High dose chemotherapy with autologous stem cell rescue is an accepted and standard of care approach for relapsed or nonresponding testicular cancer. It is recommended by several guidelines, including NCCN. however, they do not explicitly address single versus tandem transplants. A tandem transplant is on that has a pre-planned second transplant with another infusion of stem cells after competion and recovery from the first transpalnt procedure.There are no prospective studies but retrospective reviews from Indiana University, which has the largest referral base of germ cell tumors in the world suggest that tandem transplantation for testicular cancer is the treatment of choice for this malignancy. A review from the Cleveland clinic concludes: ” Tandem autotransplants for testicular cancer are associated with less treatment-related mortality than a planned single transplant, with no differences in disease-related outcomes or overall survival at 3 years. Patient selection bias for either transplant approach, however, may affect the results of this observational study; a randomized trial is needed to determine which approach, if either, is better.”
The newest guideline is Canadian and published in 2010. It says: ” It appears the best results for HDCT have been obtained if a tandem transplant has been performed and thus, patients should have enough stem cells collected for a planned tandem procedure”. Subsequently, triple transplant therapy has been published. Feldman et al. at Memorial Sloan-Kettering Cancer Center reported their TI-CE regimen for relapsed germ cell tumors using 2 cycles of preoperative chemotherapy (paclitaxel plus ifosfamide) before stem cell collection followed by triple transplantation with high-dose carboplatin and etoposide. They reported DFS in 5 of 21 patients in relapsed PMNSGCT (24%) with a median DFS of 8.6 months. Lorch et al10 report their long-term results with two different approaches to high-dose salvage chemotherapy. They are to be congratulated for initiating one of the few phase III studies in this patient population and for reporting the results with a median follow-up of 7.5 years. From November 1999 to November 2004, 211 patients were enrolled. They were randomly assigned to one cycle of VIP followed by three courses of high-dose carboplatin (1500 mg/m2) and etoposide (1,500 mg/m2) versus three cycles of VIP followed by a single cycle of high-dose carboplatin (2,200 mg/m2), etoposide (1,800 mg/m2), and cyclophosphamide (6,400 mg/m2). Despite the different doses and drugs with one cycle versus three cycles of high-dose chemotherapy, it was nevertheless disappointing that there was no difference in the 5-year progression-free survival (47% v 45%; P = .454). There was an improvement in 5-year survival favoring the three cycles of high-dose chemotherapy (49% v 39%; P = .057). However, this did not result from improved therapeutic efficacy but increased treatment-related mortality with the higher doses of the single cycle that also included cyclophosphamide (14% v 4%; P = .01).
L.E Einhorn, Salvage Chemotherapy for Patients With Germ Cell Tumors: Is There a Best Regimen?JCO March 10, 2012 vol. 30 no. 8 771-772
D.R. Feldman, J. Sheinfeld, D.F. Bajorin, et al. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol, 28 (2010), pp. 1706–1713
orch A, Kleinhans A, Kramer A, et al. (2012) Sequential versus single high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: Long-term results of a prospective randomized trial. J Clin Oncol 30:800–805.
NCCN.ORG, Testicular, 2016
Lazarus HM, Stiff PJ, Carreras J, Logan BR, Akard L, Bolwell BJ, Childs RW, Gale RP, Klein JP, Lill MC, Pérez WS, Stadtmauer EA, Rizzo JD.Utility of single versus tandem autotransplants for advanced testes/germ cell cancer: a center for international blood and marrow transplant research (CIBMTR) analysis.Biol Blood Marrow Transplant. 2007 Jul;13(7):778-89.
Lori Wood et al, Canadian consensus guidelines for the management of testicular germ cell cancer. Can Urol Assoc J. 2010 April; 4(2): e19–e38.