The new FIGO classification in endometrial carcinoma

The new FIGO classification in endometrial carcinoma Poster No.: C-1073 Congress: ECR 2012 Type: Educational Exhibit Authors: A. IGLESIAS CASTAÑON, M. Arias Gonzales, J. Mañas Uxó, 1 2 1 2 2 2 B. NIETO BALTAR ; VIGO/ES, Vigo/ES Keywords: Pelvis, MR, Diagnostic procedure, Neoplasia DOI: 10.1594/ecr2012/C-1073 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 25

Learning objectives To get familiar with the new FIGO staging of endometrial carcinoma (published in January 2010) To correlate the new FIGO staging and the magnetic resonance imaging (MRI) findings in endometrial carcinoma To show the impact of the new FIGO staging of endometrial carcinoma in the treatment planning Background Endometrial carcinoma is the most common malignancy of the female reproductive tract. Incidence is rising because of increased life expectancy and obesity. Most of the times (75-90%) it presents with abnormal uterine (intermenstrual or posmenopausal) bleeding. Diagnosis requires hystopathological confirmation (biopsy or curettage). Adverse risk factors are age, positive lymphovascular invasion, tumor size and cervical involvement. The WHO defines the following histological classification for endometrial carcinomas: Endometriod type (the most common 80-90%) - Grade G1 (well formed glands with no more than 5% solid non-squamous areas) - Grade G2 (6% - 50% solid non squamous areas) - Grade G3 (more than 50% solid non-squamous areas) Serous papillary adenocarcinoma (incidence 5-10%) (Grade G3) Clear cell adenocarcinoma (incidence 1-5%) (Grade G3) Mucinous carcinoma Page 2 of 25

Mixed carcinoma Squamous cell carcinoma Undifferentiated carcinoma In both serous papillary and clear cell adenocarcinomas, the risk of extrauterine disease does not correlate with the depth of myometrial invasion, because nodal or intraperitoneal metastases can be found even when there is no myometrial invasion. For this reason they are classified directly as grade G3 tumors. The International Federation of Gynecology and Obstetrics (FIGO) has been defining the staging and initial treatment in endometrial carcinoma since 1988. The purposes of this staging system are to allow comparison of patients between centers and to be able to classify patients and their tumors into prognostic groups. FIGO was the first organization to develop and propose rules for classification and staging of gynecologic cancers in 1958. In 1966 the UICC (International Union Against Cancer), and in 1976 the AJCC (American Joint Commission on Cancer) established their own staging system. FIGO, UICC and AJCC have tried to coordinate their efforts to adopt a single staging system since then. In 1971 a new FIGO classification for endometrial carcinoma was proposed using the clinical staging but adding the prognostic factor of the grade of the tumor. The size of the uterus (less than or greater than 8 cm in depth) was used to differentiate between Stage IA and IB, and with the addition of the histological differentiation, six substages within stage I were defined. In the 1970s and early 1980s, several studies with systematic evaluation of surgicalpathological spread pattern, with emphasis on the pelvis and para-aortic lymph nodes were carried out showing that 25% patients with clinical Stage I endometrial carcinoma presented disease outside of the corpus. Pelvic lymph nodes were involved with an increasing frequency as the grade of the tumor became more poorly differentiated and as the depth of myometrial invasion increased. As a result of these studies, in 1988, the FIGO decides that endometrial carcinoma should be surgically staged. The myometrium is divided in two halves and three types of stage I are defined: Stage IA: Tumor limited to the endometrium Stage IB: Tumor in the inner one-half Page 3 of 25

Stage IC: Tumor in the outer one-half of the myometrium When applying the histologic grade of the tumor, there were now nine substages within Stage I of endometrial carcinoma. At the same time, the more advanced extent of the disease was categorized appropriately. For instance, lymph node metastases were classified as stage IIIC even if invasion in the myometrium was superficial and the histological grade 1 or 2. For the following 20 years, a large amount of data of different individual institutions around the world were collected and analyzed by the FIGO, to better identify prognostic factors, and apply these to individual patients, with a new FIGO classification for endometrial carcinoma appearing in January 2010. Imaging findings OR Procedure details The main changes in the new FIGO classification for endometrial carcinoma appearing in January 2010 are: Combination of stage IA and IB Stage II (cervical stromal invasion) no longer has a subset A and B There is no stage for parametrial invasion, this is now a IIIB Stage IIIC is categorized as IIIC1 (positive pelvic nodes) or IIIC2 (positive para-aortic nodes with or without positive pelvic nodes) Citology has been eliminated as a staging criteria Uterine sarcomas have their own separate staging system 1) Combination of stage IA and IB Stage I states for the 80% of endometrial carcinomas. In the face of negative nodes little survival difference between no myometrial invasion and less than 50% invasion was observed. Incidence of metastatic lymph nodes (pelvic, paraaortic or both) changes from 3% in stage IA, to 46% in stage IB, that's why stage IA requires lymph node sampling and stage IB requires radical lymphadenectomy. Page 4 of 25

Now Stage IA means endometrial carcinoma involving the endometrium and/or less than one-half of the myometrium and Stage IB is endometrial carcinoma involving equal to or greater than 50% of the myometrium. The three histological grades still apply, so substages within Stage I, decrease now from nine to six. 2) Stage II (cervical stromal invasion)no longer has a subset A and B Involvement in the endocervical glandular portion of the cervix that does not invade the stroma (stage IIA in prior classification) is now considered Stage I. 3) There is no stage for parametrial invasion, this is now a IIIB. 4) Stage IIIC is categorized as IIIC1 (positive pelvic nodes) and IIIC2 (positive para-aortic nodes with or without positive pelvic nodes). Pelvic and para-aortic node involvement has been separated to better evaluate prognosis. Prognosis is worse if para-aortic nodes are involved. 5) Citology has been eliminated as staging criteria though it must be reported. Sampling of washings is highly variable and offers widely disparate survival data results. 6) Uterine sarcomas have their own separate staging system based on the criteria used in the other soft tissue sarcomas and because survival is different in endometrial carcinoma and uterine sarcomas. Comparison between previous (2000) FIGO classification and actual (January 2010) classification is made in the following figure: Page 5 of 25

Fig. 1: 1 References: M. Arias Gonzales; Vigo, SPAIN Main changes in both classifications are summarized in the following figure: Page 6 of 25

Fig. 2: 2 References: M. Arias Gonzales; Vigo, SPAIN Main PROGNOSTIC FACTORS defined in endometrial carcinoma are: 1) Metastatic disease in regional lymph nodes, which is the most important prognostic factor in carcinomas clinically confined to the uterus. 2) Grade of the tumor and depth of myometrial invasion. Both are important prognostic factors, and surgeon must be aware that preoperative endometrial biopsy does not accurately correlate with final tumor grade and depth of myometrial invasion. 3) Lymphovascular space involvement of the myometrium, as when it is present increases the probability of nodal metastases. 4) Histological type, because serous papillary and clear cell adenocarcinomas have a higher incidence of nodal or intraperitoneal metastases and are directly classified as grade 3 tumors. Page 7 of 25

MANAGEMENT of patients with endometrial carcinoma includes: 1) Screening Endovaginal ultrasound is the technique of choice in the screening of endometrial carcinoma, as it is highly reliable and cheap. MRI can help in some patients, when ultrasound is inconclusive. 2) Diagnosis Diagnosis of endometrial carcinoma has to be established with an endometrial biopsy 3) Presurgical staging The endometrial biopsy establishes the histological grade but there is a 25-32% of disagreement between histological type and grade before and after surgery. Imaging is needed before surgery to define depth of myometrial invasion, cervical stroma invasion, lymph nodes and extrauterine extension. Imaging should identify low risk patients in order to tailor treatment. Endovaginal ultrasound offers a global accuracy of 70-80% whereas MRI global accuracy is up to 85-93%. 4) Surgical staging Intraoperative biopsy gives the final staging for endometrial carcinoma. The following cases show the MRI findings in endometrial carcinoma and the correlation with the new FIGO staging. CASE 1 Page 8 of 25

myometrium with an intact stripe of normal outer myometrium that excludes uterine serosa invasion This was a previous FIGO classification IC (invasion into myometrium of more than one half). In the new FIGO classification it is IB (invasion into myometrium of more than one half). References: M. Arias Gonzales; Vigo, SPAIN CASE 3 Fig. 5: 5. Sagittal T2 weighted (A), coronal T2 weighted (B) and fat saturated sagittal contrast enhanced T1 weighted (C) images show a diffusely thickened endometrium with disruption of the junctional zone. Tumor extends less than 50% into the myometrium (arrowhead) and into the cervical canal. Normal enhancement of the cervical mucosa (arrow) excludes cervical stroma invasion This was a previous FIGO classification IIA (invasion of endocervical glands). In the new FIGO classification it is IA (limited to endometrium or invasion into myometrium less than or equal to one half). References: M. Arias Gonzales; Vigo, SPAIN CASE 4 Page 10 of 25

Fig. 6: 6. Sagittal T2 weighted (A), and fat saturated sagittal contrast enhanced T1 weighted (B) images show a diffusely thickened endometrium with disruption of the junctional zone. Tumor extends more than 50% into the myometrium (arrowhead) and into the cervical canal with disruption of the cervical stroma (arrows). This was a previous FIGO classification IIB (invasion of cervical stroma). In the new FIGO classification it is II (invasion of cervical stroma). References: M. Arias Gonzales; Vigo, SPAIN CASE 5 Fig. 7: Sagittal fat saturated contrast enhanced T1 weighted (A), sagittal T2 weighted (B) and coronal T2 weighted (C) images show an endometrial carcinoma extending into the cervical canal, invading the cervical stroma bilaterally and extending into Page 11 of 25

right parametrium (arrow). Hematometra. This was a previous FIGO classification IIB (invasion of cervical stroma). In the new FIGO classification it is IIIB (parametrial invasion). References: M. Arias Gonzales; Vigo, SPAIN CASE 6 Fig. 8: Axial fat saturated contrast enhanced T1 weighted images (A, B) show an enlarged (more than 1cm in short axis) right iliac lymph node (arrow) with heterogeneous internal signal, reflecting partial necrosis. This was a previous FIGO classification IIIC (spread to pelvic and/or paraaortic lymph nodes). In the new FIGO classification it is IIIC1 (spread to pelvic lymph nodes). References: M. Arias Gonzales; Vigo, SPAIN CASE 7 Page 12 of 25

Fig. 9: 9. Axial T2 weighted images (A, B) show a right retrocrural lymph node (arrow) and a left paraaortic lymph node (arrowhead). This was a previous FIGO classification IIIC (spread to pelvic and/or paraaortic lymph nodes). In the new FIGO classification it is IIIC2 (spread to paraortic lymph nodes with or without positive pelvic nodes). References: M. Arias Gonzales; Vigo, SPAIN To get the most accurate information from MRI images it is important to prepare the patient with fasting for six hours before examination to reduce artifact from bowel motion and a multichanel pelvic phased array coil must be used. High resolution T2-weighted fast spin-echo images in the axial, sagittal and coronal planes, perpendicular to the long axis of the uterine corpus for the evaluation of the primary tumor must be obtained. Sagittal and axial multiphase contrast-enhanced 3D T1-weighted fat-saturated images through the uterine corpus must be acquired: 0-1 minute: To identify the subendometrial zone 2-3 minutes (equilibrium): To evaluate deep myometrial invasion 4-5 minutes (delayed): To evaluate cervical stroma invasion Then, axial T2 weighted images with a large field of view to evaluate the entire pelvis and upper abdomen for lymphadenopathy must be performed. The following images show the utility of multiphase contrast-enhanced 3D T1-weighted fat-saturated images through the uterine corpus to appreciate disruption of the junctional zone. Page 13 of 25

Fig. 10: 10. Sagittal T2 weighted fast spin echo (A) and gadolinium enhanced fat suppressed T1 weighted in the early phase (1 minute) (B) show endometrial carcinoma with superficial myometrial invasion. Disruption of junctional zone which is better appreciated on T1 weighted images (arrows). References: M. Arias Gonzales; Vigo, SPAIN Why is preoperative MRI so useful? Five-year survival rates vary between 96% for stage I disease and 25% for stage IV disease. Prognosis depends on stage, depth of myometrial invasion, lymphovascular invasion, nodal status and hystologic grade. Surgical technique consists of an exploratory laparotomy, with total histerectomy, bilateral oophorectomy, peritoneal washing and in selected high risk patients, omental and peritoneal biopsies and lymphadenectomy. Preoperative local staging and distant lymph node involvement define the radicalness of surgery MRI is able to identify the size of the tumor, has proved to be the most accurate preoperative method in evaluating the depth of myometrial invasion (accuracy 65-91%), is also helpful to asses the extent of cervical invasion (accuracy 90-96%), can identify enlarged pelvic and lumboaortic lymph nodes, is able to identify patients Page 14 of 25

with parametrial, adnexal, bladder or rectal extension (cystoscopy and/or rectoscopy can be avoided. Negative predictive value = 100%). This MRI shows preoperative sigma infiltration (arrows) that will determine a transabdominal surgical approach in this patient. Fig. 11: 11 References: M. Arias Gonzales; Vigo, SPAIN So MRI can define accurately preoperatively some important prognostic factors Tumor size (smaller or greater than 2 cm) Depth of myometrial invasion (more or less than 50%) Cervical stroma invasion Lymph node size Extrauterine invasion Applying these to our individual patients assists in appropriate management, helping to determine the type of surgical approach or the planning of nonsurgical treatment options (radiotherapy or hormonal therapy) in high risk patients. HOW TO PROCEED There isn't any single reliable method to establish the individual risk in a patient with endometrial carcinoma, either presurgically or perisurgically. Page 15 of 25

As it has been shown, MRI is the most reliable technique to stage endometrial carcinoma before surgery, although it is not included in the FIGO stadification system. Surgical management in endometrial carcinoma is no uniform. A total abdominal hysterectomy and bilateral oophorectomy is the most common intervention Although a complete surgical staging includes lymphadenectomy, it is not generally considered justifiable in the management of early disease. Selection of patients on the basis of pre (MRI) and intraoperative prognostic information is being practiced in many centers to avoid the high morbidity rates of lymphadenopathy. Fig. 12: 12 References: M. Arias Gonzales; Vigo, SPAIN Images for this section: Page 16 of 25

Fig. 1: 1 Page 17 of 25

Fig. 2: 2 Page 18 of 25

Fig. 3: 3. Sagittal T2 weighted (A) and fat saturated contrast enhanced T1 weighted (B) images show a diffusely thickened endometrium with disruption of the junctional zone. Tumor extends less than 50% into the myometrium. This was a previous FIGO classification IB (invasion into myometrium less than or equal to one half). In the new FIGO classification it is IA (limited to the endometrium, or invasion into myometrium less than or equal to one half. Fig. 4: 4. Sagittal T2 weighted (A), axial T2 weighted (B) and fat saturated axial contrast enhanced T1 weighted (C) images show a diffusely thickened endometrium with disruption of the junctional zone. Tumor extends more than 50% into the myometrium with an intact stripe of normal outer myometrium that excludes uterine serosa invasion This was a previous FIGO classification IC (invasion into myometrium of more than one half). In the new FIGO classification it is IB (invasion into myometrium of more than one half). Fig. 5: 5. Sagittal T2 weighted (A), coronal T2 weighted (B) and fat saturated sagittal contrast enhanced T1 weighted (C) images show a diffusely thickened endometrium with disruption of the junctional zone. Tumor extends less than 50% into the myometrium Page 19 of 25

(arrowhead) and into the cervical canal. Normal enhancement of the cervical mucosa (arrow) excludes cervical stroma invasion This was a previous FIGO classification IIA (invasion of endocervical glands). In the new FIGO classification it is IA (limited to endometrium or invasion into myometrium less than or equal to one half). Fig. 6: 6. Sagittal T2 weighted (A), and fat saturated sagittal contrast enhanced T1 weighted (B) images show a diffusely thickened endometrium with disruption of the junctional zone. Tumor extends more than 50% into the myometrium (arrowhead) and into the cervical canal with disruption of the cervical stroma (arrows). This was a previous FIGO classification IIB (invasion of cervical stroma). In the new FIGO classification it is II (invasion of cervical stroma). Fig. 7: Sagittal fat saturated contrast enhanced T1 weighted (A), sagittal T2 weighted (B) and coronal T2 weighted (C) images show an endometrial carcinoma extending Page 20 of 25

into the cervical canal, invading the cervical stroma bilaterally and extending into right parametrium (arrow). Hematometra. This was a previous FIGO classification IIB (invasion of cervical stroma). In the new FIGO classification it is IIIB (parametrial invasion). Fig. 8: Axial fat saturated contrast enhanced T1 weighted images (A, B) show an enlarged (more than 1cm in short axis) right iliac lymph node (arrow) with heterogeneous internal signal, reflecting partial necrosis. This was a previous FIGO classification IIIC (spread to pelvic and/or paraaortic lymph nodes). In the new FIGO classification it is IIIC1 (spread to pelvic lymph nodes). Fig. 9: 9. Axial T2 weighted images (A, B) show a right retrocrural lymph node (arrow) and a left paraaortic lymph node (arrowhead). This was a previous FIGO classification IIIC (spread to pelvic and/or paraaortic lymph nodes). In the new FIGO classification it is IIIC2 (spread to paraortic lymph nodes with or without positive pelvic nodes). Page 21 of 25

Fig. 12: 12 Page 23 of 25

Conclusion New FIGO classification of endometrial carcinoma adapts better to different treatment options, taking into account several prognostic factors such as cervical stromal invasion or depth of myometrial invasion 1. - Stages IA and IB fuse into stage IA (myometrial depth invasion less than 50%) - Stage IC becomes stage IB (myometrial depth invasion # than 50%) - Stage IIA is included in stage I - Stage IIB becomes stage II (cervical stromal invasion) - Stage IIIB includes parametrial involvement - Stage IIIC divides into IIIC1 (pelvic lymph nodes) and IIIC2 (paraaortic lymph nodes) 2. 3. 4. 5. 6. MRI is necessary in the preoperative staging of endometrial carcinoma, as it can accurately evaluate most of the prognostic factors 1. 2. 3. 4. 5. - Tumor size (smaller or greater than 2 cm) - Depth of myometrial invasion (more or less than 50%) - Cervical stromal invasion - Lymph node size - Extrauterine invasion MRI can help in the appropriate management of endometrial carcinoma Personal Information Alfonso Iglesias Castañón Unidad de Diagnóstico por Imagen (Galaria) Complejo Hospitalario Universitario de Vigo Vigo SPAIN alfonso.iglesias.castanon@sergas.es Page 24 of 25

References The new FIGO staging system for cancers of the vulva, cervix, endometrium and sarcomas. Gynecologic Oncology. 2009; 115: 325-328 Magnetic resonance imaging of endometrial carcinoma. S. Peungjesada, P.R. Bhosale, A. Balachandran et al. J Comput Assist Tomogr. 2009; 33: 601-608 Page 25 of 25