Laparoscopy versus laparotomy in the treatment of patients with early stage endometrial cancer Claudia B.M. Bijen Department of Gynecologic Oncology, University Medical Center Groningen, the Netherlands

Endometrial carcinoma Most common gynecologic malignancy in developing world Peak incidence: 55-65 year Incidence increases by obesity and age 1400 patients yearly, of which 75% stage I

Standard treatment Worldwide: The Netherlands: TAH + BSO with or without lymphadenectomy, through a vertical midline incision The Netherlands: General gynecologist, TAH + BSO without lymphadenectomy

Disadvantages of standard treatment Highly invasive Visibly scarring Substantial morbidity laparotomy due to frequent obesity and co-morbidity Hospital stay ±1wk Manolitsas 2002, Obermair 2005

TLH, a good alternative?

The McCartney tube

The McCartney tube

Background 1 Potential pro’s of laparoscopy Less post-operative pain Quicker return to daily activity Shorter hospital stay (2-3 vs 7 days) Less wound complications (2% vs 48%) Higher quality of life Similar recurrence rate Especially feasible for obese and elderly! Eltabbakh 2001,Fram 2002, Manolitsas 2002, Obermair 2003) Obermair 2004)

Laparoscopy in the obese Safe and feasible Similar complication rates Shorter hospitalization Less pain, less wound infections Increased conversion risk Heinberg 2004, Eltabbakh 2000, Obermair 2005, Holub 2000

Laparoscopy in the elderly Shorter hospital stay Less (wound)complications Overall: age not a contraindication for laparoscopy Tozzi 2005, Scribner 2001

Background 2 Potential disadvantages of laparoscopy Longer operation time Longer learning curve Higher per-operative costs (disposables, OR time) More per-operative complications (ureter lesions)

Background 3 Laparoscopy seems safe and effective, however… Only retrospective data Pittfall: patient selection! Also unexperienced gynecologists participated Hysterectomy with lymphadenectomy Not randomised !

Pilot study - aim Investigate the feasibility of TLH in patients with early stage EC Evaluate the concept of visiting surgeon and the use of OSATS during the learning curve

Pilot Study -design Participating centres: UMCG and 7 northern clinics TLH procedure instead of abdominal hysterectomy Early stage endometrial carcinoma Benign pathology One (or 2) gynecologist per center Visiting surgeon evaluated learning curve with help of OSATS Before and after pass grade OSATS score Complications per- en postoperative Duration of procedure (min)

Pilot Study - major complications

Pilot Study - complications During learning curve N=78 After learning curve N=66 Major complications Complications peroperative Complications postoperative 6 (7,7%) 3 1 (1,5%) 1 Minor complications 9 (11,5 %) 6 6 (9,1%) 2 4 Conversions to laparotomy 7 (9%) 9 (13,6%) Operating time 2:13 ± 0:46* 1:57± 0:30*

Pilot Study - complications During learning curve N=78 After learning curve N=66 Major complications Complications peroperative Complications postoperative 6 (7,7%)# 3 1 (1,5%)# 1 Minor complications 9 (11,5 %) 6 6 (9,1%) 2 4 Conversions to laparotomy 7 (9%) 9 (13,6%) Operating time 2:13 * ± 0:46 1:57 * ± 0:30 # p = 0.08 * P < 0.05

Pilot Study -conclusions Experienced gynaecologists reach the cut off value of 28 points in reasonable time (3-13 x) The use of OSATS to evaluate the competence of the gynaecologists to perform a TLH seems feasible

Golden standard…… Randomised Controlled Trial !

Randomised controlled trial TLH study Only RCT can answer the question, which procedure is the best for the patient No randomised data about laparoscopy (without lymphadenectomy) in patients with early stage endometrial cancer No cost-effectiveness data available Complication rate is low with experienced gynecologists ↓ RCT was assigned January 2007!

RCT -design Multi –centre: 20 participating centers Duration: 3 years (start January 2007) Total number of patients needed: 275

RCT – outcome Primary outcome: - major complications Secundary outcome: - costs effectiveness - minor complications - quality of life

RCT -inclusion Endometrioid adenocarcinoma stage I, grade 1-2 Without cervical involvement (curettage/biopsy) Premalignant lesions (atypical hyperplasia) Uteri not larger than ~12 weeks pregancy Age ≥18 jaar Signed informed consent

RCT- exclusion Severe cardiopulmonary disease Unfavourable histopathology papillary serous carcinoma clear cell adenocarcinoma grade 3 adenocarcinoma sarcoma Earlier pelvic radiotherapy

RCT- state of affairs Participating centres: Amsterdam - Vrij Universitair Medisch Centrum Amsterdam Amsterdam - Onze Lieve Vrouwe Gasthuis Amsterdam Amsterdam - St Lucas Andreas ziekenhuis Amsterdam Amsterdam - Academisch Medisch Centrum Amsterdam Arnhem - Ziekenhuis Rijnstate Arnhem Assen - Wilhelmina Ziekenhuis Assen Drachten - Ziekenhuis Nij Smellinghe Emmen - Scheper Ziekenhuis Emmen Enschede - Medisch Spectrum Twente Gouda - Groene Hart Ziekenhuis Gouda Groningen - Universitair Medisch Centrum Groningen Groningen - Martini ziekenhuis Groningen Haarlem - Kennemer Gasthuis Haarlem Hengelo - Ziekenhuisgroep Twente Leeuwarden - Medisch Centrum Leeuwarden Leiden - Leids Universitair Medisch Centrum Maastricht - Academisch Ziekenhuis Maastricht Nijmegen - UMC St. Radboud Sneek - Antonius Ziekenhuis Sneek Veldhoven - Maxima Medisch Centrum Venlo - Vie Curie Medisch Centrum Noord-Limburg Zwolle - Isala Klinieken (Locatie Sophia)

RCT- state of affairs Number of included patients: 11

UMCG Justine M. Briët Monique Kenkhuis Truuske de Bock Ate G.J. van der Zee Marian J.E. Mourits Henriette G.J. Arts