Treatment of clinical stage I testicular cancer and a possible role for new biological prognostic parameters.

Three different treatment strategies for patients with stage I non-seminomatous testicular cancer are available that will all result in long-term survival in more than 98% of the patients: a "wait and see" strategy with follow-up and chemotherapy in cases of tumour progression, retroperitoneal lymphadenectomy, with or without application of systemic chemotherapy, in cases of retroperitoneal metastases (pathological stage II disease) or primary adjuvant chemotherapy following inguinal orchiectomy. Each treatment strategy is associated with specific side-effects. In several studies histological characteristics of the primary tumour, particularly the presence of vascular invasion and of embryonal carcinoma cells, have been demonstrated to be significant prognostic factors for the risk of occult retroperitoneal metastases in patients with stage I disease. In addition, new biological prognostic factors determined by flow cytometry, cytogenetic analysis or molecular-biological DNA or RNA analysis have been investigated, among which alterations of the p53 tumour-suppressor gene may represent a promising new prognostic factor. Although alterations of p53 gene expression seem to be associated with advanced tumour stage and may predict retroperitoneal metastatic disease, the independent role of these molecular genetic alterations needs to be prospectively studied. Currently a risk-adapted treatment strategy based on the histological criteria of vascular invasion and the presence of embryonal carcinoma can be used to stratify patients into a "high-" and "low-risk" group with respect to tumour progression. While primary-nerve-sparing retroperitoneal lymphadenectomy or adjuvant chemotherapy with two cycles of platinum, etoposide and bleomycin may be appropriate for patients with a high risk (above 40%) for tumour progression, a "wait-and-see" strategy can be used for "low-risk" (less than 15% risk of progression) patients. Molecular investigations of prognostic factors may be able to improve further the stratification of patients into these different risk categories.