The Next Iteration of the Radical Hysterectomy?
Abstract & Commentary
By Robert L. Coleman, MD, Professor, University of Texas; M.D. Anderson Cancer Center, Houston, is Associate Editor for OB/GYN Clinical Alert.
Dr. Coleman is a consultant to GlaxoSmithKline, Eli Lilly Co., Abbott Laboratories, Sanofi-Aventis, and Pfizer, and serves on the speakers bureaus for GlaxoSmithKline, Eli Lilly Co., and OrthoBiotech.
Synopsis: Anatomical resection of the embryologically Müllerian anlage defines a new "radical hysterectomy" procedure for women with early-stage cervix cancer with superior survival rates in a single-institution prospective study.
Source: Höckel M, et al. Resection of the embryologically defined uterovaginal (Müllerian) compartment and pelvic control in patients with cervical cancer: A prospective analysis. Lancet Oncol 2009;10:683-692.
Radical hysterectomy remains the primary surgical procedure of choice for women with early-stage cervix cancer because of its ability to remove the primary site and surrounding tissues, which help to classify risk for recurrence and in some cases, indicate adjuvant therapy. The procedure itself is defined by anatomical landmarks and surgical volume to produce a "margin" of tumor-free tissue. The radical resection of the uterine corpus, fallopian tubes, broad ligament and mesosalpinx or peritoneal mesometrium, the cervix, upper vagina, lateral tissue or subperitoneal mesometrium, the pelvic tissues defining the bladder mesometrium, the anterior and lateral mesorectum, and endopelvic fascia or ligamentous mesometrium has been recently described based on embryological development paths and is termed the total mesometrial resection (TMMR) procedure. The primary difference between the two radical procedures is the extent and locality of resection, which, in the case of the latter, is directed to tissues of a common developmental ancestry. The authors prospectively compiled the outcomes of 212 consecutive patients with stage IB-IIA (and selected IIB) cervix cancer treated with the approach. In no case was adjuvant radiation therapy administered; however, patients with more than two positive nodes were administered adjuvant chemotherapy. At a median follow-up of 41 months, only 10 recurrences were identified; three of these were pelvic only, two with pelvic and distant components, and five with distant-only disease. Recurrence-free and overall survival at 5 years was 94%. Treatment-related grade 2 morbidity was 9% and was most commonly vascular. Anatomical topography from two historical patient cohorts with local recurrent disease following standard radical hysterectomy demonstrated the pelvic tissues of highest probability for recurrence were in the area of mesometrium not typically approached by the standard procedure. The authors conclude that TMMR is a viable procedure developed by embryologically guided principles that produces superior survival characteristics in the absence of adjuvant pelvic radiotherapy.
The current standard for primary surgical extirpation of early-stage cervix cancer includes radical resection of the uterine corpus, upper vagina, parametrium, and a portion of the utero-sacral ligaments accompanied by pelvic lymphadenectomy. Despite current trends in surgical approach (e.g., endoscopic, vaginal, and robotic techniques), the surgical procedure itself, particularly in terms of resection goals, has been modified little since its inception. Indeed, the procedure was developed according to oncological principles of wide tumor-free margins around the primary tumor. Inability to achieve these goals essentially defines patients considered poor candidates for surgery and these patients are usually referred for primary chemoradiation therapy. The current article challenges this "standard" on several important layers that are noteworthy. For instance, the TMMR procedure is designed around the embryological Müllerian anlage of development for the uterus and cervix. The hypothesis, which the authors contend drives not only metastatic spread but also the unfortunate local recurrence, is carefully supported by their outstanding survival data, despite the absence of adjuvant therapy for "high-risk" individuals (close margins and positive node) and a graphic topographical anatomical description of recurrences in two retrospective cohorts detailing incomplete resection of this "at-risk" tissue with standard radical resection. In addition, the authors contend that cases of metastatic spread to the nodal basins require only adjuvant chemotherapy. This is based on their confidence that resection of nearly all of the mesometrial tissues (except the lowest portion of the vagina) essentially removes the local recurrence risk. This appears to be supported by the remarkably low pelvic recurrence rate, despite including nearly 100 patients with "near" margins (< 5 mm) and 50 patients with stage IIB disease.
The series is large and prospective, and deserving of further validation, particularly in the multi-institutional setting. This is an important "next step," as the research team is quite expert in the target pelvic anatomy, and in the procedure itself. Replication of their results in not only the target resection volume and survival outcome, but also the safety of the procedure in less experienced hands, is a requisite for generalization and a call for a new standard. Indeed, even in the hands of this team the median operative time was more than 7 hours, with a high incidence of intraoperative transfusion and prolonged hospitalization (median 12 days). Nevertheless, there is a certain intrigue about anatomical-specific resection for this disease and the surgical finesse, which may indeed maximize survival for this group of usually young women, if exportable.