Prediction of non-resectability using the updated Predictive Index Value model assessed by imaging and surgery in tubo-ovarian cancer: a prospective multicenter ISAAC study.

BACKGROUND: A laparoscopy-based scoring system was developed by Fagotti et al (Fagotti or Predictive Index Value (PIV)score) based on the intraoperative presence or absence of carcinomatosis on predefined sites. Later, the authors updated the PIV score calculated only in the absence of one or both absolute criteria of non-resectability (mesenteric retraction and miliary carcinomatosis of the small bowel) (updated PIV model). OBJECTIVE: The aim was to demonstrate the non-inferiority of ultrasound to other imaging methods (contrast enhanced computed tomography (CT) and whole-body diffusion-weighted (WB DWI)/MRI) in predicting non-resectable tumor (defined as residual disease>1 cm) using the updated PIV model in patients with tubo-ovarian cancer. The agreement between imaging and intraoperative findings as a reference was also calculated. STUDY DESIGN: This was a European prospective multicenter observational study. We included patients with suspected tubo-ovarian carcinoma who underwent preoperative staging and prediction of non-resectability at ultrasound, CT, WB-DWI/MRI and surgical exploration. The predictors of non-resectability were suspicious mesenteric retraction and/or miliary carcinomatosis of the small bowel or if absent, a PIV>8 (updated PIV model). The PIV score ranges from 0 to 12 according to the presence of disease in six predefined intra-abdominal sites (great omentum, liver surface, lesser omentum/stomach/spleen, parietal peritoneum, diaphragms, bowel serosa/mesentery). The reference standard was surgical outcome, in terms of residual disease>1 cm, assessed by laparoscopy and/or laparotomy. The area under the receiver operating characteristic curve (AUC) to assess the performance of the methods in predicting non-resectability was reported. Concordance between index tests at detection of disease at six predefined sites and intraoperative exploration as reference standard was also calculated using Cohen's kappa. RESULTS: The study was between 2018 and 2022 in five European gynecological oncology centers. Data from 242 patients having both mandatory index tests (ultrasound and CT) were analyzed. 145/242 (59.9%) patients had no macroscopic residual tumor after surgery (R0) (5/145 laparoscopy and 140/145 laparotomy) and 17/242 (7.0%) had residual tumor ≤1cm (R1) (laparotomy). In 80/242 patients (33.1%), the residual tumor was >1 cm (R2), 30 of them underwent laparotomy and maximum surgery was carried out and 50/80 underwent laparoscopy and cytoreduction was not feasible in all of them. After excluding 18/242 (7.4%) patients operated on but not eligible for extensive surgery, the predictive performance of three imaging methods was analyzed in 167 women. The AUCs of all methods in discriminating between resectable and non-resectable tumor was 0.80 for ultrasound, 0.76 for CT, 0.71 for WB-DWI/MRI and 0.90 for surgical exploration. Ultrasound had the highest agreement (Cohen's kappa ranging from 0.59 to 0.79) compared to CT and WB-DWI/MRI to assess all parameters included in the updated PIV model. CONCLUSIONS: Ultrasound showed non-inferiority to CT and to WB-DWI/MRI in discriminating between resectable and non-resectable tumor using the updated PIV model. Ultrasound had the best agreement between imaging and intraoperative findings in the assessment of parameters included in the updated PIV model. Ultrasound is an acceptable method to assess abdominal disease and predict non-resectability in patients with tubo-ovarian cancer in the hands of specially trained ultrasound examiners.

Sentinel node mapping, sentinel node mapping plus back-up lymphadenectomy, and lymphadenectomy in Early-sTage cERvical caNcer scheduled for fertilItY-sparing approach: The ETERNITY project.

OBJECTIVE: To investigate the safety of sentinel node mapping for patients with early-stage cervical cancer undergoing cervical conization plus nodal evaluation. METHODS: The ETERNITY project is a retrospective, multi-institutional study collecting data of patients with early-stage cervical cancer undergoing fertility-sparing treatment. Here, we compared outcomes related to three methods of nodal assessment: sentinel node mapping (SNM), SNM plus backup lymphadenectomy (SNM + LND); pelvic lymphadenectomy (LND). RESULTS: Charts of 123 patients (with stage IA1-IB1 cervical cancer) were evaluated. Median patients' age was 34 (range, 22-44) years. SNM, SNM + LND, and LND were performed in 32 (26 %), 31 (25.2 %), and 60 (48.8 %) patients, respectively. Overall, eight (6.5 %) patients were diagnosed with positive nodes. Two (3.3 %), three (9.7 %), and three (9.4 %) patients were detected in patients who had LND, SNM + LND, and SNM respectively. Considering the 63 patients undergoing SNM (31 SNM + LND and 32 SNM alone), macrometastases, micrometastases, and isolated tumor cells were detected in four (3.2 %), three (2.4 %), and one (0.8 %) patients, respectively. All patients with positive nodes discontinued the fertility sparing treatment. Other two patients (one (1.7 %) in the LND group and one (3.1 %) in the SNM group) required hysterectomy even after negative nodal evaluation. After a median follow-up of 53.6 (range, 1.3, 158.0) months, nine (7.3 %) and two (1.6 %) patients developed cervical and pelvic nodes recurrences, respectively. Disease-free (p = 0.332, log-rank test) and overall survival (p = 0.769, log-rank test) were similar among groups. CONCLUSIONS: In this retrospective experience, SNM upholds long-term oncologic effectiveness of LND, reducing morbidity.

Artificial Intelligence in the Management of Women with Endometriosis and Adenomyosis: Can Machines Ever Be Worse Than Humans?

Artificial intelligence (AI) is experiencing advances and integration in all medical specializations, and this creates excitement but also concerns. This narrative review aims to critically assess the state of the art of AI in the field of endometriosis and adenomyosis. By enabling automation, AI may speed up some routine tasks, decreasing gynecologists' risk of burnout, as well as enabling them to spend more time interacting with their patients, increasing their efficiency and patients' perception of being taken care of. Surgery may also benefit from AI, especially through its integration with robotic surgery systems. This may improve the detection of anatomical structures and enhance surgical outcomes by combining intra-operative findings with pre-operative imaging. Not only that, but AI promises to improve the quality of care by facilitating clinical research. Through the introduction of decision-support tools, it can enhance diagnostic assessment; it can also predict treatment effectiveness and side effects, as well as reproductive prognosis and cancer risk. However, concerns exist regarding the fact that good quality data used in tool development and compliance with data sharing guidelines are crucial. Also, professionals are worried AI may render certain specialists obsolete. This said, AI is more likely to become a well-liked team member rather than a usurper.

Predicting the Risk of nOdal disease with histological and Molecular features in Endometrial cancer: the prospective PROME trial.

OBJECTIVE: To assess the role of histopathological and molecular features in predicting the risk of nodal metastases in apparent early-stage endometrial cancer patients undergoing sentinel node mapping. METHODS: This is a prospective trial. Consecutive patients with apparent early-stage endometrial cancer, undergoing laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and sentinel node mapping, were enrolled. Histological and molecular features were used to predict the node positivity. RESULTS: Charts of 223 apparent early-stage endometrial cancer patients were included in this study. Four (1.8%) patients were excluded from this study due to the lack of data about molecular features. Additionally, nine (4%) patients did not meet the inclusion criteria (due to the presence of peritoneal carcinomatosis or bulky nodes (the presence of p53 abnormality correlated with the presence of advanced stage disease (p<0.001)). The study population included 178 (84.8%) and 32 (15.2%) patients with endometrioid and non-endometrioid endometrial cancer, respectively. According to pathological uterine risk factors, 93 (44.3%), 45 (21.4%), 40 (19.1%), and 32 (15.2%) were classified as low, intermediate, intermediate-high, and high-risk, respectively. Using the surrogate molecular classification, 10 (4.8%), 42 (20%), 57 (27.1%), and 101 (48.1%) were included in the POLE mutated, p53 abnormal, MMRd/MSI-H, and NSMP, respectively. Overall, 41 (19.5%) patients were detected with positive nodes. Molecular features were not associated with the risk of having nodal metastases (OR 1.03, 95% CI 0.21 to 5.05, p=0.969 for POLE mutated; OR 0.788, 95% CI 0.32 to 1.98, p=0.602 for p53 abnormal; OR 1.14, 95% CI 0.53 to 2.42, p=0.733 for MMRd/MSI-H). At multivariable analysis, only deep myometrial invasion (OR 3.318, 95% CI 1.357 to 8.150, p=0.009) and lymphovascular space invasion (OR 6.584, 95% CI 2.663 to 16.279, p<0.001) correlated with the increased risk of positive nodes. CONCLUSION: Our data suggest that molecular classification does not seem useful to tailor the need of nodal dissection in apparent early-stage endometrial cancer. p53 abnormality predicts the risk of having advanced disease at presentation. Further external validation is needed. CLINICAL TRIAL REGISTRATION: NCT05793333.

Endometriosis-associated ovarian cancer: a different clinical entity.

OBJECTIVE: To compare survival outcomes and patterns of recurrence between endometriosis-associated ovarian cancer patients and non-endometriosis-associated ovarian cancer patients. METHODS: This retrospective study included data of consecutive patients with endometrioid or clear cell ovarian cancer treated at the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano between January 2010 and June 2021. Patients were assigned to one of two groups according to the absence or presence of endometriosis together with ovarian cancer at final histological examination. Survival outcomes were assessed using Kaplan-Meier and Cox hazard models. Proportions in recurrence rate and pattern of recurrence were evaluated using the Fisher exact test. RESULTS: Overall, 83 women were included in the endometriosis-associated ovarian cancer group and 144 in the non-endometriosis-associated ovarian cancer group, respectively. Patients included in the non- endometriosis-associated ovarian cancer group had a shorter disease-free survival than those in the endometriosis-associated ovarian cancer group (23.4 (range 2.0-168.9) vs 60.9 (range 4.0-287.8) months; p<0.001). Univariable and multivariable analyses showed that the association with endometriosis, previous hormonal treatment, early stage at presentation, and endometrioid histology were related to better disease-free survival in the entire study population. Similarly, patients in the non-endometriosis-associated ovarian cancer group had a shorter median (range) overall survival than those in the endometriosis-associated ovarian cancer group (54.4 (range 0.7-190.6) vs 77.6 (range 4.5-317.8) months; p<0.001). Univariable and multivariable analyses showed that younger age at diagnosis, association with endometriosis, and early stage at presentation were related to better overall survival. The recurrence rate was higher in the non-endometriosis-associated ovarian cancer group (63/144 women, 43.8%) than in the endometriosis-associated ovarian cancer group (17/83 women, 20.5%; p<0.001). CONCLUSIONS: Endometriosis-associated ovarian cancer patients had significantly longer disease-free survival and overall survival than non-endometriosis-associated ovarian cancer patients, while the recurrence rate was higher in non-endometriosis-associated ovarian cancer patients.

Patient satisfaction with ultrasound, whole-body CT and whole-body diffusion-weighted MRI for pre-operative ovarian cancer staging: a multicenter prospective cross-sectional survey.

BACKGROUND: In addition to the diagnostic accuracy of imaging methods, patient-reported satisfaction with imaging methods is important. OBJECTIVE: To report a secondary outcome of the prospective international multicenter Imaging Study in Advanced ovArian Cancer (ISAAC Study), detailing patients' experience with abdomino-pelvic ultrasound, whole-body contrast-enhanced computed tomography (CT), and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) for pre-operative ovarian cancer work-up. METHODS: In total, 144 patients with suspected ovarian cancer at four institutions in two countries (Italy, Czech Republic) underwent ultrasound, CT, and WB-DWI/MRI for pre-operative work-up between January 2020 and November 2022. After having undergone all three examinations, the patients filled in a questionnaire evaluating their overall experience and experience in five domains: preparation before the examination, duration of examination, noise during the procedure, radiation load of CT, and surrounding space. Pain perception, examination-related patient-perceived unexpected, unpleasant, or dangerous events ('adverse events'), and preferred method were also noted. RESULTS: Ultrasound was the preferred method by 49% (70/144) of responders, followed by CT (38%, 55/144), and WB-DWI/MRI (13%, 19/144) (p<0.001). The poorest experience in all domains was reported for WB-DWI/MRI, which was also associated with the largest number of patients who reported adverse events (eg, dyspnea). Patients reported higher levels of pain during the ultrasound examination than during CT and WB-DWI/MRI (p<0.001): 78% (112/144) reported no pain or mild pain, 19% (27/144) moderate pain, and 3% (5/144) reported severe pain (pain score >7 of 10) during the ultrasound examination. We did not identify any factors related to patients' preferred method. CONCLUSION: Ultrasound was the imaging method preferred by most patients despite being associated with more pain during the examination in comparison with CT and WB-DWI/MRI. TRIAL REGISTRATION NUMBER: NCT03808792.

Comparison of the ADNEX and ROMA risk prediction models for the diagnosis of ovarian cancer: a multicentre external validation in patients who underwent surgery.

BACKGROUND: Several diagnostic prediction models to help clinicians discriminate between benign and malignant adnexal masses are available. This study is a head-to-head comparison of the performance of the Assessment of Different NEoplasias in the adneXa (ADNEX) model with that of the Risk of Ovarian Malignancy Algorithm (ROMA). METHODS: This is a retrospective study based on prospectively included consecutive women with an adnexal tumour scheduled for surgery at five oncology centres and one non-oncology centre in four countries between 2015 and 2019. The reference standard was histology. Model performance for ADNEX and ROMA was evaluated regarding discrimination, calibration, and clinical utility. RESULTS: The primary analysis included 894 patients, of whom 434 (49%) had a malignant tumour. The area under the receiver operating characteristic curve (AUC) was 0.92 (95% CI 0.88-0.95) for ADNEX with CA125, 0.90 (0.84-0.94) for ADNEX without CA125, and 0.85 (0.80-0.89) for ROMA. ROMA, and to a lesser extent ADNEX, underestimated the risk of malignancy. Clinical utility was highest for ADNEX. ROMA had no clinical utility at decision thresholds <27%. CONCLUSIONS: ADNEX had better ability to discriminate between benign and malignant adnexal tumours and higher clinical utility than ROMA. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT01698632 and NCT02847832.

Sentinel lymph node biopsy in endometrial cancer: When, how and in which patients.

The role of nodal dissection in patients with endometrial cancer has been intensively studied in several studies. Historically, systematic pelvic and para-aortic lymphadenectomy represented the gold standard surgical treatment to assess potential nodal involvement and consequently define the appropriate stage of the tumor. Over the last years, sentinel node biopsy (SLNB) has been introduced as a more targeted alternative to lymph node dissection for lymph node staging and it has become popular among gynecologic oncologists. However, no level A evidence is still available, and several features of the SLNB technique have been matter of discussion among clinicians and a universally accepted methodology is still not currently available. This narrative review aims to summarize the body of knowledge on SLNB to offer the reader a complete picture about the evolution of this technique over the last decades.

Epidemiology of infertility in women with endometriosis.

Endometriosis is a benign, chronic, inflammatory condition affecting up to 10 % of women and characterised by the presence of glands and stroma tissue outside the uterus. Epidemiological and clinical studies demonstrate a consistent association between endometriosis and infertility. However, this relationship is far to be clearly understood and several mechanisms are involved. Available data show that patients with endometriosis have an increased estimated risk of infertility between two and four times compared with the general population. On the other hand, the probability of patients with infertility to have endometriosis is reported up to about 50 % of the cases. Future studies should aim to better elucidate the mechanisms behind endometriosis-associated infertility in order to offer the more appropriate and tailored management for the patients.