Clinicopathological characteristics of multiple-classifier endometrial cancers: a cohort study and systematic review.

BACKGROUND: Endometrial cancers with more than one molecular feature-POLE mutations (POLEmut), mismatch repair protein deficiency (MMRd), p53 abnormality (p53abn)-are called 'multiple classifiers'. OBJECTIVE: To describe our cohort of multiple classifiers and to report the results of a review on their incidence and the techniques used to identify them. METHODS: Multiple classifiers identified at the European Institute of Oncology, Milan, between April 2019 and Decmber 2022, were included. Clinicopathological, molecular characteristics, and oncologic outcomes were summarized and compared between single and multiple classifiers sharing common features. Studies on molecular classification of endometrial cancer were searched in the PubMed Database to collect data on the incidence of multiple classifiers and the techniques used for classification. RESULTS: Among 422 patients, 48 (11.4%) were multiple classifiers: 15 (3.6%) POLEmut-p53abn, 2 (0.5%) POLEmut-MMRd, 28 (6.6%) MMRd-p53abn, and 3 (0.7%) POLEmut-MMRd-p53abn. MMRd-p53abn and MMRd differed in histotype (non-endometrioid: 14.8% vs 2.0%, p=0.006), grade (high-grade: 55.6% vs 22.2%, p=0.001), and MMR proteins expression, whereas they differed from p53abn in histotype (non-endometrioid: 14.8% vs 50.0%, p=0.006). POLEmut-p53abn and POLEmut differed only in grade (high-grade: 66.7% vs 22.7%, p=0.008), while they differed from p53abn in age (56.1 vs 66.7 years, p=0.003), stage (advanced: 6.7% vs 53.4%, p=0.001), and histotype (non-endometrioid: 6.7% vs 50.0%, p=0.002). Two (7.1%) patients with MMRd-p53abn, 4 (4.0%) with MMRd, and 25 (34.3%) with p53abn had a recurrence. No recurrences were observed in POLEmut-p53abn and POLEmut. TP53 sequencing allowed the detection of additional 7 (18.9%) multiple classifiers with normal p53 immunostaining. The incidence of multiple classifiers ranged from 1.8% to 9.8% in 10 published studies including >100 patients. When only p53 immunohistochemistry was performed, the highest incidence was 3.9%. CONCLUSIONS: The characteristics of POLEmut-p53abn resembled those of POLEmut, whereas MMRd-p53abn appeared to be intermediate between MMRd and p53abn. The high proportion of multiple classifiers may be related to the methods used for molecular classification, which included both p53 immunohistochemistry and TP53 sequencing.

A novel algorithm to implement the molecular classification according to the new ESGO/ESTRO/ESP 2020 guidelines for endometrial cancer.

OBJECTIVE: To compare the risk class attribution with molecular classification unknown to those with molecular classification known, according to the European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) 2020 guidelines on endometrial cancer, with a focus on risk group migration. Additionally, to evaluate the capability of a novel molecular analysis algorithm to reduce the number of required tests. METHODS: We conducted a retrospective study including all consecutive patients with endometrial cancer undergoing surgery and comprehensive molecular analyses between April 2019 and December 2021. Molecular analyses including immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for POLE exonuclease domain were performed to classify tumors as POLE-mutated (POLE), MMR-deficient (MMR-d), p53 abnormal (p53abn), or non-specific molecular profile (NSMP). The two risk classifications of the ESGO/ESTRO/ESP 2020 guidelines were compared to estimate the proportion of patients in which the molecular analysis was able to change the risk class attribution. We developed a novel algorithm where the molecular analyses are reserved only for patients in whom incorporation of the molecular classification could change the risk class attribution. RESULTS: A total of 278 patients were included. Molecular analyses were successful for all cases, identifying the four subgroups: 27 (9.7%) POLE, 77 (27.7%) MMR-d, 49 (17.6%) p53abn, and 125 (45.0%) NSMP. Comparison of risk class attribution between the two classification systems demonstrated discordance in the risk class assignment in 19 (6.8%, 95% CI 4.2% to 10.5%) cases. The application of our novel algorithm would have led to a reduction in the number of POLE sequencing tests by 67% (95% CI 61% to 73%) and a decrease of p53 immunohistochemistry by 27% (95% CI 22% to 33%), as compared with the application of molecular classification to all patients. CONCLUSION: Molecular categorization of endometrial cancer allows the reallocation of a considerable proportion of patients in a different risk class. Furthermore, the application of our algorithm enables a reduction in the number of required tests without affecting the risk classification.

Oncologic Outcomes of Robotic Radical Hysterectomy (RRH) for Patients with Early-Stage Cervical Cancer: Experience at a Referral Cancer Center.

PURPOSE: To evaluate oncologic outcomes of early stage cervical cancer patients who underwent robotic radical hysterectomy (RRH) in a referral center, a retrospective analysis was performed. METHODS: From January 2010 to December 2018, medical records of stage IA2-IIA1 cervical cancer patients, who underwent radical hysterectomy at our institute, were retrospectively reviewed. We focused our analysis on those who underwent RRH. RESULTS: A total of 198 patients were included in the final analysis. Median follow up was 52 months. At last follow-up, 188 (94.9%) women were disease-free, 9 (4.5%) had died, and 1 (0.5%) was alive with recurrent disease. At 4.5 years, PFS was 93.1% (SE ± 2.1) and OS was 95.1% (SE ± 1.8). Stratified by tumor size, PFS for tumor < 2 cm versus tumor ≥ 2 cm was statistically different (96.8% ± 2.3 and 87.9% ± 4.1 respectively, p = 0.01), as well as OS (100% and 89.8% ± 40 respectively, p = 0.01).Stratified by evidence of tumor at time of robotic surgery, PFS was statistically different in women with no residual tumor after conisation versus those with residual disease (100% ± 2.5 and 90.8% ± 2.8 respectively, p = 0.04). A recurrence occurred in 11 patients (5.6%). CONCLUSIONS: Based on our results, we could speculate that robotic approach, along with some technical precautions to avoid spillage, might be safe as primary treatment of early-stage cervical cancer, especially for tumor < 2 cm and in case of no evidence of disease at time of radical hysterectomy after previous conisation.

Multidisciplinary approach in the management of advanced ovarian cancer patients: A personalized approach. Results from a specialized ovarian cancer unit.

OBJECTIVE: The aim of the present study was to evaluate the impact of a multidisciplinary approach in patients' selection with advanced ovarian cancer (AOC) for different therapeutic strategies. METHODS: Patients referred at our institution between 2009 and 2012 for AOC were included. Primary multidisciplinary evaluation was performed in all patients. Different strategies included: 1. patients referred to primary neoadjuvant chemotherapy (NACT) and interval surgery (IDS) (group A); 2. patients considered for surgical exploration. After surgical exploration, patients were either considered for primary debulking (PDS; group B), or NACT (group C). RESULTS: A total of 363 patients were included. Of 38 patients (10.5%) in group A, 24 (63%) had sovradiaphragmatic/multiple liver metastases; 14 (37%) were excluded for PDS for anestehesiologic/medical reasons. Of 325 (89.5%) considered for surgical exploration, 295 (91%; group B) had primary surgery with debulking intent (N: 277) and were cytoreduced to no macroscopic disease (R0: N:200; 68%) o minimal RD<5mm (R1: N:77; 26%) or palliative intent (N:18; 6%); 30 (9%; group C) were referred for NACT. Of those, 27 (90%) underwent IDS, 3 had progressive disease. Overall survival (OS) and progression free survival (PFS) was different between the groups: OS: Group A: 34months; Group B: 59months; Group C: 29months; p<0.001. PFS: Group A: 10months; Group B; 21months; Group C: 12months; p<0.001. CONCLUSIONS: A multidisciplinary approach to patients referred to a tertiary center with AOC allows optimization of the treatment strategy, based on patients' characteristics (age, performance/nutritional status, comorbidities, functional status) and tumor diffusion (evaluated pre- and intraoperatively).

Minimally Invasive Surgery to Treat Gynecological Cancer: Conventional Laparoscopy and/or Robot-Assisted Surgery.

Robotic-assisted surgery is a technological advancement derived from conventional laparoscopy, which facilitates the application of minimally invasive techniques for complex operations in the field of gynecological oncology. However, its introduction in gynecological cancer has been scarce in most hospitals worldwide. Most publications on robotic surgery are still retrospective or descriptive in nature. Some studies compare robotic-assisted laparoscopy with open procedures, which is a questionable analysis, because the advantages of minimally invasive surgery have been already well established. Robotic surgery should be directly compared with conventional laparoscopy to determine whether its additional direct and indirect costs are in accordance with some improvements within patient clinical outcomes. On the other hand, the role of robotic-assisted surgery in allowing more patients to receive the benefits of the minimally invasive approach should also be considered. The objective of this article was, therefore, to review the literature regarding the role of conventional and robotic-assisted laparoscopy to treat women with gynecologic cancer.

Feasibility of Transabdominal Cardiophrenic Lymphnode Dissection in Advanced Ovarian Cancer: Initial Experience at a Tertiary Center.

OBJECTIVES: The purpose of this retrospective report is to define the safety and feasibility, based on our preliminary experience, of surgical transdiaphragmatic resection of enlarged cardiophrenic lymph nodes (CPLNs), as a part of upfront debulking surgery. Supradiaphragmatic nodes located between the diaphragm and the heart are frequently a location for lymph node metastasis in advanced ovarian cancer, and their removal is aimed to obtain no gross residual disease at the primary cytoreductive surgery often requiring aggressive surgical procedures. PATIENTS AND METHODS: Between May 2012 and October 2016, a total of 22 patients among 443 with advanced high-grade serous ovarian cancer underwent cytoreductive procedures involving transdiaphragmatic resection of enlarged CPLNs at European Institute of Oncology in Milan. RESULTS: All patients who underwent CPLN resection had an extensive disease (median peritoneal cancer index, 18), and more than 77% required complex surgical procedures (complexity score, 3). No residual abdominal disease less than 5 mm at the end of surgery was described in 20 (90%) out of 22. All patients but one had confirmed CPLN positive nodes at histopathological study. The average operative time was 333 min (range, 244-455 min), and the average estimated blood loss was 1000 mL (range, 400-2000 mL). Blood transfusion was necessary in 13 out of 22 patients. Only 7 (33%) out of 21 patients required chest tube placement during the postoperative period. CONCLUSIONS: Transdiaphragmatic enlarged CPLN resection seems to be safe and feasible procedure when indicated to achieve no or minimal tumor residual disease. Nevertheless, its impact on survival of patients with stage IV ovarian cancer needs to be determined.

Robot-assisted Surgery in Gynecologic Cancers.

Robotic-assisted surgery is a technological advancement that facilitates the application of minimally invasive techniques for complex operations in gynecologic oncology. The objective of this article was to review the literature regarding the role of robotic-assisted surgery to treat women with gynecologic cancers. The majority of publications on robotic surgery are still retrospective or descriptive in nature; however, the data for managing patients with a robotic-assisted approach show comparable, and at times improved, outcomes compared with both laparoscopy (2-dimensional) and laparotomy approaches. Robotic-assisted surgery has been used for patients with endometrial cancer and resulted in the increased use of minimally invasive surgery with improved outcomes compared with laparotomy and partially with laparoscopy. This has been shown in large cohorts of patients as well as in obese patients in whom the complication rates have significantly decreased. For early cervical cancer, robotic radical hysterectomy seems to be safe and feasible and to be preferable to laparotomy with seemingly comparable oncologic outcomes. Robotic-assisted surgery and conventional laparoscopy to stage women with early-stage ovarian cancer seem to have similar surgical and oncologic outcomes, with a shorter learning curve for robotic-assisted surgery. However, robotic-assisted surgery appears to be more expensive than laparotomy and traditional laparoscopy. In conclusion, robotic-assisted surgery appears to facilitate the surgical approach for complex operations to treat women with gynecologic cancers. Although randomized controlled trials are lacking to further elucidate the equivalence of robot-assisted surgery with conventional methods in terms of oncologic outcome and patients' quality of life, the technology appears to be safe and effective and could offer a minimally invasive approach to a much larger group of patients.

Robotic Versus Open Radical Hysterectomy in Women With Locally Advanced Cervical Cancer After Neoadjuvant Chemotherapy: A Single-institution Experience of Surgical and Oncologic Outcomes.

STUDY OBJECTIVE: To compare the surgical and oncologic outcomes of robotic radical hysterectomy (RRH) versus laparotomy in women with locally advanced cervical cancer (LACC) after neoadjuvant chemotherapy (NACT). SETTING: Oncology referral center. DESIGN: A retrospective comparative observational study was performed in 30 patients with LACC Fédération Internationale de Gynécologie et d'Obstétrique stage IB2-IIB who underwent RRH after NACT between February 2008 and December 2014. This group was compared with a cohort of 44 patients with similar characteristics who underwent abdominal radical hysterectomy after NACT (Canadian Task Force classification II2). PATIENTS: Patients with LACC FIGO stage IB2-IIB. INTERVENTIONS: A retrospective comparative observational study. MEASUREMENTS AND MAIN RESULTS: The mean (standard deviation [SD]) operative time was significantly longer in the robotic group (307.8 minutes [40.2] vs 233.7 minutes [61.9], p ≤ .001). On the contrary, the mean (SD) estimated blood loss was significantly lower in the robotic group (111.0 mL [69.6] vs 286.9 mL [159.1], p ≤ .001), and length of stay was significantly shorter (4.1 [2.4] days vs 5.8 days [3.3], p = .015). The incidence of intraoperative and early and late complications was not statistically significantly different between the 2 groups. The mean (SD) follow-up of patients was 35.6 months (28.4) and 43.7 months (23.2) in the open and robotic groups, respectively (p = .137). The disease recurrence rate (27.2% vs 20%) was similar between the 2 groups; sites and types of recurrences were also similar. Kaplan-Meier survival analysis for median progression-free survival and median overall survival were not statistically different comparing cohorts by surgery type. CONCLUSIONS: RRH after NACT in women with LACC is associated with similar perioperative and oncologic outcomes to open procedure. These results require further investigation to establish a more robust conclusion.

Fertility-enhancing hysteroscopic surgery.

Uterine abnormalities, including congenital pathologies, polyps, submucous leiomyomata, intrauterine adhesions, and chronic endometritis, have been reported in 21 to 47% of patients undergoing in vitro fertilization cycles. The position of hysteroscopy in current fertility practice is under debate. Although there are many randomized controlled trials on technical feasibility and patient compliance demonstrating that the procedure is well tolerated and effective in the treatment of intrauterine pathologies, there is no consensus on the effectiveness of hysteroscopic surgery in improving the prognosis of subfertile women. However, in patients with at least two failed cycles of assisted reproductive technology, diagnostic hysteroscopy and, if necessary, operative hysteroscopy is mandatory to improve reproductive outcome. Office hysteroscopy is a powerful tool for the diagnosis and treatment of intrauterine benign pathologies. It is a simple, safe, reproducible, effective, quick, well-tolerated, and low-cost surgical procedure, with no need for an operating room.