Die neue FIGO-Klassifikation © AGO

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Ivo Meinhold-Heerlein, Aachen

AGO State of the Art 2013 22. Juni 2013 Berlin

Cancer of Ovary, Fallopian Tube and Peritoneum: FIGO staging © AGO

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 Deliberations on October 7th, 2012 in Roma at Fieri Di Roma  FIGO GYNAECOLOGY ONCOLOGY COMMITTEE in collaboration with ESGO, UICC, AJCC, SGO, GCIG, IGCS

Cancer of Ovary, Fallopian Tube and Peritoneum: FIGO staging © AGO

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The process of the proposed changes to staging of Ovarian Cancer (OV), Fallopian Tube (FT) and Primary Peritoneal Cancer (PPC) started 3 years ago with a proposal that was sent to all relevant gynaecology oncology organisations and societies throughout the world and input was collated, evaluated and formulated into the staging that is presented below. All suggestions are based on the best AVAILABLE evidence. The committee acknowledges that there are areas that are not supported by strong evidence and have been careful to ensure that changes are not made without quality evidence. The new staging below was reached by consensus of all participating in the meeting on October 7th, 2012, some of whom were representatives of their organisations. The new staging was presented to the FIGO EXCECUTIVE BOARD on Friday 12th October 2012 and approved two weeks later. The proposal will now be presented to the boards of UICC and AJCC. Only once approval has been given from these organisations will FIGO be able to publish the new staging globally.

Cancer of Ovary, Fallopian Tube and Peritoneum: FIGO staging © AGO

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FIGO OV FT P X

TNM Primary tumor, ovary Tov Primary tumor, fallopian tube Tft Primary tumor, peritoneum Tp Primary tumor cannot be assessed Tx

Molecular similarity of SBOT/SCA-G1 and SCA-G2/3 tumors © AGO

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Meinhold-Heerlein et al., 2005: Molecular and prognostic distinction between serous ovarian tumors of varying grade and malignant potential. Oncogene 24 (6), 1053-65

Pathogenesis of serous ovarian cancer: Progression Model © AGO

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Type I tumors Genetically stable KRAS/BRAF, β-Catenin, PTEN, ErbB2 mutations LOH Ch1p+Ch19q Unique gene expression Type II tumors De novo Aggressive Genetically unstable TP53 mutations Unique gene expression Shih and Kurman, 2005: Ovarian Tumorigenesis – A Proposed Model Based on Morphological and Molecular Genetic Analysis American Journal of Pathology 164 (5), 1511-18

Fallopian tube: Origin of high grade ovarian cancer? © AGO

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Serous tubal intraepithelial cancers (STICs): Origin of Type II cancer? Ovarian cancer is of Müllerian, not mesothelial cell type! STICs are concomitant and molecular identical with ovarian cancer. p53 Mutations in normal tubal tissue identical with concomitant ovarian cancer. Peritoneal washings of patients without cancer showed STIC cells.

Kurman and Shih, 2010: The Origin and Pathogenesis of Epithelial Ovarian Cancer – A Proposed Unifying Theory American Journal of Surgical Pathology 34 (3), 433-443

Paradigm of serous ovarian cancer development © AGO

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Kurman and Shih, 2010: The Origin and Pathogenesis of Epithelial Ovarian Cancer – A Proposed Unifying Theory American Journal of Surgical Pathology 34 (3), 433-443

Histological subtype © AGO

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 High Grade Serous (HGS)

 Endometrioid (E)  Clear Cell (CC)  Mucinous (M)

 Low Grade Serous (LG)  Other or cannot be classified (O)  Germ Cell (GC)  Sex-Cord Stromal Cell Tumor (SC)

FIGO Stage I © AGO

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FIGO I Tumor confined to ovaries or fallopian tube(s) Tumor limited to the ovaries (one or both)

TNM T1

IA

Tumor limited to one ovary (capsule intact) or fallopian tube No tumor on ovarian or fallopian tube surface No malignant cells in the ascites or peritoneal washings Tumour limited to one ovary; capsule intact No tumour on ovarian surface No malignant cells in ascites or peritoneal washings

T1a

IB

Tumor limited to both ovaries (capsules intact) or fallopian tubes T1b No tumor on ovarian or fallopian tube surface No malignant cells in the ascites or peritoneal washings Tumour limited to both ovaries; capsule intact No tumour on ovarian surface No malignant cells in ascites or peritoneal washings

FIGO Stage I © AGO

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New Old FIGO IC Tumor limited to one or both ovaries or fallopian tubes, with any of the following: Tumour limited to one or both ovaries with any of the following: Capsule ruptured, tumour on ovarian surface, malignant cells in ascites or peritoneal washings IC1 Surgical spill intraoperatively

IC2 Capsule ruptured before surgery or tumor on ovarian or fallopian tube surface IC3 Malignant cells in the ascites or peritoneal washings

TNM T1c

FIGO Stage II © AGO

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New Old FIGO TNM II Tumor involves one or both ovaries or fallopian tubes with pelvic T2 extension (below pelvic brim) or primary peritoneal cancer (Tp) Tumour involves one or both ovaries with pelvic extension IIA Extension and/or implants on the uterus and/or fallopian tubes/and/or ovaries Extension and/or implants on uterus and/or tube(s); no malignant cells in ascites or peritoneal washings

T2a

IIB Extension to other pelvic intraperitoneal tissues Extension to other pelvic tissues No malignant cells in ascites or peritoneal washings

T2b

IIC Pelvic extension (IIa or IIb) with malignant cells in ascites or peritoneal washings

T2c

FIGO Stage III © AGO

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New Old FIGO III Tumor involves one or both ovaries, fallopian tubes, or primary peritoneal cancer, with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastasis to the retroperitoneal lymph nodes Tumour involves one or both ovaries with microscopically Confirmed peritoneal metastasis outside the pelvis and / or regional lymph node metastasis

TNM T3

FIGO Stage III © AGO

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New Old FIGO IIIA

IIIA1

Metastasis to the retroperitoneal lymph nodes with or without microscopic peritoneal involvement beyond the pelvis Microscopic peritoneal metastasis beyond pelvis

TNM T1, T2, T3aN1

Positive retroperitoneal lymph nodes only (cytologically or histologically proven) IIIA1 (i) Metastasis ≤ 10 mm in greatest dimension IIIA1 (ii) Metastasis > 10 mm in greatest dimension

IIIA2

Microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes

T3a, T3aN1

FIGO Stage III © AGO

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New Old

IIIB Macroscopic peritoneal metastases beyond the pelvic brim ≤ 2 cms in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes Macroscopic peritoneal metastasis beyond the pelvis, 2 cm or less in greatest dimension.

T3b/T3bN1

IIIC Macroscopic peritoneal metastases beyond the pelvic brim

T3c/T3cN1

> 2 cms in greatest dimension, with or without metastases to the retroperitoneal nodes (includes extension of tumor to capsule of liver and spleen without parenchymal involvement of either organ) Peritoneal metastasis beyond pelvis, more than 2 cm in greatest dimension and / or regional lymph node metastasis

FIGO Stage IV © AGO

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New Old IV

Distant metastasis excluding peritoneal metastases Distant metastasis (excludes peritoneal metastasis)

IVA: Pleural effusion with positive cytology IVB:

Note:

Metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside of abdominal cavity) Parenchymal metastases are Stage IV B

Any T, Any N, M1

Stage Grouping © AGO

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FIGO IA IB IC IIA IIB IIC IIIA

IIIB IIIC IV

T T1a T1b T1c T2a T2b T2c T3a T3a T3b T3b T3c T3c Any T

N N0 N0 N0 N0 N0 N0 N0 N1 N0 N1 N0 N1 Any N

M M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M0 M1

Notes © AGO

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1. The primary site - i.e. ovary, fallopian tube or peritoneum – should be designated where possible. In some cases, it may not be possible to clearly delineate the primary site, and these should be listed as ‘undesignated’. 2. The histologic type of should be recorded. 3. The staging includes a revision of the stage III patients and allotment to stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination, because an analysis of these patients indicates that their survival is significantly better than those who have intraperitoneal dissemination. 4. Involvement of retroperitoneal lymph nodes must be proven cytologically or histologically. 5. Extension of tumor from omentum to spleen or liver (Stage III C) should be differentiated from isolated parenchymal splenic or liver metastases (Stage IVB)

Vielen Dank für die Aufmerksamkeit! © AGO

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