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.

Inclusion Criteria:

- Histologically confirmed primary adenocarcinoma, squamous cell carcinoma or
adenosquamous carcinoma of the uterine cervix;

- Patients with Histologically confirmed stage IA1 (with lymph vascular invasion), stage
IA2, or stage IB1 disease

- Patients undergoing either a Type II or III radical hysterectomy (Piver
Classification)

- Patients with adequate bone marrow, renal and hepatic function:

- ECOG Performance Status of 0 or 1.

- Patient must be suitable candidates for surgery.

- Patients who have signed an approved Informed Consent

- Patients with a prior malignancy allowed if > 5 years ago with no current evidence of
disease

- Females, aged 18 years or older

- Negative serum pregnancy test within <30 days of surgery in pre-menopausal women and
women < 2 years after the onset of menopause

Exclusion Criteria:

- Any histology other than adenocarcinoma, squamous cell carcinoma or adenosquamous
carcinoma of the uterine cervix;

- Tumor size greater than 4 cm;

- FIGO stage II-IV;

- Patients with a history of pelvic or abdominal radiotherapy;

- Patients who are pregnant;

- Patients with contraindications to surgery;

- Patients with evidence of metastatic disease by conventional imaging studies, enlarged
pelvic or aortic lymph nodes > 2cm; or histologically positive lymph nodes

- Unfit for Surgery: serious concomitant systemic disorders incompatible with the study
(at the discretion of the investigator);

- Patients unable to withstand prolonged lithotomy and steep Trendelenburg position

- Patient compliance and geographic proximity that do not allow adequate follow-up