1. Oncology / Dysplasia Unit Royal Women’s Hospital, Carlton, Victoria Do all patients with invasive cervical carcinoma need a radical hysterectomy? Leuven May 2007

2. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Stage IA – can only be diagnosed microscopically Stage IA – can only be diagnosed microscopically IA 1 ≤ < 3 mm invasion; extension no wider than 7 mm IA 1 ≤ < 3 mm invasion; extension no wider than 7 mm IA 2 > 3 mm - 5 mm; extension no wider than 7 mm IA 2 > 3 mm - 5 mm; extension no wider than 7 mm Microinvasive Carcinoma of the Cervix FIGO, 1995

3. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Cold-knife or loop excision? Cold-knife or loop excision? Mx of microinvasive squamous disease Mx of microinvasive squamous disease Mx of microadenocarcinoma Mx of microadenocarcinoma MX of small volume early invasive disease MX of small volume early invasive disease Controversial Areas

4. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Issues (1) Histological subtype Histological subtype Type of cone….cold knife/laser/Leep Type of cone….cold knife/laser/Leep Tissue preparation..method/number of sections Tissue preparation..method/number of sections Margin Status Margin Status LVSI LVSI

5. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Both cheap Both cheap Both LA / GA Both LA / GA Margins are the critical factor Margins are the critical factor When any suggestion of cancer/lesion out of range…cold knife bestWhen any suggestion of cancer/lesion out of range…cold knife best Cold Knife or Loop Excision?

6. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Pregnancy Outcomes and Loop excision/Cone Sadler,NZ,2004,JAMA…increased PRM with Loop Sadler,NZ,2004,JAMA…increased PRM with Loop Kyrgiou,2006,Lancet…RR 2.59 cone and prematurity,1.7 Loop.Laser OK(= RWH data) Kyrgiou,2006,Lancet…RR 2.59 cone and prematurity,1.7 Loop.Laser OK(= RWH data) Bruinsma et al,2007…both treated and untreated women have increased risk of prematurity Bruinsma et al,2007…both treated and untreated women have increased risk of prematurity

7. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Issues (2) Risk of parametrial spread Risk of parametrial spread Risk of adnexal spread Risk of adnexal spread Risk of nodal spread Risk of nodal spread What to do after childbirth What to do after childbirth Summary recommendations Summary recommendations

8. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Specimen Processing Critical Radial Radial Sagittal Sagittal Whole specimen Whole specimen Step section of nodes Step section of nodes Special stains Special stains

9. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Multiple comparisons of management of CIN111 No studies comparing management of microinvasive carcinoma

10. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Cone adequate no matter age Cone adequate no matter age Early Stromal Invasion

11. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Micro-invasive Carcinoma Cervix.. Node Positivity (Ostor,1998)

12. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria FIGO Biannual Report 2006 968 Cases Ia1,384 1a2 968 Cases Ia1,384 1a2 92% Ia1 treated by surgery, 65% Ia2 92% Ia1 treated by surgery, 65% Ia2

13. Oncology / Dysplasia Unit Royal Women’s Hospital, Carlton, Victoria n = 402 with < 5 mm invasion n = 402 with < 5 mm invasion LN +ve,1.2% if 3 mm or less invasion 6.8% if > 3 – 5 mm invasion LN +ve,1.2% if 3 mm or less invasion 6.8% if > 3 – 5 mm invasion 4 recurrences, 3 of whom had > 7 mm horizontal spread 4 recurrences, 3 of whom had > 7 mm horizontal spread(Tokyo) Microinvasive Carcinoma of the Cervix Takeshima et al, 1999

14. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria 1-3 mm risk of nodes +ve ~0.5% 3-5 mm risk of nodes +ve ~3.4% LVS +ve ~ doubles LN risk Microinvasive Disease

15. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Micro-invasive Squamous Disease Management 1-3 mm…..treat as if ESI,unless LVS +ve. Consider Hyst if fertility complete 1-3 mm…..treat as if ESI,unless LVS +ve. Consider Hyst if fertility complete 3-5mm…simple hyst and nodes/cone and nodes if fertility an issue 3-5mm…simple hyst and nodes/cone and nodes if fertility an issue

16. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Conclusions Meticulous, accurate pathology essential. Meticulous, accurate pathology essential. Treatment by cone alone is safe treatment in stage 1a1 without LVSI. Treatment by cone alone is safe treatment in stage 1a1 without LVSI. The role of cone alone in stage1a2 needs further study (cf,rad trachelectomy/amputation) The role of cone alone in stage1a2 needs further study (cf,rad trachelectomy/amputation) Role of lymph node dissection needs further assessment. Role of lymph node dissection needs further assessment. Evaluation of the place of sentinel node detection is needed. Evaluation of the place of sentinel node detection is needed.

17. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Rationale for the existence of microadenocarcinoma All would agree that ACIS exists All would agree that ACIS exists Adenoca is HPV related Adenoca is HPV related Morphologically,small lesions exist Morphologically,small lesions exist There is an inflammatory reaction around the glands There is an inflammatory reaction around the glands

18. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Microadenocarcinoma Endocervical Endocervical Villoglandular Villoglandular Intestinal Intestinal Endometrioid Endometrioid Clear Cell Clear Cell Adenosquamous Adenosquamous

19. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria 30 years old Nulliparous Nulliparous Lesion is 2.4 mm deep,4 mm long Lesion is 2.4 mm deep,4 mm long Glandular abnormality Glandular abnormality No LVSI No LVSI Margins normal Margins normal Specimen is a Loop excision Specimen is a Loop excision

20. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria

21. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Would you? Cone Cone Simple hysterectomy Simple hysterectomy Cone/Simple hysterectomy and nodes Cone/Simple hysterectomy and nodes Radical Hysterectomy Radical Hysterectomy Radical Hysterectomy and Nodes Radical Hysterectomy and Nodes Radical Trachelectomy and Nodes Radical Trachelectomy and Nodes

22. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Invasion 5 mm or less, complete obliteration of normal endocervical crypts, extension beyond normal glandular field, stromal response. Invasion 5 mm or less, complete obliteration of normal endocervical crypts, extension beyond normal glandular field, stromal response. 126/436 – rad hyst – no parametrial involvement 126/436 – rad hyst – no parametrial involvement 155 cases – no adnexal involvement 155 cases – no adnexal involvement 5/219 cases – +ve Nodes (2%) 5/219 cases – +ve Nodes (2%) 15 recurrences 15 recurrences 6 deaths from disease 6 deaths from disease Microinvasive Adenocarcinoma of the Cervix Ostor, 2000

23. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria n = 20 IA n = 20 IA 2 x simple; 14 x radical hyst; 4 conization 2 x simple; 14 x radical hyst; 4 conization No recurrence No recurrence ACIS  n = 42  n = 20 conization ACIS  n = 42  n = 20 conization No recurrence in conization cases; median follow-up 48 months (UC Irvine) No recurrence in conization cases; median follow-up 48 months (UC Irvine) Microinvasive Adenocarcinoma McHale et al, 2001

24. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria SEER data SEER data 200 IA 1 ; 286 IA 2 200 IA 1 ; 286 IA 2 Simple hyst 48.6%; rad hyst 37.5% Simple hyst 48.6%; rad hyst 37.5% 1.5% +ve LN (n = 197) 1.5% +ve LN (n = 197) Survival 98.5%; 98.6% (Alberquerque) Survival 98.5%; 98.6% (Alberquerque) Microinvasive Adenocarcinoma of the Cervix Smith et al, 2001

25. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria 585 IA 1 ; 358 IA 2 585 IA 1 ; 358 IA 2 531 lymphadenectomies – 1.3% +ve 531 lymphadenectomies – 1.3% +ve No significant difference in nodal positivity or survival vs stage (Alberquerque) No significant difference in nodal positivity or survival vs stage (Alberquerque) Microinvasive Adenocarcinoma of the Cervix (2) Smith et al, 2002 : Summary Data

26. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria 131 Stage IA 1 ; 170 Stage IA 2 131 Stage IA 1 ; 170 Stage IA 2 1/140 had +ve nodes (single) 1/140 had +ve nodes (single) 4 tumour related deaths (1 x IA 1, 3 x IA 2 ) 4 tumour related deaths (1 x IA 1, 3 x IA 2 ) Overall survival 99.2% IA 1 ; 98.2% IA 2 Overall survival 99.2% IA 1 ; 98.2% IA 2 30% simple + 70% radical ops (Mayo Clinic) 30% simple + 70% radical ops (Mayo Clinic) Microinvasive Adenocarcinoma Webb et al, 2001

27. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Microinvasive Adenocarcinoma Poynor e al, 2006 N=33…6 1-2mm;6>2- 3mm;6>3-4mm;6>4-5mm N=33…6 1-2mm;6>2- 3mm;6>3-4mm;6>4-5mm No patient of the 16 with neg cone margins had residual ca on the hyst specimen No patient of the 16 with neg cone margins had residual ca on the hyst specimen No patient had parametrial spread nor pos nodes No patient had parametrial spread nor pos nodes

28. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Pathologist critical Pathologist critical Limited data Limited data Lymphadenectomy if LVS +ve Lymphadenectomy if LVS +ve Conization for <3 mm Conization for < 3 mm ? Simple hyst and nodes 3-5 mm ? Simple hyst and nodes 3-5 mm Re-cone if any doubt Re-cone if any doubt Microadenocarcinoma

29. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria What about following pregnancy? What is the rationale for hysterectomy? What is the rationale for hysterectomy?

30. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria When do we move from minor surgery to major surgery in microinvasive and small cancers of the cervix?

31. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria

32. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria

33. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria

34. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Issues in Small Cancers How often is the parametrium involved? How often is the parametrium involved? Is there a surrogate for parametrial involvement such as LVSI? Is there a surrogate for parametrial involvement such as LVSI? Is parametrial involvement embolic or by direct infiltration? Is parametrial involvement embolic or by direct infiltration? Is there a difference between squamous and glandular lesions? Is there a difference between squamous and glandular lesions?

35. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Covens et al, 2002 842 patients with 1A1/1A2/1B1Cancers 842 patients with 1A1/1A2/1B1Cancers 8 patients has pos parametrial nodes and 25 pos parametrial infiltration 8 patients has pos parametrial nodes and 25 pos parametrial infiltration Only 0.6% had parametrial infiltration if </=2cm,neg nodes and <10mm invasion Only 0.6% had parametrial infiltration if </=2cm,neg nodes and <10mm invasion

36. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Parametrial involvement in small cancers Stegeman et al,2007 Stegeman et al,2007 N=103 N=103 2cm or less,<10mm infiltration,neg pelvic nodes 2cm or less,<10mm infiltration,neg pelvic nodes Two cases of parametrial spread (0.43%) Two cases of parametrial spread (0.43%) Both LVSI +ve Both LVSI +ve

37. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Worldwide Context 3 major centres- Lyons, Toronto, Barts/RMH 3 major centres- Lyons, Toronto, Barts/RMH 500 worldwide 500 worldwide 10 years= 105 at Barts/Royal Marsden 10 years= 105 at Barts/Royal Marsden 43 pregnancies in 28 women 43 pregnancies in 28 women 26 live births, 6 <32weeks gestation 26 live births, 6 <32weeks gestation 3 recurrences of cancer and one death 3 recurrences of cancer and one death

38. Oncology / Dysplasia Unit Royal Women’s Hospital, Carlton, Victoria Radical Trachelectomy ?An operation with no indication

39. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Conisation for Stage 1B disease Rob et al,2007 MRI/USG..<2cm/<10mm deep MRI/USG..<2cm/<10mm deep Lap sentinal nodes…if neg…lympadenectomy Lap sentinal nodes…if neg…lympadenectomy 7 days later cone/trachelectomy 7 days later cone/trachelectomy No cerclage No cerclage

40. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Rob et al,2007 Results 6x 1a2/20x1b1 6x 1a2/20x1b1 7 cones/15 trachelectomies 7 cones/15 trachelectomies 4 x pos nodes…n=22 4 x pos nodes…n=22 11/15 pregnant,8/11 delivered 11/15 pregnant,8/11 delivered 1 x Intra-abdominal pregnancy 1 x Intra-abdominal pregnancy 1 x Recurrence (1b1/8x7mm/lvsi+/27- ve nodes) 1 x Recurrence (1b1/8x7mm/lvsi+/27- ve nodes)

41. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria

42. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria CUFF OF VAGINA

43. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Small Cancers of the Cervix Role of radical trachelorrhaphy not Role of radical trachelorrhaphy not established but probably safe in established but probably safe in lesions </= 2 cm …recurrence rates 5%,delivery rate 60% lesions </= 2 cm …recurrence rates 5%,delivery rate 60%

44. Oncology / Dysplasia Unit Royal Women’s Hospital, Carlton, Victoria Time to think of Cervical Amputation A MORE RATIONAL OPERATION

45. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria Choice of surgery The need for a rational approach to very early malignancies is a product of screening programmes The need for a rational approach to very early malignancies is a product of screening programmes The artificial cut-offs of 5 x 7 mm which lead to a huge change in radicality need some more thought The artificial cut-offs of 5 x 7 mm which lead to a huge change in radicality need some more thought More thorough pathological assessment should lead to safer and more conservative therapy More thorough pathological assessment should lead to safer and more conservative therapy

46. Oncology / Dysplasia Unit The Royal Women’s Hospital, Carlton, Victoria THANK YOU