Abstract
The majority of metastatic germ cell tumors (GCTs) are cured with cisplatin-based chemotherapy, but 20–30% of patients will relapse after first-line chemotherapy and require additional salvage strategies. The two major salvage approaches in this scenario are high-dose chemotherapy (HDCT) with autologous stem cell transplant (ASCT) or conventional-dose chemotherapy (CDCT). Both CDCT and HDCT have curative potential in the management of relapsed/refractory GCT. However, due to a lack of conclusive randomized trials, it remains unknown whether sequential HDCT or CDCT represents the optimal initial salvage approach, with practice varying between tertiary institutions. This represents the most pressing question remaining for defining GCT treatment standards and optimizing outcomes. The authors review prognostic factors in the initial salvage setting as well as the major studies assessing the efficacy of CDCT, HDCT, or both, describing the strengths and weaknesses that formed the rationale behind the ongoing international phase III “TIGER” trial.
Highlights
Germ cell tumors (GCTs), comprising 1% of male cancers and 5% of male genitourinary malignancies, are the most common tumor in young men
Due to a lack of conclusive randomized trials, it remains unknown whether sequential high-dose chemotherapy (HDCT) or conventional-dose chemotherapy (CDCT) represents the optimal initial salvage approach, with practice varying between tertiary institutions. is represents the most pressing question remaining for defining GCT treatment standards and optimizing outcomes. e authors review prognostic factors in the initial salvage setting as well as the major studies assessing the efficacy of CDCT, HDCT, or both, describing the strengths and weaknesses that formed the rationale behind the ongoing international phase III “TIGER” trial
Fizazi et al reported on a phase II trial combining gemcitabine with ifosfamide and cisplatin (GIP) in the initial salvage treatment of 37 patients with GCT and the favorable criteria used in the Memorial Sloan Kettering Cancer Center (MSKCC) TIP study [17]
Summary
Germ cell tumors (GCTs), comprising 1% of male cancers and 5% of male genitourinary malignancies, are the most common tumor in young men. The majority of patients requiring salvage chemotherapy will die, with death from GCT accounting for the greatest number of average life years lost of any nonchildhood malignancy [2]. The two major salvage approaches include conventional-dose chemotherapy (CDCT) and high-dose chemotherapy (HDCT) with autologous stem cell transplant (ASCT). Due to inconsistencies between retrospective and randomized data comparing these two strategies and the rarity of the patient population, a universally recommended approach in the initial salvage setting is lacking. E objective of this review is to outline the prognostic factors that affect outcome in the salvage setting, the data supporting both salvage chemotherapy strategies (CDCT and HDCT), and an ongoing randomized clinical trial that seeks to definitively establish one of these approaches as the standard of care in the initial salvage setting Practices vary widely throughout the world and patients are highly encouraged to participate in clinical trials. e objective of this review is to outline the prognostic factors that affect outcome in the salvage setting, the data supporting both salvage chemotherapy strategies (CDCT and HDCT), and an ongoing randomized clinical trial that seeks to definitively establish one of these approaches as the standard of care in the initial salvage setting
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