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Objective: To compare outcomes after hysterectomy and hysterectomy plus sentinel node mapping (SNM) in endometrial cancer (EC) patients. Materials and methods: This is a retrospective study, collecting data of EC patients treated between 2006 and 2016 in nine referral centers. Results: The study population included 398 (69.5%) and 174 (30.5%) patients having hysterectomy and hysterectomy plus SNM. As the results of the adoption of a propensity-score matched analysis, we selected two homogeneous cohort of patients (150 having hysterectomy only vs. 150 having hysterectomy plus SNM). The SNM group had a longer operative time, but did not correlate with length of hospital stay and estimated blood loss. Overall severe complication rates were similar between groups (0.7% in the hysterectomy group vs. 1.3% in the hysterectomy plus SNM group; p = 0.561). No lymphatic-specific complication occurred. Overall, 12.6% of patients having SNM were diagnosed with disease harboring in their lymph nodes. Adjuvant therapy administration rate was similar between groups. Considering patients having SNM, 4% of patients received adjuvant therapy on the basis of nodal status alone; all the other patients received adjuvant therapy also on the basis of uterine risk factors. Five-year disease-free (p = 0.720) and overall (p = 0.632) survival was not influenced by surgical approach. Conclusions: Hysterectomy (with or without SNM) is a safe and effective method for managing EC patients. Potentially, these data support the omission of side specific lymphadenectomy in case of unsuccessful mapping. Further evidence is warranted in to confirm the role SNM in the era of molecular/genomic profiling.

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.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

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.

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

Objective: 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). Methods: 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. Results: 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. Conclusions: 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.

Olaparib is currently approved in maintenance treatment of advanced ovarian cancer after response to first-line chemotherapy for breast related cancer antigens (BRCA) mutated patients. The use of this agent is based on data from SOLO1 study that observed a decreased risk of disease progression or death and a median progression-free survival about 36 months longer in case of therapy with olaparib. However, this trial recruited only patients with advanced stage ovarian cancer. The aim of this review is to retrace the available data in order to clarify the potential efficacy and feasibility of olaparib administration in newly diagnosed epithelial ovarian cancer also in early stages.

Background: This randomized phase II study tested the hypothesis that schedule dependent chemo-immunotherapy with oregovomab improves progression free survival (PFS) and overall survival (OS) in optimally resected, Stage III/IV ovarian cancer. Methods: Patients from both academic centers and private practice in the US and Italy with Stage III/IV optimally cytoreduced ovarian cancer were randomized to standard six cycle IV carboplatin-paclitaxel chemotherapy (CP) versus CP plus four immunizations with oregovomab (CPO). A translational assessment of a cellular immune response was the primary endpoint; PFS and OS were measured as secondary endpoints. Findings: 97 patients at thirteen centers were accrued to the protocol, 47 to CPO and 50 to CP. Technical issues led to inconsistent performance of the primary CA125 ELISPOT leading to unevaluable results. At a median follow up of 42 months, PFS and OS outcomes revealed an unexpectedly large treatment effect for CPO relative to CP alone, with median PFS of 41.8 months (95% C.I.: 21.8 - N.E.) for CPO and 12.2 months (10.4–18.6) for CP (p = 0.0027, HR 0.46, CI 0.28–0.7). For OS, the median for CPO has not yet been reached (NE) (45.2-NE) and for CP was 43.2 months (31.8-NE) (p = 0.043, HR 0.35, CI 0.16–0.74). The oregovomab treatment resulted in no change in toxicity profile from CP. Interpretation: The previously identified potential clinical benefit of IV CP when administered with oregovomab was further refined in this randomized phase II study. Increases of PFS and OS of statistically and clinically significant magnitude were evident in this study of a front line chemo-immunotherapy treatment of ovarian cancer.

Ovarian cancer is the fifth most common cause of cancer death in women in Europe. Despite the progress, almost 70% of the patients relapse. The standard treatment is cytoreductive surgery followed by platinum-taxane chemotherapy; in patients with a disseminated disease, one option is neoadjuvant chemotherapy with delayed surgery (ie, interval debulking surgery). The most important change in the last decades involved the schedule treatment and the addition of new drugs to first-line therapy. Because of the pathogenetic role of angiogenesis in solid-tumor growth and metastasis, research has been concentrated on anti-angiogenetic drug. Bevacizumab, the most promising anti-angiogenetic drug, is a humanized monoclonal IgG antibody that targets vascular endothelial growth factor receptor. It was approved on December 23, 2011 by the European Medicines Agency and on June 13, 2018 by the Food and Drug administration as first-line treatment in epithelial ovarian, fallopian tube, or primary peritoneal cancer stage III or IV in combination with carboplatin and paclitaxel. There are still some doubts, regarding the schedule, dosage, duration of the treatment, safety, and tolerability, both in first-line and in neoadjuvant chemotherapy treatments. This review tries to answer clinical practice questions and summarizes the evidence from Phase III studies, emerging data, and ongoing trials.

Background: Endometrial cancer (EC) is one of the most frequent tumors in women. Despite recent advances in treatment approaches, the prognosis in advanced, recurrent, or metastatic disease remains poor. The aim was to provide the clinician with an update, the current status, and the new developments in the management of EC. Based on the new EC molecular classification, we focused on the impact of immune check-point inhibitors. Methods: Pivotal trials, published literature, and conference proceedings were reviewed. PubMed and Scopus databases were searched to select English-language articles. Results: Immune check-point inhibitors are the subject of ongoing studies and their benefit seems to be related to microsatellite instability (MSI) status. Conclusions: Immune check-point inhibitors should be considered a promising treatment option to better personalize therapeutic strategies in EC.

Objective: This meta-analysis investigated the effectiveness of PARP inhibitors (PARPis) as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC), stratifying results based on BRCA mutational status into five different categories: whole population, germ-line BRCA mutated patients, somatic BRCA mutated patients, HRD patients and wild type population. Methods: PubMed, Medline, Scopus, EMBASE and clinicaltrials.gov, as well as meeting proceedings were searched for eligible studies that described RCTs testing the efficacy of PARPis as maintenance treatment in platinum sensitive ROC. Data were extracted independently and analysed using RevMan statistical software version 5.3. Primary end-point was progression free survival (PFS). Results: The analysis confirmed the positive effect of PARPis in patients with platinum sensitive ROC in case of germinal or somatic BRCA mutations. Specifically, HR for PFS was 0.26, 95% CI 0.21–0.31, p < 0.00001 for the mutation of BRCA gene and 0.24, 95%, CI 0.12–0.48, p < 0.0001 for the somatic alteration. In addition, in the HRD population, studies that analysed the efficacy of PARPis reported a PFS improvement with HR 0.34, 95% CI 0.26–0.43, p < 0.00001. Finally, our analysis confirms the role of these drugs in prolonging PFS in the whole population with HR 0.36, 95% CI 0.32–0.42, p < 0.00001, although to a lesser extent, with a significant improvement even in wild type cancers with HR 0.49, 95%, CI 0.41–0.59, p < 0.00001). Conclusions: PARPis are effective regardless of BRCA mutational status. Future investigations are necessary to explore the use of different PARPis as monotherapy, comparing them among each other in terms of efficacy and toxicity, and exploring their potential re-use.

Purpose The purpose of this study was to develop nomograms for predicting the probability of overall survival (OS) and progression-free survival (PFS) in locally advanced cervical cancer treated with neoadjuvant chemotherapy and radical surgery. Materials and Methods Nomograms to predict the 5-year OS rates and the 2-year PFS rates were constructed. Calibration plots were constructed, and concordance indices were calculated. Evaluated variables were body mass index, age, tumor size, tumor histology, grading, lymphovascular space invasion, positive parametria, and positive lymph nodes. Results In total 245 patients with locally advanced cervical cancer who underwent neoadjuvant chemotherapy and radical surgery were included for the construction of the nomogram. The 5-year OS and PFS were 72.6% and 66%, respectively. Tumor size, grading, and parametria status affected the rate of OS, whereas tumor size and positive parametria were the main independent PFS prognostic factors. Conclusion We constructed a nomogram based on clinicopathological features in order to predict 2-year PFS and 5-year OS in locally advanced cervical cancer primarily treated with neoadjuvant chemotherapy followed by radical surgery. This tool might be particularly helpful for assisting in the follow-up of cervical cancer patients who have not undergone concurrent chemoradiotherapy.

Due to substantial improvement in the diagnosis and treatment of gynaecologic cancers, a better understanding of patient care needs to be revised. We reviewed the literature related to fertility preservation strategies in gynaecological cancer and discussed current general management approaches. New technical modalities and patients’ own desire for motherhood should be integral and paramount in the clinical evaluation to significantly contribute to preserving fertility in those women diagnosed with gynaecologic cancers during the reproductive years.

Background: Cutaneous relapse from endometrial cancer is a rare event, and often is part of a plurimetastatic disease with poor prognosis. Besides palliative chemotherapy, no consensus is present in literature about the specific treatment of skin metastases, in particular in order to improve symptoms. Objectives: In this paper the authors present a case of multi-metastatic endometrial cancer patient with also cutaneous metastasis, treated with palliative systemic therapy and electrochemotherapy. In particular the authors will describe the clinical, dermatoscopic, and pathological features of cutaneous metastases and their management. A literature review on cutaneous metastasis from endometrial cancer is also presented. Materials and Methods: A PubMed research was made using the terms "endometrial carcinoma", "skin", "cutaneous", "metastasis", and "spread". Discussion: The present case of unusual localization of skin metastases from endometrial cancer is the second described in the literature. The other known cases of cutaneous metastasis from endometrial cancer are summarized and reviewed. Electrochemotherapy can be proposed as an effective and safe loco-regional therapy for skin metastases, especially in case of multiple lesions. To the present authors' knowledge this is the first case of cutaneous metastases from endometrial cancer treated with electrochemotherapy.

Ovarian endometriomas affect 17 to 44% of women with endometriosis, and are often associated with pelvic pain and infertility. Treatment options include expectant management, medical and/or surgical treatment, and in vitro fertilization and embryo transfer (IVF-ET). The choice of treatment depends mostly on the associated symptoms. In most cases, surgery is the preferred choice, since endometriomas do not respond to medical treatment, which may only treat associated pain. In case of infertility, IVF-ET may be a suitable alternative to surgery, particularly when there is no associated pain. According to the best available scientific evidence, laparoscopic excision of the endometrioma wall should be considered the procedure of choice. Concerns have been raised as to the possibility that surgical excision may damage the ovarian reserve, but recent evidences demonstrate that part of the damage may be due to the presence of the endometrioma itself. Indication to surgical treatment should balance the possible risks of damaging the ovarian reserve with the advantages of surgery in terms of satisfactory pain relief rates and pregnancy rates, and of obtaining tissue specimen for ruling out the rare cases of unexpected ovarian malignancy. A score system to guide the clinician in the decision to perform or withhold surgery is presented.

Background: During the last decades many successful efforts have been made in order to increase life expectancy in ovarian cancer (OC) patients. However, just a few studies have investigated the impact of OC on quality of life (QoL) and sexual function in OC cases during treatment. Objective: The aim of this study was to evaluate the QoL and sexual function of OC patients during chemotherapy (CT). Patients and Methods: Forty-nine subjects were enrolled and filled in the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OV28, Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) questionnaires. The results were evaluated globally and consequently stratified into several groups: single surgery versus multiple surgeries, age ≤48 years versus >48 years, and first-line CT versus multiple lines of CT. Results: Menopause-related symptoms, body image and attitude toward the disease were significantly worse during first-line CT (p = 0.018, p = 0.029 and p = 0.006, respectively). Sexual outcomes resulted in better scores in younger patients in all questionnaires (FSFI: p = 0.001; FSDS: p = 0.048; specific EORTC QLQ-OV28 items: p = 0.022). Scores concerning body image, attitude toward the disease and CT-associated symptoms resulted worse in patients after the first surgery (p = 0.017, p = 0.002 and p = 0.012, respectively). Conclusion: Our study confirms that OC has a detrimental impact on QoL and intimacy, particularly in younger patients, during the first course of CT and after the first cytoreductive surgery.

Ovarian cancer is a most lethal gynecologic tumor. The mainstay treatment is cytoreductive surgery followed by platinumbased chemotherapy. However, a high percentage of patients recur, thus needing multiple treatments with a frequently poor prognosis. In the last two decades, research has focused on the potential of target therapies to improve the survival of patients affected by ovarian cancer. Bevacizumab is one of the most studied target therapies, and it is approved for first- and second-line treatment of advanced epithelial ovarian, fallopian tube, and primary peritoneal tumors. Despite its widespread use with favorable results, controversy regarding patient selection and the best schedule, dosage, and timing of bevacizumab still exists. This review summarizes the state of the art on the use of bevacizumab for ovarian cancer in front-line, recurrence, and neoadjuvant settings. This study focuses on the results of pivotal trials, emerging data, ongoing research, and still unanswered questions about the most adequate dosage of bevacizumab and its potential activity after disease progression or rechallenge in previously treated patients.

Objective: The aim of this study was to evaluate the feasibility and safety of type B radical hysterectomy (RH) in the management of patients affected by locally advanced cervical cancer with favorable prognostic factors (tumor diameter <40 mm, negative nodes, or lymphovascular space involvement) and clinical response to neoadjuvant chemotherapy (NACT). Methods: The data of women undergoing platinum-based NACT followed by RH plus bilateral systematic pelvic lymphadenectomy were collected. Patients undergoing type B RH (Group A) were compared with those undergoing type C RH (Group B); a propensity-matched comparison (1:1) was carried out to minimize selection biases. Postoperative complications were reported and 5-year survival outcomes were assessed using the Kaplan–Meier model. Results: Thirty-six node-negative patients undergoing type B RH (Group A) were compared with 36 propensity-matched patients undergoing type C RH (Group B). The bladder dysfunction rate was significantly lower in Group A compared with Group B (13.9 vs. 69.4 %; p < 0.0001), and no statistically significant difference in 5-year overall survival (OS) and disease-free survival (DFS) between groups was reported (OS 93.0 vs. 96.7 %, p = 0.42; DFS 88.6 and 85.5 %, p = 0.77). Conclusions: Type B RH after NACT in well-selected patients is a safe procedure that upholds the results of type C, reducing operative time and late postoperative morbidity, without detrimental effect on survival. Further prospective trials are warranted to confirm our results on a large scale.

Despite the dramatic improvements achieved in cancer treatment through a better understanding of the tumor biology, ovarian cancer is still characterized by a poor prognosis: most patients diagnosed with this disease will ultimately die from it. In various clinical trials conducted over a time span of two decades, new combinations of conventional chemotherapy regimens have failed to achieve significant improvements in oncologic outcome in ovarian cancer patients. We have now entered an era of “personalized medicine” in which new medications are designed to specifically target molecular pathways involved in carcinogenesis and cancer progression. Encouraging results in different tumor types have been reported, applying an increasing number of target therapies that are still under evaluation. In this setting, one of the most successfully targeted molecular pathways is tumor angiogenesis. Bevacizumab, a monoclonal antibody binding vascular endothelial growth factor (VEGF), has been recently incorporated in the treatment of primary and recurrent ovarian cancer patients after multiple phase III randomized controlled trials have proven its clinical benefit. Based on these positive results, more anti-angiogenic molecules using different mechanisms of action have been developed and are currently under investigation. Among these molecules, the tyrosine kinases inhibitors are probably the most promising ones. Cediranib is a tyrosine kinase inhibitor targeting VEGF receptors that has been tested in various trials with promising results. The aim of this manuscript is to review the current role of cediranib in the treatment of ovarian cancer and to present an overview of the ongoing clinical trials in this setting.

Background: The role of surgery in recurrent ovarian cancer (ROC) is debated. Multiple prospective and retrospective series reported improved survival with optimal secondary surgical cytoreduction, but definitive results from randomized trials are needed. Up to the fourth cytoreductive surgery for recurrent disease in an attempt to improve patients' prognosis has been reported. Case report: We report the first case of multiple ROC in an Italian woman, 50 years old at diagnosis, who underwent 9 cytoreductive surgeries during her 17 years of disease with no serious postoperative complications. Conclusions: Multiple surgeries should not be considered as the standard treatment for ROC. In carefully selected patients, optimal cytoreductive surgery performed by highly specialized gynecologic oncologists might represent a useful tool in adjunction to chemotherapy for the management of ROC.

Aim: Three weeks paclitaxel and carboplatin has been considered the standard of care for primary treatment of ovarian cancer (OC). Whether weekly therapy will further improve the clinical outcomes or not is still unclear. We conducted a metaanalysis to compare the two regimens. Method: Articles were selected with a systematic approach, using PubMed databases. Trials concerning comparison between carboplatin plus weekly paclitaxel (dose-dense regimen) and carboplatin plus paclitaxel every 3 weeks were considered. Outcomes included overall survival (OS), progression free survival (PFS) and severe acute toxicity. Results: Dose-dense regimen was associated with significant improvement of PFS compared with standard schedule, with HR of 0.73 (95% CI 0.61-0.88, p = 0.001). There was no difference in OS between treatment regimens (HR 0.95, 95% CI 0.77- 1.16, p=0.06), as well as in term of severe acute toxicity. Conclusion: Dose-dense regimen is superior to standard schedule in terms of PFS. Further studies are necessary to firmly confirm this evidence in advanced OC treatment.

Background: To analyze the efficacy and toxicity of bevacizumab on survival outcomes in recurrent ovarian cancer. Results: Bevacizumab was associated with significant improvement of PFS and OS compared with standard treatment with HRs of 0.53 (95% CI 0.44 - 0.63; p < 0.00001) and 0.87 (95% CI, 0.77 to 0.99; p = 0.03), respectively. Bevacizumab increased the incidence of G3/G4 hypertension (RR 19.01, 95% CI 7.77 - 46.55; p < 0.00001), proteinuria (RR 17.31, 95% CI 5.42 - 55.25; p < 0.00001), arterial thromboembolic events (ATE) (RR 4.99, 95% CI 1.29 - 19.27; p = 0.02) and bleeding (RR 3.14, 95% CI 1.35 - 7.32; p = 0.008). Materials and Methods: Three randomized phase III trials representing 1502 patients were identified. Pooled hazard ratio (HR), odd ratio (OR), risk ratio (RR) with 95% confidence interval (CI) were calculated using fixed or random effects model. Conclusions: Adding bevacizumab to standard chemotherapy improved ORR, PFS and OS, and it had a higher, but manageable, incidence of toxicities graded 3 to 4.

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum- taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.

Urethral cancer is a rare female urogenital tract cancer. There is scarce literature about it, consisting mostly of small-scale retrospective analyses and case reports and no unanimous consensus on standard treatment is available. We report a case of complete clinical response to chemotherapy of primary carcinoma of the female urethra.

Objective To evaluate the excised specimen with histologic analysis and to assess the antral follicle count (AFC) at follow-up. This is to determine whether excisional surgery for recurrent endometriomas is more harmful to ovarian tissue and to the ovarian reserve than first surgery. Design Prospective controlled study. Setting University hospital. Patient(s) Consecutive patients with pelvic pain and/or infertility undergoing laparoscopic excision of a monolateral ovarian endometrioma for the first time (17 patients) or for recurrence after previous surgery (11 patients). Intervention(s) Laparoscopic excision of ovarian endometrioma and ultrasonographic evaluation 3 months after surgery. Main Outcome Measure(s) Cyst wall histologic evaluation (specimen thickness, presence and morphology of ovarian tissue) and evaluation of ovarian reserve with AFC and ovarian volumes of both the operated and contralateral, nonoperated ovary at follow-up. Result(s) The cyst wall specimen was significantly thicker in the recurrent endometrioma group than in the first surgery group (1.7 ± 0.3 mm vs. 1.1 ± 0.3 mm). Both main components of the cyst specimen (i.e., endometriosis tissue and ovarian tissue) were more represented in the recurrent endometrioma group than in the first surgery group. At sonographic follow-up, the operated ovary had a significantly lower AFC and volume than the contralateral nonoperated ovary in the recurrent endometrioma group, but not in the primary surgery group. Conclusion(s) Surgery for recurrent endometriomas is associated with evidence of a higher loss of ovarian tissue and is more harmful to the ovarian reserve evaluated by AFC and ovarian volume, if compared with endometriomas operated for the first time. Indications to surgery for recurrent endometriomas should be reconsidered with caution.

Ovarian cancer is a multifaceted and genomically complex disease and has emerged as leading cause of death among gynecological malignancies. Gold-standard treatment consisted of cytoreductive surgery and paclitaxel-carboplatin chemotherapy. Recently, promising results of randomized trials have definitively confirmed the importance of angiogenesis in oncogenesis and ovarian cancer behavior, by showing a significant prolongation of progression-free survival with the addiction of an angiogenesis inhibitor to standard treatment in the first and second line setting. Research over the years has sequentially provided a rapidly broadening signaling landscape and many drugs targeting different signaling pathways of angiogenesis have been developed and investigated. Recently accumulating scientific evidence has started to shed light on the efficacy of AMG 386, a new peptibody reported to neutralize the interaction between angiopoietins (Ang1/2) and their Tie2 receptors, thus representing a promising alternative, both in terms of efficacy and toxicity profile and is considerably under investigation. The aim of this review is to summarize the recent researches and clinical progresses of AMG 386 as a novel target agent in ovarian cancer.

Ovarian cancer is the most important cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease. Although surgery and chemotherapy can improve survival rates, it is necessary to integrate alternative strategies to improve the outcomes. Advances in understanding the role of immune system in the pathogenesis of cancer have led to the rapid evolvement of immunotherapy, which might establish a sustained immune system response against recurring cancer cells. Recently, it has emerged that powerful immunologic effector cells may be blocked by inhibitory regulatory pathways controlled by specific molecules often called "immune checkpoints," which turn off the immune system. Similarly, cancer cells are able to use these checkpoints to avoid immune control and rejection. Inhibition of these inhibitory pathways represents a potent strategy in the fight against cancer and is currently under investigation with encouraging results in some cancers, such as melanoma. In ovarian cancer researches are still in an early phase, but with promising results. In this review we will explore the rationale of immunotherapy in ovarian cancer with a special focus on these emerging molecules.

Background: The purpose of this study was to observe the role of secondary cytoreductive surgery in platinum-resistant recurrent ovarian cancer (OC) patients. Methods: We collected data of patients affected by recurrent OC treated between 1995 and 2013. Inclusion criteria were: invasive epithelial OC histologically documented, cytoreductive surgery and platinum-based chemotherapy at first-line treatment with evidence of complete response to treatment, disease-free interval <6 months, and no concomitant neoplasia. Patients considered susceptible of cytoreductive surgery (group A) were compared with a historical series of patients with similar characteristics but not eligible for surgery (group B). Results: Of 122 platinum-resistant patients, 18 met the inclusion criteria for the study and were enrolled. They were compared with a historical series of 18 patients not surgically treated with analogous clinical and pathological features. The most frequent sites of relapse included pelvic and aortic lymph nodes (39 %), peritoneum (33 %), bowel (28 %), and pelvis (22 %). A low rate of intraoperative and postoperative complications was reported. No deaths were recorded. Overall survival was significantly longer in cytoreductive group when compared with the control group (P = 0.035). Median overall survival was 44 months. Estimated 5-year overall survival rates were 57 versus 23.5 % for groups A and B, respectively. Conclusions: Surgery could represent a useful adjunct to chemotherapy in the management of platinum-resistant recurrent OC patients, carefully selected, in highly selected centers. Larger prospective trials are needed to further confirm our experience.

Objective: To assess the efficacy and toxicity profile of dose-dense cisplatin-based neoadjuvant chemotherapy (NACT) followed by radical surgery in patients affected by locally advanced cervical cancer. Methods: Patients affected by carcinoma of the uterine cervix FIGO (International Federation of Obstetrics and Gynecology) stage IB2-IIIB were enrolled into the study. The treatment schedule consisted of 5 cycles of intravenous paclitaxel 60 mg/m2 plus cisplatin 60 mg/m2 every 10 days; patients were then submitted to radical hysterectomy and pelvic lymphadenectomy. Results: From January 2011 to March 2013, 22 patients were enrolled. Median age was 47 (26-83) years. FIGO stages included 1 IIA, 15 IIB, 1 IIIA, and 5 IIIB. Ninety-one percent of patients completed all the 5 planned cycles of NACT. Three patients experienced allergic reactions to paclitaxel. Grade 3-4 hematological toxicity was observed in 18% of cases. In 3 cases, grade 3-4 extra-hematological adverse and life-threatening events were reported (1 ototoxicity, 1 transient ischemic attack, and 1 myocardial infarction). No treatment-related death occurred. The operability rate was 86.4%. The overall response rate was 52.6%: 5 patients (26.3%) experienced clinical complete response, and 5 (26.3%) showed a clinical partial response. Stable disease was observed in 47.4% of patients, with no progressive disease recorded. Pathological response was observed in 57.9% of cases. Six out of 19 (31.6%) patients were submitted to adjuvant treatment. Conclusion: Dose-dense cisplatin-based NACT showed a response rate in approximately half of patients. However, in consideration of the reported extra-hematological toxicity, further studies on and new strategies with dose-dense platinum-based NACT are required to improve outcome in cervical cancer patients.

Several improvements in ovarian cancer treatment have been achieved in recent years, both in surgery and in combination chemotherapy with targeting. However, ovarian tumors remain the women's cancers with highest mortality rates. In this scenario, a pivotal role has been endorsed to the immunological environment and to the immunological mechanisms involved in ovarian cancer behavior. Recent evidence suggests a loss of the critical balance between immune-activating and immune-suppressing mechanisms when oncogenesis and cancer progression occur. Ovarian cancer generates a mechanism to escape the immune system by producing a highly suppressive environment. Immune-activated tumor infiltrating lymphocytes (TILs) in ovarian tumor tissue testify that the immune system is the trigger in this neoplasm. The TIL mileau has been demonstrated to be associated with better prognosis, more chemosensitivity, and more cases of optimal residual tumor achieved during primary cytoreduction. Nowadays, scientists are focusing attention on new immunologically effective tumor biomarkers in order to optimize selection of patients for recruitment in clinical trials and to identify relationships of these biomarkers with responses to immunotherapeutics. Assessing this point of view, TILs might be considered as a potent predictive immunotherapy biomarker.