|Primary Objective |
To test the hypothesis that laparoscopic-assisted resection for rectal cancer is not inferior to open rectal resection, based on a composite primary endpoint of oncologic factors which are indicative of a safe and feasible operation.
Changes to Primary Endpoint Oncologic Parameters in Amendment 4
The current standard of care for all Stage II and III rectal cancer patients is neoadjuvant therapy. In the setting of neoadjuvant therapy, the clinical implications of a close distal margin compared to a negative distal margin are minor. Also, efforts by surgeons to minimize the distance from the distal margin to the tumor in reconstructive procedures have not resulted in an increase in local recurrence. However, true positivity of a distal margin is clearly an undesirable outcome. Therefore, the presence of a negative distal margin (as opposed to a distal margin of a certain distance from the tumor) as a success indicator is preferable and warranted as an endpoint.
Completeness of TME
Combining complete and nearly complete TME categories is based on emerging data that demonstrates that the incidence of (y)pCRM < 1 mm is the same for complete and nearly complete (14.6% and 11%, respectively) but significantly greater (28.2%) (p<0.004) for incomplete. In a pooled analysis of the MRC CR07 and NCIC-CTG CO16 trials, local recurrence rates were nearly the same for complete and nearly complete TME (4% and 7%, respectively), but 13% for incomplete.
The definitions of complete TME and nearly complete TME are subjective. Conversely the distinction between incomplete TME and complete or nearly complete TME is not subtle. The majority of the violations of the mesentery are less than 5 mm, which is usually caused by traction injury rather than cancer surgery violations. The patho-physiological implications of the small encroachment are negligible since there is no tissue left in the pelvis because of the encroachment. For these reasons, an endpoint for surgical success that includes both complete and nearly complete TME (rather than just complete TME) is appropriate.
Revised primary endpoint oncologic parameters:
- Circumferential margin > 1 mm
- Negative distal margin
- Completeness of TME
o A complete TME is defined as a rectal resection specimen that has an intact mesorectum and covering peritoneal envelope all the way to the level of rectal transection with no coning in of the mesorectum above the point of transection. The surface of the peritoneal covering should be smooth and shiny with no defects exposing the underlying fat.
o A nearly complete TME is defined as a rectal resection specimen where the mesentery is all present, without coning or missing fat. A < 5 mm deep defect may be present in the envelope covering the mesenteric fat caused either by a wayward incision or traction injury during extraction of the TME specimen through a small extraction site.
A patient will be considered to have a successful resection on either arm if and only if all oncologic
parameters are satisfied. Based on historical data, we expect the rate of successful resection for the
parameters for standard open resection to be 90% for the oncologic parameters. We will accept a 6%
decrement from the successful resection rate of the open (laparotomy) arm of the study to be considered noninferior.
rectal resection (blood loss, length of stay, pain medicine utilization)
- To assess patient-related benefit of laparoscopic-assisted resection for rectal cancer vs. open
throughout the trial.
- To assess disease free survival and local pelvic recurrence at two years.
- To assess quality of life, sexual function, bowel and stoma function at scheduled time points