic area following a unilateral mapping plus side-specific pelvic lymphadenectomy). Most recurrences (9/10 cases) were patients in whom a completion lymphadenectomy was performed. No deaths were reported after a mean follow-up of 47.7 months. CONCLUSIONS: Hysteroscopic injection of tracers for SLN mapping in endometrial cancer is as accurate as cervical injection with a higher detection rate in the aortic area. ICG improves the bilateral detection rate. Adding lymphadenectomy to SLN mapping does not reduce the risk of relapse.

Pelvic sentinel lymph node biopsy in endometrial cancer-a simplified algorithm based on histology and lymphatic anatomy.

OBJECTIVE: To achieve the full potential of sentinel lymph node (SLN) detection in endometrial cancer, both presumed low- and high-risk groups should be included. Perioperative resource use and complications should be minimized. Knowledge on distribution and common anatomical sites for metastatic SLNs may contribute to optimizing the concept while maintaining sensitivity. Proceeding from previous studies, simplified algorithms based on histology and lymphatic anatomy are proposed. METHODS: Data on mapping rates and locations of pelvic SLNs (metastatic and non-metastatic) from two previous prospective SLN studies in women with endometrial cancer were retrieved. Cervically injected indocyanine green was used as a tracer and an ipsilateral re-injection was performed in case of non-display of the upper and/or lower paracervical pathways. A systematic surgical algorithm was followed with clearly defined SLNs depicted on an anatomical chart. In high-risk endometrial cancer patients, removal of SLNs was followed by a pelvic and para-aortic lymphadenectomy. RESULTS: 423 study records were analyzed. The bilateral mapping rates of the upper and lower paracervical pathways were 88.9% and 39.7%, respectively. 72% of all SLNs were typically positioned along the upper paracervical pathway (interiliac and/or proximal obturator fossa) and 71 of 75 (94.6%) of pelvic node positive women had at least one metastatic SLN at either of these positions. Women with grade 1-2 endometroid cancers (n=275) had no isolated metastases along the lower paracervical pathway compared with two women with high-risk histologies (n=148). CONCLUSION: SLNs along the upper paracervical pathway should be identified in all endometrial cancer histological subtypes; removal of nodes at defined typical positions along the upper paracervical pathway may replace a site-specific lymphadenectomy in case of non-mapping despite tracer re-injection. Detection of SLNs along the lower paracervical pathway can be restricted to high-risk histologies and a full pre-sacral lymphadenectomy should be performed in case of non-display.

Comparison of surgical and pathological parameters after laparoscopic transperitoneal pelvic/para-aortic lymphadenectomies.

OBJECTIVE: Lymphadenectomy is an integral part of surgical staging and treatment for patients with gynecologic malignancies. Since its introduction, laparoscopic lymphadenectomy has proved feasible, safe, and oncologically adequate compared with open surgery while morbidity is lower and hospital stay considerably shorter. The aim of this study was to examine if surgical outcomes may be improved after the initial learning curve is complete. METHODS: An analysis of 2535 laparoscopic pelvic and/or para-aortic lymphadenectomies was performed between July 1994 and March 2018 by one team of gynecologic oncology surgeons but with the consistent supervision of a consultant surgeon. Data were collected prospectively evaluating operative time, intra-operative and post-operative complications, number of lymph nodes, and body mass index (BMI). Previously published data of 650 patients treated after introduction of the method (period 1, 1994-2003) were compared with the latter 524 patients (period 2, 2014-2018). RESULTS: The median age of the 2535 patients was 43 years (IQR 34-57). The most common indication for pelvic and/or para-aortic lymphadenectomy was cervical cancer (n=1893). Operative time for para-aortic lymph node dissection was shorter in period 2 (68 vs 100 min, p<0.001). The number of harvested lymph nodes was increased for pelvic (19.2 (range 2-52) vs 21.9 (range 4-87)) and para-aortic lymphadenectomy (10.8 (range 1-52) vs 14.4 (range 4-64)), p<0.001. BMI did not have a significant influence on node count or operative time, with BMI ranging from 14.6 to 54.1 kg/m2. In contrast to period 1 (n=18, 2.9%), there were no intra-operative complications in period 2 (n=0, 0.0%, p<0.001) whereas post-operative complications were similar (n=35 (5.8%) in period 1; n=38 (7.6%) in period 2; p=0.32). CONCLUSION: In this large cohort of patients who underwent laparoscopic transperitoneal lymphadenectomy, lymph node count and peri-operative complications improved after the initial learning curve.