Validation of MiROvaR, a microRNA-based predictor of early relapse in early stage epithelial ovarian cancer as a new strategy to optimise patients' prognostic assessment.

AIM: Early-stage epithelial ovarian cancer (eEOC) patients have a generally favorable prognosis but unpredictable recurrence. Accurate prediction of risk of relapse is still a major concern, essentially to avoid overtreatment. Our robust tissue-based miRNA signature named MiROvaR, predicting early EOC recurrence in mostly advanced-stage EOC patients, is here challenged in an independent cohort to extend its classifying ability in the early-stage EOC setting. METHODS: We retrospectively selected patients who underwent comprehensive surgical staging at our institution including stages from IA to IIB. miRNA expression profile was analysed in 89 cases and MiROvaR algorithm was applied using the previously validated cut-off for patients' classification. The primary endpoint was progression-free survival (PFS) at 5 years. Complete follow-up time (median = 112 months) was also considered as secondary analysis. RESULTS: MiROvaR was assessable on 87 cases (19 events of disease progression) and classified 68 (78%) low-risk and 19 (22%) high-risk patients. Recurrence rate at primary end-point was 39% for high-risk patients as compared to 9.5% for low-risk ones. Accordingly, their Kaplan-Meier PFS curves were significantly different at both primary and secondary analysis (p = 0.0006 and p = 0.03, respectively). While none of the prominent clinical variables had prognostic relevance, MiROvaR significantly predicted disease recurrence at the 5-year assessment (primary endpoint analysis; HR:5.43, 95%CI:1.82-16.1, p = 0.0024; AUC = 0.78, 95%CI:0.53-0.82) and at complete follow-up time (HR:2.67, 95%CI:1.04-6.8, p = 0.041; AUC:0.68, 95%CI:0.52-0.82). CONCLUSIONS: We validated MiROvaR performance in identifying at diagnosis eEOC patients' at higher risk of early relapse thus enabling selection of the most effective therapeutic approach.

Preoperative frailty assessment in patients undergoing gynecologic oncology surgery: A systematic review.

OBJECTIVE: The aim of the present article was to discuss currently available evidence on the impact of frailty assessment on adverse postoperative outcomes and survival in patients undergoing surgery for gynecological cancer. METHODS: Systematic search of Medline (PubMed) and Embase databases until September 30, 2020. Key inclusion criteria were: (1) randomized or observational studies; (2) patients undergoing non-emergent surgery for gynecological malignancies; (3) preoperative frailty assessment. RESULTS: Through the process of evidence acquisition, twelve studies including 85,672 patients were selected and six tools were evaluable: 30-item frailty index, 40-item frailty index, modified frailty index (mFI), John Hopkins Adjusted Clinical Groups index, Fried frailty criteria, Driver's tool. The prevalence of frailty varied roughly from 6.1% to 60% across different series included. The mFI was the most adopted and predictive instrument. Pooled results underlined that frail patients were more likely to develop 30-day postoperative complications (OR:4.16; 95%CI 1.49-11.65; p:0.007), non-home discharge (OR:4.41; 95%CI: 4.09-4.76; p < 0.001), ICU admission (OR:3.99;3.76-4.24; p < 0.001) than the non-frail counterpart. Additionally, frail patients experienced worse oncologic outcomes (disease-free and overall survivals) than non-frail patients. CONCLUSION: The present systematic review demonstrated that preoperative frailty assessment among gynecologic oncology patients is essential to predict adverse outcomes and tailor a personalized treatment. The mFI appeared as the most used and feasible tool in daily practice, suggesting that tailored therapeutic strategies should be considered for patients with 3 or more frailty-defining items.

Spotlight on the role of human papillomavirus vaccines.

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.

New prophylactics human papilloma virus (HPV) vaccines against cervical cancer.

Human papillomavirus (HPV) is causatively associated with cervical cancer (CC), the fourth most common malignant disease of women worldwide. The introduction of first generation prophylactic HPV vaccines in several national vaccination programmes has substantially decreased the global incidence of HPV cervical infections. Despite the success obtained, the two-licenced bivalent and quadrivalent L1 (the major HPV capsid protein) virus-like particle (VLP)-based vaccines (2vHPV and 4vHPV) present some limitations, such as a virus-type restricted protection, the high cost of the manufacture, and an absence of therapeutic activity on the established lesions. The second-generation prophylactic HPV vaccines, constituted by alternative viral components (such as capsomere or minor capsid HPV L2 protein) or made by more cost-effective strategies of production, are undergoing an intense clinical evaluation. This review aims to offer the reader a complete and updated overview on the HPV vaccination. The authors describe the effectiveness and the limitations of the approved HPV vaccines, and highlight the main characteristics of the new generation vaccines. IMPACT STATEMENT What is already known on this subject? CC is the fourth most common cancer of women in the world. HPV is the etiologic cause of almost all CCs. After being approved by the FDA, the first prophylactic 2vHPV and 4vHPV have been implemented into a routine vaccination schedule around the world, substantially decreasing the incidence of HPV and related-diseases in countries with high coverage rates. Currently, research is focusing on finding innovative and alternative systems to produce and deliver new HPV vaccines, overcoming all of the limitations that have partly restricted the potential benefit of previous vaccines on public health. What do the results of this study add? This narrative review was performed to find all the published studies reporting the efficacy and limitations of 2vHPV and 4vHPV, and evaluating the new HPV vaccines under pre- and clinical investigation. What are the implications of these findings for clinical practice and/or further research? Next generation of HPV vaccines will address many, if not all, of the limitations associated with current vaccines and will represent a step forward in the fight against CC.

Factors Predictive of 90-Day Morbidity, Readmission, and Costs in Patients Undergoing Pelvic Exenteration.

OBJECTIVE: Pelvic exenteration for recurrent gynecological malignancies is characterized by a high rate of severe complications. Factors predictive of morbidity, readmission, and cost were analyzed. METHODS: Data of consecutive patients undergoing pelvic exenteration between January 2007 and December 2016 were prospectively evaluated. RESULTS: Fifty-eight patients were included in the analysis. Anterior, posterior, and total exenterations were executed in 39 (67%), 9 (16%), and 10 (17%) patients, respectively. Ten (15.5%) severe complications occurred: 8 (20.5%), 0 (0%), and 1 (10%) after anterior, posterior, and total exenterations, respectively. Radiotherapy dosage, time between radiotherapy and surgery, and previous administration of chemotherapy did not influence 90-day complications and readmission. At multivariable analysis, albumin levels less than 3.5 g/dL (odds ratio, 16.2 [95% confidence interval, 2.85-92.8]; P = 0.002) and history of deep vein thrombosis (odds ratio, 9.6 [95% confidence interval, 0.93-98.2]; P = 0.057) were associated with 90-day morbidity. Low albumin levels independently correlated with readmission (P = 0.011). The occurrence of 90-day postoperative complications and readmission increased costs of a median of +12,500 and +6000 euros, respectively (P < 0.05). CONCLUSIONS: Preoperative patient selection is a key point for the reduction of postoperative complications after pelvic exenteration. Further prospective studies are warranted to improve patient selection.

Incorporating robotic-assisted surgery for endometrial cancer staging: Analysis of morbidity and costs.

OBJECTIVE: To evaluate how the introduction of robotic-assisted surgery affects treatment-related morbidity and cost of endometrial cancer (EC) staging. METHODS: We retrospectively reviewed the records of consecutive patients with stage I-III EC undergoing surgical staging between 2007 and 2012 at our institution. Costs (from surgery to 30days after surgery) were set based on the Medicare cost-to-charge ratio for each year and inflated to 2014 values. Inverse probability weighting (IPW) was used to decrease the allocation bias when comparing outcomes between surgical groups. RESULTS: We focused our analysis on the 251 EC patients who had robotic-assisted surgery and the 384 who had open staging. During the study period, the use of robotic-assisted surgery increased and open staging decreased (P<0.001). Correcting group imbalances by using IPW methodology, we observed that patients undergoing robotic-assisted staging had a significantly lower postoperative complication rate, lower blood transfusion rate, longer median operating time, shorter median length of stay, and lower readmission rate than patients undergoing open staging (all P<0.001). Overall 30-day costs were similar between the 2 groups, with robotic-assisted surgery having significantly higher median operating room costs ($2820 difference; P<0.001) but lower median room and board costs ($2929 difference; P<0.001) than open surgery. Increasing experience with robotic-assisted staging was significantly associated with a decrease in median operating time (P=0.002) and length of stay (P=0.003). CONCLUSIONS: The implementation of robotic-assisted surgery for EC staging improves patient outcomes. It provides women the benefits of minimally invasive surgery without increasing costs and potentially improves patient turnover.

A critical assessment on the role of sentinel node mapping in endometrial cancer.

Endometrial cancer is the most common gynecologic malignancy in the developed countries. Although the high incidence of this occurrence no consensus, about the role of retroperitoneal staging, still exists. Growing evidence support the safety and efficacy of sentinel lymph node mapping. This technique is emerging as a new standard for endometrial cancer staging procedures. In the present paper, we discuss the role of sentinel lymph node mapping in endometrial cancer, highlighting the most controversies features.

Role of pelvic and para-aortic lymphadenectomy in endometrial cancer: current evidence.

The aim of the present review is to summarize the current evidence on the role of pelvic and para-aortic lymphadenectomy in endometrial cancer. In 1988, the International Federation of Obstetrics and Gynecology recommended surgical staging for endometrial cancer patients. However, 25 years later, the role of lymph node dissection remains controversial. Although the findings of two large independent randomized trials suggested that pelvic lymphadenectomy provides only adjunctive morbidity with no clear influence on survival outcomes, the studies have many pitfalls that limit interpretation of the results. Theoretically, lymphadenectomy may help identify patients with metastatic dissemination, who may benefit from adjuvant therapy, thus reducing radiation-related morbidity. Also, lymphadenectomy may eradicate metastatic disease. Because lymphatic spread is relatively uncommon, our main effort should be directed at identifying patients who may potentially benefit from lymph node dissection, thus reducing the rate of unnecessary treatment and associated morbidity. This review will discuss the role of lymphadenectomy in endometrial cancer, focusing on patient selection, extension of the surgical procedure, postoperative outcomes, quality of life and costs. The need for new surgical studies and efficacious systemic drugs is recommended.