Journal discussion regarding Laparoscopic vs Open Approach to Carcinoma Endometrium

1. LACE TRIAL
Dr. D. Pradeep
MCh Postgraduate in Surgical Oncology
Prof. M.P. Viswanathan, MS MCh
Prof. D. Suresh Kumar, MS(AIIMS), DNB, MCh,
DNB
TN Govt Multi Super Speciality Hospital, Chennai
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2. BACKGROUND
• Standard treatment for endometrial cancer involves removal
of Uterus, Tubes, Ovaries and Pelvic Lymph nodes
• Initially it was done as Total Abdominal hysterectomy
• 1990’s – started with LAVH
• 1995 – Total Laparoscopic Hysterectomy came into practice
• Laparoscopic Hysterectomy
• Associated with less morbidity
• Early recovery
• Less pain, better QoL
• Decreased risk of adverse surgical events 2/15/2019

3. NEED FOR TRIAL
• Little data to confirm its efficacy in regard to disease free and
overall survival
• Previous trials compared LAVH vs TAH in treatment and not
TLH
• 2005 this Trial started after 10 years learning curve for
surgeons since the inception of Lap Staging procedures
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4. OBJECTIVE
• To investigate whether total laparoscopic hysterectomy
(TLH) is equivalent to total abdominal hysterectomy (TAH)
in women with treatment-naive endometrial cancer.
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5. LACE TRIAL DESIGN
• Multinational Phase 3 Randomized equivalence trial
• Oct 7, 2005 to June 30, 2010
• 20 Tertiary centers in Australia, NZ and Hong Kong
• 760 patients randomized to TLH vs TAH
• Follow up ended on March 2016
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6. INCLUSION
CRITERIA
• Endometrioid Histology
• Any Grade
• No evidence of Extrauterine
disease from CECT abdomen
and chest/USG and CxR
EXCLUSION
CRITERIA
• Histology other than
Endometrioid
• Uterus size >10 weeks size
• Bulky nodes on imaging
• Stages II – IV
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7. PHASE I
• Focus on Quality of Life
• 2:1 allocation used TLH vs TAH for first 150 patients
• PHASE II
• Allocation of 1:1 carried out
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8. SURGERY DETAILS
• Open through Vertical or Transverse incision
• LAP – Using McCartney tube
• In both, Pelvic lymph node dissection is done
• Not done in
• Morbidly obese patients,
• Medically unfit,
• Institutional policy against Nodal dissection,
• Gr I or II in Stage IA on FS
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9. PROFICIENCY
• Gynaecologic oncologist
• 20 lap surgeries as main surgeon
• Submit unedited video of Laparoscopic surgical staging
• Able to seal uterine vessels at uterine surface
• Able to close vault laparoscopically
• Able to do retroperitoneal pelvic node dissection
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10. DATA AND FOLLOW UP
• First RCT to use Electronic case report forms e CRFs
• Histological diagnosis
• 1 week, 1 month, 3 and 6 months after surgery
• Every 3 months up to 2 years and 6 months there after with
Gynaecological examination
• Recurrence needs to be proved by histological diagnosis
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11. OUTCOMES
• Disease Free Survival (Interval between surgery and date of
first recurrence/disease progression/new primary
cancer/death)
• Disease Recurrence
• Patterns of Recurrence
• Overall Survival
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12. PREVIOUS LACE COMMITTEE
TRIAL
• Quality of Life (Functional Assessment of Cancer Therapy
General Questionnaire)
• Improvement of 10% or more from baseline to 4 weeks
• 31% from TLH and 14% in TAH group achieved this
threshold (13% difference, p<0.001)
• Postoperative adverse events less frequent in TLH
• Costs were lower for TLH
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13. STATISTICAL ANALYSES
• Design and sample calculated for 4.5 year DFS of 90% in TAH
group and 7% equivalence margin at 4.5 years
• Sample size 755 patients
• Prespecified equivalence margin 7%
• Predicted DFS in TLH is 83% to declare its equivalence
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14. STATISTICAL ANALYSES
• Analyses based on Intention to treat principle
• Continuous data by t test and Categorical variables by Chi
square test
• DFS using Kaplan Meier methods
• Hazard ratios calculated for DFS and OS
• Multivariate analyses for prognostic factors like age, grade,
FIGO stage, nodal status, ECOG score, BMI, etc.
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15. RESULTS
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21. OUTCOMES
• Intention to treat analyses DFS 81.6% TLH vs 81.3% TAH
• Per Protocol analyses, DFS 83% TLH vs 81.4% TAH
• 2 port site metastases in TLH, 2 abdominal wound
metastases in TAH group
• 4.5 year OS of 92.4% TLH vs 92.0% TAH (difference -0.34%)
• Hazard ratio for OS 1.08
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25. PROGNOSTIC FACTORS
SUBGROUP ANALYSES
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28. PROS
• First multicenter, international trial
• Technical competence of surgeons assessed
• Outcomes were similar for survival rates and Hazard ratios in
both Intention to treat and per protocol analyses
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29. VIEWS
• DFS benefit in patients with BMI >30 in TLH group may be a
statistical artefact
• TLH has benefits with regard to short term outcomes
• Meta Analyses needed to determine whether TLH should
become the standard approach
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30. PUBLISHED REPORTS
• LAP2 Trial (GOG 222)
• Dutch Trial
• Cochrane Review Updated 2018
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31. LAP2 TRIAL
• 2616 women
• Result: TLH not as good as the TAH
• 3 year recurrence rate 11.4% vs 10.2%
• All histologies included, all underwent Pelvic and Para aortic
nodal dissection
• Conversion rate from Lap to open Higher 25.8% (6% in our
trial)
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33. RESULTS
• Review from 9 RCTs (assessing 4389 women)
• No difference in Overall Survival (HR 1.04)
• No difference in Recurrence Free Survival (HR 1.14)
• Shorter overall hospital stay
• No difference in operative morbidity
• No difference (in fact less blood loss) compared to open
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35. OTHER REPORTS
• Adverse Events
• LAP2 – Lesser postoperative complications in TLH
• Our Trial – Same as above
• Quality of Life Outcomes
• All trials favoured TLH over TAH
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36. LIMITATIONS
• No blinding
• Randomization performed prior to patient scheduling
• Funding constraints
• No standardization with regard to Nodal dissection
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37. CONCLUSION
• Stage I Endometrial Cancer
• Equivalent DFS at 4.5 years and No difference in
Overall survival in patients undergoing TLH vs TAH
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38. THANK YOU
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39. MCCARTNEY TUBE
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