Zaterdag 5 oktober 2013

Isabelle Cadron, MD, PhD

Dienst Gynaecologie

Oncologie Kempen 2013

Chirurgie in de Gynaecologische

Oncologie

Ovarium

I. Beperkt tot ovarium

II. Uitbreiding in klein bekken

III. Uitbreiding buiten het klein bekken of aangetaste

lymfeklieren

IV. Aantasting extra-abdominaal (vb pleura) of levermeta’s

→ Beeldvorming +/- diagnostische laparoscopie

Stadium

1. Stadium I-II: stadieringslaparotomie:

TAH+BSO+omentectomie+pelviene en

para-Aortale LAD

2. Stage IIb-IIIb: primaire debulking = standard of care

3. IIIc - IV: neo-adj chemotherapie – intervaldebulking – adjuvante chemotherapie

Voor start therapie : Open scopie

• Altijd eerst biopsie voor diagnose OvC

• evaluatie operabiliteit ?

Behandeling

DEBULKING = wegname van alle macroscopisch zichtbare

tumorhaarden

= cytoreductie

Uitgebreidheid = f(pat en tumorload)

uterus + ovaria

omentum (infra- en/of supracolisch)

peritoneale ziekte (hele abdominale holte moet

geïnspecteerd worden)

evt darm-resectie, milt, galblaas, diafragma

lymfadenectomie (klieren bekken en para-aortaal)

Extraperitoneal hysterectomy with

resection of pelvic peritoneum

Extraperitoneal hysterectomy with

resection of pelvic peritoneum

Lymfeklieraantasting

Voor- en nadelen :

• operatietijd,

• perop verwikkelingen, oa bloeding (7% vs 1%)

• postop mortaliteit (2,7% vs 1,3%)

Cijfers : in OS ?

EORTC studie : neen

Primaire debulking

Intervaldebulking

Rest = 0 is enige doel

IGCS Meeting October 25th 2008 Bangkok;

NEJM 2010

Randomisation

Ovarian, tuba or peritonal cancer: FIGO stage IIIc-IV (n = 718)

Primary Debulking Surgery

Neoadjuvant chemotherapy

3 x Platinum based CT

Interval debulking (not obligatory)

Interval debulking if no PD

3 x Platinum based CT

> 3 x Platinum based CT > 3 x Platinum based CT

similar OS and PFS

NACT + IDS versus PDS: ITT

Median survial

PDS: 29 months

IDS: 30 months

HR for IDS: 0.98

(0.84, 1.13)

Contra-indicaties primaire HK

Neo-adj ChT gevolgd door intervalDS

1. tumor > 2cm rond a mesent sup of aan porta hepatis

2. Intrahepatische (multiple) metastases of verschillende extra-abdominale metastases (uitgezonderd reseceerbare inguinale / supraclaviculaire LK) >2 cm

3. slechte algemene toestand van pat (> 80j, cardiaal belast, dement,…) waardoor R=0 niet haalbaar is

4. Extensieve serosale invasie (plaques) op darmen, waarvoor multipele of grote darmresecties noodzakelijk zijn.

Cervix

Rond de baarmoederhals Stadium Ib = zichtbaar letsel

Ib1: < 4cm

Ib2: > 4cm

II: vag/parametrium

IIA1: ≤ 4 cm

IIA2: > 4cm

A: vagina

B: parametrium

III: vag/parametrium

A: vagina onderste 1/3

B: parametrium tot bekken

IV: buiten bekken of invasie mucosa

Stadium IVa Aantasting van blaas- of rectum-mucosa.

Stadium IVb Metastasen op afstand of ziekte buiten het kleine bekken

Lymfeklieren Lymfeklieraantasting

Stadium Pos LK pelv (%)

Ia1 0,2-0,8

Ia2 6 - 8

Ib 8 - 21

IIa 20 - 31

IIb 30 - 45

III >50

Pos LK para-Ao (%)

Ib 6

II 12

III 30

Behandeling

• Stadium Ia1 (< 1% LN + geen lymphadenectomie):

• Nog kinderwens: conisatie

• Kinderwens voldaan: hysterectomie zonder BSO

• Stadium Ia2-II a

• Wertheim-Meigs:

1) correcte stadiëring

2) verwijderen pathologische klieren (prognose ~ microM+)

3) behoud sexuele/ovariële functie

Wertheim-Meigs

verwijderen baarmoeder

met parametria en pelviene

lymfeklieren

- via laparoscopie

- via laparotomie

(+/- eierstokken)

Zenuwsparend

• Ureter- en blaasfistel (1%)

• Mortaliteit (0.1-0.25%)

• Dysfunctie blaas en rectum

• Dyspareunie

Voordeel HK:

• Bewaren ovariele functie

• Geen fibrose vagina

• LK status

HK + RT 5% fistulisatie en 10-15% lymfoedeem

Complicaties Wertheim-Meigs

↓ bij laparoscopie

• Stadium IIb-IVa:

radiochemotherapie ( pelvien +/- paraAo)

• Stadium IVb:

chemotherapie

Laparoscopische para-Ao lymfadenectomie:

aangetaste klieren?

Uterus

Stage I* Tumor confined to the corpus uteri

IA* No or less than half myometrial invasion (< 50%)

IB* Invasion equal to or more than half of the myometrium

Stage II* Tumor invades cervical stroma, but does not extend beyond the uterus**

Stage III* Local and/or regional spread of the tumor

IIIA* Tumor invades the serosa of the corpus uteri and/or adnexae#

IIIB* Vaginal and/or parametrial involvement#

IIIC* Metastases to pelvic and/or para-aortic lymph nodes#

IIIC1* Positive pelvic nodes

IIIC2* Positive para-aortic nodes with or without positive pelvic nodes

Stage IV* Tumor invades bladder and/or bowel mucosa, and/or distant metastases

IVA* Tumor invasion of bladder and/or bowel mucosa

IVB* Distant metastases, including intra-abdominal metastases and/or inguinal nodes

* G1, G2 of G3

** Endocervical glandular involvement only should be considered as Stage I and no longer as Stage II

# Positive cytology has to be reported separately without changing the stage

Stadium

‘apparent’ early stage endometriumca • Endometrioid

• Serous, clear cell, carcinosarcoma

→ TLH / TAH + BSO +/- pelviene en para-Ao LAD

advanced endometriumca • Stadium IV: beperkt tot peritoneale caviteit: primaire/interval

debulking

• Stadium IV: Parenchymateuse M+: chemotherapie or hormonale behandeling

recidief • Repeat Heelkunde

• Chemotherapie / Radiotherapie

• Hormonale therapie

Behandeling

33

Separate type of endometrial cancer Lauchlan S, Arch Pathol Lab med 1981;105:615-8

Hendrickson M, Am J Surg Pathol 1982;6:93-108

Bokhman J, Gynecol Oncol 1983;15:10-7

Represents 10% of all endometrial cancer diagnoses but accounts

for 39% of endometrial cancer related deaths Ueda et al., AJOG 2008;198:218

Cirisano et al., Gynecol Oncol 1999;74:385-94

Hamilton et al., Br J Cancer 2006;94:642-6

46% stage II-IV at presentation vs 21% in Endometrioid EC Creasman et al., Gynecol Oncol 2004;95:593-6

Sereus endometriumca

Overview on spread pattern in different subtypes of

endometrial cancer as reported in literature

N (%) Peritoneal

cytology

Adnexal Omental Pelvic LN

Grade 3 E 86/668 (13) 41/721 (6) 3/25 (12) 78/734 (11)

Carcinosarcoma 72/373 (19) 75/512 (15) 15/96 (16) 80/423 (19)

Serous 17/57 (13) 27/125 (22) 47/202 (23) 72/244 (30)

Clear cell 7/20 (35) 3/32 (9) 3/6 (50) 9/20 (45)

Amant et al., Gynecol Oncol 2005;98:274-80

Endometrial Carcinoma Clinical Stage I – FIGO 2009

< 2cm, Stage Ia G1-G2 or

> 2cm, G1 < 1/3 infiltr

TAH / TLH + BSO

Peritoneal Cytology

No Adjuvant Therapy

Endometrioid Stage Ib, or G3, or > 2cm, G1 >

1/3 , clear cell or serous

TAH / TLH + BSO

Peritoneal Cytology

Pelvic Lymphadenectomy

Neg Pelvic Ln

No Adjuvant Therapy, unless Endometrioid G3:

Paclitaxel Carbo x 6

Pos Pelvic Ln

Paclitaxel/Carbo 6x

Pelvic RT (?)

Macro/frozen section Pelv Ln + Macro Pos

Adnex Growth through serosa

Paraaortic Lymphadenectomy to

renal vessels

Neg PAO/Pos Pelvic:

Paclitaxel/Carbo

Pelvic RT

Pos PAO and Pelvic: Paclitaxel/Carbo x 6

Pelvic + PAO RT

G1 G2 G3

Endometrium 0% 3% 0%

Inner 1/3 3% 5% 9%

Middle 1/3 0% 9% 4%

Outer 1/3 11% 19% 34%

ENDOMETRIOID (N = 621)

PELVIC LYMPH NODE METASTASES

Creasman et al., Cancer 1987;60:2035-41

N = 328 grade 1 or 2, myometrial invasion < 50%, no extrauterine disease

Pelvic lymphadenectomy in 57%: 9/187 (5%) positive nodes

No patient with tumour < 2cm: pos nodes or DOD

Hysterectomy only if

grade 1-2

< 2cm

myometrial invasion < 50%

no extra-uterine disease

NEED FOR LYMPHADENECTOMY IN

ENDOMETRIOID ENDOMETRIAL CANCER

Mariani et al., Am J Obstet Gynecol 2000;182:1506-19

Compared to TAH, TLH is associated with a significantly

decreased risk of major surgical Aes and shorter hospital stay.

A laparoscopic surgical approach to early stage endometrial

cancer is safe.

Laparoscopie en safety?

LAP2 study, Walker et al. JCO 2009; Kornblith et al . JCO 2009; Mourits et al., Lancet

Oncol 2010; LACE study, Janda et al., Lancet Oncol 2010; Obermair A, Eur J ca 2012;

Walker J L et al. JCO 2012;

Laparotomy or laparoscopy for endometrial cancer:

Gynecologic Oncology Group LAP2 Study. Walker J L et al. JCO 2012;30:695-700

Cumulative incidence of recurrence by randomly

assigned treatment group.

Overall survival by randomly assigned treatment group.

median follow-up time of 59 months for 2,181 patients

Minimally invasive surgery versus laparotomy in women with

high grade endometrial cancer: A multi-site study performed at

high volume cancer center

Fader et al., Gynecol Oncol 2012

FREQUENCY OF OBSERVED METASTASES TO PELVIC

OR PARA-AORTIC OR BOTH NODE-BEARING REGIONS*

Mariani et al., Gynecol Oncol 2008;109:11-18

*In patients with lymphatic dissemination who underwent systematic pelvic and para-aortic lymphadenopathy.

Node site Endometrioid,

number (%) (n=32)

Nonendometrioid,

number (%) (n=25)

Total,

number (%) (n=57)

Pelvic only 12 (37) 7 (28) 19 (33)

Pelvic plus para-aortic 14 (44) 15 (60) 29 (51)

Para-aortic only 6 (19) 3 (12) 9 (16)

47/48 with aortic node metastases had :

a. Grossly positive pelvic lymph nodes (55% + paraAO nodes)

b. Grossly positive adnexal metastases (43% + paraAO nodes)

c. Outer 1/3 myometrial invasion (18% + paraAO nodes)

40 % of patients with aortic node metastases survive

In patients without extra-uterine metastases, grade was the most important prognostic variable

ENDOMETRIOID CARCINOMA, N=895

PARA-AORTIC LYMPHADENECTOMY

Morrow et al., Gynecol Oncol 1991;40:55-65 – Benedetti et al., Int J Gynecol Cancer

1998;8:322-7

Advanced Stage endometrial cancer: NACT + IDS