High-dose chemotherapy as salvage treatment in germ-cell cancer: when, in whom and how.
Over the past two decades, the use of well-validated, guideline-based strategies resulted in high cure rates in patients with germ-cell cancer (GCC) often despite widespread metastatic disease at initial presentation. Yet, about 30 % of patients diagnosed with metastatic disease corresponding to about 5-10 % of GCC patients overall will experience disease progression or recurrence at some time point of their disease with the need for salvage treatment. Salvage treatment is more complex and less well validated than first-line treatment: Its rare patient cohorts are more heterogeneous and prognostic factors impact more compared to other treatment scenarios. In patients with metastatic GCC, there are several scenarios in which first-line treatment strategies can fail (Fig. 1). Prior to initiation of any salvage treatment, several considerations have to be made, which will be addressed in this review: verification that first-line treatment has indeed failed, estimation of the adequacy and the effectiveness of first-line treatment, search for metastatic sites and extent of disease recurrence, assessment of known prognostic factors and finally the choice of the optimal salvage strategy taking into account the aforementioned variables. High-dose chemotherapy will be a rational choice for many patients in need of salvage treatment, but careful patient selection will be required to avoid overtreatment and unnecessary long-term toxicity.
Department of Urology, University Hospital Düsseldorf, Moorenstrasse 5, Duesseldorf, Germany.
Anja
A
Lorch
Department of Oncology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland. joerg.beyer@usz.ch.
Jörg
J
Beyer
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D018579:Patient Selection; D016879:Salvage Therapy / Q000379:methods; D013736:Testicular Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000008:administration & dosage
D014747:Vinblastine; D005047:Etoposide; D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide
Germ-cell cancer; High-dose chemotherapy; Prognosis; Review; Salvage chemotherapy; Salvage surgery
J Clin Oncol. 2006 Dec 10;24(35):5503-11
17158535
Ann Oncol. 2015 Dec;26(12):2507-8
26487577
Ann Intern Med. 1988 Oct 1;109(7):540-6
2844110
Ann Oncol. 2010 Apr;21(4):820-5
19822531
J Clin Oncol. 2007 Jul 1;25(19):2778-84
17602082
J Clin Oncol. 1989 Jul;7(7):932-9
2544687
Ann Oncol. 2005 Jul;16(7):1152-9
15928070
J Clin Oncol. 2005 Oct 1;23(28):6999-7004
16192587
J Cancer. 2011;2:374-7
21750688
Urol Clin North Am. 2015 Aug;42(3):343-6
26216821
Ann Oncol. 2014 May;25(5):987-91
24595454
J Urol. 2010 Jul;184(1):168-73
20483152
J Clin Oncol. 2011 Jun 1;29(16):2178-84
21444870
Ann Oncol. 2002 Apr;13(4):599-605
12056711
Ann Oncol. 2013 Apr;24(4):878-88
23152360
J Clin Oncol. 2012 Mar 10;30(8):800-5
22291076
J Clin Oncol. 2005 Sep 1;23(25):6149-56
16135481
J Clin Oncol. 2010 Nov 20;28(33):4906-11
20956623
J Clin Oncol. 2008 Dec 1;26(34):5524-9
18936477
Clin Genitourin Cancer. 2014 Feb;12(1):63-69.e1
24161525
J Clin Oncol. 2005 Sep 20;23(27):6549-55
16170162
J Clin Oncol. 2016 Feb 1;34(4):345-51
26460295
J Clin Oncol. 2007 Jan 1;25(1):85-90
17194908
J Clin Oncol. 2003 Nov 15;21(22):4100-4
14615439
Br J Cancer. 2005 Jul 25;93(2):178-84
15999102
Ann Oncol. 2008 Feb;19(2):259-64
18042838
J Clin Oncol. 2007 Feb 10;25(5):513-6
17290059
J Clin Oncol. 2003 Dec 1;21(23):4285-91
14645417
Ann Oncol. 2014 Sep;25(9):1775-82
24894084
J Clin Oncol. 2004 Sep 15;22(18):3713-9
15365067
BJU Int. 2011 Apr;107(7):1088-94
20868391
Eur Urol. 2015 Dec;68(6):1054-68
26297604
J Clin Oncol. 1995 Jun;13(6):1328-35
7538556
N Engl J Med. 2007 Jul 26;357(4):340-8
17652649
Eur J Cancer. 2000 Jul;36(11):1389-94
10899652
Eur Urol. 2011 Oct;60(4):850-5
21704446