Nomogram Predicting the Likelihood of Parametrial Involvement in Early-Stage Cervical Cancer: Avoiding Unjustified Radical Hysterectomies

Background: We aimed to establish a tool predicting parametrial involvement (PI) in patients with early-stage cervical cancer and select a sub-group of patients who would most benefit from a less radical surgery. Methods: We retrospectively reviewed patients from two prospective multicentric databases—SENTICOL I and II—from 2005 to 2012. Patients with early-stage cervical cancer (FIGO 2018 IA with lympho-vascular involvement to IIA1), undergoing radical surgery (hysterectomy or trachelectomy) with bilateral sentinel lymph node (SLN) mapping with no metastatic node or PI on pre-operative imaging, were included. Results: In total, 5.2% patients (11/211) presented a histologic PI. After univariate analysis, SLN status, lympho-vascular space invasion, deep stromal invasion and tumor size were significantly associated with PI and were included in our nomogram. Our predictive model had an AUC of 0.92 (IC95% = 0.86–0.98) and presented a good calibration. A low risk group, defined according to the optimal sensitivity and specificity, presented a predicted probability of PI of 2%. Conclusion: Patients could benefit from a two-step approach. Final surgery (i.e. radical surgery and/or lymphadenectomy) would depend on the SLN status and the probability PI calculated after an initial conization with bilateral SLN mapping

<< Low-volume metastases >> dans le cancer débutant du col de I'utérus

Le cancer du col utérin est le deuxième cancer de la femme et la troisième cause de décès liés au cancer. L'incidence et la mortalité du cancer du col varient d'un pays à I'autre et ont diminué grâce à la mise en place de programmes de dépistage, l'éducation des patientes, une modification des comportements sexuels et la mise en place de la vaccination anti-HpV. Le statut ganglionnaire constitue un facteur pronostique majeur des cancers du col utérin aux stades précoces ayant justifié son intégration dans la dernière révision de la classification FIGO 2018. Dans cette nouvelle classification, les patientes avec des macrométastases ou micrométastases (MlC) sont classées lllC. La présence de cellules tumorales isolées (lTC) ne change cependant pas le stade. De plus, l'impact clinique et la prise en charge de ces low-volume metastases (MlC et ITC) n'est pas consensuelle. A partir des données prospectives des cohortes SENTICOL I et SENTICOL ll, nous avons évalué la validité et l'impact des ITC et des MIC dans les cancers du col utérin aux stades précoces. Les bases de données de 2 études prospectives multicentriques françaises (sENTlcOL I et ll) ont été analysées' SENTICOL I était une étude prospective qui évaluait la valeur diagnostique du ganglion sentinelle {GS} dans les cancers du col utérin. Entre 2005 et 2007,139 patientes avec un cancer du col aux stades précoces (lA1 avec emboles jusqu'à llAl) et sans ganglions suspects à l'imagerie, ont été incluses. SENTICOL ll était un essai prospectif randomisé qui évaluait la morbidité et la qualité de vie du ganglion sentinelle. Entre 2009 et 2012, 267 patientes ont été incluses et 206 patientes avec des ganglions sentinelles négatifs à l'examen extemporané ont été randomisées dans les bras GS seuls (105 patientes) et GS associés à un curage pelvien (101 patientes). Au total, 28 centres français ont participé aux 2 études. Dans la cohorte SENTICOL I incluant 139 patientes, au moins un GS a été détecté chez 13G patientes (97.80/.1, et de manière bilatérale chez 104 patientes (74.8%1. Au total,454 GS et 2055 ganglions non-sentinelles (cNS) ont été analysés. Après ultrastadification et relecture centralisée, 23 patientes avaient des G5 positifs et 6 patientes de GNS positifs (3 MAC, 2 MIC et 1 ITC). En cas de détection unilatérale, le taux de faux négatif était de 3% (1/32) et la valeur prédictive négative était de 97% (C95% = [80-100]). En cas de détection bilatérale, aucun cas de faux-négatifs n'était rapporté et la valeur prédictive négative était de 100%. Au cours du suivi des 139 patientes de la cohorte SENTICoL I (médiane de 36 mois [1-69]], 13 récidives ont été diagnostiquées :2 parmi les patientes avec GS métastatiques (1 MAc et 1 MIC) et 11 parmi les patientes sans atteinte ganglionnaire. Aucune récidive n'avait été mise en évidence chez les I patientes avec des ITC et uniquement une seule récidive parmi les 8 patientes avec des MlC. Dans cette cohorte, la présence de ITC ou de MIC n'avait pas d'impact sur la survie. Ces résultats ont été confirmés par une analyse poolée avec la cohorte SENTICOL ll. Parmi les 321 patientes analysées, 13 patientes avaient des lTÇ 11 des MlC, 17 MAC et 280 étaient indemnes de métastases ganglionnaires. La présence de métastases de faible volume était associée significativement evec la présence d'emboles lymphovasculaires (p=g.621 et des stades plus avancés (p=0.02). la survie des patientes avec des MIC ou des ITC étaient similaires à celles des patientes sans métastases ganglionnaires (92.7% versus 93.6%, p=0.99). Habituellement seuls les GS sont analysés par ultrastadification tandis que les GNS ne sont analysés que par une technique standard. Or, les métastases de faible volume sont souvent ratées par l'analyse standard. L'étude SENTICOL publiée en 2011 avait montré une excellente prédiction du statut ganglionnaire pelvien en cas de détection bilatérale du G5. Les résultats initialement publiés prenaient en compte l'ultrastadification des GS mais pas celui des GNS. cette cohorte a donc fait I'objet d'une relecture centralisée de tous les GN5 par ultrastadification. Cette analyse secondaire a confirmé la fiabilité de la technique du GS car même les métastases de faible volume dans les GNS ne sont pas manquées en cas de détection bilatérale du GS. Conclusions: L'analyse de Senticol I a permis de démontrer que la présence de low-volume metastases n'avait pas d'impact sur la survie sans récidive nisur la survie globale. ll s'agissait de la première analyse prospective évaluant I'impact des métastases de faible volume sur le risque de récidive à 3 ans. Ces résultats initiaux ont été confirmés par une analyse poolée des 2 cohortes SENTICOL I et ll. En ce qui concerne la prise en charge thérapeutique des low-volume metastases, on peut estimer que la radiothérapie n'est pas utile en adjuvant dans ces circonstances de petite atteinte ganglionnaire, car son administration ne change pas la survie globale ni la survie sans récidive de ces patientes. Nous avons publié 4 articles sur ce sujet : 1. Benedetta Guani et aI. IMPACT OF MICROMETASTASIS OR ISOLATED TUMOR CELLS ON RECURRENCE AND SURVIVAL IN PATIENTS WITH EARTY CERVICAL CANCER: SENTICOL TRIAL. lnternational Journal of Gynecologic Cancer 2019;29;447-452 2. Benedetta Guani et aI. THE CLINICAL IMPACT OF LOW-VOLUME LYMPH NODAL METASTASES IN EARLY-STAGE CERVICAL CANCER: THE SENTICOL 1 AND SENTICOL 2 TRIALS. Cancers 2020, 12 (5), 1061 3. P. Mathevet, B. Guani et aI. HISTOPATHOLOGIC VALIDATION OF THE SENTINEL NODE TECHNIQUE FOR EARLY-STAGE CERVICAL CANCER PATIENTS. Ann Surg Oncol https: / / doi.org/10.1245/ s10434-020-09328-2 4. B.Guani, P. Mathevet. VALIDATION BASED ON LOW-VOLUME METASTASIS OF THE SENTINEL LYMPH NODE BIOPSY IN EARLY-STAGE CERVICAL CANCER. Ann Surg Oncol, DOl : 10.1245/s10434-020-09353-

The Clinical Impact of Low-Volume Lymph Nodal Metastases in Early-Stage Cervical Cancer: The Senticol 1 and Senticol 2 Trials

Background: With the development of the sentinel node technique in early-stage cervical cancer, it is imperative to define the clinical significance of micrometastases (MICs) and isolated tumor cells (ITCs). Methods: We included all patients who participated in the Senticol 1 and Senticol 2 studies. We analyzed the factors associated with the presence of low-volume metastasis, the oncological outcomes of patients with MIC and ITC and the correlation of recurrences and risk factors. Results: Twenty-four patients (7.5%) had low-volume metastasis. The risk factors associated with the presence of low-volume metastasis were a higher stage (p = 0.02) and major stromal invasion (p = 0.01) in the univariate analysis. The maximum specificity and sensitivity were found at a cutoff of 8 mm of stromal invasion. In multivariate analysis, the higher stage (p = 0.02) and the positive lymphovascular space invasion (p = 0.02) were significantly associated with the MIC and ITC. Patients with low-volume metastasis had similar disease-free survival (DFS) (92.7%) to node-negative patients (93.6%). The addition of adjuvant treatment in presence of low-volume metastasis did not modify the DFS. Conclusions: These results confirm our previous analysis of Senticol 1: the presence of low-volume metastasis did not decrease the DFS in early-stage cervical cancer patients

Histopathologic Validation of the Sentinel Node Technique for Early-Stage Cervical Cancer Patients

International audienceAbstract Background The sentinel lymph node (SLN) biopsy may be an alternative to systematic lymphadenectomy in early cervical cancer. The SLN biopsy is less morbid and has been shown to have high sensitivity for metastasis detection. However, the sensitivity of the SLN technique might be overevaluated because SLNs are examined with ultra-staging, and non-sentinel nodes usually are examined only with routine techniques. This study aimed to validate the negative predictive value (NPV) of the SLN technique by the ultra-staging of SLNs and non-sentinel nodes (NSLNs). Methods The SENTICOL 1 study data published in 2011 were used. All nodes (i.e., SLNs and NSLNs) were secondarily subjected to ultra-staging. The ultra-staging consisted of sectioning every 200 µm, in addition to immunohistochemistry. Moreover, the positive slides and 10% of the negative slides were reviewed. Results The study enrolled 139 patients, and SLNs were detected in 136 (97.8%) of these patiets. Bilateral SLNs were detected in 104 (76.5%) of the 136 patients. A total of 2056 NSLNs were identified (median, 13 NSLNs per patient; range 1–54). Of the 136 patients with SLNs, 23 were shown to have positive SLNs after serial sectioning and immunohistochemical staining. The NSLNs were metastatic in six patients. In the case of bilateral SLN detection, the NPV was 100%, with no false-negatives (FNs). Conclusions The pelvic SLN technique is safe and trustworthy for determining the nodal status of patients with early-stage cervical cancer. In the case of optimal mapping with bilateral detection, the NPV was found to be 100%

Endometriosis and Infertility: Prognostic Value of #Enzian Classification Compared to rASRM and EFI Score

This study&rsquo;s objective was to compare the predictive validity of the three most utilized classification scores for endometriosis, #Enzian, EFI, and rASRM, in achieving a spontaneous pregnancy or pregnancy via assisted reproductive technology (ART) after surgery for endometriosis. The monocentric retrospective study was carried out from January 2012 to December 2021 at the gynaecology department of the cantonal hospital of Fribourg. Patients consulting for infertility and operated on for endometriosis with histological confirmation were included. The predictive value of #Enzian, rASRM, and EFI was evaluated and compared concerning the prediction of fertility after surgery, both spontaneous and ART, during the following 12 months. A total of 58 women (mean age 33.1 &plusmn; 4.57 years) were included. Overall, 30 women achieved a pregnancy, seven spontaneously. Among all women who achieved a pregnancy, there was a lower prevalence of rASRM stage III&ndash;IV (16.67% vs. 39.29%, p = 0.054). Women achieving a pregnancy had a significantly higher EFI score than others (p &lt; 0.05). No significant differences were observed concerning the #Enzian score. In conclusion, the revised #Enzian score is not correlated with pregnancy achievement; EFI score is the only score significantly associated with the pregnancy outcome in women affected by endometriosis

Validation of the 2018 FIGO Classification for Cervical Cancer: Lymphovascular Space Invasion Should Be Considered in IB1 Stage

Background: The aim of this study was to assess the prognostic impact of Lymphovascular space invasion (LVSI) in IB1 stage of the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) classification for cervical cancer. Methods: A secondary analysis of two French prospective multicentric trials on Sentinel Lymph node biopsy for cervical cancer was performed. Patients with 2009 FIGO IB1 stage who underwent radical surgery between January 2005 and July 2012 from 28 French expert centers were included. The stage was modified retrospectively according to the new 2018 FIGO staging system. Results: According to the 2009 FIGO classification, 246 patients had IB1 disease stage and fulfilled the inclusion criteria. The median follow-up was 48 months (4–127). Twenty patients (8.1%) experienced a recurrence, and the 5-year Disease Free Survival (DFS) was 90.0%. Compared to 2018 IB1 staged patients, new IB2 had significantly decreased 5-year DFS, 78.6% vs. 92.9%, p = 0.006 whereas IIIC patients had similar 5-year DFS (91.7%, p = 0.95). In the subgroup of patients with FIGO 2018 IB1 stage, the presence of LVSI was associated with a significant decrease in DFS (82.5% vs. 95.8%, p = 0.04). Conclusions: LVSI is associated with decreased 5-year DFS in IB1 2018 FIGO stage and LVSI status should be considered in early-stage cervical cancer for a more precise risk assessment

Adenomyosis: An Updated Review on Diagnosis and Classification

Adenomyosis is a commonly diagnosed benign condition characterized by the presence of ectopic endometrial glands within the underlying myometrium. The most common presenting signs and symptoms are abnormal uterine bleeding, chronic pelvic pain, and infertility. The clinical relevance of this condition is evident in both medical and surgical care. Histopathology and imaging studies are used for the diagnosis and classification of adenomyosis, which are hallmarks of the advancement of our ability to diagnose adenomyosis. Importantly, the diagnosis and classification of adenomyosis lacks standardization due to the nature of imaging techniques, features of adenomyosis, and the clinical spectrum of adenomyosis. We reviewed the literature to summarize the available classification systems for adenomyosis and highlight the different imaging approaches and histologic criteria used in diagnosis. Despite the high prevalence of the disease, there is no clear consensus on one classification system. We provide a review of some of the classification systems available and discuss their strengths and limitations