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Nodal status is one of the most important prognostic factors for patients with apparent early stage endometrial cancer. The role of retroperitoneal staging in endometrial cancer is controversial. Nodal status provides useful prognostic data, and allows to tailor the need of postoperative treatments. However, two independent randomized trials showed that the execution of (pelvic) lymphadenectomy increases the risk of having surgery-related complication without improving patients' outcomes. Sentinel node mapping aims to achieve data regarding nodal status without increasing morbidity. Sentinel node mapping is the removal of first (clinically negative) lymph nodes draining the uterus. Several studies suggested that sentinel node mapping is not inferior to lymphadenectomy in identifying patients with nodal disease. More importantly, thorough ultrastaging sentinel node mapping allows the detection of low volume disease (micrometastases and isolated tumor cells), that are not always detectable via conventional pathological examination. Therefore, the adoption of sentinel node mapping guarantees a higher identification of patients with nodal disease than lymphadenectomy. Further evidence is needed to assess the value of various adjuvant strategies in patients with low volume disease and to tailor those treatments also on the basis of the molecular and genomic characterization of endometrial tumors. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy plus radical surgery could be a safe alternative to chemo-radiation in cervical cancer patients who are not willing to receive radiotherapy. The response to neoadjuvant chemotherapy is the main factor influencing the need for adjunctive treatments and survival. In the present paper we aim to develop a machine learning model based on cervix magnetic resonance imaging (MRI) images to stratify the single-subject risk of cervical cancer. We collected MRI images from 72 subjects. Among these subjects, 28 patients (38.9%) belonged to the "Not completely responding" class and 44 patients (61.1%) belonged to the 'Completely responding' class according to their response to treatment. This image set was used for the training and cross-validation of different machine learning models. A robust radiomic approach was applied, under the hypothesis that the radiomic features could be able to capture the disease heterogeneity among the two groups. Three models consisting of three ensembles of machine learning classifiers (random forests, support vector machines, and k-nearest neighbor classifiers) were developed for the binary classification task of interest ("Not completely responding" vs. "Completely responding"), based on supervised learning, using response to treatment as the reference standard. The best model showed an ROC-AUC (%) of 83 (majority vote), 82.3 (mean) [79.9–84.6], an accuracy (%) of 74, 74.1 [72.1–76.1], a sensitivity (%) of 71, 73.8 [68.7–78.9], and a specificity (%) of 75, 74.2 [71–77.5]. In conclusion, our preliminary data support the adoption of a radiomic-based approach to predict the response to neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggested the detrimental effects of adopting minimally invasive surgery in the management of early-stage cervical cancer. However, long-term evidence on the role of minimally invasive radical hysterectomy in "low-risk" patients exists. This is multi-institutional retrospective study comparing minimally invasive and open radical hysterectomy in low-risk early-stage cervical cancer patients. A propensity-score matching algorithm (1:2) was used to allocate patients into the study groups. Kaplan-Meir model was used to estimate 10-year progression-free and overall survival. Charts of 224 "low-risk" patients were retrieved. Overall, 50 patients undergoing radical hysterectomy were matched with 100 patients undergoing open radical hysterectomy. Minimally invasive radical hysterectomy was associated with a longer median operative time (224 (range, 100–310) vs. 184 (range, 150–240) minutes; p < 0.001), lower estimated blood loss (10 (10-100) vs. 200 (100−1000) ml, p < 0.001), and shorter length of hospital stay (3.8 (3-6) vs. 5.1 (4-12); p < 0.001). Surgical approach did not influence the risk of having intra-operative (4% vs. 1%; p = 0.257) and 90-day severe (grade 3+) postoperative complication rates (4% vs. 8%; p = 0.497). Ten-year disease-free survival was similar between groups (94% vs. 95%; p = 0.812; HR:1.195; 95%CI:0.275, 5.18). Ten-year overall survival was similar between groups (98% vs. 96%; p = 0.995; HR:0.994; 95%CI:0.182, 5.424). Our study appears to support emerging evidence suggesting that, for low-risk patients, laparoscopic radical hysterectomy does not result in worse 10-year outcomes compared to the open approach. However, further research is needed and open abdominal radical hysterectomy remains the standard treatment for cervical cancer patients. • 10-year overall survival in low-risk cervical cancer patients is higher than 95%. • Surgical approach does not influence survival outcomes in the low-risk population. • Minimally invasive radical hysterectomy does not reduce morbidity in the low-risk population. [ABSTRACT FROM AUTHOR]

Endometrial cancer is the most common gynecological disease in developed countries. Although it is considered an indolent disease, advanced and recurrent endometrial carcinomas are characterized by poor prognosis. In the metastatic setting, after the failure of first-line platinum-based chemotherapy, patients have limited therapeutic options. However, endometrial cancer should not be considered as a single entity but as a group of heterogeneous diseases with specific genomic, molecular, and biological features by suggested the analysis of The Cancer Genome Atlas (TCGA). Accumulating data highlighted the effectiveness and safety of the adoption of immune checkpoint inhibitors (ICIs) for several types of solid tumors. In particular, immunotherapy showed promising results in MSI-H/dMMR solid tumors. Endometrial cancer is not an exception. Endometrial cancer has the highest prevalence of MSI across human cancer types, and approximately 30% of primary endometrial cancers are MSI-H/dMMR and 13% to 30% of recurrent endometrial cancers are MSI-H/dMMR. The preliminary results of the KEYNOTE-158, the Australian NCT03015129 and the GARNET trial strongly supported the adoption of ICIs as monotherapy in patients with advanced or recurrent endometrial cancer, after the failure of first-line treatments. Unfortunately, those impressive results are not achieved in patients with MMR proficient disease. Hence, other combinations were tested. In particular, the adoption of ICIs plus tyrosine kinase inhibitors (TKI) showed very compelling results. Recently, the updated results of the KEYNOTE-775 showed that pembrolizumab plus lenvatinib led to significantly longer progression-free and overall survival than chemotherapy among patients with advanced endometrial cancer, irrespective of MMR status. After EMA approval, pembrolizumab plus lenvatinib represents the new standard second-line treatment in endometrial cancer patients, regardless MMR status. Further studies are investigating the role of ICIs and TKIs in the first line and are testing new combinations (e.g. ICIs plus PARP inhibitors). • Patients with advanced / recurrent endometrial cancer have limited therapeutic options. • Chemotherapy still represent the current 1L treatment in advanced/recurrent endometrial cancer. • MSI-H/dMMR is an agnostic biomarker suggesting the efficacy of immunotherapy. • Endometrial cancer is the solid tumor with the highest prevalence of MSI-H/dMMR. • Immunotherapy is the emerging standard 2L in MSI-H/dMMR endometrial cancer • Immunotherapy plus TKI provides is the emerging standard 2L in pMMR endometrial cancer [ABSTRACT FROM AUTHOR]

To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer. This is a retrospective, a multi-institutional study evaluating 90-day surgery-related outcomes of patients undergoing treatment for early-stage cervical cancer before (period I: 01/01/2016–06/01/2018) and after (period II: 01/01/2019–06/01/2021) the publication of the results of the LACC trial. Charts of 1295 patients were evaluated: 581 (44.9%) and 714 (55.1%) before and after the publication of the LACC trial, respectively. After the publication of the LACC trial, the number of patients treated with minimally invasive radical hysterectomy decreased from 64.9% to 30.4% (p < 0.001). Overall, 90-day complications occurred in 110 (18.9%) and 119 (16.6%) patients in the period I and period II, respectively (p = 0.795). Similarly, the number of severe (grade 3 or worse) complications did not differ between the two periods (38 (6.5%) vs. 37 (5.1%); p = 0.297). Overall and severe 90-day complications were consistent between periods even evaluating stage IA (p = 0.471), IB1 (p = 0.929), and IB2 (p = 0.074), separately. The present investigation highlighted that in referral centers the shift from minimally invasive to open radical hysterectomy does not influence 90-day surgery-related morbidity. • The publication of the LACC trial determined a shift from the use of minimally invasive to open surgery. • Overall and severe 90-day complication rates were not influenced by the surgical approach. • The paradigm shift from minimally invasive to open radical hysterectomy does not increase the complication rate. [ABSTRACT FROM AUTHOR]

Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment. This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors. Our study highlighted that SNM provides similar long-term oncologic outcomes than LND. • Sentinel node mapping (SNM) allows an accurate detection of nodal involvement. • Low volume disease accounts for about 50% of nodal disease diagnosed with SNM. • Backup lymphadectomy does not improve oncologic outcomes in comparison to SNM alone. [ABSTRACT FROM AUTHOR]

Surgery is the mainstay of treatment in the management of early-stage cervical cancer. Until the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, minimally invasive radical hysterectomy was the recommended approach to treat patients with early-stage disease. The results of the LACC trial questioned the adoption of minimally invasive surgery in cervical cancer. In comparison with the open approach, minimally invasive surgery correlated with worse disease-free and cancer-specific survival. Similarly, other retrospective studies highlighted this correlation, thus corroborating the results of the LACC trials. In the present review, we evaluated current evidence and further prospective of the adoption of minimally invasive radical hysterectomy in cervical cancer. Moreover, we sought to assess some unsolved issues regarding the role of minimally invasive surgery in early-stage cervical cancer patients. [ABSTRACT FROM AUTHOR]

The role of retroperitoneal staging in endometrial cancer is still unclear. Although the prognostic value of lymphadenectomy has been demonstrated no data support the therapeutic value of nodal dissection. Sentinel node mapping represents an evolution of lymphadenectomy. Sentinel node mapping allows a more accurate identification of low-volume diseases (i.e., micrometastasis and isolated tumor cells) that are not always detectable via conventional histopathological evaluation. Adjuvant therapy might play a role in patients with low-volume disease. However, the presence of isolated tumor cells alone seems to not impact outcomes of endometrioid endometrial cancer patients. Hence, the choice to deliver adjuvant therapies has to be tailored based on uterine factors only. The introduction of molecular and genomic profiling would be useful in selecting appropriate surgical and adjuvant treatments. The molecular-integrated risk profile should be integrated in clinical practice to overcome the need of retroperitoneal staging (in case of non-bulky nodes) in patients at low risk. [ABSTRACT FROM AUTHOR]

Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma. • Clear cell endometrial cancer represents uncommon uterine tumor. • Multi-modal treatment should be considered in patient with clear cell endometrial cancer. • Immunotherapy might play a role in patients with MMRd clear cell endometrial cancer. • ATr , PIK3CA , DDR , and HER2 might be potential targets in clear cell endometrial cancer [ABSTRACT FROM AUTHOR]

Objective: Coronavirus disease 2019 (COVID-19) outbreak has correlated with the disruption of screening activities and diagnostic assessments. Endometrial cancer (EC) is one of the most common gynecological malignancies and it is often detected at an early stage, because it frequently produces symptoms. Here, we aim to investigate the impact of COVID-19 outbreak on patterns of presentation and treatment of EC patients. Methods: This is a retrospective study involving 54 centers in Italy. We evaluated patterns of presentation and treatment of EC patients before (period 1: March 1, 2019 to February 29, 2020) and during (period 2: April 1, 2020 to March 31, 2021) the COVID-19 outbreak. Results: Medical records of 5,164 EC patients have been retrieved: 2,718 and 2,446 women treated in period 1 and period 2, respectively. Surgery was the mainstay of treatment in both periods (p=0.356). Nodal assessment was omitted in 689 (27.3%) and 484 (21.2%) patients treated in period 1 and 2, respectively (p<0.001). While, the prevalence of patients undergoing sentinel node mapping (with or without backup lymphadenectomy) has increased during the COVID-19 pandemic (46.7% in period 1 vs. 52.8% in period 2; p<0.001). Overall, 1,280 (50.4%) and 1,021 (44.7%) patients had no adjuvant therapy in period 1 and 2, respectively (p<0.001). Adjuvant therapy use has increased during COVID-19 pandemic (p<0.001). Conclusion: Our data suggest that the COVID-19 pandemic had a significant impact on the characteristics and patterns of care of EC patients. These findings highlight the need to implement healthcare services during the pandemic. [ABSTRACT FROM AUTHOR]

Objective: To investigate factors predicting the risk of developing 90-day postoperative complications and lymphatic-specific morbidity in patients undergoing surgical staging for high-risk endometrial cancer.Methods: This is a multi-institutional retrospective cohort study. Patients affected by apparent early-stage high-risk endometrial cancer (endometrioid FIGO grade 3 with deep myometrial invasion and non-endometrioid endometrial cancer) undergoing surgical staging between 2007 and 2019. Complications were graded according to the Clavien-Dindo classification system. Martin criteria were applied to improve quality of complications reporting.Results: Charts of 279 patients were evaluated. Lymphadenectomy, sentinel node mapping (SNM), and SNM followed by back-up lymphadenectomy were performed in 83 (29.7%), 50 (17.9%), and 146 (52.4%) patients, respectively. The former group of patients included 13 patients who had lymphadenectomy after the failure of the SNM technique. Thirteen (4.6%) patients developed severe postoperative events (grade 3 or worse). At multivariate analysis, body mass index (OR: 1.08 (95%CI: 1.01, 1.17)) and open abdominal surgery (OR: 2.27 (95%CI: 1.02, 5.32)) were the two independent factors predictive of surgery-related morbidity. Seven severe lymphatic complications occurred. The adoption of laparoscopic approach (p < 0.001, log-rank test) and SNM (p = 0.038, log-rank test) correlated with a lower risk of developing surgery-related events. Independently, open abdominal surgery was associated with an increased risk of developing lymphatic morbidity (OR: 37.4 (95%CI: 4.38, 319.5); p = 0.001).Conclusion: The adoption of the laparoscopic approach and SNM technique were associated with lower 90-day complication rates than open surgery in high-risk endometrial cancer undergoing staging surgery. [ABSTRACT FROM AUTHOR]

Serous endometrial cancer represents a relative rare entity accounting for about 10% of all diagnosed endometrial cancer, but it is responsible for 40% of endometrial cancer-related deaths. Patients with serous endometrial cancer are often diagnosed at earlier disease stage, but remain at higher risk of recurrence and poorer prognosis when compared stage-for-stage with endometrioid subtype endometrial cancer. Serous endometrial cancers are characterized by marked nuclear atypia and abnormal p53 staining in immunohistochemistry. The mainstay of treatment for newly diagnosed serous endometrial cancer includes a multi-modal therapy with surgery, chemotherapy and/or radiotherapy. Unfortunately, despite these efforts, survival outcomes still remain poor. Recently, The Cancer Genome Atlas (TCGA) Research Network classified all endometrial cancer types into four categories, of which, serous endometrial cancer mostly is found within the "copy number high" group. This group is characterized by the increased cell cycle deregulation (e.g., CCNE1 , MYC, PPP2R1A , PIKCA, ERBB2 and CDKN2A) and TP53 mutations (90%). To date, the combination of pembrolizumab and lenvatinib is an effective treatment modality in second-line therapy, with a response rate of 50% in advanced/recurrent serous endometrial cancer. Owing to the unfavorable outcomes of serous endometrial cancer, clinical trials are a priority. At present, ongoing studies are testing novel combinations of various targeted and immunotherapeutic agents in newly diagnosed and advanced/recurrent endometrial cancer - an important strategy for serous endometrial cancer, whereby tumors are usually p53+ and pMMR, making response to PD-1 inhibitor monotherapy unlikely. Here, the rare tumor working group (including members from the European Society of Gynecologic Oncology (ESGO), Gynecologic Cancer Intergroup (GCIG), and Japanese Gynecologic Oncology Group (JGOG)), performed a narrative review reporting on the current landscape of serous endometrial cancer and focusing on standard and emerging therapeutic options for patients affected by this difficult disease. • Uterine serous carcinoma (USC) is a rare and aggressive variant of endometrial cancer. • USCs are generally mismatch repair proficient and have extensive copy number alterations. • Multi-modal treatment including surgery, chemotherapy and/or radiotherapy should be considered in the majority patient with USC. • Novel combinations of immune checkpoint inhibitors with targeted therapies are under evaluation. [ABSTRACT FROM AUTHOR]

To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data. • Overall, 10–15% of patients with high-grade cervical dysplasia are HR-HPV negative. • Patients with HR-HPV-positive lesions experience a 8-fold increase in the risk of recurrence than HPV-negative patients. • In case of HR-HPV-negative patients, achieving complete excision of the lesion the risk of recurrence is negligible. [ABSTRACT FROM AUTHOR]

Sentinel node mapping (SLN) has replaced lymphadenectomy for staging surgery in apparent early-stage low and intermediate risk endometrial cancer (EC). Only limited data about the adoption of SNM in high risk EC is still available. Here, we evaluate the outcomes of high-risk EC undergoing SNM (with or without back-up lymphadenectomy). This is a multi-institutional international retrospective study, evaluating data of high-risk (FIGO grade 3 endometrioid EC with myometrial invasion >50% and non-endometrioid histology) EC patients undergoing SNM followed by back-up lymphadenectomy and SNM alone. Chart of consecutive 196 patients were evaluated. The study population included 83 and 113 patients with endometrioid and non-endometrioid EC, respectively. SNM alone and SNM followed by back-up lymphadenectomy were performed in 50 and 146 patients, respectively. Among patients having SNM alone, 14 (28%) were diagnosed with nodal disease. In the group of patients undergoing SNM plus back-up lymphadenectomy 34 (23.2%) were diagnosed with nodal disease via SNM. Back-up lymphadenectomy identified 2 (1%) additional patients with nodal disease (in the para-aortic area). Back-up lymphadenectomy allowed to remove adjunctive positive nodes in 16 (11%) patients. After the adoption of propensity-matched algorithm, we observed that patients undergoing SNM plus back-up lymphadenectomy experienced similar disease-free survival (p = 0.416, log-rank test) and overall survival (p = 0.940, log-rank test) than patients undergoing SLN alone. Although the small sample size, and the retrospective study design this study highlighted that type of nodal assessment did not impact survival outcomes in high-risk EC. Theoretically, back-up lymphadenectomy would be useful in improving the removal of positive nodes, but its therapeutic value remains controversial. Further prospective evidence is needed. • Back-up lymphadectomy does not improve disease-free survival of high-risk EC undergoing SNM. • Back-up lymphadectomy does not improve overall survival of high-risk EC undergoing SNM. • Back-up lymphadenectomy increases positive node detection rate by 1%. [ABSTRACT FROM AUTHOR]

Purpose: To investigate oncological outcomes and patterns of recurrence of patients undergoing adjuvant "sandwich" chemo-radio-chemotherapy for locally advanced endometrial cancer. Methods: This is a multi-institutional retrospective study evaluating chart of consecutive patients undergoing chemo-radio-chemotherapy for FIGO stage III–IVA endometrial caner. Results: The study population included 45 patients who had adjuvant sandwich regimen. Median age of the study population was 66 years. The majority of patients were diagnosed with endometrioid histology and with stage III disease. After a median follow-up of 35 months, 15 patients developed recurrent disease. Three-year disease-free and overall survivals was 45% and 81%, respectively. Three-years site-specific disease-free survival was 85%, 92% and 48% for local, loco-regional, and distant recurrence, respectively. All patients included in the study had nodal dissection. Nodal assessment included: sentinel node mapping, sentinel node mapping plus backup lymphadenectomy and lymphadenectomy in 15, 6 and 24 patients, respectively. The latter group included four patients detected by suspected enlarged nodes, intraoperatively. Even after the exclusion of patients with enlarged nodes, the type of nodal assessment did not impact on survival outcomes (p > 0.2). Positive peritoneal cytology was the only factor associated with an increased risk of developing (any site) recurrence and distant-specific recurrence, independently. No factor predicted for overall survival. Conclusion: Adjuvant "sandwich" chemo-radio-chemotherapy for locally advanced endometrial cancer guarantee promising local and loco-regional controls, but distant failure rate is high, thus suggesting the need for applying other systemic treatment strategies for these patients. [ABSTRACT FROM AUTHOR]

In high income setting, the massive implementation of screening programs has reduced the incidence of cervical cancer, dramatically. However, cervical cancer still remains a major health concern, being one of the most common cause of death for cancer among women. The adoption of primary prevention through vaccination against HPV aims to reduce the prevalence of HPV-related lesions and cervical cancer. Accumulating data highlighted the cost-effectiveness of introducing HPV vaccination for adolescent and young adults. In the present review, we critically evaluated the role of vaccination against HPV, focusing much more on the role of vaccination in specific cluster of subjects (eg, post-treatment and older adults). Additionally, we evaluated the available evidence on the role of vaccination in HIV-positive subjects and in women receiving solid organs transplantation. We observed that although vaccination might be considered effective in those cluster of subjects; further evidence is needed to assess the cost-effectiveness of vaccination in these settings. • The implementation of vaccination against HPV reduced the burden of cervical cancer. • Vaccination against HPV might have a role in patients undergoing conization. • Cost-effectiveness of HPV vaccination in HIV positive individuals deserves to be addressed. [ABSTRACT FROM AUTHOR]

Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%; p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [ 5- ]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia. Unlabelled Image • HPV persistence correlates with an increased risk of [5-]year recurrence in women undergoing cervical conization • Patients undergoing laser conization experience a slightly lower risk of recurrence in comparison to LEEP • Further evidence regarding fertility and obstetrical issues is necessary [ABSTRACT FROM AUTHOR]

Objective: Coronavirus disease 2019 (COVID-19) has caused rapid and drastic changes in cancer management. The Italian Society of Gynecology and Obstetrics (SIGO), and the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of gynecologist oncologists and to assess the implementation of containment measures against COVID-19 diffusion. Methods: The survey consisted of a self-administered, anonymous, online questionnaire. The survey was sent via email to all the members of the SIGO, and MITO groups on April 7, 2020, and was closed on April 20, 2020. Results: Overall, 604 participants completed the questionnaire with a response-rate of 70%. The results of this survey suggest that gynecologic oncology units had set a proactive approach to COVID-19 outbreak. Triage methods were adopted in order to minimize in-hospital diffusion of COVID-19. Only 38% of gynecologic surgeons were concerned about COVID-19 outbreak. Although 73% of the participants stated that COVID-19 has not significantly modified their everyday practice, 21% declared a decrease of the use of laparoscopy in favor of open surgery (19%). However, less than 50% of surgeons adopted specific protection against COVID-19. Additionally, responders suggested to delay cancer treatment (10%-15%), and to perform less radical surgical procedures (20%-25%) during COVID-19 pandemic. Conclusions: National guidelines should be implemented to further promote the safety of patients and health care providers. International cooperation is of paramount importance, as heavily affected nations can serve as an example to find out ways to safely preserve clinical activity during the COVID-19 outbreak. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether primary conization might overcome the risk of local dissemination in patients undergoing laparoscopic radical hysterectomy.Methods: Consecutive data of 262 patients with early stage cervical cancer were retrieved: 88 women had conization followed by radical hysterectomy. A propensity-matched comparison (1:1) was carried out in order to compare laparoscopy and open surgery. Accumulating data highlighted that minimally invasive surgery has been associated with higher recurrence rates and worse overall survival than open surgery in women with early stage cervical cancer.Results: Data of 35 paired patients (total 70 patients) were analyzed. No between-group differences in baseline, disease, and pathological variables were observed. Patients undergoing laparoscopy correlated with lower blood loss (50 [range 30-100] vs 150 [range 50-500] mL; P<0.001) and shorter length of stay (3 ± 0.8 vs 5.4 ± 1.4 days; P<0.001) compared to open surgery. One local recurrence was observed per group (P=1.00). Type of surgical approach did not influence site of recurrence (P=1.00) or survival outcomes, in terms of 10-year disease-free (P=0.549, log-rank test) and overall survivals (P=0.615, log-rank test).Conclusions: The data show that primary conization might overcome the risk of local recurrence after laparoscopic radical hysterectomy in early stage cervical cancer. Further prospective evidence is needed. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify predictors of recurrence/persistence of cervical intraepithelial neoplasia grade 2+ (CIN2+) lesion (r-CIN2+) after primary conization. Methods: Retrospective analysis involving all consecutive women having conization for CIN2+ between 1998 and 2018. The risk of r-CIN2+ was assessed using Kaplan-Meier and Cox models. Results: Data of 3,212 women were retrospectively identified. After a mean follow-up of 47 (±22.2) months, 112 (3.5%) patients developed r-CIN2+. Mean time interval between prior conization and diagnosis of r-CIN2+ was 26.2 (±13.2) months. Via multivariate analysis, presence of high-risk human papillomavirus (HPV) types at the time of CIN2+ diagnosis, hazard ratio (HR)=3.40 (95% confidence interval [CI]=1.66-6.95) for HPV16/18 and HR=2.59 (95% CI=1.21-5.55) for HPV types other than 16/18, positive margins at primary conization, HR=4.11 (95% CI=2.04-8.26) and HPV persistence after conization, HR=16.69 (95% CI=8.20-33.9), correlated with r-CIN2+, independently. Considering age-specific HPV types distribution, we observed that HPV16/18 infection correlated to an increased risk of r-CIN2+ only in young women (aged ≤25 years; p=0.031, log-rank test); while in the older population (>25 years) HPV type(s) involved had not impact on r-CIN2+ risk (p>0.200, log-rank test). Conclusion: HPV persistence is the main factor predicting r-CIN2+. Infection from HPV16/18 has a detrimental effect in young women, thus highlighting the need of implementing vaccination against HPV in this population. Further prospective studies are warranted for tailoring clinical decision-making for post-conization follow-up on the basis of risk factors. [ABSTRACT FROM AUTHOR]

Objective: Uterine serous carcinoma (USC) is a rare highly aggressive disease. In the present study, we aimed to investigate the survival implication of the systematic lymphadenectomy in patients who underwent surgery for apparent early-stage USC. Methods: Consecutive patients with apparent early-stage USC surgically treated at six Italian referral cancer centers were analyzed. A comparison was made between patients who underwent retroperitoneal staging including at least pelvic lymphadenectomy "LND" vs. those who underwent hysterectomy alone "NO-LND". Baseline, surgical and oncological outcomes were analyzed. Kaplan- Meier curves were calculated for disease-free survival (DFS) and disease-specific survival (DSS). Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). Results: One hundred forty patients were analyzed, 106 LND and 34 NO-LND. NO-LND group (compared to LND group) included older patients (median age, 73 vs.67 years) and with higher comorbidities (median Charlson Comorbidity Index, 6 vs. 5) (p<0.001). No differences in terms of recurrence rate (LND vs. NO-LND, 33.1% vs. 41.4%; p=0.240) were observed. At Cox regression analysis lymphadenectomy did not significantly influence DFS (HR=0.59; 95% confidence interval [CI]=0.32-1.08; p=0.09), and DSS (HR=0.14; 95% CI=0.02-1.21; multivariable analysis p=0.07). Positive node was independently associated with worse DFS (HR=6.22; 95% CI=3.08-12.60; p<0.001) and DSS (HR=5.51; 95% CI=2.31- 13.10; p<0.001), while adjuvant chemotherapy was associated with improved DFS (HR=0.38; 95% CI=0.17-0.86; p=0.02) and age was independently associated with worse DSS (HR=1.07; 95% CI=1.02-1.13; p<0.001). Conclusions: Although lymphadenectomy did not show survival benefits in patients who underwent surgery for apparent early-stage USC, the presence of lymph node metastasis was the main adverse prognostic factors, supporting the prognostic role of the retroperitoneal staging also in this histological subtype. [ABSTRACT FROM AUTHOR]

Ovarian cancer is characterized by a high mortality on incidence ratio. Although the majority of patients achieve complete response after primary treatment, approximately 65–80% of patients recur with the first 5 years. Platinum-free interval is one of the main prognostic factors. Patients recurring with 6 months within the end of platinum-based chemotherapy are characterized by poor prognosis. To date no effective treatment modality are identified for those patients. The mainstay of treatment for platinum-resistant ovarian cancer is single agent chemotherapy. Other treatment modalities have tested in this setting with discouraging results. Growing evidence suggested that immunotherapy would improve outcomes of patients with various types of solid tumors including melanoma, non-small cell lung cancer as well as uterine malignancies. Here, we reviewed current evidence on the adoption of immunotherapy in platinum-resistant ovarian cancer. To date no mature evidence supports the routine adoption of immunotherapy in ovarian cancer patients. Further strategies have to be explored. • Patients with platinum-resistant ovarian cancer experience poor oncologic outcomes. • PD-L1 expression is associated with tumor-infiltrating T cells and favourable prognosis in high-grade serous ovarian cancer. • Combining immune check point blockage to PARP inhibitors represents a new emerging therapeutic option. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 pandemic is continuing to spread. There are growing concerns on the impact of COVID-19 in cancer patients. Several papers reporting recommendations and guidelines are published. But few data on cancer patients affected by COVID-19 are available. This is a retrospective study including all consecutive patients affected by gynecological cancer who developed COVID-19. All patients were treated in an academic setting (in Milan, Lombardy, Italy) between February and March 2020. Overall, 355 patients had active treatment during the study period due to newly diagnosed or recurrent gynecological disease. Among those, 19 (5.3%) patients affected developed COVID-19. All patients were asymptomatic at the time of COVID-19 detection. Six patients were diagnosed before starting planned treatments; while the remaining 13 were diagnosed for COVID-19 after their started their treatments. Considering the first group of six patients, one patient died due to COVID-19 3 days after the diagnosis; while the other patients recovered from COVID-19 after a median of three weeks. The latter group of 13 patients (treatments started) included five patients who underwent surgery and eight patients who underwent chemotherapy. Focusing on five patients who were diagnosed after surgery, we observed that two patients died during postoperative course, while in other two cases prolonged hospitalization was needed. One patient had no issues. Chemotherapy was delayed for the remaining patents without sequelae. Our report highlights that COVID-19 impacts the quality of treatments for cancer patients. Mortality rate is high, especially after surgery. More important, patients under active treatment for cancer are at high risk of developing severe evolution of COVID-19. Prioritizing patients journey during COVID-19 is of paramount importance. • There are growing concerns on the impact of COVID-19 in cancer patients. • COVID-19 is impacting oncologic practice directly and indirectly. • Prioritizing patients journey during COVID-19 is of paramount importance. [ABSTRACT FROM AUTHOR]

Objective: To evaluate long-term outcomes after surgery for apparent early-stage ovarian cancer (OC).Methods: Retrospective analysis of women who underwent staging surgery for apparent early-stage OC at a single center in Milan, Italy, from 1990 to 2008, and had a follow-up longer than 10 years (living women with no recurrence). Univariate and multivariate analyses and propensity score matching were carried out.Results: Overall, 182 women underwent radical (n=148, 81.3%) or conservative (n=34, 18.7%) procedures for early-stage OC. Ten-year disease-free and overall survival were 82.9% (n=151) and 87.9% (n=160), respectively. Conservative or radical surgery had similar disease-free (log-rank test, P=0.783) and overall (log-rank test, P=0.783) survival. These data were confirmed after the application of propensity score matching. High-risk features correlated with non-significant worse disease-free survival (P=0.080). In the high-risk group (≥Grade 3 or ≥ Stage IC), type of surgical approach (conservative vs radical) did not affect survival (hazard ratio, 0.81; 95% confidence interval, 0.18-3.56; P=0.781).Conclusion: Women with early-stage OC had encouraging long-term survival. The presence of high-risk disease had detrimental effects on survival, regardless of surgical approach. High-risk disease should not be considered a contraindication to conservative surgery. [ABSTRACT FROM AUTHOR]

• Sentinel node mapping allows a more accurate identification of patients with nodal disease compared to lymphadenectomy. • Patients having sentinel node mapping experience similar outcomes than patients having lymphadenectomy. • Even in high-risk group sentinel node mapping ensures the oncologic safety of lymphadenectomy. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) classified the novel coronavirus (i.e., coronavirus disease 2019 [COVID-19]) as a global public health emergency. COVID-19 threatens to curtail patient access to evidence-based treatment. Medicine is changing, basically due to the limited available resources. In the field of gynecologic oncology, we have to re-design our treatments' paradigm. During COVID-19 pandemic outbreak, the highest priority is to achieve the maximum benefit from less demanding procedures. Extensive procedures should be avoided, in order to reduce hospitalization and postoperative events that might increase the in-hospital spread of the virus. There are ongoing concerns on the use of laparoscopic procedures, related to the possible contamination of the staff working in the operation room. Other minimally invasive techniques, including, vaginal surgery as well as robotic-assisted and isobaric procedures would be preferred over laparoscopy. A fair allocation of resources is paramount adequate treatments. [ABSTRACT FROM AUTHOR]

The role of adjuvant chemotherapy in surgically staged stage I clear cell ovarian cancer (OCCC) is unclear. Here, we performed a systematic review and meta-analysis in order to evaluate the role of chemotherapy vs. observation in stage I OCCC. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; ID: #129628). A protocol was defined prior to the search include the population criteria, description of interventions, comparisons, and the outcomes of interest, according to the PRIMA guidelines. Overall, the study population included 5073 women. Stage I OCCC experienced a 5-year disease-free survival and a 5-year overall survival of 83.7% and 86.9%, respectively. Pooled data suggested that in the overall population adjuvant chemotherapy did not impact on 5-year disease free survival (test for overall effect, Z = 0.18; p = 0.86) and 5-year overall survival (test for overall effect, Z = 0.62; p = 0.53). Focusing on 2264 stage IC OCCC we observed that adjuvant correlated with an improvement in overall survival (OR: 0.70 (95%CI: 0.52 to 0.93); Z = 2.44; p = 0.01). In conclusion our study underlines that adjuvant chemotherapy could be reserved for patients with stage IC OCCC; while in stage IA and IB it could be safely omitted. Owing to the inherent biases of the studies included in the meta-analysis further prospective evidences are needed. • Patients with stage IC OCCC experience good oncologic outcomes regardless the use of adjuvant chemotherapy. • More than 70% of patients with OCCC have adjuvant chemotherapy. • Adjuvant chemotherapy does not improve outcomes in stage IA and IB OCCC. • Adjuvant chemotherapy improves overall survival in stage IC OCCC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the characteristics of women developing cervical intraepithelial neoplasia who had had a vaccination against human papillomavirus (HPV).Methods: A retrospective cohort study was carried out of women diagnosed with moderate or severe cervical dysplasia (CIN2+) in four Italian centers between 2015 and 2017. All women included had had previous bivalent or quadrivalent vaccination against HPV.Results: The present study included 43 patients affected by CIN2+. The median age was 28 (range, 21-41) years. Ten (23.3%) patients did not have a diagnosis of specific HPV type(s) involved: high-risk HPV was detected in 7 (16.3%) women while HPV testing was negative in 3 (6.9%) women. Lesions related to HPV16 were found in two patients. HPV types covered by nonavalent vaccination were diagnosed in 27/33 (81.8%) women. HPV types not covered by nonavalent vaccination were diagnosed in 6 (18.2%) women. Co-infections are most commonly detected in women with HPVs other than those included in the nonavalent vaccination (P=0.024).Conclusion: Cervical dysplasia occurring after HPV vaccination is a rare condition. Theoretically, nonavalent vaccination should improve protection against more than 80% of HPV-related lesions compared to other vaccines. [ABSTRACT FROM AUTHOR]

In the recent years, minimally invasive surgery has emerged as the gold standard for the treatment of both benign and malignant gynecological conditions. Growing evidence suggest that laparoscopic and robotic-assisted treatments allow to archived the same long-term outcomes than conventional open abdominal treatments, minimizing peri-operative morbidity. In the present review we analyzed the advances in the treatment of cervical cancer patients, reporting the advances in both the evolution of concept of radical hysterectomy and of the adoption of minimally invasive surgery. We discussed the advantages related to the introduction of minimally invasive treatment for cervical cancer patients; innovation of conventional laparoscopic surgery as discussed as well. Recent evidence suggested a potential detrimental effect on long-term survival outcomes related to the use of minimally invasive surgery in patients affected by cervical cancer. However, reasons why minimally invasive surgery might have a detrimental effect are still unclear. Further evidence is needed in order to improve quality of treatment for cervical cancer patients. [ABSTRACT FROM AUTHOR]

To evaluate the long-term outcomes of young early stage cervical cancer patients wishing to preserve their childbearing potential. Data of young (aged <40 years) patients with early stage cervical cancer were prospectively collected. All patients with stage IA2, IB1 and IB2 cervical cancer were included; they have cervical conization and pelvic node dissection performed via minimally invasive surgery. Survival outcomes were assessed with the Kaplan-Meier model. Overall, 32 patients met the inclusion criteria. Mean (SD) age of the population included was 33 (±4). According to the FIGO 2018 staging system, the stage of disease was IA2, IB1 and IB2 in 9 (28%), 21 (66%) and 2 (6%) cases, respectively. All patients included had cervical conization and laparoscopic pelvic node assessment, including systematic pelvic lymphadenectomy (N = 30, 94%) and sentinel node mapping (N = 2, 6%). In six (19%) patients the planned conservative treatment was discontinued. Median follow-up was 75 (range, 12–184) months. No recurrent disease was diagnosed among patients undergoing conservative treatment; while 2 out of 6 patients having definitive surgical or radiotherapy treatments developed recurrent disease. Five-year disease free and overall survivals were 94% and 97%, respectively. Considering reproductive outcomes, 11 (69%) out of 16 patients who attempted to conceive got pregnant. Cervical conization and pelvic nodes assessment could be considered a valid treatment modality for early-stage cervical cancer patients who are wishing to preserve their childbearing potential. • Cervical conization plus lymph node dissection is a valuable option for early-stage stage cervical cancer. • About 20% for patients initially submitted to fertility sparing procedure required radical treatments. • In case of negative margins, cervical conization guarantees a good local disease control rate. [ABSTRACT FROM AUTHOR]

Sentinel node mapping is increasingly being utilized for endometrial cancer staging. However, only limited evidence supporting the adoption of sentinel node mapping instead of conventional lymphadenectomy is still available. Here, we aimed to review the current evidence comparing sentinel node mapping and lymphadenectomy in endometrial cancer staging. This systematic review was registered in the International Prospective Register of Systematic Reviews. Six comparative studies were included. Overall, 3536 patients were included: 1249 (35.3%) and 2287 (64.7%), undergoing sentinel node mapping and lymphadenectomy, respectively. Pooled data suggested that positive pelvic nodes were detected in 184 out of 1249 (14.7%) patients having sentinel node mapping and 228 out of 2287 (9.9%) patients having lymphadenectomy (OR: 2.03; (95%CI: 1.30 to 3.18); p = 0.002). No difference in detection of positive nodes located in the paraaortic was observed (OR: 93 (95%CI: 0.39 to 2.18); p = 0.86). Overall recurrence rate was 4.3% and 7.3% after sentinel node mapping and lymphadenectomy, respectively (OR: 0.90 (95%CI: 0.58 to 1.38); p = 0.63). Similarly, nodal recurrences were statistically similar between groups (1.2% vs. 1.7%; OR: 1.51 (95%CI: 0.70 to 3.29); p = 0.29). In conclusion, our meta-analysis underlines that sentinel node mapping is non-inferior to standard lymphadenectomy in term of detection of paraaortic nodal involvement and recurrence rates (any site and nodal recurrence); while, focusing on the ability to detect positive pelvic nodes, sentinel node mapping could be consider superior to lymphadenectomy. Further randomized studies are needed to asses long term effectiveness of sentinel node mapping. • Sentinel node mapping allows an accurate identification of nodal disease in the pelvic area in comparison to lymphadenectomy. • Sentinel node mapping is non inferior to lymphadenectomy in terms of para-aortic detection rate. • Sentinel node mapping does not increase nodal-specific recurrence. [ABSTRACT FROM AUTHOR]

Nodal assessment represents an integral part of staging procedure for endometrial cancer. The widespread diffusion of sentinel node mapping determinates a phenomenon of migration from stage I to stage III disease, especially for low-risk endometrial cancer patients. The adoption of sentinel node mapping and pathological ultrastaging increase the detection of low volume disease (i.e., micrometastasis and isolated tumor cells), being low volume disease detected in >30% of patients with positive nodes. The prognostic role of low volume disease is discussed as well as the possible adjuvant strategies for patients diagnosed with micrometastasis and isolated tumor cells. The role of further prospective treatments in endometrial cancer, including molecular and genetic profiling, is critically reviewed. • Sentinel node mapping improves detection of stage IIIC endometrial cancer. • Patients at low risk of lymphatic spread are more likely to be diagnosed with low volume disease. • Patients with micrometastasis in sentinel nodes should be receive adjuvant treatment. • Patients with isolated tumor cells in sentinel nodes deserve to be treated on the basis of uterine factors. [ABSTRACT FROM AUTHOR]

Objective: Neoadjuvant chemotherapy plus interval debulking surgery is growing treatment strategy for advanced ovarian cancer patients with unresectable disease. Here, we aimed to assess predictors of surgical unresectability and survival of patients submitted to neoadjuvant chemotherapy plus interval debulking surgery.Methods: Data of consecutive 193 patients undergoing neoadjuvant chemotherapy plus interval debulking surgery were retrospectively evaluated in four Italian oncologic centers. RECIST 1.1 guidelines were used to assess response to neoadjuvant chemotherapy. Survival outcomes were evaluated using Kaplan-Meier and Cox proportional hazard models.Results: Overall, 155 (80.3%) and 38 (19.7%) patients had optimal and non-optimal cytoreduction at the time of interval debulking surgery. Via multivariate analysis, age (OR: 2.87 (95%CI: 1.29, 6.36) per 10-year increase) and radiological response to neoadjuvant chemotherapy (OR: 48.1 (95%CI: 6.33, 365.3)) impact on the inability to perform a complete cytoreduction. Patients having complete or partial response experienced a significant better disease-free survival than patients having stable or progressive disease at radiological examination (median disease-free survival 16.8 vs. 11.0 months; HR: 0.42 (95%CI: 0.09, 0.78); p = .001). Radiological response did not predict for overall survival (p = .719).Conclusions: RECIST1.1 response criteria might be helpful to predict surgical resectability and disease-free survival of advanced stage ovarian cancer patients undergoing neoadjuvant chemotherapy plus interval debulking surgery. [ABSTRACT FROM AUTHOR]

Objective: We have investigated outcomes of women presenting with recurrent high-grade vaginal intra-epithelial neoplasia. Methods: Data of consecutive women diagnosed with recurrent high-grade vaginal intraepithelial neoplasia after primary treatment(s) were retrieved. Risk of developing new recurrence over the time was assessed using Kaplan-Meier and Cox models. Results: Data of 117 women were available for the analysis. At primary diagnosis, 41 (35%), 4 (3.4%) and 72 (61.6%) patients had had laser, pure surgical and medical treatments, respectively. Secondary treatments included: laser ablation and medical treatment in 95 (81.2%) and 22 (18.8%) cases, respectively. After a mean (standard deviation) follow-up of 72.3 (±39.5) months, 37 (31.6%) out of the entire cohort of 117 patients developed a second recurrence. Median time to recurrence was 20 (range, 5-42) months. Patients with recurrent high-grade vaginal intra-epithelial neoplasia undergoing medical treatments were at higher risk of developing a second recurrence in comparison to women having laser treatment (p=0.013, log-rank test). After we corrected our results for type of treatment used for recurrent disease, we observed that the execution of primary laser treatment was independently associated with a lower risk of developing new recurrences (hazard ratio [HR]=0.46; 95% confidence interval [CI]=0.21-0.99; p=0.050). The other variable that is independently associated with a new recurrence is the persistent infection from HPV16 or 18 (HR=3.87; 95% CI=1.15-13.0; p=0.028). Conclusion: Patients with recurrent high-grade vaginal intra-epithelial neoplasia are at high risk of developing new recurrences. Our data underline that the choice of primary treatment might have an impact of further outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Nerve-sparing radical hysterectomy has been implemented in order to reduce pelvic floor dysfunctions in women undergoing radical surgery for cervical cancer. Here, we aimed to investigate if the adoption of laparoscopic surgery impacts on patients' outcomes. Methods: Data of consecutive patients affected by cervical cancer who had laparoscopic nerve-sparing radical hysterectomy were matched 1:1 with an historical cohort of patients undergoing open procedure. A propensity-score matched algorithm was applied. Results: Thirty-five patients' pairs (70 patients: 35 undergoing laparoscopic vs. 35 undergoing open abdominal nerve-sparing radical hysterectomy) were included. Demographic and baseline oncologic characteristics were balanced between groups. Patients undergoing laparoscopic surgery had similar operative time than patients undergoing open abdominal procedures (249 [±91.5] vs. 223 [±65.0] minutes; p=0.066). Laparoscopic approach correlated with lower blood loss (30.5 [±11.0] vs. 190 [90.4] mL; p<0.001) and shorter hospital stay (3.2 [±1.2] vs. 5.4 [2.0] days; p=0.023). Patients undergoing laparoscopy experienced a lower 30-day pelvic floor dysfunction rate than patients having open surgery. Moreover, they experienced shorter recovery of bladder function than patients having open procedures (median, 7 vs. 9 days; p=0.004, log-rank test). Conclusion: Laparoscopic approach resulted in a faster recovery of bladder function in comparison to open surgery for patients undergoing nerve-sparing radical hysterectomy. [ABSTRACT FROM AUTHOR]

Objective: To examine outcomes of patients having treatments for newly diagnosed advanced stage low-grade serous ovarian cancer (LGSC). Methods: We conducted a retrospective case series of women affected by advanced stage (stage IIIB or more) LGSC undergoing surgery in a single oncologic center between January 2000 and December 2017. Survival outcomes were assessed using Kaplan-Meier and Cox models. Results: Data of 72 patients were retrieved. Primary cytoreductive surgery was attempted in 68 (94.4%) patients: 19 (27.9%) had residual disease (RD) >1 cm after primary surgery. Interval debulking surgery (IDS) was attempted in 15 of these 19 (78.9%) patients and the remaining 4 patients having not primary debulking surgery. Twelve out of 19 (63.1%) patients having IDS had RD. After a mean (±standard deviation) follow-up was 61.6 (±37.2) months, 50 (69.4%) and 22 (30.5%) patients recurred and died of disease, respectively. Via multivariate analysis, non-optimal cytoreduction (hazard ratio [HR]=2.79; 95% confidence interval [CI]=1.16-6.70; p=0.021) and International Federation of Obstetrics and Gynecologists (FIGO) stage IV (HR=3.15; 95% CI=1.29-7.66; p=0.011) were associated with worse disease-free survival. Via multivariate analysis, absence of significant comorbidities (HR=0.56; 95% CI=0.29-1.10; p=0.093) and primary instead of IDS (HR=2.95; 95% CI=1.12-7.74; p=0.027) were independently associated with an improved overall survival. Conclusion: LGSC is at high risk of early recurrence. However, owing to the indolent nature of the disease, the majority of patients are long-term survivors. Further prospective studies and innovative treatment modalities are warranted to improve patients care. [ABSTRACT FROM AUTHOR]

Objective: To assess the risk of developing high-grade cervical dysplasia among women with low-grade cervical cytology and nonvisible squamocolumnar junction (SCJ) at colposcopic examination. Methods: Data of consecutive women with low-grade intraepithelial lesion(≤LSIL) undergoing colposcopic examination, which was unsatisfactory (due to the lack of the visualization of the entire SCJ), were retrospectively reviewed. The risk of developing high-grade cervical intraepithelial neoplasia (CIN2+) was assessed using Kaplan-Meier and Cox models. Results: Data of 86 women were retrieved. Mean (standard deviation [SD]) age was 36.3 (13.4) years. A total of 71 (82.5%) patients had high-risk human papillomavirus (HR-HPV) at the time of diagnosis. Among the 63 patients undergoing repetition of HPV testing, 15 (24%) and 48 (76%) women had positive and negative tests for HR-HPV at 12 months, respectively. We observed that 5 (33%) of 15 patients with HPV persistence developed CIN2+, while only 1 (2%) patient of 48 patients without HPV persistence developed CIN2+ (odds ratio [OR]: 23.5; 95% confidence interval [CI]: 2.46-223.7; P < .001). The length of HR-HPV persistence correlated with an increased risk of developing CIN2+ (P < .001; P for trend). High-risk HPV persistence is the only factor predicting for CIN2+ (hazard ratio: 3.19; 95% CI: 1.55-6.57; P = .002). Conclusions: High-risk HPV persistence predicts the risk of developing CIN2+ in patients with unsatisfactory colposcopic examination. Further studies are warranted in order to implement the use of HPV testing in patients with unsatisfactory colposcopy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of full lymphadenectomy in patients with isolated nodal recurrence of ovarian cancer.Methods: In a retrospective study, the data of women undergoing secondary cytoreduction at the National Cancer Institute, Milan, Italy, between January 1, 2001, and December 31, 2015, were collected and patients with isolated nodal recurrence were identified. Factors predicting for disease-free interval (DFI) and overall survival were estimated using Kaplan-Meier survival analysis and Cox regression analysis.Results: Of the 199 consecutive patients whose data were collected, isolated nodal recurrence (defined as the presence of lymphatic disease) was observed in 35 women. Among this study cohort, lymphadenectomy and bulky node removal were performed in 11 (31%) and 24 (69%) patients, respectively. Women who underwent lymphadenectomy experienced better DFI compared with those who had bulky node removal only (median 21 and 12 months, respectively; P=0.019), and lymphadenectomy, but not bulky node removal, significantly improved rates of DFI (P=0.043). No factors were independently associated with overall survival; however, a trend toward an improved overall survival rate was observed in patients undergoing complete resection at the time of primary surgery (P=0.055).Conclusion: Lymphadenectomy at the time of secondary cytoreduction improved DFI but did not have a significant effect on overall survival. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) represents the most common gynecological neoplasm in developed countries. Surgery is the mainstay of treatment for EC. Although EC is characterized by a high prevalence several features regarding its management are still unclear. In particular the execution of lymphadenectomy is controversial. The recent introduction of sentinel node mapping represents the mid-way between the execution and omission of node dissection in EC patients. In the present review we discuss the emerging role of sentinel node mapping in EC. In addition, we discussed how type of tracers utilized and site of injection impacted on sentinel node detection rates. Future perspective regarding EC management are also discussed. [ABSTRACT FROM AUTHOR]

No clear evidence supports the advantage of fixed (up to two years (2yICI)) or continuous treatment (more than two years (prolonged ICI)) in cancer patients achieving stable disease or response on immune checkpoint inhibitors (ICIs). We performed a systematic review and meta-analysis of randomized controlled trials reporting the duration of ICIs (alone or in combination with standard of care (SoC)) across various solid tumors. Overall, we identified 28,417 records through database searching. Based on the eligibility criteria, 57 studies were identified for the quantitative synthesis, including 22,977 patients receiving ICIs (with or without SoC). Prolonged ICI correlated with better overall survival (OS) than 2yICI in patients with melanoma (HR:1.55; 95%CI: 1.22,1.98), while 2yICI-SoC led to better OS than prolonged ICI-SoC in patients with NSCLC (HR: 0.84; 95%CI: 0.68,0.89). Prospective randomized trials are needed to assess the most appropriate duration of ICIs. No clear evidence supports the advantage of fixed (up to two years (2yICI)) or continuous treatment (more than two years (prolonged ICI)) in cancer patients achieving stable disease or response on immune checkpoint inhibitors (ICIs). Here, we assessed the optimal treatment duration for ICIs in solid tumors. Prolonged ICIs administration does not seem to improve the outcomes of patients with NSCLC an RCC. [Display omitted] • The optimal duration of immune checkpoint inhibitors (ICI) is still unclear. • This meta-analysis compared prolonged ICI vs. 2-year schedule. • Prolonged ICIs seems beneficial in patients with melanoma. • In other solid tumor prolonged ICI does not correlated with improved survival. [ABSTRACT FROM AUTHOR]

Objective: Accumulating evidence support that complete cytoreduction (CC) at the time of secondary cytoreductive surgery (SCS) improves survival in patients affected by recurrent ovarian cancer (ROC). Here, we aimed to determine whether artificial intelligence (AI) might be useful in weighting the importance of clinical variables predicting CC and survival. Methods: This is a retrospective study evaluating 194 patients having SCS for ROC. Using artificial neuronal network (ANN) analysis was estimated the importance of different variables, used in predicting CC and survival. ANN simulates a biological neuronal system. Like neurons, ANN acquires knowledge through a learning-phase process and allows weighting the importance of covariates, thus establishing how much a variable influences a multifactor phenomenon. Results: Overall, 82.9% of patients had CC at the time of SCS. Using ANN, we observed that the 3 main factors driving the ability of achieve CC included: disease-free interval (DFI) (importance: 0.231), retroperitoneal recurrence (importance: 0.178), residual disease at primary surgical treatment (importance: 0.138), and International Federation of Gynecology and Obstetrics (FIGO) stage at presentation (importance: 0.088). Looking at connections between different covariates and overall survival (OS), we observed that DFI is the most important variable influencing OS (importance: 0.306). Other important variables included: CC (importance: 0.217), and FIGO stage at presentation (importance: 0.100). Conclusion: According to our results, DFI should be considered as the most important factor predicting both CC and OS. Further studies are needed to estimate the clinical utility of AI in providing help in decision making process. [ABSTRACT FROM AUTHOR]

Objective: To test the theoretical utility of incorporating nonavalent vaccination against HPV into a clinical setting.Methods: The present retrospective study included data from consecutive patients who underwent HPV-DNA testing between January 1, 1998, and December 31, 2015. Changes in the prevalence of different HPV types were assessed during three periods (T1, 1998-2003; T2, 2004-2009; and T3, 2010-2015) using XY analysis.Results: The study included a total of 13 665 patients. Overall, 1361, 5130, and 7174 patients were included in the T1, T2, and T3 periods, respectively. The quadrivalent vaccine would have potentially protected against HPV in 71.5% (973/1361), 46.5% (2385/5130), and 26.5% (1901/7174) of patients in T1, T2, and T3, respectively (P<0.001 for trend). The nonavalent vaccine could have protected against HPV in 92.5% (1259/1361), 72.3% (3709/5130), and 58.1% (4168/7174) of patients in T1, T2, and T3, respectively (P<0.001 for trend). The proportion of patients with genital dysplasia grade 2+ who did not have infections with HPV genotypes covered by the quadrivalent or nonavalent vaccines increased across the three periods (P<0.001 for trend). For all study periods, the protection provided by the nonavalent vaccine would have been superior to the quadrivalent vaccine (χ2 test P<0.001).Conclusion: The introduction of a nonavalent vaccine could improve protection against HPV infections and HPV-related genital dysplasia. [ABSTRACT FROM AUTHOR]

In the recent years, angiogenetic inhibitors have emerged for the treatment of several malignancies. In particular, bevacizumab has proved to be effective in many types of cancers (including sarcoma), but the limitations of antiangiogenic therapy have been shown in practice. Here, we sought to review the current evidence on the role and efficacy of bevacizumab in patients affected by uterine leiomyosarcoma. On April 2017, Literature was searched in order to identify studies reporting outcomes of patients affected either by early stage or advanced/recurred uterine leiomyosarcoma undergoing treatment with bevacizumab, alone or in combination with other chemotherapeutic regimens. Searching the literature data of 69 patients affected by metastatic, unresectable uterine leiomyosarcoma were retrieved; on the contrary, no data regarding the use of bevacizumab in patients with early-stage uterine leiomyosarcoma was published. Current evidence suggested that the addiction of bevacizumab to standard treatment modality does not increase grade 3 or worse toxicity (assessed by CTCAE). Pooled data regarding response rate suggested that 35%, 28%, 26% and 11% of patients experienced objective cure (complete + partial response), stable disease, progressive disease and unknown response, respectively. Data from the only one randomized controlled trial suggested that objective cure rate does not differ from standard chemotherapy treatment, thus limiting the indication to add bevacizumab in patients affected by metastatic, unresectable uterine leiomyosarcoma. The current evidence does not justify the use of bevacizumab into clinical practice. Further randomized studies testing the role of bevacizumab are warranted. [ABSTRACT FROM AUTHOR]

Objective: Nerve-sparing radical hysterectomy (NSRH) was introduced with the aim to reduce pelvic dysfunctions related to conventional radical hysterectomy (RH). Here, we sought to assess the effectiveness and safety of NSRH in a relatively large number of the patients of cervical cancer (CC) patients undergoing either primary surgery or neoadjuvant chemotherapy (NACT) followed by surgery. Methods: Outcomes of consecutive patients undergoing NSRH and of a historical cohort of patients undergoing conventional RH were retrospectively reviewed. Results: This study included 325 (49.8%) and 327 (50.2%) undergoing NSRH and RH, respectively. Via a multivariable model, nodal status was the only factor predicting for DFS (hazard ratio [HR]=2.09; 95% confidence interval [CI]=1.17-3.73; p=0.01). A trend towards high risk of recurrence was observed for patients affected by locally advanced cervical cancer (LACC) undergoing NACT followed by surgery (HR=2.57; 95% CI=0.95-6.96; p=0.06). Type of surgical procedures (NSRH vs. RH) did not influence risk of recurrence (p=0.47). Similarly, we observed that the execution of NSRH rather than RH had not a detrimental effect on OS (HR=1.19; 95% CI=0.16-9.01; p=0.87). Via multivariable model, no factor directly correlated with OS. No difference in early complication rates was observed between the study groups. Conversely, a significant higher number of late complications was reported in RH versus NSRH groups (p=0.02). Conclusion: Our data suggested that NSRH upholds effectiveness of conventional RH, without increasing recurrence and complication rates but improving pelvic dysfunction rates. [ABSTRACT FROM AUTHOR]

Objective: To test the applicability of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) and Memorial Sloan Kettering (MSK) criteria in predicting complete cytoreduction (CC) in patients undergoing secondary cytoreductive surgery (SCS) for recurrent ovarian cancer (ROC). Methods: Data of consecutive patients undergoing SCS were reviewed. The Arbeitsgemeinschaft Gynäkologische Onkologie OVARian cancer study group (AGO-OVAR) and MSK criteria were retrospectively applied. Nomograms, based on AGO criteria, MSK criteria and both AGO and MSK criteria were built in order to assess the probability to achieve CC at SCS. Results: Overall, 194 patients met the inclusion criteria. CC was achieved in 161 (82.9%) patients. According to the AGO-OVAR criteria, we observed that CC was achieved in 87.0% of patients with positive AGO score. However, 45 out of 71 (63.4%) patients who did not fulfilled the AGO score had CC. Similarly, CC was achieved in 87.1%, 61.9% and 66.7% of patients for whom SCS was recommended, had to be considered and was not recommended, respectively. In order to evaluate the predictive value of the AGO-OVAR and MSK criteria we built 2 separate nomograms (c-index: 0.5900 and 0.5989, respectively) to test the probability to achieve CC at SCS. Additionally, we built a nomogram using both the aforementioned criteria (c-index: 0.5857). Conclusion: The AGO and MSK criteria help identifying patients deserving SCS. However, these criteria might be strict, thus prohibiting a beneficial treatment in patients who do not met these criteria. Further studies are needed to clarify factors predicting CC at SCS. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is the most common sexually transmitted disease, worldwide. Primary prevention thorough vaccination si able to reduce the burden of HPV-related lesions. Ten years ago the Food and drug Administration (FDA) approved the first vaccine against HPV. In the last decades, growing data on safety and effectiveness have been collected. In the present review we report the current knowledge on vaccine against HPV, highlighting the current value and prospective regarding the widespread diffusion of HPV vaccines. The role of emerging therapeutic vaccines is reviewed. [ABSTRACT FROM AUTHOR]

Objective To estimate the prevalence of lymph node involvement in early-stage epithelial ovarian cancer in order to assess the prognostic value of lymph node dissection. Methods Data of consecutive patients undergoing staging for early-stage epithelial ovarian cancer were retrospectively evaluated. Logistic regression and a nomogram-based analysis were used to assess the risk of lymph node involvement. Results Overall, 290 patients were included. All patients had lymph node dissection including pelvic and para-aortic lymphadenectomy. Forty-two (14.5%) patients were upstaged due to lymph node metastatic disease. Pelvic and para-aortic nodal metastases were observed in 22 (7.6%) and 42 (14.5%) patients. Lymph node involvement was observed in 18/95 (18.9%), 1/37 (2.7%), 4/29 (13.8%), 11/63 (17.4%), 3/41 (7.3%) and 5/24 (20.8%) patients with high-grade serous, low-grade-serous, endometrioid G1, endometrioid G2&3, clear cell and undifferentiated, histology, respectively ( p = 0.12, Chi-square test). We observed that high-grade serous histology was associated with an increased risk of pelvic node involvement; while, histology rather than low-grade serous and bilateral tumors were independently associated with para-aortic lymph node involvement ( p < 0.05). Nomograms displaying the risk of nodal involvement in the pelvic and para-aortic areas were built. High-grade serous histology and bilateral tumors are the main characteristics suggesting lymph node positivity. Conclusions Our data suggested that high-grade serous and bilateral early-stage epithelial ovarian cancer are at high risk of having disease harboring in the lymphatic tissues of both pelvic and para-aortic area. After receiving external validation, our data will help to identify patients deserving comprehensive retroperitoneal staging. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the outcomes of women diagnosed with high-risk HPV without cytology evidence of cervical dysplasia.Methods: The present retrospective observational study enrolled consecutive women aged at least 18 years diagnosed with high-risk HPV types with negative cytology results at the National Cancer Institute, Milan, Italy, between January 1, 2005, and December 31, 2015. The development of cervical intraepithelial neoplasia (CIN) was assessed.Results: There were 212 patients with high-risk HPV infections with negative cytology included in the analysis. After a mean ± SD follow-up period of 48 ± 33 months, 65 (30.7%) and 26 (12.3%) patients had developed cytologic or histologic cervical dysplasia (low-grade squamous intraepithelial lesion [LSIL]/CIN1+) and high-grade cervical dysplasia (CIN2+), respectively. No patients had invasive cancer. No correlations were observed between type-specific HPV infections and LSIL/CIN1+ and CIN2+. HPV persistence correlated with both LSIL/CIN1+ (P<0.001) and CIN2+ (P<0.001) in univariate analyses; a 6-month increase in HPV persistence was associated with increased risk of developing LSIL/CIN1+ (P=0.010) and CIN2+ (P=0.012) in multivariate analyses.Conclusions: Regardless of cytology findings, patients diagnosed with high-risk HPV types should receive strict colposcopy follow-up, particularly with persistent HPV infections. Further prospective studies are needed to defined optimal surveillance strategies for these patients. [ABSTRACT FROM AUTHOR]