Trial Information

A Phase III Randomized Clinical Trial of Laparoscopic or Robotic Radical Hysterectomy Versus Abdominal Radical Hysterectomy in Patients With Early Stage 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.