Sentinel Node Methods in Penile Cancer - a Historical Perspective on Development of Modern Concepts

Malignant penile tumors are of squamous cell origin in more than 95% of cases and the occurrence of a distant metastasis without prior inguinal lymph node metastatic deposits is very rare. This makes inguinal lymph node staging very reliable and of great prognostic significance since undiscovered and untreated inguinal metastases may lead to a fatal clinical course. In lack of a sufficiently accurate noninvasive lymph node staging modality, penile cancer relies on surgical lymph node removal for regional staging. In this respect sentinel node biopsy offers a favourable minimally invasive alternative to prophylactic inguinal lymph node dissection which is associated with significant surgery-related morbidity. Today sentinel node biopsy is widely used in surgical oncology within high volume cancers such as breast cancer and melanoma. In rare cancers sentinel node biopsy is also emerging as a minimal invasive staging tool in patients with no obvious lymph node involvement. At several specialized units across Europe sentinel node biopsy has been practiced by dedicated specialist within vulva and penile cancer for more than two decades. In fact, the rare disease penile cancer was a model entity for development of the original sentinel node concept as early as the 1970'es due to work by the Paraguayan penile cancer pioneer, Cabañas, the sentinel node concept was subsequently successfully adapted in breast cancer and melanoma. This turned out mutually beneficial since the sequential development of sentinel node biopsy in penile cancer in the 1990s eventually adopted new insights and added conceptual details from the experiences harvested in the broader clinical application possible in these high-volume diseases. The prerequisite to conceptualising the sentinel node approach was the gradual anatomical and functional understanding of the lymphatic system which in western medicine rooted in ancient Greece and gradually increased in details and comprehension with significant contributions from many great notabilities during the last centuries including Hippocrates, Galen, Fallopio, Malpighi, Virchow, Starling, Cabañas, Hodgkin and Horenblas. Sentinel node biopsy in penile cancer is a complex multimodality procedure involving inguinal ultrasonography by radiologists, precise tracer-injection and interpretation of nuclear images by nuclear medicine physicians, radio-tracer- and dye guided open surgical biopsies by urologists and thorough step-sectioning, immunostaining and accurate lymph node specimen analysis by pathologists. This team effort requires well-tested protocols, experience and good collaboration and in rare diseases this calls for centralization of service.