Impact of different follow-up regimens on health-related quality of life and costs in endometrial cancer patients: Results from the TOTEM randomized trial.

PURPOSE: To investigate whether intensive follow-up (INT) after surgery for endometrial cancer impact health-related quality of life (HRQoL) and healthcare costs compared to minimalist follow-up (MIN), in the absence of evidence supporting any benefit on 5-year overall survival. METHODS: In the TOTEM trial, HRQoL was assessed using the SF-12 and the Psychological General Well-Being (PGWB) questionnaires at baseline, after 6 and 12 months and then annually up to 5 years of follow-up. Costs were analyzed after 4 years of follow-up from a National Health Service perspective, stratified by risk level. The probability of missing data was analyzed for both endpoints. RESULTS: 1847 patients were included in the analyses. The probability of missing data was not influenced by the study arms (MIN vs INT OR: 0.97 95%CI: 0.87-1.08). Longitudinal changes in HRQoL scores did not differ between the two follow-up regimens (MIN vs INT SF-12 PCS: -0.573, CI95%: -1.31; 0.16; SF-12 MCS: -0.243, CI95%: -1.08; 0.59; PGWB: -0.057, CI95%: -0,88; 0,77). The mean cost difference between the intensive and minimalist arm was €531 for low-risk patients and €683 for high-risk patients. CONCLUSION: In the follow-up of endometrial cancer after surgery, a minimalist treatment regimen did not affect quality of life and was cost-saving in both low-risk and high-risk recurrence patients. As previous results showed no survival benefit, a minimalist approach is justified. The relevant proportion of missing data on secondary outcomes of interest could be a critical point that deserves special attention.

Implementing Enhanced Recovery After Surgery for hysterectomy in a hospital network with audit and feedback: A stepped-wedge cluster randomised trial.

OBJECTIVE: To evaluate the effectiveness of implementing the Enhanced Recovery After Surgery (ERAS) protocol in patients undergoing elective hysterectomy in a network of regional hospitals, supported by an intensive audit-and-feedback (A&F) approach. DESIGN: A multi-centre, stepped-wedge cluster randomised trial (ClinicalTrials.gov NCT04063072). SETTING: Gynaecological units in the Piemonte region, Italy. POPULATION: Patients undergoing elective hysterectomy, either for cancer or for benign conditions. METHODS: Twenty-three units (clusters), stratified by surgical volume, were randomised into four sequences. At baseline (first 3 months), standard care was continued in all units. Subsequently, the four sequences implemented the ERAS protocol successively every 3 months, after specific training. By the end of the study, each unit had a period in which standard care was maintained (control) and a period in which the protocol, supported by feedback, was applied (experimental). MAIN OUTCOME MEASURES: Length of hospital stay (LOS), without outliers (>98th percentile). RESULTS: Between September 2019 and May 2021, 2086 patients were included in the main analysis with an intention-to-treat approach: 1104 (53%) in the control period and 982 (47%) in the ERAS period. Compliance with the ERAS protocol increased from 60% in the control period to 76% in the experimental period, with an adjusted absolute difference of +13.3% (95% CI 11.6% to 15.0%). LOS, moving from 3.5 to 3.2 days, did not show a significant reduction (-0.12 days; 95% CI -0.30 to 0.07 days). No difference was observed in the occurrence of complications. CONCLUSIONS: Implementation of the ERAS protocol for hysterectomy at the regional level, supported by an A&F approach, resulted in a substantial improvement in compliance, but without meaningful effects on LOS and complications. This study confirms the effectiveness of A&F in promoting important innovations in an entire hospital network and suggests the need of a higher compliance with the ERAS protocol to obtain valuable improvements in clinical outcomes.

The Use of Artificial Intelligence for Complete Cytoreduction Prediction in Epithelial Ovarian Cancer: A Narrative Review.

INTRODUCTION: In patients affected by epithelial ovarian cancer (EOC) complete cytoreduction (CC) has been associated with higher survival outcomes. Artificial intelligence (AI) systems have proved clinical benefice in different areas of healthcare. OBJECTIVE: To systematically assemble and analyze the available literature on the use of AI in patients affected by EOC to evaluate its applicability to predict CC compared to traditional statistics. MATERIAL AND METHODS: Data search was carried out through PubMed, Scopus, Ovid MEDLINE, Cochrane Library, EMBASE, international congresses and clinical trials. The main search terms were: Artificial Intelligence AND surgery/cytoreduction AND ovarian cancer. Two authors independently performed the search by October 2022 and evaluated the eligibility criteria. Studies were included when data about Artificial Intelligence and methodological data were detailed. RESULTS: A total of 1899 cases were analyzed. Survival data were reported in 2 articles: 92% of 5-years overall survival (OS) and 73% of 2-years OS. The median area under the curve (AUC) resulted 0,62. The model accuracy for surgical resection reported in two articles reported was 77,7% and 65,8% respectively while the median AUC was 0,81. On average 8 variables were inserted in the algorithms. The most used parameters were age and Ca125. DISCUSSION: AI revealed greater accuracy compared against the logistic regression models data. Survival predictive accuracy and AUC were lower for advanced ovarian cancers. One study analyzed the importance of factors predicting CC in recurrent epithelial ovarian cancer and disease free interval, retroperitoneal recurrence, residual disease at primary surgery and stage represented the main influencing factors. Surgical Complexity Scores resulted to be more useful in the algorithms than pre-operating imaging. CONCLUSION: AI showed better prognostic accuracy if compared to conventional algorithms. However further studies are needed to compare the impact of different AI methods and variables and to provide survival informations.

Uterine smooth muscle tumors: a multicenter, retrospective, comparative study of clinical and ultrasound features.

OBJECTIVE: To evaluate a wide range of clinical and ultrasound characteristics of different uterine smooth muscle tumors to identify features capable of discriminating between these types. METHODS: This was a retrospective, multicenter study that included 285 patients diagnosed with uterine smooth muscle tumors (50 leiomyosarcomas, 35 smooth muscle tumors of uncertain malignant potential, and 200 leiomyomas). The patients were divided into three groups based on the histological type of their tumors, and the groups were compared according to the variables collected. RESULTS: Leiomyosarcomas were more common in older and post-menopausal women. Compared with leiomyomas, smooth muscle tumors of uncertain malignant potential and leiomyosarcomas had similar ultrasound features such as absence of normal myometrium, multilocular appearance, hyper-echogenicity in case of uniform echogenicity, absence of posterior shadows, echogenic areas, and hyperechoic rim. Leiomyosarcomas were larger, had more cystic areas, and were associated with a higher prevalence of pelvic free fluid. Smooth muscle tumors of uncertain malignant potential were characterized by a higher frequency of International Federation of Gynecology and Obstetrics (FIGO) type 6-7, the absence of internal shadows, and, in the case of cystic area, the presence of a regular internal wall. Tumor outline varied among the three histological types. A color score of 1 was typical of leiomyoma, a color score 2 was mainly observed in leiomyomas and smooth muscle tumors of uncertain malignant potential, a color score 3 did not differ among the tumors, while a color of score 4 was related to leiomyosarcomas. When combining color scores 3 and 4, leiomyosarcomas and smooth muscle tumors of uncertain malignant potential showed a high percentage of both circumferential and intra-lesional vascularization. A cooked appearance was not statistically different among the tumors. CONCLUSIONS: Based on our findings, specific ultrasonographic features as well as age and menopausal status are associated with different uterine smooth muscle tumor types. Integration of these data can help the pre-operative assessment of these lesions for proper management.

Clinical pathways of recovery after surgery for advanced ovarian/tubal/peritoneal cancer: an NSGO-MaNGO international survey in collaboration with AGO-a focus on surgical aspects.

OBJECTIVES: This survey assessed the implementation of enhanced recovery after surgery (ERAS) for patients undergoing surgery for advanced ovarian cancer in three European cooperative study groups in Scandinavia, Italy, and Austria. The aim was to evaluate the landscape for future trials on ERAS pathways in ovarian cancer, because high-level evidence for such interventions is lacking. METHODS: In July 2017, a web-based questionnaire (SurveyMonkey Inc, Palo Alto, CA, USA) was sent to centers conducting surgery for advanced ovarian cancer within the Nordic Society of Gynecologic Oncology (NSGO), Mario Negri Gynecologic Oncology Group (MaNGO) and other Italian institutions, and the Association for Gynecologic Oncology Austria (AGO Austria) (n = 100). The survey covered all aspects of an ERAS pathway including surgery, nursing, and anesthesia. We herein report on the survey findings relating to surgery, including nursing care issues; however, anesthesiologic issues will be discussed in a separate report. RESULTS: The overall response rate was 62%. Only a third of the centers in Italy and Austria follow a written ERAS protocol compared with 60% of the Scandinavian centers. Only a minority of centers have completely abandoned bowel preparation, with the highest proportion in Scandinavia (36%). Two hours of fasting for fluids before surgery is routinely practiced in Scandinavia and Austria (67-57%, respectively), but not in Italy (5%). Carbohydrate loading is routinely administered only in Scandinavia (67%). Peritoneal drainage is used by 22% routinely and by 61% in cases of bowel resection/lymphadenectomy/peritonectomy. Early feeding with a light diet on day 0 or 1 is the standard of care in Scandinavia and Austria, but not in Italy. CONCLUSIONS: The degree of implementation of ERAS protocols varies across and within cooperative groups. The centralization of ovarian cancer care seems to facilitate standardization of peri-operative protocols. Currently, the high heterogeneity in patterns of care may challenge an international approach to a clinical trial.

Sentinel Lymph Node Biopsy in the Treatment of Endometrial Cancer: Why We Fail? Results of a Prospective Multicenter Study on the Factors Associated with Failure of Node Mapping with Indocyanine Green.

BACKGROUND: The sentinel lymph node (SLN) mapping for endometrial cancer staging is gaining wide diffusion, but there is no definitive evidence on the factors associated with the failure of mapping. OBJECTIVES: To analyze the factors associated with the possible failure of bilateral SLN mapping with indocyanine green (ICG). METHODS: A prospective observational study without control on 110 patients with endometrial cancer apparently confined to the uterus, underwent laparoscopic surgical staging with SLN mapping with ICG. RESULTS: Possible risk factors associated with bilateral mapping failure were analyzed, and a multivariate analysis was performed. The bilateral detection rate for SLNs mapping was 72.7%, whereas at least one SLN was detected in 79.1% of patients. No SLNs were identified in 6.3%. None of the patients or features related to tumor were associated with a risk of failure of the method. The only factor analyzed that was significantly associated with the success of bilateral mapping was the surgeon (p = 0.003). CONCLUSIONS: Neither obesity nor the presence of lymph node metastases was associated with mapping failure. However, there remains a need for further studies to understand all the mechanisms linked to the unsuccessful method results and to reduce the use of systematic lymphadenectomy in the case of mapping failure.

Report From the 20th Meeting of the European Society of Gynaecological Oncology (ESGO 2017).

This is a report from the 20th Meeting of the European Society of Gynaecological Oncology (ESGO) held in Vienna, Austria on November 4 to 7, 2017. The conference offered state-of-the-art educational sessions and oral and poster abstract presentations. The general sessions throughout the meeting focused not only on prevention, screening, diagnosis, treatment, and translational research but also emerging trends, and current innovations in gynecological cancers were discussed. The ESGO-European Society for Radiotherapy and Oncology-European Society of Pathology guidelines on management of cervical cancers were reported for the first time in public. Here, we highlight the key results of the latest trials for gynecological cancers presented for the first time at the ESGO 2017 Meeting and added great value to the congress scientific level.

Is Ovarian Cancer Being Managed According to Clinical Guidelines? Evidence From a Population-Based Clinical Audit.

BACKGROUND: In the northwestern Italian region of Piedmont, current statistics on hospitalizations show that surgical treatment for ovarian cancer (OC) is taking place in many small hospitals, as opposed to a more centralized approach. A population-based clinical audit was promoted to investigate whether OC is being managed according to clinical guidelines, identify determinants of lack of adherence to guidelines, and evaluate the association between adherence to guidelines and survival. PATIENTS AND METHODS: Residents diagnosed with OC in 2009 were identified in the regional hospital discharge records database. All hospitalizations within 2 years from diagnosis were reviewed. Patients were classified according to their initial pattern of care, defined as "with curative intent" (CIPC) if including debulking surgery aimed at maximal cytoreduction. Adherence to guidelines for surgery and chemotherapy and the effects of this adherence on OC survival were investigated with logistic regression and Cox models. RESULTS: The final study sample consisted of 344 patients with OC, 215 (62.5%) of whom received CIPC. Increasing age, comorbidities, and metastases were negatively associated with receiving CIPC. In the CIPC group, surgical treatment was adherent to guidelines in 35.2%, whereas chemotherapy was adherent in 87.8%. Surgical treatment that was adherent to guidelines [hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.45-1.15] and absence of residual tumor (HR, 0.55; 95% CI, 0.32-0.94) were associated with better survival in the CIPC group, and chemotherapy that was adherent to guidelines was associated with a significant reduction in the risk of death (HR, 0.49; 95% CI, 0.28-0.87). CONCLUSIONS: Results support the need to reorganize the clinical pathway of patients with OC in the Piedmont Region and the need for better adherence to current guidelines.

The role of HE4 in ovarian cancer follow-up: a review.

OBJECTIVE: The aim of this review was to analyze the state of the art about HE4 and follow-up in patients treated for ovarian cancer. METHODS: A literature search was conducted in the MEDLINE database using the key words "HE4" and "ovarian cancer" and "recurrence" or "relapse" or "follow up." RESULTS: Seven of 28 clinical studies were selected. Four studies were prospective, and all of them were based on a small number of patients (8-73 women). A failure of HE4 levels to normalize at completion of standard therapy may indicate a poor prognosis, thus suggesting the need of a closer follow-up. Moreover, HE4 showed better sensibility and specificity in the diagnosis of ovarian cancer recurrence with respect to CA-125, being also an earlier indicator of the relapse with a lead time of 5 to 8 months. HE4 showed a better performance in this setting if performed in association with other markers (CA-125, CA-72.4). HE4 seems to be an independent predictive factor for the surgical outcome at secondary cytoreductive surgery and to maintain its prognostic role even after the recurrence. CONCLUSIONS: These preliminary data start to suggest a superiority of HE4 over CA-125 in the detection of ovarian cancer recurrence. Moreover, the prognostic role of HE4 could help clinicians to personalize the follow-up program, whereas its predictive role could be useful to plan the treatment of the relapse. The role of HE4 in ovarian cancer follow-up deserves to be further investigated in prospective randomized multicentric studies.

Complications after the treatment of endometrial cancer: a prospective study using the French-Italian glossary.

INTRODUCTION: The evaluation of treatment complications is crucial in modern oncology because they heavily influence the every day life of patients. Several authors confirmed the reproducibility of the French-Italian glossary to score the complications in patients with endometrial cancer after radiotherapy (RT), but the treatment of endometrial carcinoma is primarily surgical and chemotherapy is often used for high-risk disease. OBJECTIVES: This study aimed to analyze the incidence of complications in our patients treated for endometrial cancer and to verify whether the glossary is a suitable instrument in the description of complications after surgery, RT, and chemotherapy. METHODS: The data of patients affected by endometrial cancer treated in the Gynecology and Obstetrics Academic Department, Azienda Ospedaliera Mauriziano Umberto I in Turin from 2000 to 2009 (with surgery alone or integrated treatments) were prospectively collected, and complications were described using the glossary. Every patient included in the analyses had a minimum of 18 months follow-up. RESULTS: Of the 271 patients, 68 (25%) experienced at least 1 complication with 87 overall complications. Most of the complications were mild (63%) and were found in the urinary (30%) or cutaneous systems (30%). Forty-four (50%) complications appeared within 1 year after treatment, but 9 (10%) complications appeared after 60 months of follow-up. Patients who were submitted to both surgery and RT showed a trend of higher rate of at least 1 complication (19/58 [32.7%]) if compared with surgery alone (36/135 [26.6%]), even if the difference was not statistically significant (P = 0.09). The incidence of complications in patients treated or not with lymphadenectomy was not statistically different (P = 0.088), whereas patients treated with laparotomy had a higher rate of cutaneous complications if compared with the laparoscopic approach (P = 0.018). The glossary included all observed complications. CONCLUSIONS: One every 4 women treated for endometrial cancer develops a complication. Clinicians should check for complications especially after integrated treatments maintaining surveillance even in the long term. The glossary is a comprehensive instrument to describe the complications of endometrial cancer, regardless of the type of treatment delivered.

Pathological response on surgical samples is an independent prognostic variable for patients with Stage Ib2-IIb cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy: an Italian multicenter retrospective study (CTF Study).

OBJECTIVES: The purpose of this retrospective multicenter study was to correlate patterns of recurrences and clinical outcome of cervical cancer patients who underwent neoadjuvant chemotherapy [NACT] to surgery. METHODS: This study was conducted on 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent NACT to surgery with pelvic lymphadenectomy. The median follow-up was 66.5 months (range, 8-212 months). Overall optimal response rate was the sum of complete and optimal partial response rates. RESULTS: An overall optimal response was obtained in 64 patients (19.2%). As for the 220 sub-optimal responders (66.1%), 127 patients had negative nodes and negative parametria and/or surgical margins, 75 patients had positive nodes with positive or negative parametria and/or surgical margins, and 18 patients had positive parametria and/or surgical margins with negative nodes. At the time of the present analysis, 79 (23.7%) of the 333 patients had a recurrence after a median time of 14.9 months (range, 4.5-123 months). Recurrent disease was pelvic in 50 (63.3%), extra-pelvic in 22 (27.9%), and both in 7 (8.8%). On multivariate analysis, pathological response to NACT was an independent prognostic variable for recurrence-free and overall survival. Patients who did not achieve an overall optimal response had a 2.757-fold higher risk of recurrence and a 5.413-fold higher risk of death than those who obtained an overall optimal response. CONCLUSIONS: Results appear to suggest that the chemo-surgical approach is an effective therapeutic option for patients with stage Ib2-IIb cervical cancer and that pathological response to NACT is the strongest prognostic factor for the outcome.

Total microlaparoscopic radical hysterectomy in early cervical cancer.

BACKGROUND AND OBJECTIVE: In less than 2 decades, laparoscopy has contributed to modification in the management of early cervical cancer patients, and all comparisons between open and laparoscopic-based radical operations showed an identical oncological outcome. The aim of this study is to describe surgical instrumentations and technique to perform total microlaparoscopy radical hysterectomy in early cervical cancer patients and report our preliminary results in terms of operative time and perioperative outcomes. METHODS: Between January 1, 2012, and March 25, 2012, 4 consecutive early cervical cancer patients were enrolled in this study. RESULTS: We performed 3 type B2 and 1 type C1-B2 total microlaparoscopy radical hysterectomy, and in all cases concomitant bilateral salpingo-oophorectomy and pelvic lymphadenectomy were carried out. Median operative time was 165 minutes (range: 155 to 215) (mean: 186), and median estimated blood loss was 30 mL (range: 20 to 50). Median number of pelvic lymph nodes removed was 12 (range: 11 to 15). All procedures were completed without 5-mm port insertion and without conversion. No intraoperative or early postoperative complications were reported. CONCLUSIONS: This report suggests a role of microlaparoscopy in the surgical management of early cervical cancer with adequate oncological results, superimposable operative time, and perioperative outcomes with respect to standard laparoscopy.

Cytoreductive surgery plus HIPEC in platinum-sensitive recurrent ovarian cancer patients: a case-control study on survival in patients with two year follow-up.

OBJECTIVES: To compare survival data in platinum-sensitive recurrent ovarian cancer patients submitted to secondary cytoreduction (SCR) plus hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) (Cases) and a similar group of women not experiencing HIPEC (Controls). METHODS: Case-control study, matching 30 Cases with 37 Controls, with at least 24 months of follow-up. RESULTS: Groups were comparable for all characteristics, except for a higher proportion of patients with single-nodule relapses is the Controls (19 vs. 6; p=0.011). Median follow-up time was 46 months in the Cases and 36 months in the Controls. Twenty patients (66.6%) experienced secondary recurrence in the Cases and 37 women (100%) in the Controls (p=0.001). Moreover, 7 (23.3%) and 23 (62.2%) patients died of disease in the Cases and Controls respectively (p=0.003). The duration of secondary response was 26 months in the Cases and 15 months in the Controls (p=0.004). CONCLUSIONS: The combination of SCR and HIPEC seems to improve survival rate in patients suffering from platinum-sensitive EOC recurrence with respect to no-HIPEC treatments. This result further supports the need of a randomized trial.

A search for predictive factors for hypersensitivity reactions to paclitaxel and platinum salts in chemotherapy for gynecologic pelvic neoplasms.

AIMS: To investigate the frequency of and predictive factors for hypersensitivity reactions (HR) to taxanes and platinum salts in a cohort of patients treated for pelvic gynecologic malignancies. METHODS: The medical records of all patients with gynecologic pelvic neoplasms treated with chemotherapy at the Department of Gynecologic Oncology, AO Mauriziano Umberto I of Turin, from September 2007 through August 2008, were retrospectively reviewed. Two multivariate models, regarding carboplatin and taxane chemotherapy, respectively, were performed to evaluate the potential predictive value of various clinical features. RESULTS: The incidence of HR was 14% (22/157). Multivariate models showed that menopausal women had a significantly lower probability of HR (OR 0.12, CI 0.02-1.13, p = 0.06 for the carboplatin model and OR 0.05, CI 0.01-0.63, p = 0.02 for the taxane model) while a history of systemic hypersensitivity was associated with a higher but non-significant risk of HR (OR 2.64, CI 0.78-8.95, p = 0.11, for the carboplatin model and OR 3.42, CI 0.94-12.45, p = 0.06, for the taxane model). CONCLUSION: We confirmed a history of hypersensitivity as a risk factor for HR. Other larger cohorts should be analyzed: we need to find new predictive factors in order to select women who should be submitted to experimental prophylactic strategies.

Implementation of the ERAS (Enhanced Recovery After Surgery) protocol for hysterectomy in the Piedmont Region with an audit&feedback approach: Study protocol for a stepped wedge cluster randomized controlled trial. A study of the EASY-NET project.

INTRODUCTION: ERAS (Enhanced Recovery After Surgery) is a perioperative program combining multiple evidence-based interventions designed to reduce the surgical stress response. Despite the publication of dedicated guidelines, ERAS application to gynecologic surgery outside clinical studies has been slow and fragmented. To promote the systematic adoption of the ERAS program in the entire regional hospital network in Piedmont an Audit-and-Feedback approach (A&F) has been adopted within a cluster randomized controlled trial, aiming to estimate the true impact of the protocol on a large, unselected population. METHODS: The study protocol provides for a multicenter stepped wedge cluster randomized trial, focused on women undergoing an hysterectomy, for comparison between standard perioperative management and perioperative management according to the ERAS protocol. The primary outcome is the length of hospital stay (LOS). Secondary outcomes are: post-operative complications, quality-of-recovery at 24-hours after surgery, 30-day readmissions, patients' satisfaction, healthcare costs. The compliance to all the ERAS items is monitored with an A&F approach. All the gynecologic units of Piedmont hospitals are involved and all the patients hospitalized for elective hysterectomy in the period of the study are included. Centers, stratified by surgical volume and randomly assigned to four groups, are randomly ordered to activate the ERAS protocol in four periods, every three months. The planned calendar and the total duration of the study have been extended for six months due to the COVID-19 pandemic. The expected sample size of about 2400 patients has a high statistical power (99%) to detect a reduction of LOS of 1 day (effect size 0.5) and to estimate clinically meaningful changes in the other study endpoints. The study protocol has been approved by the Ethical Committee of all participating centers. Study results will be timely circulated within the hospital network and published in peer-reviewed journals. CONCLUSION: Results are expected to demonstrate positive clinical outcomes of the ERAS protocol even when its implementation is directed towards an entire regional network of gynecologic units, and not only towards selected and highly motivated centers. TRIAL REGISTRATION: NCT04063072.

Low-Grade Uterine Endometrial Stromal Sarcoma: Prognostic Analysis of Clinico-Pathological Characteristics, Surgical Management, and Adjuvant Treatments. Experience From Two Referral Centers.

Objective: Low-grade uterine endometrial stromal sarcoma (LG-ESS) is a rare tumor characterized by an overall good survival but showing a indolent behavior and a variable risk of recurrence. There is no clear consensus on the optimal management of these tumors and no prognostic or predictive factors have been established. With this study, we evaluated the prognostic relevance of several clinical, surgical, and pathological features in patients affected by LG-ESS to identify risk factors associated with recurrence. Methods: We retrospectively analyzed 52 LG-ESS cases, treated from January 1st, 1994, to May 31st, 2020, in two referral centers. The relationship between recurrence and clinicopathological characteristics as well as surgical treatment was investigated. Risk of recurrence and disease-free survival (DFS) were estimated by Cox regression and the Kaplan-Meier analysis, respectively. Results: Of 52 patients with LG-ESS, 8 experienced recurrence (15%). The median follow-up was 100 months (SD ± 96, range: 15-336). By univariate analysis, fragmentation/morcellation, tumor size, FIGO stage, higher mitotic count, presence of necrosis, and lymphovascular space invasion (LSVI) resulted associated with a poorer outcome. Conversely, the surgical modality (laparotomic vs laparoscopic and hysterectomy with bilateral salpingo-oophorectomy vs local excision) and pelvic lymphadenectomy were not. Even the different modalities of adjuvant therapy (hormonal therapy, radiotherapy, and chemotherapy) showed no prognostic significance. Tumor fragmentation/morcellation and higher mitotic count resulted independent prognostic variables at multivariate analysis. Conclusions: This data supports the avoidance of any type of morcellation if LG-ESS is suspected preoperatively. Higher mitotic count and, possibly, tumor size, advanced FIGO stage, necrosis, and LVSI could be exploited to tailor the adjuvant therapy, but these results need to be confirmed in larger prospective studies.

Effectiveness of Intensive Versus Minimalist Follow-Up Regimen on Survival in Patients With Endometrial Cancer (TOTEM Study): A Randomized, Pragmatic, Parallel Group, Multicenter Trial.

PURPOSE: In the absence of clear evidence from randomized trials, the intensity of follow-up regimens after surgical treatment of endometrial cancer is highly variable in clinical practice. To reduce this uncertainty, we conducted a randomized trial to test whether an intensive (INT) versus a minimalist (MIN) follow-up regimen improves overall survival (OS) in patients undergoing operation for endometrial cancer. METHODS: The TOTEM study was a large, pragmatic randomized trial, conducted in 42 hospitals (in Italy and France) including patients surgically treated for endometrial cancer, in complete clinical remission, International Federation of Gynecology and Obstetrics stage I-IV. After stratification by center and risk of relapse (low or high), patients were randomly assigned (1:1) to INT or MIN hospital-based follow-up regimens. The study was powered to demonstrate an absolute improvement of 5% of the 5-year OS with the INT regimen. RESULTS: In total, 1,871 patients were randomly assigned between November 2008 and July 2018, and 1,847 patients (98.7%) were available for the final analysis (60% low risk). After a median follow-up of 69 months, the 5-year OS was 90.6% in the INT and 91.9% in the MIN arms (hazard ratio, 1.13, 95% CI, 0.86 to 1.50, P = .380). No differences in OS were found in subgroup analyses considering age, cancer treatment, risk of relapse, and degree of adherence of the center to the scheduled follow-up. The probability of detecting a relapse was slightly higher in the INT arm (hazard ratio, 1.17; 95% CI, 0.92 to 1.48; P = .194). CONCLUSION: An INT follow-up in endometrial cancer-treated patients does not improve OS, even in high-risk patients. According to available evidence, there is no need to routinely add vaginal cytology, laboratory, or imaging investigations to the MIN regimens used in this trial.

Factor structure of post-operative quality of recovery questionnaire (QoR-15): An Italian adaptation and validation.

Background: The Quality of Recovery questionnaire (QoR-15) is an English instrument for measuring quality of recovery in surgical patients, not yet translated and validated in Italian when the Enhanced Recovery After Surgery (ERAS) Piemonte studies were planned. Objective: To produce the Italian version of the QoR-15 questionnaire, to evaluate its factorial structure and to assess the invariance between two types of surgery. Methods: The Italian version (QoR-15I) was obtained translating and adapting the original version to the Italian context. The validation was performed suppling the QoR-15I to 3,784 patients enrolled in two parallel stepped wedge cluster randomised trials (ERAS Colon-rectum Piemonte; ERAS Gyneco Piemonte). The factor structure and its invariance between types of surgery was tested using confirmatory bifactor model and multi-group analysis. Comparative fit index (CFI), root mean square error of approximation (RMSEA), and standardized root mean square residual (SRMR) fit indices and their changes between nested models were used to assess the factor structure and the invariance. Results: The bifactor model showed good fit (RMSEA = 0.049, CFI =0.957, SRMR = 0.036) and provided a general recovery factor and two specific factors for physical and mental recovery. Eighty-four percent of the common variance is attributable to the general factor, and thus the QoR-15I is sufficiently 'one-dimensional' with an adequate reliability (ωh = 0.70). The ωs values for the physical and mental recovery factors were 0.01 and 0.13, respectively. Multigroup analysis supported configural (RMSEA = 0.053, CFI = 0.950, SRMR = 0.035) and metric invariance (ΔRMSEA = -0.004; ΔCFI = -0.002; ΔSRMR = 0.014), whereas the intercept constraint was removed from item 15 to obtain partial scalar invariance (ΔRMSEA = 0.002; ΔCFI = 0.007; ΔSRMR = 0.004). Construct validity was supported by a negative association of QoR-15I scores with all variables related to worse patient condition and more complex surgery. Conclusion: Our results support the use of the QoR-15I as a valid, reliable, and clinically feasible tool for measuring the quality of recovery after surgery. The results of the confirmatory factor analyses suggest that a unique recovery score can be calculated and support measurement invariance of the QOR-15I across the two type of surgery, suggesting that the questionnaire has the same meaning and the same measurement parameters in colorectal and gynaecologic patients.

Surveillance procedures for patients treated for endometrial cancer: a review of the literature.

OBJECTIVES: The aim of this review was to analyze the role of follow-up in patients treated for endometrial cancer and to provide some compelling issues that may contribute to improve daily practice while waiting for evidence-based guidelines. METHODS/MATERIALS: A literature search has been conducted in MEDLINE database using key words "endometrial neoplasms" and "follow up". RESULTS: Endometrial cancer represents the most common gynecologic malignancy after breast cancer. The overall recurrence rate is 13% and correlates with prognostic factors of the primary tumor. The anatomic sites of endometrial cancer relapse are mostly equivalently distributed between local (pelvic) and distant (abdominal and chest). Most endometrial cancer recurrences are symptomatic, even if vaginal vault relapses represent a particular setting of a more frequently asymptomatic disease. Most of endometrial cancer recurrences occur within 3 years since diagnosis of primary tumor. Long-term surveillance programs are mainly addressed to the early detection of recurrence, the rationale of follow-up being that an earlier diagnosis of relapse correlates with lower morbidity and mortality rates. Adjunctive objectives of routine follow-up are identification of treatment complications and detection of possible second tumors associated with endometrial cancer. CONCLUSIONS: No rationale (examination sensitivity/sensibility, cost-effectiveness, or patient's survival benefit) is available today for any particular follow-up protocol; follow-up procedures should probably be tailored according to different prognostic factors; only physical examination, including pelvic-rectal examination, showed some utility in detecting recurrence. In this uncertain setting, follow-up interval should be defined with the consideration of the patient's will.

Pretreatment platelet and hemoglobin levels are neither predictive nor prognostic variables for patients with locally advanced cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy: a retrospective Italian study.

BACKGROUND: To assess the predictive and prognostic values of pretreatment platelet and hemoglobin levels in patients with locally advanced cervical cancer who underwent neoadjuvant chemotherapy followed by radical hysterectomy. METHODS: The authors retrospectively assessed 140 patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB2-IIB cervical cancer who underwent chemosurgical treatment. RESULTS: Median pretreatment platelet and hemoglobin levels were 272,000/µL and 12.5 g/dL, respectively. Fourteen patients achieved a pathologically complete response, and 26 had an optimal partial response, with an optimal pathological response rate of 28.6%. By univariate analysis, optimal pathological response rate was associated with well/moderately differentiated grade (P = 0.02) and platinum-/paclitaxel-based chemotherapy regimen (P = 0.04), but not with platelet and hemoglobin levels. Multiple logistic regression confirmed that tumor grade (odds ratio, 2.827; 95% confidence interval [95% CI], 1.250-6.397; P = 0.01) and chemotherapy regimen (odds ratio, 5.416; 95% CI, 1.459-20.110; P = 0.01) were independent predictors of optimal pathological response. Five-year recurrence-free survival and 5-year overall survival were 66 % and 73%, respectively. By log-rank test, recurrence-free survival and overall survival were associated with pathological response (P = 0.0002 and P = 0.001), lymph node status, (P = 0.008 and P = 0.002), lymphovascular space status (P = 0.005 and P = 0.003), and parametrial and/or surgical margin status (P = 0.004 and P = 0.001), but not with platelet and hemoglobin levels. On multivariate analysis, pathological response (hazard ratio [HR], 7.999; 95% CI, 1.916-33.394; and HR, 6.007; 95% CI, 1.426-25.307) and parametrial and/or surgical margin status (HR, 2.061; 95%CI, 1.047-4.058; and HR, 2.561; 95% CI, 1.244-5.271) were independent prognostic variables of recurrence-free survival and overall survival. CONCLUSIONS: The achievement of an optimal pathological response is the strongest independent prognostic variable for patients with cervical cancer treated with neoadjuvant chemotherapy and radical hysterectomy, whereas pretreatment platelet and hemoglobin levels seem to be neither predictive of response to chemotherapy nor prognostic of long-term outcome.