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.

Adult ovarian granulosa cell tumors: analysis of outcomes and risk factors for recurrence.

OBJECTIVE: Adult granulosa cell tumors represent less than 5% of all ovarian malignancies. The aim of this study was to analyze the clinicopathological parameters and their impact on progression-free and overall survival. METHODS: Patients with primary adult granulosa cell tumors treated in three international referral centers between July 1999 and December 2018 were included. The following data were anonymously exported from the prospective database: age at diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, adjuvant therapy, surgical procedures, progression-free survival, and overall survival. Descriptive statistical analysis regarding tumor and treatment characteristics was performed. Survival analyses included Kaplan-Meier functions and Cox proportional hazard ratios (HR). RESULTS: A total of 168 patients with primary adult granulosa cell tumors were included. Median age was 50 years (range 13-82). With regard to stage distribution, 54.2% (n=91) of patients were FIGO stage IA, 1.2% (n=2) were stage IB, 26.8% (n=45) were stage IC, and 17.9% (n=30) were FIGO stage II-IV. 66.7% (n=112) of patients underwent surgical restaging, of whom 17.9% (n=20) were moved to a higher stage. In addition, 36 (21.4%) patients underwent fertility-sparing surgery. After a median follow-up of 61 months (range 0-209), 10.7% of patients (n=18) had recurrent disease and 4.8% (n=8) died of disease. Five-year progression-free survival was 86.1% and estimated overall survival was 95.7%. Five-year progression-free survival was worse for patients with advanced stages (FIGO stage IA/B vs IC: HR 5.09 (95% CI 1.53 to 16.9); FIGO stage IA/B vs II-IV: HR 5.62 (95% CI 1.58 to 19.9)). Nineteen patients receiving adjuvant chemotherapy had lower estimated 5-year progression-free survival compared with patients not receiving chemotherapy (49.7% vs 91.1%, p<0.001; HR 9.15 (95% CI 3.62 to 23.1)). CONCLUSION: The prognosis of patients with primary adult granulosa cell tumors is mainly determined by FIGO stage. The outcome of patients with FIGO stage IC is comparable to those with advanced stages. Fertility-sparing surgery seems to be a safe procedure in stage IA. Our data do not support the use of adjuvant chemotherapy in early and advanced stages of adult granulosa cell tumors.

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

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

Advanced low grade serous ovarian cancer: A retrospective analysis of surgical and chemotherapeutic management in two high volume oncological centers.

Simple summary: Low-grade serous ovarian cancer (LGSOC) represents an uncommon histotype of serous ovarian cancer (accounting for approximately 5% of all ovarian cancer) with a distinct behavior compared to its high-grade serous counterpart, characterized by a better prognosis and low response rate to chemotherapeutic agents. Similar to high-grade serous ovarian cancer, cytoreductive surgery is considered crucial for patient survival. This retrospective study aimed to analyze the outcomes of women affected by advanced stages (III-IV FIGO) of LGSOC from two high-volume oncological centers for ovarian neoplasm. In particular, we sought to evaluate the impact on survival outcomes of optimal cytoreductive surgery [i.e., residual disease (RD) <10 mm at the end of surgery]. The results of our work confirm the role of complete cytoreduction (i.e., no evidence of disease after surgery) in the survival of patients and even the positive prognostic role of a minimal RD (i.e., <10 mm), whenever complete cytoreduction cannot be achieved. Background: Low-grade serous ovarian cancer (LGSOC) is a rare entity with different behavior compared to high-grade serous (HGSOC). Because of its general low chemosensitivity, complete cytoreductive surgery with no residual disease is crucial in advanced stage LGSOC. We evaluated the impact of optimal cytoreduction on survival outcome both at first diagnosis and at recurrence. Methods: We retrospectively studied consecutive patients diagnosed with advanced LGSOCs who underwent cytoreductive surgery in two oncological centers from January 1994 to December 2018. Survival curves were estimated by the Kaplan-Meier method, and 95% confidence intervals (95% CI) were estimated using the Greenwood formula. Results: A total of 92 patients were included (median age was 47 years, IQR 35-64). The median overall survival (OS) was 142.3 months in patients with no residual disease (RD), 86.4 months for RD 1-10 mm and 35.2 months for RD >10 mm (p = 0.002). Progression-free survival (PFS) was inversely related to RD after primary cytoreductive surgery (RD = 0 vs RD = 1-10 mm vs RD >10 mm, p = 0.002). On multivariate analysis, RD 1-10 mm (HR = 2.30, 95% CI 1.30-4.06, p = 0.004), RD >10 mm (HR = 3.89, 95% CI 1.92-7.88, p = 0.0004), FIGO stage IV (p = 0.001), and neoadjuvant chemotherapy (NACT) (p = 0.010) were independent predictors of PFS. RD >10 mm (HR = 3.13, 95% CI 1.52-6.46, p = 0.004), FIGO stage IV (p <0.0001) and NACT (p = 0.030) were significantly associated with a lower OS. Conclusions: Optimal cytoreductive surgery improves survival outcomes in advanced stage LGSOC s . When complete debulking is impossible, a RD <10 mm confers better OS compared to an RD >10 mm in this setting of patients.

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.

Same-day discharge protocol for laparoscopic treatment of adnexal disease: management and acceptance.

OBJECTIVE: Develop a 'same-day discharge' setting for laparoscopic treatment of adnexal disease. SETTING: Preventive Gynecology, European Institute of Oncology, Milan, Italy. POPULATION: Two hundred patients undergoing laparoscopic procedures. MATERIAL AND METHODS: Data were retrospectively collected through clinical, surgical and laboratory reports. After discharge patients were contacted by phone and e-mail. MAIN OUTCOME MEASURES: The rate of discharge, adverse events and readmission was measured. The need for adjunctive care provided by our on-call service or by a primary care physician and the acceptability of the same-day discharge protocol were also investigated. RESULTS: One hundred and sixty-five patients out of 200 were discharged on the same day. Of the 35 patients hospitalized, the most frequent causes for overnight admission were: uncontrolled pain, surgical length or complexity of the procedure in nine patients, nausea/vomit in four patients. One hundred and one out of 200 patients answered the mailed questionnaire. None of the discharged patients were readmitted. Eighty-five percent of the answering patients evaluated the length of their hospital stay as adequate or moderately adequate. Ninety-two percent of the patients would recommend the day surgery to other patients. CONCLUSIONS: our experience demonstrates that the same-day discharge protocol for laparoscopic treatment of adnexal disease is safe and acceptable.

Early-stage clear cell ovarian cancer compared to high-grade histological subtypes: An outcome exploratory analysis in two oncology centers.

OBJECTIVE: advanced stage clear cell ovarian cancer (CCOC) carries a higher risk of relapse and death compared to other histological subtypes. The prognosis of early-stage CCOC is controversial. METHODS: Early-stage high-grade OC patients from two Italian oncologic centers were included. Patients with early-stage CCOC were compared with those with high-grade endometrioid (HGE) and serous (HGS) OC in terms of relapse-free interval (RFI), cancer-specific survival (CSS) and post relapse cancer-specific survival (prCSS). The Cox proportional hazard model and the restricted mean survival time were used. RESULTS: Between 1981 and 2012, 134 patients with CC, 152 with HGE and 160 with HGS were treated at two referral centers. Median follow-up was 11.5 years. Ten years RFI rates were 80.6%, 72.1%, 60.6%, and CSS rates were 84.3%, 82.6%, 81.7% respectively. Adjuvant chemotherapy significantly improved RFI (aHR 0.61, 95%CI 0.40 to 0.91, P = 0.015). In the multivariable analysis HGS histotype was associated with a shorter RFI compared to CC, (Hazard Ratio [HR]: 1.81; 95%CI: 1.12-2.93; P = 0.016), whereas CSS was not statistically different. prCSS was longer in HGS compared to CCOC (HR, 0.36; 95% CI, 0.17-0.74; P = 0.006). According to the stage, IA/IB/IC1 HGSOC had a shorter RFI (HR, 2.13; 95% CI, 1.14-3.99; P = 0.018) compared to IA/IB/IC1 CCOC, but similar CSS. For prCSS, CC compared to HGS conferred a worse prognosis regardless of the initial stage. CONCLUSIONS: Early-stage CCOC is associated with a longer RFI, similar CSS and a shorter prCSS compared to HGSOC. No prognostic differences were observed between CC and HGE OC. The relapse risk was the lowest in IA/IB/IC1 CC compared to HGS, whereas CC displayed poor sensitivity to chemotherapy after relapse.

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.

A cell-of-origin epigenetic tracer reveals clinically distinct subtypes of high-grade serous ovarian cancer.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is a major unmet need in oncology. The remaining uncertainty on its originating tissue has hampered the discovery of molecular oncogenic pathways and the development of effective therapies. METHODS: We used an approach based on the retention in tumors of a DNA methylation trace (OriPrint) that distinguishes the two putative tissues of origin of HGSOC, the fimbrial (FI) and ovarian surface epithelia (OSE), to stratify HGSOC by several clustering methods, both linear and non-linear. The identified tumor subtypes (FI-like and OSE-like HGSOC) were investigated at the RNAseq level to stratify an in-house cohort of macrodissected HGSOC FFPE samples to derive overall and disease-free survival and identify specific transcriptional alterations of the two tumor subtypes, both by classical differential expression and weighted correlation network analysis. We translated our strategy to published datasets and verified the co-occurrence of previously described molecular classification of HGSOC. We performed cytokine analysis coupled to immune phenotyping to verify alterations in the immune compartment associated with HGSOC. We identified genes that are both differentially expressed and methylated in the two tumor subtypes, concentrating on PAX8 as a bona fide marker of FI-like HGSOC. RESULTS: We show that: - OriPrint is a robust DNA methylation tracer that exposes the tissue of origin of HGSOC. - The tissue of origin of HGSOC is the main determinant of DNA methylation variance in HGSOC. - The tissue of origin is a prognostic factor for HGSOC patients. - FI-like and OSE-like HGSOC are endowed with specific transcriptional alterations that impact patients' prognosis. - OSE-like tumors present a more invasive and immunomodulatory phenotype, compatible with its worse prognostic impact. - Among genes that are differentially expressed and regulated in FI-like and OSE-like HGSOC, PAX8 is a bona fide marker of FI-like tumors. CONCLUSIONS: Through an integrated approach, our work demonstrates that both FI and OSE are possible origins for human HGSOC, whose derived subtypes are both molecularly and clinically distinct. These results will help define a new roadmap towards rational, subtype-specific therapeutic inroads and improved patients' care.

Role of delayed interval debulking for persistent residual disease after more than 5 cycles of chemotherapy for primary advanced ovarian cancer. An international multicenter study.

BACKGROUND: Standard of care in patients with advanced ovarian cancer (AOC) is upfront surgery followed by chemotherapy. Neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS) is an alternative in selected patients. Most data exist with IDS following 3-4 cycles chemotherapy, however, some patients experience a delay of IDS. So far, the impact of a "delayed" interval debulking surgery (DID) is poorly defined. METHODS: We analyzed data from eight international gynecology-oncology referral centers. Patients were included if they had newly diagnosed AOC and were prone to DID (minimum 5 cycles of NACT) between 2011 and 2017. RESULTS: 308 patients underwent DID. 89.6% had a high-grade serous ovarian cancer. The median number of pre-op NACT was 6 cycles (range 5-9) and 6.1% of patients received additionally bevacizumab. The majority of patients had stage-IV disease (51.3%). Median duration of surgery was 210 min (range 34-561), the median surgical complexity score was 4 (range 1-16). Complete resection was achieved in 60.1%. The median number of post-op chemotherapy cycles was 2 (range 0-5). The rate of severe complications (Clavien-Dindo£3°) was 9.7% and 30 days post-op mortality was 0.3%. The median PFS and OS in patients with complete resection was 19.5 and 49.2 months compared to 14.8 and 33.0 months in patients with incomplete resection (p = 0.001), respectively. We did not observe any survival benefit for patients with cytoreduction to small residuals (1-10 mm) compared to residual disease >1 cm. CONCLUSION: Our data may suggest that offering surgery to patients with persistent disease after 5+ cycles could be associated with favorable outcome if a complete resection is achieved. Patients who had residual disease postoperatively may experience rather peri-operative treatment burden than any benefit from DID.

Change in practice in gynecologic oncology during the COVID-19 pandemic: a social media survey.

OBJECTIVE: COVID-19 has affected gynecologic cancer management. The goal of this survey was to evaluate changes that occurred in gynecologic oncology practice during the COVID-19 pandemic. METHODS: A anonymous survey consisting of 33 questions (https://sites.google.com/view/gyncacovidfmartinelli) regarding interaction between gynecologic cancers and COVID-19 was distributed online via social media from April 9 to April 30, 2020. Basic descriptive statistics were applied. Analytics of survey-diffusion and generated-interest (visualizations, engagement rates, response rate) were analyzed. RESULTS: The survey received 20 836 visualizations, generating an average engagement rates by reach of 4.7%. The response rate was 30%. A total of 86% of respondents completed the survey, for a total of 187 physicians surveyed across 49 countries. The majority (143/187; 76%) were gynecologic oncologists, and most were ≤50 years old (146/187; 78%). A total of 49.7% (93/187) were facing the early phase of the COVID-19 pandemic, while 26.7% (50/187) and 23.5% (44/187) were in the peak and plateau phases, respectively. For 97.3% (182/187) of respondents COVID-19 affected or changed their respective clinical practice. Between 16% (27/165) (before surgery) and 25% (26/102) (before medical treatment) did not perform any tests to rule out COVID-19 infection among patients. The majority of respondents did not alter indications of treatment if patients were COVID-19-negative, while treatments were generally postponed in COVID-19-positive patients. Treatments were considered priority for: early stage high-risk uterine cancers (85/187; 45%), newly diagnosed epithelial ovarian cancer (76/187; 41%), and locally advanced cervical cancer (76/187; 41%). Treatment of early stage low-grade endometrioid endometrial cancer was deferred according to 49% (91/187) of respondents, with hormonal treatment as the option of therapy (31%; 56/178). A total of 77% (136/177) of respondents reported no changes in (surgical) treatment for early stage cervical cancer in COVID-19-negative patients, while treatment was postponed by 54% (96/177) of respondent, if the patient tested COVID-19-positive. Neoadjuvant chemotherapy for advanced ovarian cancers was considered by over one-third of respondents as well as hypofractionation of radiation treatment for locally advanced cervical cancers. CONCLUSION: COVID-19 affected the treatment of gynecologic cancers patients, both in terms of prioritization and identification of strategies to reduce hospital access and length of stay. Social media is a reliable tool to perform fast-tracking, worldwide surveys.

Endometrial cancer: an overview of novelties in treatment and related imaging keypoints for local staging.

Endometrial cancer is the most common gynaecologic malignancy in developed countries and its incidence is increasing. First-level treatment, if no contraindicated, is based on surgery. Pre-operative imaging is needed for evaluation of local extent and detection of distant metastases in order to guide treatment planning. Radiological evaluation, based on transvaginal ultrasound, MR and CT, can make the difference in disease management, paying special attention to assessment of entity of myometrial invasion, cervical stromal extension, and assessment of lymph nodal involvement and distant metastases.

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.

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.

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).

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.

Long-term results of fertility-sparing treatment compared with standard radical surgery for early-stage epithelial ovarian cancer.

BACKGROUND: The objective of this study is to evaluate the safety of fertility-sparing surgery (FSS) for early-stage epithelial ovarian cancer (EOC). METHODS: A retrospective analysis was performed to identify patients treated for early-stage EOC and to compare the clinical outcomes of patients treated with FSS and radical surgery (RS). RESULTS: A total of 1031 patients were treated at two Institutions, 242 with FSS (group A) and 789 with RS (group B). Median duration of follow-up was 11.9 years. At univariate analyses, FSS was associated with decreased risk of relapse (P=0.002) and of tumour-related death (P=0.001). Multivariate analysis did not confirm the independent positive role of FSS neither on relapse-free interval (RFI) nor on cancer-specific survival (CSS). Tumour grade was associated with shorter RFI (P<0.001) and shorter CSS (P=0.001). The type of treatment did not influence CSS or RFI in any grade group. We also found a significant association between low-grade tumours and younger age. CONCLUSIONS: Fertility-sparing surgery is an adequate treatment for patients with stage I EOC. The clinical outcome of patients with G3 tumours, which is confirmed to be the most important prognostic factor, is not determined by the type of treatment received.

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.

Randomized phase III clinical trial evaluating weekly cisplatin for advanced epithelial ovarian cancer.

This randomized, open label, phase III clinical trial (1988-1992) compared the efficacy and safety of a dose-dense regimen of single-agent cisplatin with a standard 3-weekly schedule in first-line chemotherapy for advanced epithelial ovarian cancer. Two hundred eighty-five patients were randomly assigned to the experimental dose-dense arm (cisplatin 50 mg/m(2) weekly × nine cycles) or to the control (standard treatment) arm (cisplatin 75 mg/m(2), administered on day 1 every 21 days × six cycles). The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), overall response to chemotherapy, and toxicity. Toxicity and response to treatment were compared with the χ(2) test using trend or exact correction. PFS and OS were estimated by Kaplan-Meier analyses and treatment hazard ratios (HRs) with the Cox proportional hazards model. All statistical tests were two-sided. After a median follow-up of 16.8 years, no differences were observed between the two treatments in PFS (experimental arm: 17.2 months; control arm: 18.1 months; HR = 1.08, 95% confidence interval [CI] = 0.83 to 1.40; P = .57) and in OS (experimental arm: 35 months; control arm: 32 months; HR = 0.97, 95% CI = 0.75 to 1.26; P = .97). Thus, increasing dose intensity of cisplatin does not improve PFS or OS compared with standard chemotherapy.