Indication for Surgery in Endometrial & Cervical Cancer. everything you need to know in 30 minutes!!! Fabio Landoni, MD Gynecologic Department

Transcription

1 Indication for Surgery in Endometrial & Cervical Cancer everything you need to know in 30 minutes!!! Fabio Landoni, MD Gynecologic Department

2 Risk Factors LVSI Myometrial invasion Nodes grade Adjuvant Hysto type stage

3 Initial clinical findings

4 Primary treatment Disease limited to the uterus (endometrioid histologies)

5 520 patients, stage I endometrial cancer median follow-up of 70 months - Operating time and blood loss were statistically significantly higher for class II hysterectomy. - 5-year DFS and OS were similar between arms 87.7 and 88.9% in the class I arm and 89.7 and 92.2% in the class II arm Hazard ratio for recurrence: 0.91 (95% confidence interval, , P = 0.72) Hazard ratio for death: 0.77 (95% confidence interval, , P = 0.35) Class II hysterectomy did not improve locoregional control and survival compared to class I hysterectomy (EBMa)

6 Treatment trends vs survival in Stage II SEER DATA on ENDOMETRIAL CANCER Hysterectomy Simple Radical N. 5yrsurv 5yrsurv N. No radiation % % p<0.05 Plus radiation % % p<0.05 Cornalison (SGO 1999)

7 - 8 RCT met the inclusion criteria women were assessed

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9 Primary treatment Disease limited to the uterus (endometrioid histologies)

10 Take home message Although, no longer a part of the current FIGO staging criteria, peritoneal cytology status should still be considered for -accurate 14,704 stage risk-stratification I/II endometrial cancer of these whopatients had undergone a complete staging procedure (lymph-node removal) were included -survival was significantly worse among patients with positive peritoneal cytology (p<0.0001): 5-year disease specific survival 95.1% vs. 80.8% (endometrioid) 78.0% vs. 50.4% (clear cell/serous) PPC is an independent risk factor in patients with early stage endometrial cancer

11 Hot topic: linfadenectomy when? Different therapeutic strategies are compared 1) Extensive surgical staging with restrictive use of post-operative radiotherapy 2) Surgery limited to extrafascial hysterectomy with bilateral oophorectomy and more extensive use of postoperative radiation therapy 3) Intermediate strategy with the aid of frozen section to limit the number of lymphadenectomy

12 Current clinical practice Survey, SGO members Respondent rate 50 % (N = 406) LN staging G1 35 % G2 66 % G3 90 % Cranial anatomical border IMA 50 % renal vessels 11 % Gynecol Oncol, 2010, 119,

13 Can they answer our questions?

14 Can they answer our questions? 13% Overall of positive lymph nodes IA-IB G1 (45% of all cases) 9% Overall positive lymph nodes

15 Limited Extent of Lymphadenectomy Iliac and Pelvic LND: at least 20 nodes required Median Number of pelvic nodes = 26 Paraaortic LND at the discretion of the MD (performed in 26%) obturator nodes Median Number of Nodes = 12 35% less than 10 nodes Paraortic LND at the discretion of the physician

16 NO SURVIVAL BENEFIT Pelvic LND/sampling alone does not improve survival Patients at low risk for N+ do not need LND Do high risk patients benefit from PPALND?

17 Cochrane Lymphadenectomy for EC No evidence that lymphadenectomy decreases the risk of death or disease recurrence compared with no lymphadenectomy in women with presumed stage I disease. The evidence on serious adverse events suggests that women who receive lymphadenectomy are more likely to experience surgically related systemic morbidity or lymphoedema/lymphocyst

18 Meta-analysis 9 studies LR (2 RCT + 7 obs) N = HR JCO, 2012, 42,

19 Mayo criteria for low risk EC type I histology - grade 1 or 2 - MI 50 primary tumor diameter 2 cm Conclusion: Lymphadenectomy dramatically increases morbidity and cost of care without discernible benefits in low-risk EC as defined by the Mayo criteria

20 CONCLUSIONS Although SLN biopsy has shown good diagnostic performance in endometrial cancer, such performance should be interpreted with caution because of significant small study effects. Current evidence is not yet sufficient to establish the true performance of SLN biopsy in endometrial cancer.

21 ENDOMETRIAL CANCER: tailoring the surgical approach - Low risk: G1-G2 < 50% MI Hysterectomy with bilateral salpingooophorectomy (EBMa) - Intermediate risk: G2 > 50%, G3 < 50% Hysterectomy with bilateral salpingooophorectomy and pelvic lymphadenectomy. (EBMb)

22 ENDOMETRIAL CANCER: tailoring the surgical approach - High Risk: Grade 3 tumors and/or deep (>50%) myometrial invasion, and/or cervical stromal spread: +Radical hysterectomy with bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy. (EBMc)

23 Esmo guidelines

24 Role of surgery in Cervical Cancer stage by stage

25 Stage IA1 Conization (EBMb): If the depth of invasion is less than 3 mm, no vascular or lymphatic channel invasion is noted, and the margins of the cone are negative, conization alone may be appropriate in patients wishing to preserve fertility Total hysterectomy (EBMb): if the depth of invasion is less than 3 mm (proven by cone biopsy) with clear margins and no vascular or lymphatic channel invasion is noted, the frequency of lymph node involvement is sufficiently low that lymph node dissection is not required. Oophorectomy is optional and should be deferred for younger women.

26 Stage IA2 Modified radical hysterectomy (EBMc): For patients with tumor invasion between 3 mm and 5 mm, radical hysterectomy with pelvic node dissection has been recommended because of a reported risk of lymph node metastasis of as much as 10% Radical hysterectomy (EBMc) with node dissection may also be considered for patients where the depth of tumor invasion was uncertain because of invasive tumor at the cone margins ( FIGO-IGCS committee 2003)

27 Lymphadenectomy in C.C. Incidence of node metastasis by stromal invasion 3-5mm ( ) Author Hasumi 1980 Van Nagel 1983 Simon 1986 Maiman 1988 Buckley 1996 Creasman 1998 Total N pts nodal mets (%) (13) 3 (9,4) 1 (3,8) 4 (13) 7 (7,7) (7,3) inv rec DOD not stadet not stadet (3,1) 6 (2,3%) Some studies have included tumors with horizontal spread >7mm or clinical lesion

28 Lymphadenectomy in C.C. Incidence of node metastasis by FIGO IA2 ( ) Author N pts nodal mets (%) inv rec DOD 2 (2,5%) 0 not stadet Ostor 1994 Creasman 1998 CTF 2003 Ceballos 2006 Poynor 2006 Lee 2006 Bisseling (3,7%) 0 3 (3,8) 0 3(13%) Total (0,5) 6 (2,9) 2 (1%) 10% operative morbidity, 1% ureteric injury, 7% lymphedema suggest that the complication of Radical surgery outweigh the benefits

29 NIH Consensus Statement on C.C. Bethesda 1996 patients with stage IB and IIA cervical cancer are appropriately treated with either radical hysterectomy with pelvic lymphadenectomy or radiation therapy with equivalent result. To minimize morbidity, primary therapy should avoid the routine use of both radical surgery and radiation therapy therapy.. The combined use of radical surgery and radical radiation therapy results in high morbidity and cost cost..

30 Radical hysterectomy vs. radiotherapy in stage IB Landoni F et al, Lancet 350:535, 1997

31 Stage Ib1- IIa1 Younger patients may benefit from surgery in regard 1) ovarian preservation 2) conservative

32 Ovarian metastases in cervical cancer patients 1695 pts with BSO -multivariate analisys Ovarian mets parameter 16pts odds ratio 0,9% 95% CL p FIGO stage Histology Space uninv < (EMBb) Landoni F et al, I.J.G.C,2007

33 Our own guidelines to preserve the ovaries in R.S. Women 40 years old or younger No morphological abnormality in the ovary Stage FIGO 1a2 1b1 IIa1 Squamous, >3mm uninvolved tissue (MRI) No hystory of breast cancer No risk of familial ovarian cancer (salpingectomy)

34 Conservative Treatment in Early Stage CC

35 Laparoscopic pelvic lymphadenectomy & VRT Reference Stage Relapses SCC Adeno Other Sheperd IA2-IB1 3/112 ND ND ND Hertel IA1-IB1 4/108 1/75 3/33 -- Mathevet IA1-IIA 4/95 3/76 1/19 1/1* Covens IA1-IB1 7/93 4/40 3/50 -- Plante IB1 3/72 1/42 1/30 1/1* Sonoda IA1-IB1 1/36 ND ND ND Burnett IB1 0/ Schlaert IA2-IB1 0/ * excluded TOTAL 22/545 (4%) Beiner & Covens 2007

36 Laparoscopic pelvic lymphadenectomy & VRT < 2 cm Sheperd Relapses > 2 cm ND ND 3/107 1/1 Mathevet 0/74 4/21 Covens 6/85 1/8 Plante 0/64 2/8 Sonoda ND ND Burnett ND ND Schlaert ND ND 9/ % 8/38 21% Hertel TOTAL

37 RVT Obstetric outcomes Pregnancy rates of 41-79% 208 reported pregnancies, which resulted in 134 (64%) third trimester live births The rate of first trimester miscarriage was 18% The rate of second trimester miscarriage was 10% The rate of preterm delivery (< 37 weeks) was 20%

38 RVT KEY POINTS (EBMc) Safe and feasible procedure to perform in early-stage small volume cervical cancers The tumor recurrence rate and the mortality rate are comparable to those observed after radical surgery Lesion size > 2cm is probably the most important risk factor for recurrence Taking home message! The operation has an acceptable complication profile but is associated with a significant incidence of miscarriage and premature labour. In stage IA2 should be offered a more conservative approach with large conisation & pelvic node dissection.

39 How radical should surgery be In stage Ib1 cervical cancer is the removal of parametria always necessary?

40 IA2,IB1- < 2 cm, <½ of stromal invasion parametrial involvement? How many LN negative pts have positive findings in the medial part of parametrium? Rob et al retrospective study 40 IA2, 85 IB1 Covens et al retrospective study 3/536 Steed et al retrospective study 0/120 Plante et al radical trachelectomy 0/76 Stegeman et al retrospective study 5/799 - PI - 0% - PI - 0,6% - PI - 0% - PI - 0% - PI % Strnad P., Rob L et al prospective SLNM study 133 SLN neg. - PI - 0% 25 SLN posit. - PI - 28%!! Gynecologic Oncology 1O9 (2008)

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42 The SHAPE Trial: Simple Hysterectomy And Pelvic node dissection in Early cervix cancer Comparing radical hysterectomy and pelvic node dissection against simple hysterectomy and pelvic node dissection in patients with low risk cervical cancer Chair: Marie Plante University of Laval, Quebec City An NCIC Clinical Trials Group proposal for the Gynecological Cancer Inter Group (GCIG)

43 IEO Experience Tumor diameter < 2 cm (>/= 1cm from IUO) Laparoscopically pelvic LA & Simple trachelectomy NEGATIVE NODES F-UP if no evidence of risk factors risk factors (LVS+,<3mm safe, 2cm) chemo x3 Tumor diameter > 2 < 3 cm (>/= 1cm from IUO) Laparoscopically pelvic LA NEGATIVE NODES Platinum&taxol-based chemotherapy for 3 cycles Simple trachelectomy/cervical cone Landoni Gyn Oncol. 2007

44 All patients (n=34) FIGO st Drop-out N+ (n=4) Conservative treatment (n=30 ) Cervical cone (n=29) Adjuvant Chemo (n=6) Chemo: TEP 3 pts Carbo-taxolo 4 pts Histo IA2 9 IB1 21 SCC 21 AdeK 9 NACTH (n=1/ TEP/ pcr) Relapses (n=0) Demolitive surgery (pts desire n=5)

45 Attempt to conceive (%) 14/30 (46.7) Clinical pregnancy rate / pts (%) (2 pts after chemo) 10/14 (71.4) Abortion 1/12 Ectopic preg. 1/12 Ongoing -/- LBR 10/12 (83)

46 Simple Cone & lymphadenectomy in st IB1<2cm Italian Experience (IEO/CUSH-Rome/Monza) Follow-up:66m. (range ) Hysterectomy: 5 pts after 3-12 yrs (1pt microinv adk) Gyn.Onc. 2011, 123(3):557-60

47 Clinical pregnancy rate / pts (%) 15/17 (88.2) I trim miscarriages 3/17 II trim miscarriages 1/17 Ectopic preg. 1/17 Ongoing 1/17 LBR 14/17 (82.3)

48 PRO These data demonstrate that simple trachelectomy / cervical cone can be safely performed. Data are comparable with more radical procedure Pregnacies rate is slightly better than RVT CONS (EBMc) Low compliance Chemo-cone: alopecia & theoretical teratogenicity Endocervical involvement: isthmic surveillance (IUO preserved)

49 How radical should surgery be Radical hysterectomy is not a single operation. Many variations exist, for which there is no standard terminology and no standard description.

50 The Four Types of Radical Hysterectomy Class A : minimum resection of paracervix Class B : transection of the paracervix at the ureter Class C : transection of the paracervix at the hypogastric junction Class D : laterally extended resection Morrow & Querleu

51 Pelvic Anatomy Peham-Amreich diagram

52 Surgery in cervical cancer R A D I C A L I T Y Type C2 D1 Type C1 Type B1-2 S E Q U E L A E Compromised sexual function Decreased lubrification & genital swelling Bladder & Bowel dysfunction

53 (EBM a)

54 ISSUES NOT DISCUSSED in surgical management of CC - RADICAL SURGERY in locally advanced - NACTH to surgery in locally advanced (EORTC trial 55994) - Pelvic Exenteratio

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57 Algoritm for st Ib2-IIA2 100 pts Node neg Node pos 71 pts 29 pts Pelvic pos 15 High Risk 24,6pts(85%) Pelvic/LLAA pos LLAA pos 4pts (13,8%) 0,4pts (1,2%) RT Geographic omission

58 SURGICAL vs CLINICAL STAGING RECOMMENDATIONS FOR LACC Use PET/CT when available for treatment planning Resect bulky nodes not amenable for radiation therapy if feasible

59 THANKS FOR THE ATTENTION!!!