Are metastatic testicular tumors curable with high-dose chemotherapy and stem-cell rescue?

Abstract

Although cisplatin-based chemotherapy cures approximately 80% of patientswith newly diagnosed metastatic germ-cell tumours, the outcome in those failing initial chemotherapy is much less favourable and dependent on certainwell-defined clinical factors. Primary salvage options in patients who do not respond to firstline chemotherapy include conventionaldose cisplatin-based regimens, while high-dose chemotherapy (HDCT)with haematopoietic stem cell rescue has been actively investigated in the last two decades, with controversial results. Einhorn and colleagues have retrospectively analysed their experience of tandem HDCT with carboplatin and etoposide in a large series of consecutive men with metastatic testicular cancer that had progressed after receiving cisplatin-containing combination chemotherapy. This study shows 70%and 50% four-year disease-free survival in patients who received HDCT as second-line or third-line or later therapy, respectively.As it is a retrospective review, one may argue that the results are biased by patient selection. This does not seem to be the case, however, as even patients with very poor prognosis achieved longterm disease-free survival – 50% of survivors were classified high-risk by the International Germ Cell Cancer CollaborativeGroup classification and45% had platinum-refractory disease. It is important to note that all patients in this series receivedperipheral-bloodprogenitors as sources of haematopoietic stem cells. This strategy allowed a rapid engraftment, thereby permitting the administration of two courses of highdose carboplatin plus etoposide with planned delays at three-week intervals and acceptable toxicity. In addition, peripheral-blood progenitors were enriched for CD34+ haematopoietic cells, a procedure which may have a role in eliminating possible cancer cells from the graft. The source of stem cells and their ex vivomanipulationmaywell have contributed to the positive results of the study, although there are no evidence-based data to support this hypothesis at present. Results provided by Einhorn et al. are apparently in contradiction with data from two recently published randomised trials that fail to demonstrate a benefit of HDCT over conventional chemotherapy in patients with a poor prognosis, albeit in earlier phases of the disease. Both studies, designed in the early 1990s during an era of great expectations for HDCT, were planned to detect an overoptimistic improvement of event-free survival. The use of bonemarrow stem cells in some patients has resulted in high transplant-relatedmor-