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UROSCAN
Year : 2010  |  Volume : 26  |  Issue : 1  |  Page : 150-152
 

Optimizing the adjuvant therapy in stage I nonseminomatous germ cell tumors


Department of Urology, Chhatrapati Shahuji Maharaj Medical University (King George Medical University), Lucknow, U.P, India

Date of Web Publication23-Mar-2010

Correspondence Address:
Bhupendra P Singh
Department of Urology, Chhatrapati Shahuji Maharaj Medical University (King George Medical University), Lucknow, U.P
India
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Source of Support: None, Conflict of Interest: None


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How to cite this article:
Singh BP, Choubey VK, Pandey R. Optimizing the adjuvant therapy in stage I nonseminomatous germ cell tumors. Indian J Urol 2010;26:150-2

How to cite this URL:
Singh BP, Choubey VK, Pandey R. Optimizing the adjuvant therapy in stage I nonseminomatous germ cell tumors. Indian J Urol [serial online] 2010 [cited 2019 Sep 15];26:150-2. Available from: http://www.indianjurol.com/text.asp?2010/26/1/150/60469

Tandstad T, Dahl O, Cohn-Cedermark G, Cavallin-Stahl E, Stierner U, Solberg A, et al. Risk-adapted treatment in clinical stage I nonseminomatous germ cell testicular cancer: The SWENOTECA management program. J Clin Oncol 2009;27:2122-8.



   Summary Top


With an aim to offer minimized risk-adapted adjuvant treatment to clinical stage 1 nonseminomatous germ-cell testicular cancer patients, this study recruited 745 subjects into a prospective, community-based multicenter Swedish and Norwegian Testicular Cancer Project (SWENOTECA) management program over the period from 1998 to 2005. Treatment strategy depended on the presence or absence of vascular tumor invasion. Vascular invasion positive patients were recommended brief adjuvant chemotherapy with bleomycin, etoposide, and cisplatin (BEP), whereas vascular invasion negative patients could choose between ACT and surveillance. Results showed overall 51 relapses at a median follow-up of 4.7 years. In the surveillance group, relapse rate was 41.7% in patients with vascular invasion and 13.7% in patients without vascular invasion. In adjuvant chemotherapy (one course of BEP) group relapse rate was 3.2% in patients with vascular invasion and 1.3% in patients without vascular invasion. Authors concluded that one course of adjuvant BEP reduced the risk of relapse by approximately 90% in all (with or without vascular invasion) CS1 NSGCT and this may be a new option as initial treatment for all CS1 NSGCT. One course of adjuvant BEP for vascular invasion positive CS1 reduces the total burden of chemotherapy compared with surveillance or two courses of BEP. SWENOTECA currently recommends one course of BEP as standard treatment of VASC + CS1 NSGCT, whereas both surveillance and one course of BEP are options for VASC- CS1 NSGCT.


   Comments Top


This largest community based study (without randomization) of one BEP cycle in CS1 NSGCT(312 patients), showed the great success of nonsurgical treatment of CS1 NSGCT with very low relapse rates in all categories of patients and a cause-specific survival of nearly 100%. Although there had been some preliminary data on the efficacy of one cycle of adjuvant CT, [1],[2],[3] this study along with the study by Albers et al., [4] might put an end to the surgical approach to management of CS1 NSGCT. There are certain reasons for it: First, Albers et al., showed the RPLND to be inadequate with high abdominal recurrences in broad(community) based setting. In contrast, very low relapse rates were seen with single cycle of BEP (in SWENOTECA study 7/312; in Albers study 2/191), which were successfully managed with salvage standard therapy without any cancer specific death with any treatment approach. Second, concerns regarding compliance of patients on active surveillance/ adjuvant CT were not seen in these as well as other broad based studies, [5] ensuring a cause specific survival of 100%. Third, risks of late recurring unresectable teratoma or late relapsing chemotherapy resistant viable tumor were not seen. Only 37 (out of 745) patients in SWENOTECA study and 1 patient (out of 191 patients given one cycle of BEP) in Albers study required dissection of retroperitoneum any time. The overall late relapses were 5/745 (<1%; 1 in ACT, 4 in VASC- on surveillance) in the SWENOTECA study (median follow up; 4.7years) and only 1/388 in the study by Albers et al., (mean follow-up; 56 months). One cycle of ACT has not been shown to increase the risk of late relapses even with the median follow-ups of 8-10 years. [ 3],[6] This is in contrast to very late recurrences reported with surveillance. [7] So with nonsurgical management of CS1 NSGCT, only <5% patients needed retroperitoneal dissection and that too without any high risk of late relapse or unmanageable teratoma or cancer related deaths. As we are into an era of nonsurgical management of CS1 NSGCT, one cycle of adjuvant BEP can definitely be considered a new option for all patients (without risk stratification) of CS 1 NSGCT as it reduced the risk of relapse by >90% with minimal toxicity. However, there are certain issues related to use of one cycle of CT for all patients. First, it will overburden all patients with mild toxicity to decrease potential complications for a few. Second, although short term side effects of even one cycle of BEP are well known (hair loss, work disruption, anxiety and fear, neutropenia, vascular complications, acute chemotherapy complications and temporary effect on fertility), data regarding subtle long term effects is yet to mature. In this study, short term toxicity of BEP was low (with one cycle; infection 2%, leucopenia 33%, thrombocytopenia 1%, obstipation 1%, Neurological <1% and with 2 cycles; infection 2%, leucopenia 27%, obstipation 4%). Third, even after one cycle of BEP, patients can not completely be relieved of the fear of relapse or inconvenience of follow up imaging. Fourth, the SWENOTECA study was done with an aim to minimize risk of relapse. If the aim had been to avoid overtreatment and maintain 100% survival, surveillance would have been the best option. The SWENOTECA study provides support for both; the Canadian consensus [8] which recommends surveillance for all and the European consensus [9] which recommends surveillance for low risk and 2 BEP cycles for high risk patients. Although further longer data may be desirable to find out the best paradigm providing an optimal therapeutic ratio in long term, one thing is sure; these newer nonsurgical treatment paradigms, providing optimal quality care and survival in community settings, should provide the standard of care for these patients.

 
   References Top

1.Schefer H, Mattmann S, Borner M, Morant R, Studer UE, Nandekar M, et al. Single course of adjuvant bleomycin, etoposide and cisplatin (BEP) for high risk stage 1 non-seminomatous germ cell tumors (NSGCT). Proc Am Soc Clin Oncol 2000;19:340.  Back to cited text no. 1      
2.Klepp OH, Dahl O, Cavallin-Stahl E, Stierner U, Cohn Cedermark G, Wist E, et al. Risk-adapted, brief adjuvant chemotherapy in clinical stage 1 (CS1) nonseminomatous germ cell testicular cancer (NSGCT). Proc Am Soc Clin Oncol 2003;22:399.  Back to cited text no. 2      
3.Westermann DH, Schefer H, Thalmann GN, Karamitopoulou-Diamantis E, Fey MF, Studer UE. Long-term follow up results of 1 cycle of adjuvant bleomycin, etoposide and cisplatin chemotherapy for high risk clinical stage I nonseminomatous germ cell tumors of testes. J urol 2008;179:163-6.  Back to cited text no. 3  [PUBMED]    
4.Albers P, Siener R, Krege S, Schmelz HU, Dieckmann KP, Heidenreich A, et al. Randomized phase III trial comparing retroperitoneal lymphnode dissection with one course of bleomycin and etoposide plus cisplatinum chemotherapy in the adjuvant treatment of clinical stage I nonseminomatous testicular germ cell tumors: AUO trial AH 01/94 by the German Testicular Cancer Study Group. J Clin Oncol 2008;26:2966-72.   Back to cited text no. 4  [PUBMED]    
5.Moore CJ, Hayes-Lattin B, Daneshmand S, Nichols CR. Charateristics of replapse in patients with clinical stage I testicular cancer. J Clin Oncol 2008;26:674.  Back to cited text no. 5      
6.Gilbert DC, Norman AR, Nicholl J, Dearnaley DP, Horwich A, Huddart RA. Treating stage I nonseminomatous germ cell tumors with a single cycle of chemotherapy. BJU Int 2006;98:67-9.  Back to cited text no. 6  [PUBMED]    
7.Oldenburg J, Martin JM, Fosså SD. Late relapses of germ cell malignancies: Incidence, management, and prognosis. J Clin Oncol 2006;24:5503-11.  Back to cited text no. 7      
8.Canadian Testis Cancer Consensus Conference, King City, Ontario, Canada, October 19-20, 2007.  Back to cited text no. 8      
9.Krege S, Beyer J, Souchon R, Albers P, Albrecht W, Algaba F, et al. European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): p0 art II. Eur Urol 2008;53:479-513.  Back to cited text no. 9      




 

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