FIGO Proposal for Staging Cancer of the Ovary, Fallopian Tube and ...

FIGO Proposal for StagingCancer of the Ovary,Fallopian Tube and PeritoneumFIGO Gynecology Oncology CommitteeRome, October 2012International Union Against Cancer (UICC)TNM Annual Meeting, May 2013

Organizations who gave input• AJCC• SGO• ESGO• GCIG• National cancer researchgroup of NationalInstitute for HealthResearch, UK• EORTC• UICC• IGCS• Korean Society of GynOncology• Japanese Society of GynOncology

Clinical Staging of Cancer of theOvary, Fallopian Tube andPeritoneum (FIGO 2012)

Clinical Staging of Cancer of the OvaryFallopian Tube and Peritoneum(FIGO 2012)OV Primary tumor, ovary TovFT Primary tumor, fallopian tube TftP Primary tumor, peritoneum TpU Primary tumor cannot be assessed Tu

Histologic Subtypes of OvarianCarcinomas• Serous – high grade• Serous – low grade• Clear cell• Endometrioid• Mucinous

New classification: FrequencyHG serousLG serousClear cellEndometrioidMucinousUnclassifiableTP44

HGCLGSCMCECCCC

Ovarian Carcinomas:Stage at presentation (early vs advanced) according toHistologic SubtypeStageClearCellEndometrioid Mucinous Low-GradeSerousHigh-GradeSerousCarcinomaNOSI-II 26.2% 29.4% 8.5% 1.9% 30% 4.0%III-IV 4.9% 3.5% 1.1% 4.9% 84.2% 1.4%All 10.4% 10.3% 3.6% 3.5% 70% 2.1%Gilks CB et al.Mod Pathol 2009; 22:215A

Endometrioid and Clear Cell Tumors developfrom Ovarian EndometriosisRetrogrademenstruationEndometriosisCarcinomaBorderlinetumor

Ovarian Atypical Endometriosis →Endometrioid or Clear Cell Carcinomas15-32% of cases

Clear cell carcinoma

Designate Histological type• High-grade serous (HGSC)• Endometrioid (EC)• Clear cell (CCC)• Mucinous (MC)• Low grade serous (LGSC)• Other• Cannot be classified• Germ cell (GCT)• Sex cord stromal tumour (SCST)

ITumor confined to ovaries or fallopian tube(s) T1IA Tumor limited to one ovary (capsule intact) or fallopian tube, T1aNo tumor on ovarian or fallopian tube surfaceNo malignant cells in the ascites or peritoneal washingsIBTumor limited to both ovaries (capsules intact) or fallopian tubes T1bNo tumor on ovarian or fallopian tube surfaceNo malignant cells in the ascites or peritoneal washingsIC Tumor limited to one or both ovaries or fallopian tubes, T1cwith any of the following:IC1 Surgical spillIC2 Capsule ruptured before surgery or tumor on ovarian or fallopian tube surfaceIC3 Malignant cells in the ascites or peritoneal washings

Stage 1 Peritoneal Cancer• FIGO staging system is used with theunderstanding that it is not possible to have astage I peritoneal cancer

IITumor involves one or both ovaries or fallopian tubes withpelvic extension (below pelvic brim) or primary peritonealcancer T2IIA Extension and/or implants on the uterus and/or fallopiantubes/and/or ovaries T2aIIB Extension to other pelvic intraperitoneal tissues T2bIIC Any of above, but with ascites or positive peritoneal washings

Ovarian Carcinomas involvingRetroperitoneal LNs• Less than 10% of ovarian carcinomas haveextended beyond the pelvis with exclusivelyRetroperitoneal Lymph Node involvement• Literature evidence indicates that these caseshave better prognosis than tumors withabdominal peritoneal involvement• No pathological distinction between high-gradeserous and low-grade serous carcinomas

New Stage III - FIGO 2012IIIOne or both ovaries, fallopian tubes, or primary peritoneal cancer withpathologically proved spread to the peritoneum outside the pelvis and/ormetastasis to the retroperitoneal lymph nodesIIIA Metastasis to the retroperitoneal lymph nodes with or without microscopicperitoneal involvement beyond the pelvisIIIA1Positive retroperitoneal lymph nodes onlyIIIA1(i) Metastasis (≤ 1 cm in size)IIIA1(ii) Metastasis (> 1 cm in size)IIIA2Microscopic extrapelvic peritoneal involvement with or without positiveretroperitoneal lymph nodesIIIB Macroscopic peritoneal metastasis beyond the pelvis 2 cm or less with or withoutmetastasis to the retroperitoneal lymph nodesIIIC Macroscopic peritoneal metastasis beyond the pelvis more than 2 cm with orwithout metastasis to the retroperitoneal lymph nodes(Note 1: includes extension of tumor to capsule of liver and spleen without parenchymalinvolvement of either organ)

Ovarian CarcinomasLow-grade serous carcinomas may arisein lymph nodes from endosalpingiosisDjordjevic B, Malpica A.Am J Surg Pathol 2010, 2012

SBT in Lymph Nodes (30%)LN: Mullerian cysts (endosalpingiosis)SBT in lymph node

SBT in lymph node

SBT in lymph node (fibrosis)

LN – Endosalpingiosis SBT LGSCMetastatic HGSC in LN

Ovarian Carcinomas involving Lymph Nodes• Less than 10% of ovarian carcinomas have extended beyond the pelvis withexclusively Retroperitoneal Lymph Node involvement• Literature evidence indicates that these cases have better prognosis thantumors with abdominal peritoneal involvement• Low-grade serous carcinomas may arise in lymph nodes fromendosalpingiosis• Most of these cases probably represent separate primary low-gradeserous carcinomas arising in lymph nodes from endosalpingiosiswhich explains their favorable prognosis

New Stage III - FIGO 2012

Stage IIIIII Tumor involves one or both ovaries, fallopian tubes, orprimary peritoneal cancer, with cytologically or histologicallyconfirmed spread to the peritoneum outside the pelvis and/ormetastasis to the retroperitoneal lymph nodesT1/T2/T3aN1IIIA1 Positive retroperitoneal lymph nodes only (cytologicallyor histologically proven)IIIA1 (i) Metastasis ≤ 10 mm in greatest dimensionIIIA1 (ii) Metastasis > 10 mm in greatest dimensionIIIA 2 Microscopic extrapelvic (above the pelvic brim)peritoneal involvement with or without positive retroperitoneallymph nodesT3a/T3aN1

Stage IIIIIIB Macroscopic peritoneal metastasis beyond the pelvis2 cm or less in greatest dimension, with or without metastasis to theretroperitoneal lymph nodesT3b/T3bN1IIIC Macroscopic peritoneal metastasis beyond the pelvismore than 2 cm in greatest dimension, with or without metastasis tothe retroperitoneal lymph nodes (Note 1)T3c/T3cN1[Note 1: includes extension of tumour to capsule of liver and spleen withoutparenchymal involvement of either organ ]T3c/T3cN1

IVDistant metastasis excluding peritoneal metastasesStage IV A: Pleural effusion with positive cytologyStage IV B: Metastases to extra-abdominal organs(including inguinal lymph nodes and lymph nodesoutside of abdominal cavity)(Note 2: Parenchymal metastases are Stage IV B)

Stage IV• Stage IVA: Pleural effusion with positive cytology• Stage IVB: Parenchymal metastases and metastases toextra-abdominal organs (including inguinal lymph nodesand lymph nodes outside of abdominal cavity)Any T, Any N, M1

Notes• The primary site i.e: ovary, fallopian tube or peritoneum, shouldbe designated where possible.• In some cases, it may not be possible to clearly delineate theprimary site and these should be listed as ‘undesignated’• The histological type should be recorded• The staging includes a revision of the stage III patients andallotment to stage IIIA1 is based on spread to the retroperitoneallymph nodes without intraperitoneal dissemination, because ananalysis of these patients indicates that their survival issignificantly better than those who have intraperitonealdissemination

Notes• Involvement of retroperitoneal lymph nodes must beproven cytologically or histologically• Extension of tumour from omentum to spleen or liver(Stage IIIC) should be differentiated from isolatedparenchymal metastases (Stage IVB)

The five most common types of ovarian carcinomaHigh-gradeserousClear cell Endometrioid Mucinous Low-gradeserousUsual stage at diagnosisAdvanced Early Early EarlyEarly oradvancedPresumed tissue oforigin /precursor lesionFallopian tube ortubal metaplasiain inclusions ofOSEEndometriosis,adenofibromaEndometriosis,adenofibromaAdenoma–borderline –carcinomasequence;teratomaSerousborderlinetumorGenetic riskBRCA1/2 ? HNPCC ? ?Significant molecularabnormalitiesp53 and pRbpathwayHNF-1βARID1APTEN, β-Catenin, K-rasMI, ARID1AK-rasBRAF orK-rasProliferationHigh Low Low Intermediate LowResponse to primarychemotherapyPrognosis80% 15% ? 15% 26-28%Poor Intermediate Favorable Favorable Favorable

PIK3CA20q ampKRASBRAFERB2PTENb-cateninClear CellEndometrioidLow-gradeKRASMucinousTP53/Rb pathwayChromosomalinstabilityHig-grade Serous

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Type IPIK3CA20q ampKRASBRAFERB2PTENb-cateninClear CellEndometrioidLow-gradeKRASMucinousTP53/Rb pathwayChromosomalinstabilityHig-grade SerousType II