Endometrial CancerEndometrial Cancer Surgical StagingSurgical Staging

(Role(Role of Lymphadenectomy) of Lymphadenectomy)

Karl Podratz MD PhD FACSKarl Podratz MD PhD FACS

Endometrial CancerEndometrial CancerSurgical StagingSurgical Staging

Basis for Definitive StagingBasis for Definitive StagingExtent of DiseaseExtent of DiseaseAdjuvant Rx determinantAdjuvant Rx determinantPrognosticationPrognosticationComparative evaluationComparative evaluationPotentially therapeuticPotentially therapeutic

Endometrial CancerEndometrial Cancer Surgical StagingSurgical Staging

Definitive StagingDefinitive Staging TAH/BSO/Peritoneal cytologyTAH/BSO/Peritoneal cytologyPelvic/Paraaortic LND*Pelvic/Paraaortic LND*Biopsy/OmentectomyBiopsy/OmentectomyCytoreductionCytoreduction (Rx) (Rx)

*LND = Lymph node dissection

Endometrial CancerEndometrial CancerSurgical StagingSurgical Staging

Definitive StagingDefinitive Staging TAH/BSO/Peritoneal cytologyTAH/BSO/Peritoneal cytology

Pelvic/Paraaortic LND*Pelvic/Paraaortic LND*Biopsy/OmentectomyBiopsy/OmentectomyCytoreductionCytoreduction (Rx) (Rx)

*LND = Lymph node dissection

Endometrial CancerEndometrial CancerRole of Lymphadenectomy vs RadiotherapyRole of Lymphadenectomy vs Radiotherapy

Modality-based therapy*Modality-based therapy*

Lymphadenectomy Lymphadenectomy RadiotherapyRadiotherapy

*Traditions, physician preferences, *Traditions, physician preferences, suboptimal study designs, etc.suboptimal study designs, etc.

Endometrial CancerEndometrial CancerAnnual Incidence Cases and DeathsAnnual Incidence Cases and Deaths

ACS Estimates*ACS Estimates*Year Cases DeathsYear Cases Deaths 1987 35,000 2,9001987 35,000 2,9002007 39,080** 7,400***2007 39,080** 7,400***

*Ca 1987; CA 2007*Ca 1987; CA 2007**11.7% increase; ***155% increase **11.7% increase; ***155% increase

Endometrial CancerEndometrial CancerRole of Radiotherapy and LymphadenectomyRole of Radiotherapy and Lymphadenectomy

Paradigm shift necessaryParadigm shift necessaryMinimize overtreatmentMinimize overtreatmentMinimize undertreatmentMinimize undertreatmentMaximize outcomesMaximize outcomes

Endometrial CancerEndometrial CancerRole of Radiotherapy and LymphadenectomyRole of Radiotherapy and Lymphadenectomy

Treatment paradigm shiftTreatment paradigm shift Minimize overtreatmentMinimize overtreatment

– Identify pts not requiring LND and/or RT Identify pts not requiring LND and/or RT Minimize undertreatmentMinimize undertreatment

– Identify pts benefiting from LND and/or Identify pts benefiting from LND and/or RTRT

Maximize outcomesMaximize outcomes

Endometrioid Endometrial CancerEndometrioid Endometrial CancerRole of Radiotherapy and LymphadenectomyRole of Radiotherapy and Lymphadenectomy

Modality-based therapy Modality-based therapy Radiotherapy vs. lymphadenectomyRadiotherapy vs. lymphadenectomyUterine histologyUterine histology

Disease-based therapyDisease-based therapyBased on patterns of failureBased on patterns of failure

Predicted by pathologic determinantsPredicted by pathologic determinantsSelective Lymphadenectomy Selective Lymphadenectomy Selective Radiotherapy Selective Radiotherapy Selective ChemotherapySelective Chemotherapy

Endometrial CancerEndometrial CancerSelective LymphadenectomySelective Lymphadenectomy

(not sampling)(not sampling)

Lymph Node Dissection (LND) Lymph Node Dissection (LND) Low risk: Not indicatedLow risk: Not indicatedAll others: Systematic All others: Systematic

Endometrial CancerEndometrial CancerSelective LymphadenectomySelective Lymphadenectomy

Lymphadenectomy not indicated*Lymphadenectomy not indicated*Low risk:Low risk:

EndometrioidEndometrioidG 1&2G 1&2MI MI << 50% 50%PTD PTD << 2 cm 2 cm

*Mariani et al. Am J Ob Gyn 2000

Endometrioid Endometrial CancerEndometrioid Endometrial Cancer Grade 1 & 2 and MI Grade 1 & 2 and MI << 50% 50%

Failures according to PTD*Failures according to PTD* Sites (DOD)Sites (DOD)

PTD Pt Failures Loc +PTD Pt Failures Loc +(cm) (no.) no. % Loc Dist Dist(cm) (no.) no. % Loc Dist Dist << 2 123 3 2 3 (0) -- -- 2 123 3 2 3 (0) -- -- > 2 169 14 8 3 (1) 6 (6) 5 (4)> 2 169 14 8 3 (1) 6 (6) 5 (4)

*Primary Tumor Diameter*Primary Tumor Diameter

Endometrioid Endometrial CancerEndometrioid Endometrial CancerLow risk:Low risk: G1/2, G1/2, << 2 cm, 2 cm, << 50% MI 50% MI

Pt % 5 yrPt % 5 yrTreatment^ (no.) SurvivalTreatment^ (no.) SurvivalHysterectomy only 59 100Hysterectomy only 59 100Hyst + LND* +/or RT** 64 100Hyst + LND* +/or RT** 64 100Total 123Total 123 ^3/113 recurred (vagina) without RT; all salvaged^3/113 recurred (vagina) without RT; all salvaged *All nodes negative;*All nodes negative; **10 RT; 7 for PPC**10 RT; 7 for PPC

Mariani et al. Am J Ob Gyn 2000

Endometrioid Endometrial CancerEndometrioid Endometrial CancerLow Risk: G 1/2, MI Low Risk: G 1/2, MI << 50%, 50%, PTD PTD << 2 cm 2 cm

Lymphadenectomy not indicatedLymphadenectomy not indicated20% Over all population*20% Over all population*29%29% Endometrioid patients* Endometrioid patients*

*Mariani et al. Am J Ob Gyn 2000

Endometrioid Endometrial CancerEndometrioid Endometrial CancerSelective LymphadenectomySelective Lymphadenectomy

Lymphadenectomy not indicated (29%)Lymphadenectomy not indicated (29%)Low risk:Low risk: G 1/2, MI G 1/2, MI << 50%, PTD 50%, PTD << 2 cm 2 cm

Systematic Lymphadenectomy (71%)Systematic Lymphadenectomy (71%)All others (not low risk)All others (not low risk)

Endometrioid Endometrial CancerEndometrioid Endometrial CancerSelective LymphadenectomySelective Lymphadenectomy

Lymphadenectomy not indicatedLymphadenectomy not indicatedLow risk:Low risk: G 1/2, MI G 1/2, MI << 50%, PTD 50%, PTD << 2 cm 2 cm

Systematic LymphadenectomySystematic LymphadenectomyAll others (not low risk)All others (not low risk)17%17% positive nodes positive nodes

Endometrial Cancer FailuresEndometrial Cancer FailuresPelvic Lymphatic FailuresPelvic Lymphatic Failures

Lymphatic failures according to risk factorsLymphatic failures according to risk factorsLymphatic Failure rate PLymphatic Failure rate P Site % at 5 years ValueSite % at 5 years ValuePelvic SidewallPelvic Sidewall Low riskLow risk <1 <0.001<1 <0.001 High risk* 26High risk* 26

Low risk = absence of high risk factorsLow risk = absence of high risk factorsHigh risk = High risk = *CSI and/or LN mets*CSI and/or LN mets

Endometrial Cancer FailuresEndometrial Cancer FailuresLymphatic FailuresLymphatic Failures

Lymphatic failures according to risk factorsLymphatic failures according to risk factorsLymphatic Failure rate PLymphatic Failure rate P Site(s) % at 5 years ValueSite(s) % at 5 years ValuePelvic SidewallPelvic Sidewall Low risk <1 <0.001Low risk <1 <0.001 High risk* 26High risk* 26Para-aortic areaPara-aortic area Low risk 1 <0.001Low risk 1 <0.001 High risk** 33High risk** 33

Low risk = absence of high risk factorsLow risk = absence of high risk factorsHigh risk = *CSI and/or LN mets; High risk = *CSI and/or LN mets; **LN mets only**LN mets only

Endometrial Cancer FailuresEndometrial Cancer FailuresParaaortic Lymphatic InvolvementParaaortic Lymphatic Involvement

33%33% para-aortic failures with para-aortic failures with pelvic and/or para- pelvic and/or para-

aortic LN aortic LN mets mets 47%47% para-aortic LN mets or para-aortic LN mets or

para-aortic failures para-aortic failures with with pelvic LN mets* pelvic LN mets*

*Mariani et al 2002 (Mayo series)

Endometrioid Endometrial CancerEndometrioid Endometrial CancerRole of Radiotherapy and LymphadenectomyRole of Radiotherapy and Lymphadenectomy

Disease-based therapyDisease-based therapyBased on patterns of failureBased on patterns of failure

Predicted by pathologic determinantsPredicted by pathologic determinantsSelective Lymphadenectomy Selective Lymphadenectomy Selective RadiotherapySelective Radiotherapy

12% total population at risk12% total population at riskEBRT indicated in 12%EBRT indicated in 12%47% paraaortic risk47% paraaortic riskRT field to include PA areaRT field to include PA area

Endometrial Cancer Endometrial Cancer Therapy after LymphadenctomyTherapy after Lymphadenctomy Conclusions:Conclusions: Absent CSI or pelvic LN mets:Absent CSI or pelvic LN mets:

adjuvant Rx to pelvic or para-aorticadjuvant Rx to pelvic or para-aorticnode-bearing areas does not appear node-bearing areas does not appear

indicated indicated Positive (or at-risk* for) pelvic LN mets:Positive (or at-risk* for) pelvic LN mets:

adjuvant Rx to both the pelvic and adjuvant Rx to both the pelvic and para-aortic nodal areaspara-aortic nodal areas indicatedindicated *Patients at-risk but incompletely staged *Patients at-risk but incompletely staged

Endometrioid Endometrial CancerEndometrioid Endometrial CancerRole of Radiotherapy and LymphadenectomyRole of Radiotherapy and Lymphadenectomy

Treatment paradigm shiftTreatment paradigm shift Minimize overtreatmentMinimize overtreatment

– Identify pts not requiring LND and/or RT Identify pts not requiring LND and/or RT Minimize undertreatmentMinimize undertreatment

– Identify pts benefiting from LND and/or Identify pts benefiting from LND and/or RTRT

Maximize outcomesMaximize outcomes

Endometrioid Endometrial CancerEndometrioid Endometrial CancerRole of Radiotherapy and LymphadenectomyRole of Radiotherapy and Lymphadenectomy

Modality-based therapy Modality-based therapy Radiotherapy vs. lymphadenectomyRadiotherapy vs. lymphadenectomyUterine histologyUterine histology

Disease-based therapyDisease-based therapyBased on patterns of failureBased on patterns of failure

Predicted by pathologic determinantsPredicted by pathologic determinantsSelective Lymphadenectomy Selective Lymphadenectomy Selective Radiotherapy Selective Radiotherapy Selective ChemotherapySelective Chemotherapy