Robert Fruscio

Endometriosis in Carriers of a Pathogenic Variant in BRCA1 or BRCA2: A Descriptive Analysis of a Large Multicentral BRCA Carrier Cohort

Background: Endometriosis affects an estimated 10% of reproductive-aged women and is associated with increased ovarian cancer risk. While BRCA1/2 mutations are established risk factors for ovarian cancer, their association with endometriosis remains unclear. This study aimed to characterize the prevalence and clinical features of endometriosis within a large cohort of BRCA mutation carriers. Methods: A descriptive analysis was conducted using data from a multi-center longitudinal cohort of women with pathogenic BRCA variants. Reproductive history and related factors were collected through self-reported questionnaires and compared. Results: Among 16,950 BRCA carriers, the prevalence of endometriosis was 2.4%. Compared to BRCA carriers without endometriosis, those with endometriosis were more likely to carry a BRCA2 mutation, have post-secondary education, and experience earlier menarche. BRCA carriers with endometriosis had a lower ovarian cancer prevalence than those without (10% vs. 15%, p < 0.001). Conclusions: This is the first study of this scale to report the prevalence of endometriosis among BRCA mutation carriers, which was lower than previously reported in the general population. The association between endometriosis and ovarian cancer does not appear to be generalizable to this population. Further prospective studies are warranted to clarify this association among BRCA mutation carriers.

Postoperative Complications After Cytoreductive Surgery for Advanced Ovarian Carcinoma: A Single-Center Analysis Exploring the Value of the Comprehensive Complication Index and the Predictors of High Complications Burden

Abstract Background The comprehensive complication index (CCI) reflects the overall patient complication burden on a 0–100 scale. This single-institution retrospective analysis explores the accuracy of CCI in describing complications following cytoreductive surgery for advanced high-grade ovarian carcinoma (HGOC) and aims to identify predictive factors of high complication burden. Patients and Methods In total, 304 patients who underwent cytoreductive surgery for FIGO stage IIIA–IVB HGOC at our institution from 2015 to 2023 were analyzed. Each complication’s severity was graded using the Clavien–Dindo classification. The CCI was used to quantify the global complications burden, and patients were stratified into three groups: CCI-low (< 26.2), CCI-intermediate (26 ≤ CCI < 33.7), and CCI-high (≥ 33.7). Results Of the 200 patients (65.8%) with at least one complication, 127 (41.8%) were CCI-low, 32 (10.5%) CCI-intermediate, and 41 (13.5%) CCI-high. Median hospitalization duration (p < 0.0001) and readmission rates (p < 0.0001) correlated with CCI categories, reflecting increased CCI scores with greater surgical complexity, as assessed by the Aletti surgical complexity score (SCS). Univariate analysis showed a significant association between CCI-high and FIGO stage, surgical complexity, diaphragmatic procedures, multiple bowel resections, length of surgery and intraoperative blood loss. Multivariate analysis confirmed FIGO stage (odds ratio [OR] 2.57), multiple bowel resections (OR 5.61), and blood loss (OR 1.93) as independent risk factors for high complication burden. Conclusions The CCI is a good descriptor of postoperative complications in patients undergoing cytoreductive surgery for advanced HGOC by integrating both the severity and number of complications into a single, easily usable, and intuitive quantitative score. FIGO stage, multiple bowel resections, and blood loss—but not surgical timing—are independent predictors of a high complication burden.

Uptake of Risk‐Reducing Salpingo‐Oophorectomy and Gynaecologic Surveillance Among Germline BRCA Pathogenic Variants Carriers

ABSTRACTIntroductionRisk‐reducing salpingo‐oophorectomy (RRSO) is recommended by international guidelines in women with BRCA1/2 germline pathogenic variants (PV) to prevent ovarian cancer. Despite the solid recommendation, women frequently refuse surgery and uptake rates reported in the literature are diverse. This study analyses the uptake rate of RRSO in BRCA 1/2 PV‐carriers referred to a specialised referral centre for first counselling and investigate personal factors linked to the decision.MethodsThis is a single‐centre prospective study of BRCA1/2 PV‐carriers referred for the first counselling to IRCCS Fondazione San Gerardo de’ Tintori (Monza, Italy) between January 2010 and May 2023. Depending on individual characteristics, women were either proposed RRSO or surveillance, consisting of transvaginal ultrasound and CA125 measurement twice per year according to Regional guidelines. Women within the centre have access to a clinical psychologist, a nutritional consult and treatment of menopausal atrophy with diode vaginal laser. The primary endpoint of the study was the uptake rate of RRSO. The secondary objective was to evaluate the main reasons for refusing surgery.ResultsAmong the 287 women included, surgery was proposed to 205 women either at first counselling or during surveillance and was accepted by 197, with an uptake rate of 96.1%. 17.25% of women met the psychologist before or after surgery. The main reasons for refusing RRSO were fear of iatrogenic menopause and childbearing desire.ConclusionThis study shows a high uptake rate of RRSO in BRCA PV‐carriers. We believe that the presence of a dedicated outpatient clinic with a multidisciplinary team contributes decisively to our results. Gynaecologic surveillance, as though not beneficial in terms of oncological prevention, may play a significant role in encouraging women with BRCA PV to opt for risk‐reducing surgery.

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.

Sentinel SENECA risk factors for unsuccessful bi-lateral sentinel lymph node mapping in endometrial cancer

Our study aims to assess the risk factors associated with bi-lateral sentinel lymph node (SLN) mapping failure in endometrial cancer. The SENECA study was a retrospective multi-center international observational study that reviewed data from 2139 women with clinical stage I-to-II endometrial cancer across 64 centers in 17 countries. Between January 2021 and December 2022, patients underwent surgical treatment with SLN assessment, following the guidelines of the European Society of Gynaecological Oncology. Risk factors associated with the absence of bi-lateral mapping were analyzed using χ Among the 2139 patients, the bi-lateral lymph node detection rate was 82.7%, whereas the unilateral detection rate was 97.3%. In multi-variate analysis, 5 risk factors remained statistically associated with unsuccessful bi-lateral lymph node mapping: high-grade histology (OR 1.35, 95% CI 1.02 to 1.79, p=.03), myometrial invasion >50% (OR 1.37, 95% CI 1.07 to 1.75, p=.012), low-volume surgeon <20 cases/year (OR 2.11, 95% CI 1.55 to 2.89, p<.01), open surgical approach (OR 1.72, 95% CI 1.06 to 2.78 , p=.03), and non-indocyanine green tracer (OR 4.59, 95% CI 2.64 to 7.99, p<.01). The addition of bi-lateral pelvic lymphadenectomy and/or paraaortic lymphadenectomy to SLN biopsy caused an increased rate of intra-operative complications (2% vs 8.4%, p<.01) and all-grade post-operative complications (4.1% vs 11.2%, p<.01). Our study identifies 5 risk factors associated with unsuccessful lymph node mapping in endometrial cancer. Efforts should be made to perform this technique with indocyanine green, through minimally invasive surgery, and performed or supervised by an experienced surgeon with ≥20 endometrial cancer cases per year.

The Risk of Endometrial Malignancy and Other Endometrial Pathology in Women with Abnormal Uterine Bleeding: An Ultrasound-Based Model Development Study by the IETA Group

&lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; The aim of this study was to develop a model that can discriminate between different etiologies of abnormal uterine bleeding. &lt;b&gt;&lt;i&gt;Design:&lt;/i&gt;&lt;/b&gt; The International Endometrial Tumor Analysis 1 study is a multicenter observational diagnostic study in 18 bleeding clinics in 9 countries. Consecutive women with abnormal vaginal bleeding presenting for ultrasound examination (&lt;i&gt;n&lt;/i&gt; = 2,417) were recruited. The histology was obtained from endometrial sampling, D&amp;amp;C, hysteroscopic resection, hysterectomy, or ultrasound follow-up for &amp;#x3e;1 year. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A model was developed using multinomial regression based on age, body mass index, and ultrasound predictors to distinguish between: (1) endometrial atrophy, (2) endometrial polyp or intracavitary myoma, (3) endometrial malignancy or atypical hyperplasia, (4) proliferative/secretory changes, endometritis, or hyperplasia without atypia and validated using leave-center-out cross-validation and bootstrapping. The main outcomes are the model’s ability to discriminate between the four outcomes and the calibration of risk estimates. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; The median age in 2,417 women was 50 (interquartile range 43–57). 414 (17%) women had endometrial atrophy; 996 (41%) had a polyp or myoma; 155 (6%) had an endometrial malignancy or atypical hyperplasia; and 852 (35%) had proliferative/secretory changes, endometritis, or hyperplasia without atypia. The model distinguished well between malignant and benign histology (&lt;i&gt;c&lt;/i&gt;-statistic 0.88 95% CI: 0.85–0.91) and between all benign histologies. The probabilities for each of the four outcomes were over- or underestimated depending on the centers. &lt;b&gt;&lt;i&gt;Limitations:&lt;/i&gt;&lt;/b&gt; Not all patients had a diagnosis based on histology. The model over- or underestimated the risk for certain outcomes in some centers, indicating local recalibration is advisable. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; The proposed model reliably distinguishes between four histological outcomes. This is the first model to discriminate between several outcomes and is the only model applicable when menopausal status is uncertain. The model could be useful for patient management and counseling, and aid in the interpretation of ultrasound findings. Future research is needed to externally validate and locally recalibrate the model.

Epithelial ovarian cancer and borderline tumors during pregnancy: a report from the International Network on Cancer, Infertility, and Pregnancy

To describe the oncological and obstetrical outcomes of women diagnosed with borderline ovarian tumors or epithelial ovarian cancer during pregnancy. This is an international retrospective cohort study. Patients were eligible for inclusion if they were diagnosed with borderline tumor or invasive ovarian cancer during pregnancy, with histologic confirmation either before or after delivery, and were registered in the International Network on Cancer, Infertility and Pregnancy database between 1982 and 2019. A total of 129 patients were included, of whom 69 (53%) with borderline and 60 (47%) with invasive cancer. Diagnosis was established in the first, second, and third trimesters in 59 (46%), 48 (37%), and 22 (17%) patients, respectively. In total, 47 (36%) patients did not receive any treatment during pregnancy. The majority of patients (64%) underwent surgery with or without chemotherapy during pregnancy. Birthweight was significantly lower in women who received chemotherapy during pregnancy as compared to those who did not (median birthweight 2528 g vs 3031 g, p = .01) Among patients with borderline tumors, 20 (29%) experienced a relapse of whom 2 subsequently died from the disease. The 5-year survival probability was 98.5% (95% CI 95.6 to 100). Recurrence was associated with incomplete surgical staging (p = .02). Among patients with epithelial ovarian cancer, the relapse rate was 25% and the 5-year survival probability was 83.6% (95% CI 74.3 to 94.1). The oncological outcome was worse for patients with advanced-stage disease (p = .03). In addition, 66% of patients who relapsed after pregnancy did not undergo adequate surgical staging. Treatment of patients with ovarian cancer during pregnancy can result in favorable oncological and obstetrical outcomes. Better oncological outcomes are achieved when treatment adheres to the standard of care in non-pregnant patients, as those who did not undergo surgical staging experienced a higher relapse rate.

Malignant germ cells tumor of the ovary

Malignant ovarian germ cell tumors are rare and diverse malignancies, accounting for approximately 5% of all ovarian cancers. Primarily affecting young women, these tumors present unique challenges, particularly in balancing effective treatment with fertility preservation. Early diagnosis is common due to the rapid tumor growth and symptoms such as abdominal pain and distension, leading to favorable prognoses when combined with the high chemosensitivity of platinum-based regimens. Fertility-sparing surgery is the cornerstone of treatment for stage I disease, often followed by close surveillance to minimize the long-term toxicities of chemotherapy. Pathology is pivotal for diagnosis, incorporating immunohistochemical markers to differentiate malignant ovarian germ cell tumors subtypes, including dysgerminomas, yolk sac tumors, and immature teratomas. Advanced imaging modalities like ultrasound, magnetic resonance imaging, and computed tomography are essential for staging, monitoring treatment response, and detecting recurrences. Despite high cure rates, long-term follow-up is crucial to manage late toxicities, such as gonadal dysfunction and secondary malignancies. Recurrent malignant ovarian germ cell tumors present significant therapeutic challenges. High-dose chemotherapy with stem-cell transplantation offers promise in select cases, while the role of secondary cytoreductive surgery and radiotherapy is limited to specific indications. Emerging targeted therapies and novel approaches, such as KIT inhibitors for dysgerminomas with KIT mutations, remain experimental, with limited success reported so far. The rarity and heterogeneity of malignant ovarian germ cell tumors impede large-scale research efforts, underscoring the need for greater understanding of their molecular and genetic landscape to develop more effective and personalized therapies.

Fertility outcomes in stage I ovarian immature teratomas

To evaluate the impact of adjuvant chemotherapy, type of ovarian surgery, and the surgical approach on fertility in patients with stage I immature teratoma of the ovary. Clinicopathologic data were retrospectively collected and analyzed from a cohort of 47 patients with childbearing desire treated for a stage I immature teratoma of the ovary at IRCCS San Gerardo dei Tintori Hospital, Monza, Italy. Multivariate logistic regression was used to address the influence of chemotherapy and type of surgery on the outcome. Among the patients included, 78.7% (37/47) were able to get pregnant, with a live birth rate of 80.9% (51/63 pregnancies). These rates were not different between adjuvant chemotherapy versus surveillance group (62.5% (5/8) and 82.0% (32/39), respectively; p=0.22) nor between the type of ovarian surgery (cystectomy vs unilateral salpingo-oophorectomy; p=0.57) and surgical approach (laparotomy or laparoscopy; p=0.18). A statistically significant difference was found for stage of disease (a decrease in pregnancy rate from 86.5% (32/37) for stage IA to 50.0% for stage IC (5/10); p=0.02), but it was not confirmed in the multivariate analysis. After relapse diagnosis and management, a total of 62.5% (5/8) of patients conceived and had at least one live birth baby. The fertility-sparing approach is feasible in this population, and fertility does not depend on surgical approach or post-operative treatment. However, adjuvant chemotherapy should be carefully evaluated in this setting.

Risk of Breast Cancer After Ovarian Cancer in Women With a Pathogenic/Likely Pathogenic Variant in BRCA1 or BRCA2

PURPOSE BRCA carriers face high risks of developing both breast and ovarian/fallopian tube cancers (hereafter referred to as ovarian ). Among BRCA carriers with ovarian cancer, it is not clear whether the risk of breast cancer is sufficiently high that risk-reducing mastectomy should be offered. This study aimed to assess the risk of breast cancer BRCA carriers after a diagnosis of ovarian cancer. METHODS We included women with a pathogenic/likely pathogenic variant in BRCA1 or BRCA2 , a diagnosis of ovarian cancer, and no other cancer history and no risk-reducing bilateral mastectomy. Women were followed for incident breast cancer from the date of ovarian cancer diagnosis or the date of baseline questionnaire, whichever came last. The 5-, 10-, and 15-year cumulative risks of breast cancer were compared for women with ovarian cancer and an age-matched set of control women without ovarian cancer. RESULTS A total of 960 participants with ovarian cancer were identified (814 BRCA1 and 146 BRCA2 carriers). After a mean follow-up of 4.9 years, 41 women (4.3%) developed breast cancer, at a mean age at diagnosis of 57.5 years (range, 39-74). Actuarial cumulative breast cancer risks after ovarian cancer were 4.4%, 8.9%, and 11.5% at 5, 10, and 15 years, respectively. Only three breast cancer–related deaths occurred. Among 741 age-matched BRCA carriers without ovarian cancer, actuarial cumulative risks of breast cancer were 20.9%, 38.6%, and 47.2% at 5, 10, and 15 years, respectively. The hazard ratio for breast cancer, after an ovarian cancer diagnosis, compared with no ovarian cancer, was 0.18 ([95% CI, 0.12 to 0.27]; P &lt; .0001). CONCLUSION After ovarian cancer, BRCA carriers have a relatively low risk of breast cancer. Risk-reducing mastectomy should not be recommended routinely, but might be considered for long-term survivors. Magnetic resonance imaging surveillance and/or mammography is a realistic alternative.

Tubal histopathological abnormalities in BRCA1/2 mutation carriers undergoing prophylactic salpingo-oophorectomy: a case–control study

To describe tubal histopathological abnormalities in women with germline Consecutive women with A total of 194 women with pathogenic We found that a p53 signature is a frequent finding both in

Evaluation of family history in individuals with heterozygous BRCA pathogenic variants diagnosed with breast or ovarian cancer in a single center in Italy

AbstractBackgroundBRCA1 and BRCA2 gene mutations are responsible for 5% of breast cancer (BC) and 10–15% of ovarian cancer (EOC). The presence of a germline mutation and therefore the identification of subjects at high risk of developing cancer should ideally precede the onset of the disease, so that appropriate surveillance and risk‐reducing treatments can be proposed. In this study, we revisited the family history (FH) of women who tested positive for BRCA mutations after being diagnosed with BC or EOC.MethodsThe National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines®), and the Italian Association of Medical Oncology (AIOM) guidelines were applied to the FH of 157 women who were referred to San Gerardo Hospital for genetic counseling.ResultsAlmost 85% of women had an FH of BRCA‐related cancer. 63.7% and 52.2% of women could have undergone genetic testing according to NCCN and AIOM testing criteria (p &lt; .05) before tumor diagnosis. An FH of EOC was the most frequent NCCN criterion, followed by BC diagnosed &lt;45 years old. Sixty‐five percent of deceased women could have undergone genetic testing before developing cancer.ConclusionsFH is a powerful tool to identify high‐risk individuals eligible for genetic counseling and testing. Testing of healthy individuals should be considered when an appropriately affected family member is unavailable for testing.

Copy number alterations in stage I epithelial ovarian cancer highlight three genomic patterns associated with prognosis

Stage I epithelial ovarian cancer (EOC) encompasses five histologically different subtypes of tumors confined to the ovaries with a generally favorable prognosis. Despite the intrinsic heterogeneity, all stage I EOCs are treated with complete resection and adjuvant therapy in most of the cases. Owing to the lack of robust prognostic markers, this often leads to overtreatment. Therefore, a better molecular characterization of stage I EOCs could improve the assessment of the risk of relapse and the refinement of optimal treatment options. 205 stage I EOCs tumor biopsies with a median follow-up of eight years were gathered from two independent Italian tumor tissue collections, and the genome distribution of somatic copy number alterations (SCNAs) was investigated by shallow whole genome sequencing (sWGS) approach. Despite the variability in SCNAs distribution both across and within the histotypes, we were able to define three common genomic instability patterns, namely stable, unstable, and highly unstable. These patterns were based on the percentage of the genome affected by SCNAs and on their length. The genomic instability pattern was strongly predictive of patients' prognosis also with multivariate models including currently used clinico-pathological variables. The results obtained in this study support the idea that novel molecular markers, in this case genomic instability patterns, can anticipate the behavior of stage I EOC regardless of tumor subtype and provide valuable prognostic information. Thus, it might be propitious to extend the study of these genomic instability patterns to improve rational management of this disease.

Bilateral Oophorectomy and the Risk of Breast Cancer in BRCA1 Mutation Carriers: A Reappraisal

Abstract Background: The lack of consensus on whether bilateral oophorectomy impacts risk of developing breast cancer among BRCA1 mutation carriers might be attributed to various biases, specifically, cancer-induced testing bias due to inclusion of prevalent cases. We conducted two complementary matched case–control analyses to evaluate the association of oophorectomy and BRCA1 breast cancer. Methods: A research questionnaire was administered every two years to collect information on exposures and disease. In the first analysis, we limited the study to prevalent breast cancer cases (diagnosed prior to study entry; n = 2,962) who were matched to controls on year of birth and country of residence (n = 4,358). In the second approach, we limited to 330 incident cases (diagnosed in the follow-up period) and 1,548 matched controls. Conditional logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of invasive breast cancer. Results: In the first approach, there was a significant inverse association between oophorectomy and the risk of developing breast cancer [OR = 0.43; 95% confidence interval (CI), 0.34–0.55; P &amp;lt; 00001]. In the second approach, there was no association between oophorectomy and risk (OR = 1.21; 95% CI, 0.87–1.70; P = 0.26). Conclusions: The inclusion of women with a personal history of breast cancer prior to ascertainment likely impacts upon the association of oophorectomy and BRCA1 breast cancer risk. Impact: Oophorectomy is unlikely a determinant of breast cancer risk in BRCA1 mutation carriers but should be offered at age 35 to reduce the risk of ovarian and fallopian tube cancer.

Radical hysterectomy in early cervical cancer in Europe: characteristics, outcomes and evaluation of ESGO quality indicators

Comprehensive updated information on cervical cancer surgical treatment in Europe is scarce. To evaluate baseline characteristics of women with early cervical cancer and to analyze the outcomes of the ESGO quality indicators after radical hysterectomy in the SUCCOR database. The SUCCOR database consisted of 1272 patients who underwent radical hysterectomy for stage IB1 cervical cancer (FIGO 2009) between January 2013 and December 2014. After exclusion criteria, the final sample included 1156 patients. This study first described the clinical, surgical, pathological, and follow-up variables of this population and then analyzed the outcomes (disease-free survival and overall survival) after radical hysterectomy. Surgical-related ESGO quality indicators were assessed and the accomplishment of the stated recommendations was verified. The mean age of the patients was 47.1 years (SD 10.8), with a mean body mass index of 25.4 kg/m In this European cohort, the rate of adjuvant therapy after radical hysterectomy is higher than for most similar patients reported in the literature. The majority of centers were already following the European recommendations even 5 years prior to the ESGO quality indicator implementations.

Vulvar and vaginal cancer during pregnancy: A pooled analysis of 15 cases from the International Network on Cancer, Infertility and Pregnancy and review of the literature

Abstract Introduction Vulvovaginal cancer in pregnancy is rare. Limited data complicate decision‐making and patient counseling. Our review, coupled with new case data, fills a current gap in the literature and provides practical insights. Material and Methods Oncological and obstetric data of these pregnancies were examined by a case collection from the International Network on Cancer, Infertility and Pregnancy (INCIP) registry (vulvar n  = 10, vaginal n  = 5) and a literature review (vulvar n  = 46, vaginal n  = 37). Results Although preoperative imaging of inguinofemoral lymph nodes is feasible, only 16.1% of vulvar cancer patients underwent ultrasound or MRI. Treatment was initiated during pregnancy for 69.1% of vulvar cancer and 28.4% of vaginal cancer patients. Surgical lymph node staging of vulvar cancer was postponed until after delivery in 10 cases, although uni‐ or bilateral lymphadenectomy during pregnancy was not associated with more complications. Delivery outcomes included a live birth rate of 96.4% for vulvar cancer and 50% for vaginal cancer due to the high rate of pregnancy terminations, with most births preterm. The overall 5‐year survival rates for vulvar (81.3%) and vaginal (66.4%) cancer during pregnancy are comparable to nonpregnant populations, indicating that pregnancy does not adversely impact maternal prognosis. Conclusions This study underscores the feasibility of adapting standard oncological care for pregnant patients, emphasizing multidisciplinary teams to optimize maternal and fetal outcomes.

SUCCOR quality: validation of ESGO quality indicators for surgical treatment of cervical cancer

To evaluate whether compliance with European Society of Gynaecological Oncology (ESGO) surgery quality indicators impacts disease-free survival in patients undergoing radical hysterectomy for cervical cancer. In this retrospective cohort study, 15 ESGO quality indicators were assessed in the SUCCOR database (patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage 2009 IB1, FIGO 2018 IB1, and IB2 cervical cancer between January 2013 and December 2014), and the final score ranged between 0 and 16 points. Centers with more than 13 points were classified as high-quality indicator compliance centers. We constructed a weighted cohort using inverse probability weighting to adjust for the variables. We compared disease-free survival and overall survival using Cox proportional hazards regression analysis in the weighted cohort. A total of 838 patients were included in the study. The mean number of quality indicators compliance in this cohort was 13.6 (SD 1.45). A total of 479 (57.2%) patients were operated on at high compliance centers and 359 (42.8%) patients at low compliance centers. High compliance centers performed more open surgeries (58.4% vs 36.7%, p<0.01). Women who were operated on at centers with high compliance with quality indicators had a significantly lower risk of relapse (HR=0.39; 95% CI 0.25 to 0.61; p<0.001). The association was reduced, but remained significant, after further adjustment for conization, surgical approach, and use of manipulator surgery (HR=0.48; 95% CI 0.30 to 0.75; p=0.001) and adjustment for adjuvant therapy (HR=0.47; 95% CI 0.30 to 0.74; p=0.001). Risk of death from disease was significantly lower in women operated on at centers with high adherence to quality indicators (HR=0.43; 95% CI 0.19 to 0.97; p=0.041). However, the association was not significant after adjustment for conization, surgical approach, use of manipulator surgery, and adjuvant therapy. Patients with early cervical cancer who underwent radical hysterectomy in centers with high compliance with ESGO quality indicators had a lower risk of recurrence and death.

SUCCOR cone study: conization before radical hysterectomy

To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Onvansertib-Based Second-Line Therapies in Combination with Gemcitabine and Carboplatin in Patient-Derived Platinum-Resistant Ovarian Carcinomas

Platinum resistance represents an urgent medical need in the management of ovarian cancer. The activity of the combinations of onvansertib, an inhibitor of polo-like kinase 1, with gemcitabine or carboplatin was tested using patient-derived xenografts of high-grade serous ovarian carcinoma resistant to cisplatin (DDP). Two PDX models were selected from our xenobank: one with acquired resistance to DDP (#266R) and the other (#315) with intrinsic DDP resistance. Tumor-bearing mice were randomized to receive vehicle, single onvansertib, gemcitabine and carboplatin, and their combinations. Onvansertib/gemcitabine and onvansertib/carboplatin combinations were well tolerated. In the #266R model, single drug treatments were completely inactive, while the combinations of onvansertib/gemcitabine and onvansertib/carboplatin resulted in a significant increase in survival compared to controls and single drugs (p &lt; 0.001 versus control, onvansertib, gemcitabine and carboplatin). Similar efficacy was observed in the s.c. #315 PDX model; indeed, onvansertib and carboplatin monotherapies were inactive, gemcitabine monotherapy was marginally active, while both combinations were highly active. The molecular mechanism underlying the efficacy of the combinations suggests a higher induction of DNA damage which seems plausible considering that, in both cases, gemcitabine and carboplatin, respectively, interfere with DNA metabolism and induce alkylation damage. The results suggest that the combinations of onvansertib/gemcitabine and onvansertib/carboplatin are safe and were shown to be of therapeutic value in the platinum-resistant setting of ovarian carcinoma, strongly supporting their clinical translatability.

SLYMEC II study: Overall survival analysis of the impact of LVSI in apparent early stage endometrioid endometrial cancer

In our initial report of the SLYMEC study we published the results evaluated the prognostic impact of substantial lymphovascular space invasion (LVSI) on the sentinel lymph node status and the impact of the different types of LVSI on 3-year disease-free survival. The aim of the SLYMEC II study was to assess the impact of focal and substantial lymphovascular space invasion on 5-years overall survival in the subgroup of patients with endometrioid endometrial cancer. A total of 2030 patients were included in the analysis from the original data set. Focal LVSI were identified in 131 patients (6.4 %), whereas 319 patients (15.7 %) showed substantial LVSI at final pathology. Among 1876 patients who underwent minimally invasive surgery (92.6 %), 442 patents (21.8 %) underwent robotic assisted surgery, whereas and 150 patients (7.6 %) patients underwent open surgery. Rate of overall survival at 5 years was 83.6 % versus 100 % for substantial and focal LVSI groups, respectively (HR for death = 2.1 [95 % CI, 1.4 to 3.2]; P < 0.0001). Patients with endometrioid endometrial cancer having substantial LVSI after surgery showed an increased risk of death in the after 5-years overall survival when compared to patients with negative, or focal LVSI. The presence of positive LVSI in patients with positive sentinel nodes showed a trend toward reduced 5-year overall survival compared to SLN-negative patients, although it did not reach statistical significance.

SUROVA study: global real-world treatment strategies and mortality risk prediction in advanced ovarian cancer

This study aimed to compare 5-year overall survival between primary debulking surgery and neoadjuvant chemotherapy followed by interval surgery in patients with stage IIIB to IVB epithelial ovarian cancer, using global real-world data. Secondary objectives included evaluation of progression-free survival and the influence of race, post-operative complications, and residual disease. SUROVA is a retrospective, international cohort study involving patients treated between 2018 and 2019 across 174 centers in 55 countries. Patients underwent primary surgery or received neoadjuvant chemotherapy followed by interval surgery, per institutional protocols. Propensity score matching was based on 7 baseline variables: age, race, Eastern Cooperative Oncology Group performance status at diagnosis, CA125 level at diagnosis, FIGO (International Federation of Gynecology and Obstetrics) stage IV disease, presence of ascites, and final tumor grade. Cox regression models with time-dependent effects and interaction terms were applied. A clinical risk calculator was developed and internally validated. A total of 3286 patients had a mean age of 60.0 years (SD 12); 2978 (90.6%) had high-grade serous carcinoma, and 795 (24.7%) presented with FIGO stage IV disease. A total of 1666 patients (50.7%) underwent primary cytoreductive surgery, and 1620 (49.3%) received neoadjuvant chemotherapy. The median follow-up duration was 43.8 months (interquartile range; 22.6-59.3). After propensity score matching (n=1524), overall survival was similar between groups (67.2 vs 65.0 months; HR 1.002, 95% CI 0.85 to 1.18, p=.98). Outcomes differed by ethnicity, residual disease, and post-operative complications. Post-operative complications (28%) significantly worsened survival (66 vs 46 months; HR 1.5, 95% CI 1.2 to 1.9, p<.001), especially among patients undergoing primary surgery (73 vs 46 months; HR 1.85, 95% CI 1.43 to 2.37, p<.001). The most favorable outcomes were observed among patients with primary surgery, complete resection, and no complications, with median overall survival not reached (HR 1.25, 95% CI 1.12 to 1.40, p<.001). Although overall survival was similar between groups, treatment effects differed by ethnicity, residual disease, and complications. Post-operative complications were associated with significantly worse survival, particularly among patients undergoing primary surgery, while the best outcomes were achieved in those who had primary surgery with complete resection and no complications.

SUCCOR 10 years: a decade's perspective on radical hysterectomy outcomes in cervical cancer.

Interest in long-term outcomes of radical hysterectomy for cervical cancer has increased, especially after the LACC trial findings, which showed worse outcomes for minimally invasive surgery. However, limited information is available on 10-year oncological outcomes, particularly, recurrence and survival. The primary objective of this study was to analyze the 10-year oncological outcomes of patients with International Federation of Gynecology and Obstetrics 2009 stage IB1 cervical cancer treated with radical hysterectomy performed via minimally invasive or open approaches. This retrospective, multi-center, observational study updates the data from the SUCCOR cohort. Patients diagnosed between January 2013 and December 2014 with tumors ≤4 cm without extra-cervical metastasis and treated with radical hysterectomy as the primary treatment were included, and a 10-year follow-up after surgery was successfully conducted. A total of 556 patients were analyzed. The median age was 46 years (range; 18-82). The most common final International Federation of Gynecology and Obstetrics 2009 stage was IB1, 474 patients (85%), and the most common histology was squamous carcinoma, 376 patients (67.6%). The 5-year disease-free survival was 93%, and the 10-year disease-free survival was 90%. The overall survival was 97% at 5 years and 89% at 10 years. During follow-up, 9% (n = 49) of patients experienced recurrences, 78% (n = 38) within the first 5 years. Comparing surgical approaches, 10-year disease-free survival was 92% for minimally invasive surgery and 88% for open surgery (p = .12). Similarly, 10-year overall survival was 92% for minimally invasive surgery and 88% for open surgery (p = .12). Post-recurrence disease-specific survival was 47% at 60 months and 39% at 96 months. The 2-year survival after recurrence was 80% for late recurrences (>5 years) versus 69% for early recurrences. The overall survival after radical hysterectomy at 5-years was 97% in patients with early-stage cervical cancer. The recurrence rate at 10 years was 9%. No differences in 10-year survival were observed between the surgical approaches.

International multicenter validation of AI-driven ultrasound detection of ovarian cancer

Abstract Ovarian lesions are common and often incidentally detected. A critical shortage of expert ultrasound examiners has raised concerns of unnecessary interventions and delayed cancer diagnoses. Deep learning has shown promising results in the detection of ovarian cancer in ultrasound images; however, external validation is lacking. In this international multicenter retrospective study, we developed and validated transformer-based neural network models using a comprehensive dataset of 17,119 ultrasound images from 3,652 patients across 20 centers in eight countries. Using a leave-one-center-out cross-validation scheme, for each center in turn, we trained a model using data from the remaining centers. The models demonstrated robust performance across centers, ultrasound systems, histological diagnoses and patient age groups, significantly outperforming both expert and non-expert examiners on all evaluated metrics, namely F1 score, sensitivity, specificity, accuracy, Cohen’s kappa, Matthew’s correlation coefficient, diagnostic odds ratio and Youden’s J statistic. Furthermore, in a retrospective triage simulation, artificial intelligence (AI)-driven diagnostic support reduced referrals to experts by 63% while significantly surpassing the diagnostic performance of the current practice. These results show that transformer-based models exhibit strong generalization and above human expert-level diagnostic accuracy, with the potential to alleviate the shortage of expert ultrasound examiners and improve patient outcomes.

SENECA study: staging endometrial cancer based on molecular classification

Management of endometrial cancer is advancing, with accurate staging crucial for guiding treatment decisions. Understanding sentinel lymph node (SLN) involvement rates across molecular subgroups is essential. To evaluate SLN involvement in early-stage (International Federation of Gynecology and Obstetrics 2009 I-II) endometrial cancer, considering molecular subtypes and new European Society of Gynaecological Oncology (ESGO) risk classification. The SENECA study retrospectively reviewed data from 2139 women with stage I-II endometrial cancer across 66 centers in 16 countries. Patients underwent surgery with SLN assessment following ESGO guidelines between January 2021 and December 2022. Molecular analysis was performed on pre-operative biopsies or hysterectomy specimens. Among the 2139 patients, the molecular subgroups were as follows: 272 (12.7%) p53 abnormal (p53abn, 1191 (55.7%) non-specific molecular profile (NSMP), 581 (27.2%) mismatch repair deficient (MMRd), 95 (4.4%) POLE mutated (POLE-mut). Tracer diffusion was detected in, at least one side, in 97.2% of the cases; with a bilateral diffusion observed in 82.7% of the cases. By ultrastaging (90.7% of the cases) or one-step nucleic acid amplification (198 (9.3%) of the cases), 205 patients were identified with affected sentinel lymph nodes, representing 9.6% of the sample. Of these, 139 (67.8%) had low-volume metastases (including micrometastases, 42.9%; and isolated tumor cells, 24.9%) while 66 (32.2%) had macrometastases. Significant differences in SLN involvement were observed between molecular subtypes, with p53abn and MMRd groups having the highest rates (12.50% and 12.40%, respectively) compared with NSMP (7.80%) and POLE-mut (6.30%), (p=0.004); (p53abn, OR=1.69 (95% CI 1.11 to 2.56), p=0.014; MMRd, OR=1.67 (95% CI 1.21 to 2.31), p=0.002). Differences were also noted among ESGO risk groups (2.84% for low-risk patients, 6.62% for intermediate-risk patients, 21.63% for high-intermediate risk patients, and 22.51% for high-risk patients; p<0.001). Our study reveals significant differences in SLN involvement among patients with early-stage endometrial cancer based on molecular subtypes. This underscores the importance of considering molecular characteristics for accurate staging and optimal management decisions.

The paradigm shift in advanced ovarian cancer: Outcomes of extensive primary cytoreductive surgery. A single-center retrospective analysis

The standard surgical treatment of advanced ovarian carcinoma is primary debulking surgery (PDS) aiming to complete cytoreduction. The need to achieve complete cytoreduction has shifted the surgical paradigm to more complex procedures, whose impact on morbidity is controversial. The objective of this retrospective analysis is to explore the impact of extensive PDS on morbidity and oncologic outcomes in a real-world scenario. A retrospective single-center analysis was performed on 137 patients with advanced high-grade ovarian carcinoma (HGOC) who received PDS in 2015-2020. Patients treated in 2015-2017 (Group 1) were compared to patients treated in 2018-2020 (Group 2). The two periods were chosen according to the higher complexity of surgical procedures introduced in 2018. The increase in complete cytoreduction observed in Group2 (RD 0: 33 % vs 61 %, p = 0,008) was related to a higher surgical complexity (Aletti Score: 4 vs 6, p = 0,003) and did not reflect an increase in peri-operative complications (CCI: 20,9 vs 20,9, p = 0,11). After a median FUP of 44 months, PFS and OS at 24 months were 33,60 % vs 47,33 % (p = 0,288) and 72,10 % vs 80,37 % (p = 0,022) in Group 1 and 2, respectively. An extensive surgical effort leads to a significant increase in complete cytoreduction with acceptable morbidity. Arm-in-arm with novel maintenance therapies, it contributes to increasing the outcomes of patients with advanced HGOC.

Estimating risk of endometrial malignancy and other intracavitary uterine pathology in women without abnormal uterine bleeding using IETA‐1 multinomial regression model: validation study

ABSTRACTObjectivesTo assess the ability of the International Endometrial Tumor Analysis (IETA)‐1 polynomial regression model to estimate the risk of endometrial cancer (EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding.MethodsThis was a retrospective study, in which we validated the IETA‐1 model on the IETA‐3 study cohort (n = 1745). The IETA‐3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow‐up of non‐endometrial pathology, in the work‐up before fertility treatment or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology, or with results of clinical and ultrasound follow‐up of at least 1 year if endometrial sampling was not performed. The IETA‐1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: (1) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3) proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, endometrial thickness, color score, cysts in the endometrium, non‐uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver‐operating‐characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio).ResultsThe median age of the women in the IETA‐3 cohort was 51 (range, 20–85) years and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA‐1 model had an AUC of 0.81 (95% CI, 0.73–0.89, n = 1745) for discrimination between malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32–0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62–0.73) (n = 1532). The IETA‐1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95–0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75–0.91), compared with 0.62 (95% CI, 0.52–0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08–0.32). In postmenopausal women with measurable endometrial thickness (n = 848), the IETA‐1 model gave an AUC of 0.81 (95% CI, 0.71–0.91), while endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60–0.81) (difference in AUC, 0.11; 95% CI, 0.01–0.20).ConclusionThe IETA‐1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Lymph node staging in grade 1–2 endometrioid ovarian carcinoma apparently confined to the ovary: Is it worth?

The aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1-2 endometrioid ovarian carcinoma apparently confined to the ovary, according to surgical staging. Multicenter, retrospective, observational cohort study. Patients with endometrioid ovarian carcinoma, surgical procedure performed between May 1985 and December 2019, stage pT1 N0/N1/Nx, grade 1-2 were included. Patients were stratified according to lymphadenectomy (defined as removal of any lymph node versus no lymph node assessment), and subgroup analyses according to tumor grade were performed. Kaplan-Meier curves and cox regression analyses were used to perform survival analyses. 298 patients were included. 199 (66.8 %) patients underwent lymph node assessment. Of these, 166 (83.4 %) had unilateral/bilateral pelvic and para-aortic/caval lymphadenectomy. Eleven (5.5 %) patients of those who underwent lymph node assessment showed pathologic metastatic lymph nodes (FIGO stage IIIA1). Twenty-seven patients (9.1 %) had synchronous endometrioid endometrial cancer. After a median follow up of 45 months (95 %CI:37.5-52.5), 5-year DFS and OS of the entire cohort were 89.8 % and 96.2 %, respectively. Age ≤ 51 years (HR=0.24, 95 %CI:0.06-0.91; p = 0.036) and performance of lymphadenectomy (HR=0.25, 95 %CI: 0.07-0.82; p = 0.022) represented independent protective factors toward risk of death. Patients undergoing lymphadenectomy had better 5-year DFS and OS compared to those not receiving lymphadenectomy, 92.0 % versus 85.6 % (p = 0.016) and 97.7 % versus 92.8 % (p = 0.013), respectively. This result was confirmed after exclusion of node-positive patients. When stratifying according to tumor grade (node-positive excluded), patients with grade 2 who underwent lymphadenectomy had better 5-year DFS and OS than those without lymphadenectomy (93.0 % versus 83.1 %, p = 0.040 % and 96.5 % versus 90.6 %, p = 0.037, respectively). Staging lymphadenectomy in grade 2 endometrioid ovarian carcinoma patients was associated with improved DFS and OS. Grade 1 and grade 2 might be considered as two different entities, which could benefit from different approach in terms of surgical staging. Prospective studies, including molecular profiles are needed to confirm the survival drivers in this rare setting.

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.

Fertility-sparing vs hysterectomy for uterine STUMP: A pragmatic clinical study.

Uterine smooth muscle tumors of uncertain malignant potential (STUMP) are rare neoplasms with unpredictable clinical behavior. Optimal management, particularly in reproductive-aged women, remains controversial, with limited data comparing the safety of fertility-sparing versus hysterectomy. This multicentre retrospective cohort study included women aged 18-85 with histologically confirmed STUMP treated at 17 Italian gynecologic oncology centers from 2010 to 2023. Patients underwent either fertility-sparing surgery (myomectomy or hysteroscopic resection) or definitive surgery (hysterectomy ± salpingo-oophorectomy). Kaplan-Meier and Cox models were used to compare recurrence-free survival (RFS) and overall survival (OS). Median (range) follow-up was 51 (1-291) months. Among 401 women, 106 (26.4 %) received fertility-sparing treatment (mean [± SD] age: 35.3 ± 6.8 years) and 295 (73.6 %) underwent definitive surgery (mean [± SD] age: 47.7 ± 9.2). At total follow-up, recurrence occurred in 12.5 % of patients, predominantly within the pelvis. Median RFS was longer after definitive surgery than after fertility-sparing procedures (50.0 vs 42.5 months; HR 2.39 [95 % CI 1.36-4.19]), although this difference disappeared when benign (leiomyoma) recurrences were excluded (HR 1.74 [95 % CI 0.90-3.34]). At last available follow-up, 97.5 % of patients were alive, with no significant OS difference between treatment groups (HR 0.22 [95 % CI 0.27-1.79]). Outcomes were comparable across menopausal status and concurrent adnexal removal. Definitive surgery reduces recurrence risk, but long-term survival is similarly excellent after fertility-sparing surgery in appropriately selected women with STUMP. Conservative management represents a reasonable option for patients desiring fertility, provided they receive counseling regarding recurrence risk, diagnostic uncertainty, and the need for long-term surveillance.

Prognostic Value of Conization and Negative HPV After Conization in AIS and Early Stage Cervical Cancer

In women with cervical cancer -Squamous cell carcinoma, Adeno carcinoma, Adeno-squamous carcinoma or AIS we want to examine prospectively: 1. Examine if negative HR-HPV after conization to the HR-HPV the women had before conization has a high prognostic value for no residual tumor in the final pathology. 2. To examine if conization in women with cervical tumor up to Stage I B 2 (FIGO 2018) is corelated with better prognosis.