Do we need a new classification for radical hysterectomy? Insights in surgical anatomy and local tumor spread from human embryology

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Abstract

Objective.

Current surgical treatment of cervical carcinoma is based on the assumption of undirected intra- and transcervical local tumor propagation and is executed by tailored excision of the paracervical tissues. We have recently demonstrated that cervical carcinoma spreads for extended phases during its malignant progression within the permissive compartment of the Müllerian morphogenetic unit (Lancet Oncol 2005;6:751–56) and proposed Müllerian compartment resection as the new principle for surgical treatment of cervical cancer. Do we need a new classification of radical hysterectomy?

Methods.

The therapeutic index of the surgical treatment of cervical carcinoma FIGO stages IB1–IIB by extirpation of the Müllerian compartment through total mesometrial resection (TMMR) without adjuvant radiation is evaluated by an ongoing controlled prospective trial at the University of Leipzig.

Results.

From 7/1998 to 12/2006, 163 patients with cervical carcinoma, FIGO stages IB1 (n = 94), IB2 (n = 21), IIA (n = 14) and IIB (n = 34) have been treated with TMMR and nerve-sparing therapeutic lymph node dissection. Twenty-five patients received (neo)adjuvant chemotherapy. No patient underwent adjuvant radiotherapy although 95 patients (58%) would have needed this additional modality in case of conventional radical hysterectomy because of their high-risk histopathological tumor features. At a median follow-up time of 45 months (3–104 months), recurrence-free and disease-specific overall survival is 93% and 96%. Maximum treatment-related morbidity according to the Franco-Italian score has been grade 2 in 12 patients (8%).

Conclusions.

The developmental view of local tumor spread and surgical anatomy holds a great promise for improving the therapeutic index of surgical cervical cancer therapy and challenges both the classification of radical hysterectomy based on tailored paracervical resection and the indication for adjuvant radiation.

Introduction

Conventional concepts of local tumor spread follow the model of undirected perifocal tumor growth. Tumor propagation per continuitatem is considered to be a random process with migrating tumor cells or cell clusters favoring paths of low mechanical resistance such as vascular or perineural spaces. The translation of that view into clinical practice has led to radical organ resection and wide tumor excision as surgical treatment for local tumor control. Radical organ resection removes the macroscopically complete tumor-bearing organ together with adjacent tissue “tailored” to the clinical tumor extent. Wide excision describes the resection of a tumor surrounded by a mantle of uninvolved tissue of defined thickness within an organ. Both types of local operations are combined with more or less extended lymph node dissections for regional tumor control depending on the type and stage of the malignancy.

For carcinoma of the uterine cervix, local tumor spread with undirected intra- and transcervical growth is assumed [1] and standard surgical treatment of early macroscopic disease is time honored radical hysterectomy [2], [3], [4]. The staged resection of the paracervical tissues as main feature of conventional radical hysterectomy is based on an uterocentric and ligament-focused view of the surgical anatomy. Although the clinical results obtained with this surgical treatment are favorable for small node and vascular space negative tumors, the necessity of adding adjuvant (chemo)radiation in patients with histopathological high-risk features (which may exceed 50% in current series) and the high moderate and severe treatment-related morbidity reported for standard surgical treatment are unsatisfactory [5].

I propose that local tumor spread is not completely random but may be confined for an extended phase in malignant progression to a permissive compartment which can be morphologically deduced from the embryologic development of the organ from which the neoplasm arises. Although tumor propagation is usually undirected within that compartment the neoplasm respects the compartment borders for extended phases in malignant progression. Only late in the disease process adjacent compartments of different embryological origin are invaded and even in these late stages a hierarchy of embryological kinship is maintained.

The logic from this developmental view is compartment resection as new principle of surgical radicality for local tumor control. Depending on the tumor features surgical radicality may be reduced to sub- or intracompartment resection or has to be extended to supra- and multicompartment resection. Compartment resection should result in a high local tumor control rate without additional radiation. As tissues of different embryologic origin may be left in situ despite their close proximity to a malignant tumor, treatment-related morbidity should be significantly less than that of conventional radical organ resection.

We have deduced the Müllerian morphogenetic unit in the adult female from the study of uterovaginal development and demonstrated that its distal part represents the permissive compartment for the local spread of cervical carcinoma. We have shown that complete resection of the distal Müllerian morphogenetic unit by total mesometrial resection (TMMR) leads to excellent pelvic tumor control without adjuvant radiation and minimizes treatment-related morbidity in patients with carcinoma of the uterine cervix FIGO stages IB–IIB [6]. Herein we update the results of an ongoing prospective controlled trial at the University of Leipzig. Moreover, we provide arguments to favor the developmental view and compartment resection over the uterocentric/ligament-focused perspective and classified paracervical resection.

Section snippets

Methods

The resection of developmentally defined tissue compartments as principle of surgical radicality is evaluated at the Department of Ob/Gyn in a prospective controlled trial in patients with histologically proven carcinoma of the uterine cervix, FIGO stages IB–IIB, treated with total mesometrial resection (TMMR) abandoning adjuvant radiation irrespective of the definitive histopathological risk factors. Patients admitted for treatment are consecutively enrolled into the study unless they meet the

Müllerian compartment

The Müllerian compartment is a morphogenetic unit in the female derived from the paramesonephric ducts and the periductal mesenchyme of the uterovaginal anlage.

Assuming topographical robustness during tissue differentiation the Müllerian compartment can be deduced from the tissue complex of the uterovaginal anlage in the 8- to 9-week-old female embryo, followed morphologically through the later stages of fetal development and identified in the adult. The proximal part of the Müllerian

Classification of radical hysterectomy

The widely accepted current surgical treatment concept of cervical carcinoma FIGO stages IB–IIA is “tailored” radical hysterectomy and adjuvant (chemo)radiation in case of histopathological high-risk features. Tumor-adapted “tailoring” relates to the amount of paracervical and vaginal resection. In order to standardize this variable part of radical hysterectomy classification schemes have been proposed by several authors [15], [16], [17]. The five classes of extended hysterectomy by Piver et

Conflict of interest statement

I declare that I have no conflict of interest.

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    The ontogenetic compartment theory states that malignant tumor growth is confined to permissive compartments derived from a common primordium in embryonic development [1–4]. Höckel et al. first investigated embryonic development of the female reproductive tract with respect to embryological different compartments [5–8] and were able to define three different primordial tissue complexes from cranial to caudal: the paramesonephric–mesonephric–Müllerian tubercle complex, the deep urogenital sinus (UGS) vaginal plate complex and the superficial UGS-genital folds and tubercle. Support to this theory comes from the optimal local tumor control following total mesometrial resection (TMMR) without any subsequent adjuvant radiotherapy [9,10] in patients with cervical cancer.

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    Almost all of the study populations are cervical cancer patients, but other tumors (e.g., vaginal cancer and endometrial cancer) are also included in the NSRH studies.7,10,12 Surgical interventions of both laparotomy5,7–17 and laparoscopy18–20 can be considerable. In a study by Trimbos et al,8 the nerve sparing operation was performed unsuccessfully in two of 10 patients, because there is greater fatty configuration in western as compared to eastern populations.

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