1. Endometrial Cancer Surgical Staging (Role of Lymphadenectomy) Karl Podratz MD PhD FACS

2. Endometrial Cancer Surgical Staging Basis for Definitive Staging Extent of Disease Adjuvant Rx determinant Prognostication Comparative evaluation Potentially therapeutic

3. Endometrial Cancer Surgical Staging Definitive Staging TAH/BSO/Peritoneal cytology Pelvic/Paraaortic LND* Biopsy/Omentectomy Cytoreduction (Rx) *LND = Lymph node dissection

4. Endometrial Cancer Surgical Staging Definitive Staging TAH/BSO/Peritoneal cytology Pelvic/Paraaortic LND* Biopsy/Omentectomy Cytoreduction (Rx) *LND = Lymph node dissection

5. Endometrial Cancer Role of Lymphadenectomy vs Radiotherapy Modality-based therapy* LymphadenectomyRadiotherapy *Traditions, physician preferences, suboptimal study designs, etc.

6. Endometrial Cancer Annual Incidence Cases and Deaths ACS Estimates* ACS Estimates* Year Cases Deaths 1987 35,000 2,900 2007 39,080** 7,400*** *Ca 1987; CA 2007 **11.7% increase; ***155% increase

7. Endometrial Cancer Role of Radiotherapy and Lymphadenectomy Paradigm shift necessary Minimize overtreatment Minimize undertreatment Maximize outcomes

8. Endometrial Cancer Role of Radiotherapy and Lymphadenectomy Endometrial Cancer Role of Radiotherapy and Lymphadenectomy Treatment paradigm shift Minimize overtreatment –Identify pts not requiring LND and/or RT Minimize undertreatment –Identify pts benefiting from LND and/or RT Maximize outcomes

9. Endometrioid Endometrial Cancer Role of Radiotherapy and Lymphadenectomy Modality-based therapy Radiotherapy vs. lymphadenectomy Uterine histology Disease-based therapy Based on patterns of failure Predicted by pathologic determinants Selective Lymphadenectomy Selective Radiotherapy Selective Chemotherapy

10. Endometrial Cancer Selective Lymphadenectomy (not sampling) Lymph Node Dissection (LND) Low risk: Not indicated All others: Systematic

11. Endometrial Cancer Selective Lymphadenectomy Lymphadenectomy not indicated* Low risk: Endometrioid G 1&2 MI < 50% PTD < 2 cm *Mariani et al. Am J Ob Gyn 2000

12. Endometrioid Endometrial Cancer Grade 1 & 2 and MI < 50% Failures according to PTD* Failures according to PTD* Sites (DOD) Sites (DOD) PTD Pt Failures Loc + (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

13. Endometrioid Endometrial Cancer Low risk: G1/2, < 2 cm, < 50% MI Pt % 5 yr Pt % 5 yr Treatment^ (no.) Survival Hysterectomy only 59 100 Hyst + LND* +/or RT** 64 100 Total 123 ^3/113 recurred (vagina) without RT; all salvaged ^3/113 recurred (vagina) without RT; all salvaged *All nodes negative; **10 RT; 7 for PPC *All nodes negative; **10 RT; 7 for PPC Mariani et al. Am J Ob Gyn 2000

14. Endometrioid Endometrial Cancer Low Risk: G 1/2, MI < 50%, PTD < 2 cm Lymphadenectomy not indicated 20% Over all population* 29% Endometrioid patients* *Mariani et al. Am J Ob Gyn 2000

15. Endometrioid Endometrial Cancer Selective Lymphadenectomy Lymphadenectomy not indicated (29%) Low risk: G 1/2, MI < 50%, PTD < 2 cm Systematic Lymphadenectomy (71%) All others (not low risk)

16. Endometrioid Endometrial Cancer Selective Lymphadenectomy Lymphadenectomy not indicated Low risk: G 1/2, MI < 50%, PTD < 2 cm Systematic Lymphadenectomy All others (not low risk) 17% positive nodes

17. Endometrial Cancer Failures Pelvic Lymphatic Failures Lymphatic failures according to risk factors Lymphatic Failure rate P Site % at 5 years Value Site % at 5 years Value Pelvic Sidewall Low risk <1 <0.001 Low risk <1 <0.001 High risk* 26 High risk* 26 Low risk = absence of high risk factors High risk = *CSI and/or LN mets

18. Endometrial Cancer Failures Lymphatic Failures Lymphatic failures according to risk factors Lymphatic Failure rate P Site(s) % at 5 years Value Site(s) % at 5 years Value Pelvic Sidewall Low risk <1 <0.001 Low risk <1 <0.001 High risk* 26 High risk* 26 Para-aortic area Low risk 1 <0.001 Low risk 1 <0.001 High risk** 33 High risk** 33 Low risk = absence of high risk factors High risk = *CSI and/or LN mets; **LN mets only

19. Endometrial Cancer Failures Paraaortic Lymphatic Involvement 33% para-aortic failures with pelvic and/or para-aortic LN mets 47% para-aortic LN mets or para-aortic failures with pelvic LN mets* *Mariani et al 2002 (Mayo series)

20. Endometrioid Endometrial Cancer Role of Radiotherapy and Lymphadenectomy Disease-based therapy Based on patterns of failure Predicted by pathologic determinants Selective Lymphadenectomy Selective Radiotherapy 12% total population at risk EBRT indicated in 12% 47% paraaortic risk RT field to include PA area

21. Endometrial Cancer Therapy after Lymphadenctomy Conclusions: Absent CSI or pelvic LN mets: adjuvant Rx to pelvic or para-aortic node-bearing areas does not appear indicated Absent CSI or pelvic LN mets: adjuvant Rx to pelvic or para-aortic node-bearing areas does not appear indicated Positive (or at-risk* for) pelvic LN mets: adjuvant Rx to both the pelvic and para-aortic nodal areasindicated *Patients at-risk but incompletely staged Positive (or at-risk* for) pelvic LN mets: adjuvant Rx to both the pelvic and para-aortic nodal areasindicated *Patients at-risk but incompletely staged

22. Endometrioid Endometrial Cancer Role of Radiotherapy and Lymphadenectomy Treatment paradigm shift Minimize overtreatment –Identify pts not requiring LND and/or RT Minimize undertreatment –Identify pts benefiting from LND and/or RT Maximize outcomes

23. Endometrioid Endometrial Cancer Role of Radiotherapy and Lymphadenectomy Modality-based therapy Radiotherapy vs. lymphadenectomy Uterine histology Disease-based therapy Based on patterns of failure Predicted by pathologic determinants Selective Lymphadenectomy Selective Radiotherapy Selective Chemotherapy