Association between the mesenchymal compartment of uterovaginal organogenesis and local tumour spread in stage IB-IIB cervical carcinoma: a prospective study.

BACKGROUND

Macroscopic, microscopic, and occult local tumour spread might be restricted to a permissive territory related to the morphogenesis of the tissue or organ from which the tumour originates. We aimed to define such a morphogenetic unit in Müllerian development, and to assess the role of total mesometrial resection in the treatment of patients with stage IB-IIB cervical carcinoma.

METHODS

We analysed uterovaginal development in serial sections of female human embryos and fetuses, and defined the distal Müllerian morphogenetic unit from the Müllerian mesenchyme. We assessed prospectively the histopathological and clinical findings from patients who underwent total mesometrial resection-modified surgery for stage IB-IIB cervical carcinoma that aims to remove the uterus, proximal vagina, and extracervical mesenchyme within the borders of the distal Müllerian morphogenetic unit.

FINDINGS: The spatial extension of the Müllerian mesenchyme, its vascularisation, and its innervation during early uterovaginal organogenesis determine a tissue territory that can be followed during fetal development and identified in women as a morphogenetic unit. 105 of 106 patients who had total mesometrial resection, 63 of whom were classed as high risk, had microscopically tumour-free resection margins (ie, R0). 48 (96%) of 50 patients had pelvic recurrence-free survival at 3 years (95% CI 92-100) without adjuvant radiotherapy.

INTERPRETATION: Radical en-bloc resection of a topographically defined anatomical territory derived from common precursor tissue leads to local tumour control, preservation of autonomic nerves, and a reduced need for adjuvant radiotherapy.