Optimal Management of Retroperitoneal Metastatic Nonseminomatous Testicular Cancer: Toward a Better Selection Between Scalpel and Needle

Abstract

During the past decades, both surgery and systemic chemotherapy have emerged as critically important modalities in the treatment of nonseminomatous germ cell cancer. Before the advent of cisplatin-based chemotherapy, retroperitoneal lymph node dissection (RPLND) had been established to be potentially definitive treatment in many cases of low volume (stage IIA, 2 cm; stage IIB, 5 cm) retroperitoneal metastatic disease. A full, bilateral, or modified template RPLND is a technically demanding procedure and requires a skillful and experienced surgeon. Nonetheless, if uneventful and definitive, a RPLND is devoid of late toxicity. After the recognition of the high curative potential of bleomycin, etoposide, and cisplatin (BEP) chemotherapy, even in the setting of widespread metastatic disease, many investigators have adopted primary chemotherapy also in stage IIA and IIB disease, reserving RPLND mainly to resect postchemotherapy residuals. At first glance, this approach seems straightforward given the greater than 90% disease-free survival and 95% disease-specific survival in good prognosis (low volume) metastatic disease by chemotherapy. Following primary RPLND, chemotherapy was also increasingly being used adjuvantly if pathologic stage II was confirmed, or to treat systemic relapse after RPLND. Hence, chemotherapy has increasingly been given as primary therapy. The prospect of primary chemotherapy to eradicate virtually all lowor limited volume retroperitoneal metastatic disease, and sparing most patients double treatment in terms of an additional RPLND, however, has not come true. Several studies using primary chemotherapy have demonstrated that up to 50% of patients with stage IIA and IIB retroperitoneal metastatic disease obtain no radiologic complete remission and even the tiniest remnants ( 5 mm in previously involved sites) may harbor remaining viable cancer, or residual mature teratoma. In the greater majority of patients who undergo postchemotherapy RPLND for radiologic residual disease, the resected specimens contain mature teratoma as the dominant histology. Although mature teratoma is considered benign, there is a lifetime risk of growth and secondary transition into malignancy. Therefore, mature teratoma should be considered potentially malignant, requiring surgical resection whenever feasible. Two large European databases have allowed determination of the incidence and histology of residual masses in the retroperitoneal area following full induction chemotherapy. In a study of the Medical Research Council in 287 patients, 222 of whom had stage IIA/B nonseminoma, viable cancer was found in 18% and mature teratoma was present in 51% of patients who underwent surgery for postchemotherapy residuals. The frequency of surgery and histological findings is summarized in Table 1. A subset analysis is also available of the stage IIA/B patients treated in the study led by the European Organisation for Research and Treatment of Cancer of three versus four cycles of BEP in good prognosis testicular cancer. Of the total 812 patients entered onto the study, 300 patients had stage IIA or IIB nonseminoma. Radiologic residual disease ( 1 cm) was reported in 132 patients (44%) after the completion of chemotherapy. Of these, 73 underwent surgery and 71 patients had complete resection of residual disease; in one