Philosophy

​Principle of conventional cancer surgery: Wide tumor excision and staging lymph node dissection

Traditional surgery for local cancer control is based on functional topographic anatomy and on the dogma of isotropic tumor permeation. The clinical practice translated from these principles is wide tumor excision, i.e. the resection of the tumor with a metrically defined circumferential tissue margin free of neo- or dysplastic lesions. However, that treatment may cause considerable morbidity. Moreover, despite R0 resection, local recurrences which often indicate a poor prognosis may occur in up to 50 percent. Although fundamental for the concept of surgical tumor treatment, the prognostic robustness of margin width could never be demonstrated.
Regional lymph node dissection is performed for nodal staging. In case of proven metastases surgical treatment alone is regarded insufficient for tumor control and additional chemoradiation is recommended. Postoperative radiation therapy may reduce locoregional relapses of gynecologic malignancies but overall survival is not improved. Instead treatment morbidity is significantly increased and a great proportion of patients is overtreated.

​Association between embryonic development and malignant progression: The ontogenetic cancer field theory of locoregional tumor spread

Progressive steps in morphogenesis generate increasingly specified morphogenetic fields. From developmental metacompartments, compartments and finally subcompartments and zones are formed. Whereas metacompartments are partially overlapping and interacting morphogenetic fields of early development, compartments are independent modules of morphogenesis established by the end of the embryonic period. Through differentiation and maturation subcompartments and zones arise within compartments.

According to the cancer field theory which consideres cancer as reverse dysmorphogenesis, locoregional tumor spread is seen as manifestation of pathologically reactivated developmental steps in the mature organism with a competent adaptive immune system. During malignant progression the potential tumor propagation field, the cancer field, follows the developmental domains of the founder tissue in reverse sequence. A malignant neoplasm arising in an ontogenetic subcompartment involves during its natural course first the adult tissues of the compartment, then those of the late and next of the early metacompartment. Transition of the tumor from the tissues of one domain into those of the domain of an earlier developmental stage marks the phenotypic changes of malignant progression. The topologic relationship between the local tumor extent and the mature tissues of sequential developmental domains at various stages determines ontogenetic tumor stages (oT).

The regional lymph nodes executing the adaptive immune responses for the developmental domains provide additional permissive sites for discontinuous tumor spread, especially for epithelial neoplasms. Since the lymph nodes are invariably connected to their tributary regions through afferent lymphatics and common positional information, the potential regional propagation field can be identified for each developmental domain representing the local cancer field of the individual neoplasm. This topographic link of a cancer field to its immunologically monitoring intercalated and basin lymph nodes allows therapeutic lymph node dissection complementing the cancer field resection for regional tumor control.

​Redefining cancer surgery: Cancer field resection and therapeutic lymph node dissection

Clinical translation of these insights resulted in ontogenetic tumor staging, cancer field resection and therapeutic lymph node dissection based on ontogenetic anatomy mapping the body with regard to developmental domains. Cancer field resection preserves tissue of adjacent compartments of different embryonic origin despite close proximity to the neoplasm. Based on the ontogenetic theory of cancer fields, total mesometrial resection (TMMR), vulvar field resection (VFR) and laterally extended endopelvic resection (LEER) with therapeutic lymph node dissection (tLND) for the therapy of cervical, vulvar and vaginal cancer have been developed. These new surgical procedures achieve excellent locoregional tumor control without adjuvant radiotherapy at minimized treatment-related morbidity.