Laparoscopic Approach to Cervical Cancer

Primary Objective:

To compare disease-free survival amongst patients who undergo a total laparoscopic (TLRH)

or robotic radical hysterectomy (TRRH) verses those who undergo a total abdominal radical

hysterectomy (TARH) for early stage cervical cancer.

Secondary Objectives:

- Compare patterns of recurrence between arms.

- Compare treatment-associated morbidity within 6 months from surgery.

- Compare the cost effectiveness of TLRH/TRRH versus TARH

- Compare the impact on Quality of Life (QOL) between arms.

- Assess pelvic floor function

- Compare overall survival between arms

- Determine the feasibility of sentinel lymph node biopsy in this group of patients

RATIONALE FOR STUDY DESIGN Total abdominal radical hysterectomy (TARH) and pelvic lymph

node dissection (± aortic lymph node dissection ± postoperative [chemo-] radiotherapy) is

the current standard treatment for early cervical cancer. While this is an accepted

effective treatment, a laparotomy is highly invasive, visibly scarring and is associated

with tissue trauma, blood loss and a significant risk of wound and infectious adverse

events . Additionally, radical hysterectomy by laparotomy is associated with an average

hospital stay of approximately 5 to 7 days and an average recovery period (from surgery)

of 5 to 6 weeks.

Laparoscopic techniques have been demonstrated to be feasible and safe with previous

retrospective studies on TLH showing encouraging results . In a number of retrospective

and prospective, non-controlled series the incidence of treatment-related morbidity was

less in patients who had a laparoscopic hysterectomy compared to patients who underwent a

TAH . Retrospective data suggest that the recurrence rate and patterns of recurrence are

similar in patients who had a laparoscopic or an open approach .

Treatment recommendations ideally are based on prospective, randomized trials comparing

the current standard technique (TARH) with the proposed better technique (TLRH). However,

there are currently no prospective studies available which directly compare TLRH against

the standard treatment of TARH in regards to disease-free or overall survival.

The proposed clinical trial will be biphasic. The primary outcome variable in stage 1

will be feasibility of recruitment as determined by overall trial recruitment. Following

completion of Stage 1, the data of this study will become the basis for assessing

recurrence and disease-free survival in the Stage 2 design.

RATIONALE FOR THE QUALITY OF LIFE Retrospective studies suggest equivalency between the

laparoscopic and open approaches to radical hysterectomy in regards to surgical specimens

obtained and likely disease-free and overall survivals . Thus, quality of life could be

seen as one of the most significant factors in recommending one approach over the other

and therefore an extremely important endpoint for this protocol. In the GOG LAP-2

protocol , a trial evaluating a comparison between hysterectomy by laparotomy or

laparoscopy, the investigators found equivalency adequacy of the two surgical approaches

however a significant difference in short term quality of life favoring laparoscopy. As

expected, patients who underwent laparoscopy had a faster return to baseline functioning

compared with those patients who had undergone laparotomy which translated into improved

short-term quality of life. By 6 months, however, patients in both cohorts were reporting

equivalent quality of life parameters. Quality of life surveys employed with this Phase

III clinical trial will encompass important endpoints such as postoperative pain and

related symptoms using the MD Anderson Symptom Assessment Index (MDSAI), as well as

cancer specific Functional Assessment of Cancer Therapy (FACT-Cx) and the general 12-Item

Short-Form Health Survey (SF-12).

RATIONALE FOR LYMPHATIC MAPPING Published experience with the techniques for lymphatic

mapping and sentinel lymph node detection in women with cervical cancer has been very

limited. To date, no single study has enrolled more than 100 patients undergoing

lymphatic mapping as part of their surgical treatment for cervical cancer. In fact, the

majority of studies report on less than 50 patients. In addition, this procedure has not

yet been shown to be viable in a multi-institutional setting. The limitations of

previously published reports are important as these techniques are associated with a

significantly high learning curve with early procedures less successful than later ones.

This study will provide us the opportunity to enroll large numbers of patients for

validation of intraoperative lymphatic mapping in women with cervical cancer in an

international, multi-institutional setting.