The role of pathologic prognostic factors in squamous cell carcinoma of the penis

The aim of this review was to identify prognostic pathologic factors which are independent from other clinical or molecular variables. We reviewed the literature on morphological prognostic factors emphasizing our personal experience. We found that for a proper evaluation of prognostic factors a familiarity with penile complex anatomy is required. A biopsy of the primary tumor is not useful for a complete evaluation of prognostic factors other than malignancy and a resected specimen should be utilized. Penile carcinomas have a fairly predictable pattern of local, regional and systemic spread. Pathologic factors affecting patients outcome are multiple but it is difficult from the available studies using heterogeneous pathologic methodologies, different therapeutic approaches and ecologically variable patient populations to ascertain the independent validity of these factors. Invasion of perineural spaces by tumor, lymphatic-venous embolization and histological grade appear to be the most important pathologic predictors of nodal spread and cancer mortality. Other commonly cited factors influencing prognosis are tumor depth or thickness, anatomical site and size of the primary tumor, patterns of growth, irregular front of invasion, pathologic subtypes of the SCC, positive margins of resection and urethral invasion. A combination of two factors, histological grade and depth has been reported as significant predictor of cancer regional spread. After a preselection of significant factors, nomograms have been constructed to collectively evaluate the predictive power of various clinical and pathological indicators. Among various factors perineurial invasion, vascular invasion and high histological grade appear to be the most important adverse pathological prognostic factors.