The first real-world study on the role of carbon ion radiotherapy for oligo-metastatic, persistent, or recurrent (MPR) ovarian/fallopian tube cancer.

Introduction: In the multidisciplinary management of oligometastatic, persistent, or recurrent (MPR) ovarian cancer, radiotherapy (RT) is becoming a more and more worthwhile treatment to potentially improve the chronicity of the disease. Particle beam RT has proved to be effective in several gynecological malignancies, but so far no data are available for ovarian cancer. Material and Methods: This is a real-world, retrospective, bi-institutional, single-arm study aimed to assess the effectiveness and the safety of carbon ion RT (CIRT) in this setting. The co-first endpoints are 1-year and 2-year actuarial local control (LC) rates and the objective response rate (ORR) defined on a "per lesion" basis. The secondary endpoint was toxicity. Actuarial outcomes were evaluated using the Kaplan-Meier method while potential predictors were explored using the Log-rank test. Bi-variable logistic regression was employed in the analysis of factors predicting the complete response on a per-lesion basis. Results: 26 patients accounting for a total of 36 lesions underwent CIRT with a total median dose of 52.8 Gy[RBE] (range: 39-64 Gy[RBE]). Five patients received CIRT for re-irradiation. No concomitant systemic therapies were administered during CIRT. Within 12 months after the treatment, 17 lesions (47 %) achieved complete response while 18 (50 %) obtained a partial response with an ORR of 97 %. The achievement of a complete response is related to the dose per fraction (>4.2 Gy[RBE], p = 0.04) and total dose (>52,8 Gy[RBE], p = 0.05). The 1-year LC was 92 % and the 2-year LC was 83 %, according to the achievement of a CR (p = 0.007) and GTV ≤ 14 cm3 (p = 0.024). No grade > 3 toxicities were recorded both in naïve and re-irradiated patients. PARP-i and anti-VEGF seemed not to exacerbate the risk of severe toxicities. Conclusions: CIRT was effective and safe in MPR ovarian cancers, even in the case of re-irradiation. Largest cohort studies and longer follow-up are needed to confirm these data.

Evaluation of two alternative non-alcohol-based media for the suspension of self-collected vaginal swabs for HPV testing in cervical cancer screening.

The introduction of Human Papillomavirus (HPV) testing in cervical cancer screening enhanced the opportunity to introduce self-collection as an innovative approach to improve coverage rates. Validation and standardization of the pre-analytical and analytical procedures are crucial for the quality assurance of HPV tests on self-collected samples. This study evaluated the analytical performance and the stability of self-collected vaginal samples resuspended in 5 mL of two non-alcohol-based media, eNat® and MSwab® compared to a professionally collected cervical sample, resuspended in 20 mL ThinPrep®, for the detection of high-risk HPV (hrHPV). The impact of the suspension volumes on analytical performance was also evaluated (2 and 5 ml). A good analytical concordance in hrHPV detection in cervical and vaginal self-collected swabs suspended in 5 ml of both non-alcohol-based media was demonstrated (eNat®: 91.2 %, k = 0.821; MSwab®: 91.4 %; k = 0.798). A similar analytical performance was found for samples resuspended in 2 mL (eNat®: 92.9 %, k = 0.811; MSwab®: 92.9 %, k = 0.811) compared to cervical samples. Good nucleic acid stability was demonstrated for vaginal samples stored at 20-25 °C and 37 °C for up to 4 weeks. Results of this preliminary study support the introduction of these media for vaginal self-sampling-based prevention programs. Nevertheless, further research is necessary to evaluate clinical accuracy in larger settings.

Low-Volume Metastases in Apparent Early-Stage Endometrial Cancer: Prevalence, Clinical Significance, and Future Perspectives.

Endometrial cancer (EC) is the most diagnosed gynecologic malignancy, and its incidence and mortality are increasing. The prognosis is highly dependent on the disease spread. Surgical staging includes retroperitoneal evaluation to detect potential lymph node metastases. In recent years, systematic lymphadenectomy has been replaced by sentinel lymph node (SLN) biopsy and ultrastaging, allowing for the detection of macrometastases, micrometastases, and isolated tumor cells (ITCs). Micrometastases and ITCs have been grouped as low-volume metastases (LVM). The reported prevalence of LVM in studies enrolling more than one thousand patients with apparent early-stage EC ranges from 1.9% to 10.2%. Different rates of LVM are observed when patients are stratified according to disease characteristics and their risk of recurrence. Patients with EC at low risk for recurrence have low rates of LVM, while intermediate- and high-risk patients have a higher likelihood of being diagnosed with nodal metastases, including LVM. Macro- and micrometastases increase the risk of recurrence and cause upstaging, while the clinical significance of ITCs is still uncertain. A recent meta-analysis found that patients with LVM have a higher relative risk of recurrence [1.34 (95% CI: 1.07-1.67)], regardless of adjuvant treatment. In a retrospective study on patients with low-risk EC and no adjuvant treatment, those with ITCs had worse recurrence-free survival compared to node-negative patients (85.1%; CI 95% 73.8-98.2 versus 90.2%; CI 95% 84.9-95.8). However, a difference was no longer observed after the exclusion of cases with lymphovascular space invasion. There is no consensus on adjuvant treatment in ITC patients at otherwise low risk, and their recurrence rate is low. Multi-institutional, prospective studies are warranted to evaluate the clinical significance of ITCs in low-risk patients. Further stratification of patients, considering histopathological and molecular features of the disease, may clarify the role of LVM and especially ITCs in specific contexts.

Low-Volume Metastases in Cervical Cancer: Does Size Matter?

The implementation of sentinel lymph node (SLN) biopsy is changing the scenario in the surgical treatment of early-stage cervical cancer, and the oncologic safety of replacing bilateral pelvic lymphadenectomy with SLN biopsy is currently under investigation. Part of the undisputed value of SLN biopsy is its diagnostic accuracy in detecting low-volume metastases (LVM) via pathologic ultrastaging. In early-stage cervical cancer, the reported incidence of LVM ranges from 4 to 20%. The prognostic impact and the role of adjuvant treatment in patients with LVM is still unclear. Some non-prespecified analyses in prospective studies showed no impact on the oncologic outcomes compared to node-negative disease. However, the heterogeneity of the studies, the differences in the disease stage and the use of adjuvant treatment, and the concomitant pelvic lymphadenectomy (PLND) make reaching any conclusions on this topic hard. Current guidelines suggest considering micrometastases (MIC) as a node-positive disease, while considering isolated tumor cells (ITC) as a node-negative disease with a low level of evidence. This review aims to highlight the unanswered questions about the definition, identification, and prognostic and therapeutic roles of LVM and to underline the present and future challenges we are facing. We hope that this review will guide further research, giving robust evidence on LVM and their impacts on clinical practice.

Outcome of patients with stage I immature teratoma after surveillance or adjuvant chemotherapy.

Objective: Immature teratomas are rare malignant ovarian germ cell tumours, typically diagnosed in young women, where fertility-sparing surgery is the treatment of choice. The role of adjuvant chemotherapy in stage I disease remains controversial. We evaluated the impact of surveillance versus chemotherapy on the recurrence rate in stage I immature teratomas. Methods: We collected a single centre retrospective series of patients with stage I immature teratomas treated with fertility-sparing surgery at San Gerardo Hospital, Monza, Italy, between 1980 and 2019. Potential risk factors for recurrence were investigated by multivariate logistic regression. Results: Of the 74 patients included, 12% (9/74) received chemotherapy, while 88% (65/74) underwent surveillance. Median follow-up was 188 months. No difference in recurrence was found in stage IA/IB and IC immature teratomas [10% (6/60) vs. 28.6% (4/14) (P=0.087)], grade 1, grade 2, and grade 3 [7.1% (2/28) vs. 14.3% (4/28) vs. 22.2% (4/18) (p=0.39)], and surveillance versus chemotherapy groups [13.9% (9/65) vs. 11.1% (1/9)) (p = 1.00)]. In univariate analysis, the postoperative approach had no impact on recurrence. The 5-year disease-free survival was 87% and 90% in the surveillance and chemotherapy groups, respectively; the overall survival was 100% in both cohorts. Conclusions: Our results support the feasibility of surveillance in stage I immature teratomas. Adjuvant chemotherapy may be reserved for relapses. However, the potential benefit of chemotherapy should be discussed, especially for high-risk tumours. Prospective series are warranted to confirm our findings. What is already known on this topic: To date, no consensus has been reached regarding the role of adjuvant chemotherapy in stage I immature teratomas of the ovary. Some studies suggest that only surveillance is an acceptable choice. However, guidelines are not conclusive on this topic. What this study adds: No difference in terms of recurrence was observed between the surveillance and the adjuvant chemotherapy group. All patients who relapsed were successfully cured with no disease-related deaths. How this study might affect research practice or policy: Adjuvant chemotherapy should be appropriately discussed with patients. However, it may be reserved for relapse according to our data.

Association between Physical Activity and Menstrual Cycle Disorders in Young Athletes.

Our study aims to evaluate clinical predictors of menstrual cycle disorders in female athletes who compete in running disciplines. This is a prospective observational study. Women were recruited between January and May 2022. Fifty-three patients were enrolled and completed a questionnaire about menstrual cycle, physical activity, and food habit characteristics. Of the women in our population, 39.6% had menstrual irregularities and reported a significantly higher number of kilometers run per week (67 vs. 35, p:0.02). The number of kilometers run per week was associated with menstrual irregularities (for 10 km, OR 1.35; IC95% 1.05-1.73; p: 0.02) after adjusting for BMI, age, level of sport and caloric intake. The variable of "km run per week" appeared as a diagnostic indicator of irregular menstrual cycle with statistical significance (AUC ROC curve 0.71, IC95% 0.54-0.86, p-value=0.01) and the cut-off of 65 km run per week is a good indicator of the presence of irregular menstrual cycle (sensitivity (SE) and specificity (SP) of 55% and 81.48%). Menstrual cycle disorders are very frequent in female athletes, and the variable of km run per week may play a role in screening endurance athletes at high risk for these disorders.

SUrgical Access and Pattern of Recurrence of Endometrial Cancer: The SUPeR Study, a Multicenter Retrospective Observational Study.

STUDY OBJECTIVE: To evaluate recurrence rate and pattern in apparently early-stage endometrial cancer (EC) treated with minimally invasive surgery (MIS) and compare it to the "historical" populations treated by laparotomy. Secondary outcomes were to establish if, among MIS recurrent patients, intermediate-high/high-risk patients presented the same recurrence pattern compared to those at low/intermediate-risk and to evaluate time to first recurrence (TTR) of the study population. DESIGN: Multicenter retrospective observational study. SETTING: Five Italian Gynecologic Oncology referral centers. PATIENTS: All patients with proven recurrence of apparently early-stage EC treated with MIS from January 2017 to June 2022 . The laparotomic historical cohort was obtained from Laparoscopy Compared With Laparotomy for Comprehensive Surgical Staging of Uterine Cancer: Gynecologic Oncology Group Study (LAP2) and Laparoscopic Approach to Cancer of the Endometrium trials. INTERVENTIONS: Evaluation of recurrence rate and pattern. MEASUREMENTS AND MAIN RESULTS: Seventy-seven recurrences occurred on the total of 1028 patients treated with MIS for apparently early-stage EC during a median follow-up time of 36 months. The rate of recurrence in our cohort did not differ significantly from the rate of the historical cohort (7.4% vs 7.9%, odds ratio 0.9395, 95% CI 0.6901-1.2792). No significant differences were noticed for local, abdominal, nodal, and multiple site recurrence patterns; distant site recurrence appeared more likely in patients from the historical cohort. Postoperative low/intermediate risk patients had a higher likelihood of local recurrence compared to intermediate-high/high risk patients. Mean TTR was 19 months. No significant difference of TTR was observed for each pattern of recurrence compared to others. CONCLUSION: MIS appears to be safe for the treatment of early-stage EC. We did not identify any recurrence pattern specifically associated with MIS in early-stage EC.

Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study.

OBJECTIVE: The prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of isolated tumor cells in patients with low risk endometrial cancer who underwent SLN biopsy and did not receive adjuvant therapy. Outcomes were compared with node negative patients. METHODS: Patients with SLNs-isolated tumor cells between 2013 and 2019 were identified from 15 centers worldwide, while SLN negative patients were identified from Mayo Clinic, Rochester, between 2013 and 2018. Only low risk patients (stage IA, endometrioid histology, grade 1 or 2) who did not receive any adjuvant therapy were included. Primary outcomes were recurrence free, non-vaginal recurrence free, and overall survival, evaluated with Kaplan-Meier methods. RESULTS: 494 patients (42 isolated tumor cells and 452 node negative) were included. There were 21 (4.3%) recurrences (5 SLNs-isolated tumor cells, 16 node negative); recurrence was vaginal in six patients (1 isolated tumor cells, 5 node negative), and non-vaginal in 15 (4 isolated tumor cells, 11 node negative). Median follow-up among those without recurrence was 2.3 years (interquartile range (IQR) 1.1-3.0) and 2.6 years (IQR 0.6-4.2) in the SLN-isolated tumor cell and node negative patients, respectively. The presence of SLNs-isolated tumor cells, lymphovascular space invasion, and International Federation of Obstetrics and Gynecology (FIGO) grade 2 were significant risk factors for recurrence on univariate analysis. SLN-isolated tumor cell patients had worse recurrence free survival (p<0.01) and non-vaginal recurrence free survival (p<0.01) compared with node negative patients. Similar results were observed in the subgroup of patients without lymphovascular space invasion (n=480). There was no difference in overall survival between the two cohorts in the full sample and the subset excluding patients with lymphovascular space invasion. CONCLUSIONS: Patients with SLNs-isolated tumor cells and low risk profile, without adjuvant therapy, had a significantly worse recurrence free survival compared with node negative patients with similar risk factors, after adjusting for grade and excluding patients with lymphovascular space invasion. However, the presence of SLNs-isolated tumor cells was not associated with worse overall survival.

Genomic instability analysis in DNA from Papanicolaou test provides proof-of-principle early diagnosis of high-grade serous ovarian cancer.

Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples were taken at different time points (from 1 month to 13.5 years before diagnosis) from 113 presymptomatic women who were subsequently diagnosed with HGSOC (pre-HGSOC) and from 77 healthy women. Genome instability was detected through low-pass whole-genome sequencing of DNA derived from Pap test samples in terms of copy number profile abnormality (CPA). CPA values of DNA extracted from Pap test samples from pre-HGSOC women were substantially higher than those in samples from healthy women. Consistently with the longitudinal analysis of clonal pathogenic TP53 mutations, this assay could detect HGSOC presence up to 9 years before diagnosis. This finding confirms the continual shedding of tumor cells from fimbriae toward the endocervical canal, suggesting a new path for the early diagnosis of HGSOC. We integrated the CPA score into the EVA (early ovarian cancer) test, the sensitivity of which was 75% (95% CI, 64.97 to 85.79), the specificity 96% (95% CI, 88.35 to 100.00), and the accuracy 81%. This proof-of-principle study indicates that the early diagnosis of HGSOC is feasible through the analysis of genomic alterations in DNA from endocervical smears.

Radical Hysterectomy in Early-Stage Cervical Cancer: Abandoning the One-Fits-All Concept.

Two pillars in modern oncology are treatment personalization and the reduction in treatment-related morbidity. For decades, the one-fits-all concept of radical hysterectomy has been the cornerstone of early-stage cervical cancer surgical treatment. However, no agreement exists about the prevalent method of parametrial invasion, and the literature is conflicting regarding the extent of parametrectomy needed to achieve adequate surgical radicality. Therefore, authors started investigating if less radical surgery was feasible and oncologically safe in these patients. Two historical randomized controlled trials (RCTs) compared classical radical hysterectomy (RH) to modified RH and simple hysterectomy. Less radical surgery showed a drastic reduction in morbidity without jeopardizing oncological outcomes. However, given the high frequency of adjuvant radiotherapy, the real impact of reduced radicality could not be estimated. Subsequently, several retrospective studies investigated the chance of tailoring parametrectomy according to the tumor's characteristics. Parametrial involvement was shown to be negligible in early-stage low-risk cervical cancer. An observational prospective study and a phase II exploratory RCT have recently confirmed the feasibility and safety of simple hysterectomy in this subgroup of patients. The preliminary results of a large prospective RCT comparing simple vs. radical surgery for early-stage low-risk cervical cancer show strong probability of giving a final answer on this topic.

Accuracy of Human Papillomavirus (HPV) Testing on Urine and Vaginal Self-Samples Compared to Clinician-Collected Cervical Sample in Women Referred to Colposcopy.

In the context of cervical cancer prevention, where human papillomavirus (HPV) infection is pivotal, HPV testing is replacing Pap Smear in primary screening. This transition offers an opportunity for integrating self-sampling to enhance coverage. We evaluated the accuracy of HPV testing using self-collected urine and vaginal samples, comparing them to physician-collected cervical swabs. From a cohort of 245 women with abnormal cytology, we collected self-sampled vaginal, urine, and clinician-administered cervical specimens. Employing Anyplex™II HPV28 assay, outcomes revealed HPV positivity rates of 75.1% (cervical), 78.4% (vaginal), and 77.1% (urine). Significant, hr-HPV detection concordance was observed between self-taken cervical samples and clinical counterparts (k = 0.898 for vaginal; k = 0.715 for urine). This study extends beyond accuracy, highlighting self-collected sample efficacy in detecting high-grade cervical lesions. The insight underscores self-sampling's role in bolstering participation and aligns with WHO's goal to eliminate cervical cancer by 2030.

Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994.

PURPOSE: This multicenter trial by the European Organisation for Research and Treatment of Cancer Gynecological Cancer Group was motivated by conflicting evidence on the value of neoadjuvant chemotherapy before surgery compared with concomitant chemoradiotherapy (CCRT) in stage IB2-IIB cervical carcinoma. METHODS: Between May 2002 and January 2014, 626 patients with International Federation of Gynecology and Obstetrics stage IB2-IIb were randomly assigned between neoadjuvant chemotherapy followed by surgery (NACT-S; n = 314) and standard CCRT (n = 312). The primary end point was 5-year overall survival (OS) rate. Secondary end points were progression-free survival, OS, toxicity, and health-related quality of life (HRQOL). RESULTS: After a median follow-up of 8.7 years, 198 patients (31.6%) died. Age, stage, and cell type were balanced in both arms. Protocol treatment was completed in 223 of 314 (71%) patients in NACT-S and 257 of 312(82%) in CCRT arms. Main reasons for incomplete protocol treatment were toxicity (30 of 314; 9.6%) and progressive disease (21 of 314; 6.7%) in the NACT-S arm and toxicity (23 of 312; 7.4%) and patient refusal (13 of 312; 4.2%) in the CCRT arm. Additional radiotherapy after completed NACT-S was given to 107 patients (48%), and additional surgery to 20 patients (8%) after completed CCRT. Short-term adverse events (AEs) ≥grade 3 occurred more frequently with NACT-S (41% v 23%), and long-term AEs ≥grade 3 more often with CCRT (21% v 15%). The 5-year OS was not significantly different between NACT-S (72%; 95% CI, 66 to 77) and CCRT (76%; 95% CI, 70 to 80). CONCLUSION: This trial failed to demonstrate superiority in favor of the NACT-S arm but resulted in acceptable morbidity and HRQOL in both arms.

An Overview of PARP Resistance in Ovarian Cancer from a Molecular and Clinical Perspective.

Epithelial ovarian cancer (EOC), a primarily high-grade serous carcinoma (HGSOC), is one of the major causes of high death-to-incidence ratios of all gynecological cancers. Cytoreductive surgery and platinum-based chemotherapy represent the main treatments for this aggressive disease. Molecular characterization of HGSOC has revealed that up to 50% of cases have a deficiency in the homologous recombination repair (HRR) system, which makes these tumors sensitive to poly ADP-ribose inhibitors (PARP-is). However, drug resistance often occurs and overcoming it represents a big challenge. A number of strategies are under investigation, with the most promising being combinations of PARP-is with antiangiogenetic agents and immune checkpoint inhibitors. Moreover, new drugs targeting different pathways, including the ATR-CHK1-WEE1, the PI3K-AKT and the RAS/RAF/MEK, are under development both in phase I and II-III clinical trials. Nevertheless, there is still a long way to go, and the next few years promise to be exciting.

Survival associated with extent of radical hysterectomy in early-stage cervical cancer: a subanalysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study.

BACKGROUND: International guidelines recommend tailoring the radicality of hysterectomy according to the known preoperative tumor characteristics in patients with early-stage cervical cancer. OBJECTIVE: This study aimed to assess whether increased radicality had an effect on 5-year disease-free survival in patients with early-stage cervical cancer undergoing radical hysterectomy. The secondary aims were 5-year overall survival and pattern of recurrence. STUDY DESIGN: This was an international, multicenter, retrospective study from the Surveillance in Cervical CANcer (SCCAN) collaborative cohort. Patients with the International Federation of Gynecology and Obstetrics 2009 stage IB1 and IIA1 who underwent open type B/C1/C2 radical hysterectomy according to Querleu-Morrow classification between January 2007 and December 2016, who did not undergo neoadjuvant chemotherapy and who had negative lymph nodes and free surgical margins at final histology, were included. Descriptive statistics and survival analyses were performed. Patients were stratified according to pathologic tumor diameter. Propensity score match analysis was performed to balance baseline characteristics in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy. RESULTS: A total of 1257 patients were included. Of note, 883 patients (70.2%) underwent nerve-sparing radical hysterectomy, and 374 patients (29.8%) underwent non-nerve-sparing radical hysterectomy. Baseline differences between the study groups were found for tumor stage and diameter (higher use of non-nerve-sparing radical hysterectomy for tumors >2 cm or with vaginal involvement; P<.0001). The use of adjuvant therapy in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy was 27.3% vs 28.6%, respectively (P=.63). Five-year disease-free survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 90.1% (95% confidence interval, 87.9-92.2) vs 93.8% (95% confidence interval, 91.1-96.5), respectively (P=.047). Non-nerve-sparing radical hysterectomy was independently associated with better disease-free survival at multivariable analysis performed on the entire cohort (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P=.004). Furthermore, 5-year overall survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 95.7% (95% confidence interval, 94.1-97.2) vs non-nerve-sparing 96.5% (95% confidence interval, 94.3-98.7), respectively (P=.78). In patients with a tumor diameter ≤20 mm, 5-year disease-free survival was 94.7% in nerve-sparing radical hysterectomy vs 96.2% in non-nerve-sparing radical hysterectomy (P=.22). In patients with tumors between 21 and 40 mm, 5-year disease-free survival was 90.3% in non-nerve-sparing radical hysterectomy vs 83.1% in nerve-sparing radical hysterectomy (P=.016) (no significant difference in the rate of adjuvant treatment in this subgroup, P=.47). This was confirmed after propensity match score analysis (balancing the 2 study groups). The pattern of recurrence in the propensity-matched population did not demonstrate any difference (P=.70). CONCLUSION: For tumors ≤20 mm, no survival difference was found with more radical hysterectomy. For tumors between 21 and 40 mm, a more radical hysterectomy was associated with improved 5-year disease-free survival. No difference in the pattern of recurrence according to the extent of radicality was observed. Non-nerve-sparing radical hysterectomy was associated with better 5-year disease-free survival than nerve-sparing radical hysterectomy after propensity score match analysis.

Colposcopy Accuracy and Diagnostic Performance: A Quality Control and Quality Assurance Survey in Italian Tertiary-Level Teaching and Academic Institutions-The Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV).

Quality Control (QC) and Quality Assurance (QA) principles are essential for effective cervical cancer prevention. Being a crucial diagnostic step, colposcopy's sensitivity and specificity improvements are strongly advocated worldwide since inter- and intra-observer differences are the main limiting factors. The objective of the present study was the evaluation of colposcopy accuracy through the results of a QC/QA assessment from a survey in Italian tertiary-level academic and teaching hospitals. A web-based, user-friendly platform based on 100 colposcopic digital images was forwarded to colposcopists with different levels of experience. Seventy-three participants were asked to identify colposcopic patterns, provide personal impressions, and indicate the correct clinical practice. The data were correlated with a panel of experts' evaluation and with the clinical/pathological data of the cases. Overall sensitivity and specificity with the threshold of CIN2+ accounted for 73.7% and 87.7%, respectively, with minor differences between senior and junior candidates. Identification and interpretation of colposcopic patterns showed full agreement with the experts' panel, ranging from 50% to 82%, in some instances with better results from junior colposcopists. Colposcopic impressions correlated with a 20% underestimation of CIN2+ lesions, with no differences linked to level of experience. Our results demonstrate the good diagnostic performance of colposcopy and the need for improving accuracy through QC assessments and adhesion to standard requirements and recommendations.

Consensus statements and treatment algorithm to guide clinicians in the selection of maintenance therapy for patients with newly diagnosed, advanced ovarian carcinoma: Results of a Delphi study.

INTRODUCTION: Standard treatment of newly diagnosed, advanced ovarian carcinoma (OC) consists of cytoreductive surgery followed by platinum-based chemotherapy with or without bevacizumab. Maintenance therapy with PARP inhibitors and olaparib-bevacizumab has recently shown to significantly improve progression-free survival in the first-line setting. Some practical aspects of maintenance therapy, however, are still poorly defined. AIM OF THE STUDY: To provide guidance to clinicians in the selection of maintenance therapy for newly diagnosed, advanced ovarian carcinoma. METHODS: A board of six gynecologic oncologists with expertise in the treatment of OC in Italy convened to address issues related to the new options for maintenance treatment. Based on scientific evidences, the board produced practice-oriented statements. Consensus was reached via a modified Delphi study that involved a panel of 22 experts from across Italy. RESULTS: Twenty-seven evidence- and consensus-based statements are presented, covering the following areas of interest: use of biomarkers (BRCA mutations and presence of homologous recombination deficiency); timing and outcomes of surgery; selection of patients eligible for bevacizumab; definition of response to treatment; toxicity and contraindications; evidence of synergy of bevacizumab plus PARP inhibitor. Two treatment algorithms are also included, for selecting maintenance therapy based on timing and outcomes of surgery, response to platinum-based chemotherapy and biomarker status. A score for the assessment of response to chemotherapy is proposed, but its validation is ongoing. CONCLUSIONS: We provide here consensus statements and treatment algorithms to guide clinicians in the selection of appropriate and personalized maintenance therapy in the first-line setting of advanced OC management.

The Risk of Recurrence in Endometrial Cancer Patients with Low-Volume Metastasis in the Sentinel Lymph Nodes: A Retrospective Multi-Institutional Study.

The aim of this study was to assess the impact of low-volume metastasis (LVM) on disease-free survival (DFS) in women with apparent early-stage endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping. Patients with pre-operative early-stage EC were retrospectively collected from an international collaboration including 13 referring institutions. A total of 1428 patients were included in this analysis. One hundred and eighty-six patients (13%) had lymph node involvement. Fifty-nine percent of positive SLN exhibited micrometastases, 26.9% micrometastases, and 14% isolated tumor cells. Seventeen patients with positive lymph nodes did not receive any adjuvant therapy. At a median follow-up of 33.3 months, the disease had recurred in 114 women (8%). Patients with micrometastases in the lymph nodes had a worse prognosis of disease-free survival compared to patients with negative nodes or LVM. The rate of recurrence was significantly higher for women with micrometastases than those with low-volume metastases (HR = 2.61; p = 0.01). The administration of adjuvant treatment in patients with LVM, without uterine risk factors, remains a matter of debate and requires further evaluation.

Hysterectomy alone vs. hysterectomy plus sentinel node mapping in endometrial cancer: Perioperative and long-term results from a propensity-score based study.

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.

Evaluation of Human Papilloma Virus (HPV) Genotyping and Viral Load Determination as Diagnostic Biomarkers of Cervical Cancer Risk.

HPV testing in cervical cancer screening programs offers the possibility of introducing molecular standardized biomarkers for the triage of HPV-positive women. This study aimed to evaluate the role of HPV genotyping and viral load as possible diagnostic biomarkers of high-grade cervical lesions (CIN2+) by performing a preliminary evaluation of a new HPV test. Cervical specimens were obtained from 200 women referred for a colposcopy. Samples were tested using both Anyplex™ II HR-HPV as well as OncoPredict HPV® Screening (SCR) and quantitative typing (QT). Using a cycle threshold cutoff (Ct) of 36.8 for the SCR assay and 1.27 log10 (viral copies/104 cells) for the QT assay, relative clinical sensitivity for CIN2+ and relative clinical specificity for CIN2- as compared to Anyplex™ II HR-HPV were, respectively, 0.92 and 1.00 for SCR and 1.35 and 1.24 for QT. The distribution of high-risk HPV (HR-HPV) genotypes (p = 0.009) as well as the viral copy numbers (CIN2-: 3.7 log10 (viral copies/104 human cells); CIN2+: 4.3 log10 (viral copies/104 human cells); p = 0.047) were found to differ in women with high- and low-grade cervical lesions, suggesting a possible role of HPV genotyping and normalized viral load as potential biomarkers to identify women at increased risk of cervical lesions.

Association of Hospital Surgical Volume With Survival in Early-Stage Cervical Cancer Treated With Radical Hysterectomy.

OBJECTIVE: To evaluate the association of number of radical hysterectomies performed per year in each center with disease-free survival and overall survival. METHODS: We conducted an international, multicenter, retrospective study of patients previously included in the Surveillance in Cervical Cancer collaborative studies. Individuals with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB1-IIA1 cervical cancer who underwent radical hysterectomy and had negative lymph nodes at final histology were included. Patients were treated at referral centers for gynecologic oncology according to updated national and international guidelines. Optimal cutoffs for surgical volume were identified using an unadjusted Cox proportional hazard model, with disease-free survival as the outcome and defined as the value that minimizes the P-value of the split in groups in terms of disease-free survival. Propensity score matching was used to create statistically similar cohorts at baseline. RESULTS: A total of 2,157 patients were initially included. The two most significant cutoffs for surgical volume were identified at seven and 17 surgical procedures, dividing the entire cohort into low-volume, middle-volume, and high-volume centers. After propensity score matching, 1,238 patients were analyzed-619 (50.0%) in the high-volume group, 523 (42.2%) in the middle-volume group, and 96 (7.8%) in the low-volume group. Patients who underwent surgery in higher-volume institutions had progressively better 5-year disease-free survival than those who underwent surgery in lower-volume centers (92.3% vs 88.9% vs 83.8%, P=.029). No difference was noted in 5-year overall survival (95.9% vs 97.2% vs 95.2%, P=.70). Cox multivariable regression analysis showed that FIGO stage greater than IB1, presence of lymphovascular space invasion, grade greater than 1, tumor diameter greater than 20 mm, minimally invasive surgical approach, nonsquamous cell carcinoma histology, and lower-volume centers represented independent risk factors for recurrence. CONCLUSION: Surgical volume of centers represented an independent prognostic factor affecting disease-free survival. Increasing number of radical hysterectomies performed in each center every year was associated with improved disease-free survival.