VOLUME
33
䡠
NUMBER
20
䡠
JULY
10
2015
JOURNAL OF CLINICAL ONCOLOGY
C O R R E S P O N D E N C E
Surgery After Relapse in Stage I Nonseminomatous Testicular Cancer TO THE EDITOR: In a planned editorial1 attached to our article concerning surveillance for stage I nonseminomatous testicular cancer (CSI NSGCT),2 de Wit highlights an unexpected high frequency of postchemotherapy surgery in patients with relapse. This is put forward as an argument for risk-adapted treatment with adjuvant chemotherapy for high-risk patients. It is stated that if surveillance remains the preferred treatment modality, intensified monitoring is suggested with computed tomography scans every 3 to 4 months during the first 2 years of follow-up. The main conclusion of our study is that surveillance in CSI NSGCT is a safe management option encompassing a more than 99% disease-specific 15-year survival. Assuming that adjuvant chemotherapy results in equivalent survival (this has not been demonstrated in studies as large and with follow-up as lengthy as in the present), the main focus of discussions between experts and patients should be the long-term consequences of treatment. Chemotherapy with bleomycin etoposide, and cisplatinum has been documented to be associated with increased risk of severe late effects.3 It is beyond matters of belief that adjuvant treatment to high-risk patients results in unnecessary exposure of at least 50% of patients to chemotherapy. Presently, we have no data comparing the consequences of adjuvant treatment with one or two cycles with three cycles in relapsing patients, and only meticulous long-term follow-up of the patients will provide this answer. We found that 26% of relapsing patients, equalling less than 8% of patients in total, were operated on for residual tumor masses ⱖ 1 cm. In eight patients (8%), malignant tissue was found; 49 patients (50%) had mature teratoma; 31 (32%) had necrosis/fibrosis; and in 10 patients, histology was unknown. Irrespective of surveillance or adjuvant treatment, patients with teratoma in their metastases will be candidates for surgery, as teratoma is not sensitive to chemotherapy and should be removed surgically. This means that at least half of the patients should have had an operation also in case of adjuvant chemotherapy. It is speculative to claim that fewer patients would have residual teratoma if treated with adjuvant chemotherapy. In the remaining 49 patients, status concerning vascular invasion (VI) was known in 22 patients. For these 22 patients, nine had VI and 13 had no VI. This implies that treating high-risk patients with adjuvant chemotherapy will not protect against the risk of having postchemotherapy
surgery, and it is a misinterpretation of data if this should lead to a shift of preference toward early definitive treatment. With the present data, we do not find any rationale for an increase in the number of computed tomography scans compared with the number suggested in our study. Before starting risk adapted chemotherapy it is important to use validated risk factors. The use of vascular invasion as the only risk factor is problematic. As shown in the this study, VI alone without any of the other risk factors leads to a 5-year relapse rate of 18%. It is our hope that the presented risk factors can be tested in a prospective international validation study. Evidence-based, informed decision making is not possible before this process has been carried out.
Gedske Daugaard, Maria Gry Gundgaard, and Mette Saksø Mortensen Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Mads Agerbæk Aarhus University Hospital, Aarhus, Denmark
Niels Vilstrup Holm Odense University Hospital, Odense, Denmark
Mikael Rahbek Rørth and Hans von der Maase Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Ib Jarle Christensen The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark and Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark
Jakob Lauritsen Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. REFERENCES 1. de Wit R: Optimal management of clinical stage I nonseminoma: New data for patients to consider. J Clin Oncol 32:3792-3793, 2014 2. Daugaard G, Gundgaard MG, Mortsensen MS, et al: Surveillance for stage I nonseminoma testicular cancer: Outcomes and long-term follow-up in a population-based cohort. J Clin Oncol 32:3817-3823, 2014 3. Travis LB, Beard C, Allan JM, et al: Testicular cancer survivorship: Research strategies and recommendations. J Natl Cancer Inst 102:1114-1130, 2010
DOI: 10.1200/JCO.2014.60.2177; published online ahead of print at www.jco.org on June 1, 2015
■ ■ ■
2322
© 2015 by American Society of Clinical Oncology
Journal of Clinical Oncology, Vol 33, No 20 (July 10), 2015: pp -2322
Downloaded from jco.ascopubs.org on November 14, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
Correspondence
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Surgery After Relapse in Stage I Nonseminomatous Testicular Cancer The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Gedske Daugaard No relationship to disclose
Mikael Rahbek Rørth No relationship to disclose
Maria Gry Gundgaard No relationship to disclose
Hans von der Maase No relationship to disclose
Mette Saksø Mortensen No relationship to disclose
Ib Jarle Christensen No relationship to disclose
Mads Agerbæk No relationship to disclose
Jakob Lauritsen No relationship to disclose
Niels Vilstrup Holm No relationship to disclose
www.jco.org
© 2015 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on November 14, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
33
䡠
NUMBER
20
䡠
JULY
10
2015
JOURNAL OF CLINICAL ONCOLOGY
C O R R E S P O N D E N C E
Surgery After Relapse in Stage I Nonseminomatous Testicular Cancer TO THE EDITOR: In a planned editorial1 attached to our article concerning surveillance for stage I nonseminomatous testicular cancer (CSI NSGCT),2 de Wit highlights an unexpected high frequency of postchemotherapy surgery in patients with relapse. This is put forward as an argument for risk-adapted treatment with adjuvant chemotherapy for high-risk patients. It is stated that if surveillance remains the preferred treatment modality, intensified monitoring is suggested with computed tomography scans every 3 to 4 months during the first 2 years of follow-up. The main conclusion of our study is that surveillance in CSI NSGCT is a safe management option encompassing a more than 99% disease-specific 15-year survival. Assuming that adjuvant chemotherapy results in equivalent survival (this has not been demonstrated in studies as large and with follow-up as lengthy as in the present), the main focus of discussions between experts and patients should be the long-term consequences of treatment. Chemotherapy with bleomycin etoposide, and cisplatinum has been documented to be associated with increased risk of severe late effects.3 It is beyond matters of belief that adjuvant treatment to high-risk patients results in unnecessary exposure of at least 50% of patients to chemotherapy. Presently, we have no data comparing the consequences of adjuvant treatment with one or two cycles with three cycles in relapsing patients, and only meticulous long-term follow-up of the patients will provide this answer. We found that 26% of relapsing patients, equalling less than 8% of patients in total, were operated on for residual tumor masses ⱖ 1 cm. In eight patients (8%), malignant tissue was found; 49 patients (50%) had mature teratoma; 31 (32%) had necrosis/fibrosis; and in 10 patients, histology was unknown. Irrespective of surveillance or adjuvant treatment, patients with teratoma in their metastases will be candidates for surgery, as teratoma is not sensitive to chemotherapy and should be removed surgically. This means that at least half of the patients should have had an operation also in case of adjuvant chemotherapy. It is speculative to claim that fewer patients would have residual teratoma if treated with adjuvant chemotherapy. In the remaining 49 patients, status concerning vascular invasion (VI) was known in 22 patients. For these 22 patients, nine had VI and 13 had no VI. This implies that treating high-risk patients with adjuvant chemotherapy will not protect against the risk of having postchemotherapy
surgery, and it is a misinterpretation of data if this should lead to a shift of preference toward early definitive treatment. With the present data, we do not find any rationale for an increase in the number of computed tomography scans compared with the number suggested in our study. Before starting risk adapted chemotherapy it is important to use validated risk factors. The use of vascular invasion as the only risk factor is problematic. As shown in the this study, VI alone without any of the other risk factors leads to a 5-year relapse rate of 18%. It is our hope that the presented risk factors can be tested in a prospective international validation study. Evidence-based, informed decision making is not possible before this process has been carried out.
Gedske Daugaard, Maria Gry Gundgaard, and Mette Saksø Mortensen Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Mads Agerbæk Aarhus University Hospital, Aarhus, Denmark
Niels Vilstrup Holm Odense University Hospital, Odense, Denmark
Mikael Rahbek Rørth and Hans von der Maase Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Ib Jarle Christensen The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark and Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark
Jakob Lauritsen Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Disclosures provided by the authors are available with this article at www.jco.org. REFERENCES 1. de Wit R: Optimal management of clinical stage I nonseminoma: New data for patients to consider. J Clin Oncol 32:3792-3793, 2014 2. Daugaard G, Gundgaard MG, Mortsensen MS, et al: Surveillance for stage I nonseminoma testicular cancer: Outcomes and long-term follow-up in a population-based cohort. J Clin Oncol 32:3817-3823, 2014 3. Travis LB, Beard C, Allan JM, et al: Testicular cancer survivorship: Research strategies and recommendations. J Natl Cancer Inst 102:1114-1130, 2010
DOI: 10.1200/JCO.2014.60.2177; published online ahead of print at www.jco.org on June 1, 2015
■ ■ ■
2322
© 2015 by American Society of Clinical Oncology
Journal of Clinical Oncology, Vol 33, No 20 (July 10), 2015: pp -2322
Downloaded from jco.ascopubs.org on November 14, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
Correspondence
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Surgery After Relapse in Stage I Nonseminomatous Testicular Cancer The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I ⫽ Immediate Family Member, Inst ⫽ My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc. Gedske Daugaard No relationship to disclose
Mikael Rahbek Rørth No relationship to disclose
Maria Gry Gundgaard No relationship to disclose
Hans von der Maase No relationship to disclose
Mette Saksø Mortensen No relationship to disclose
Ib Jarle Christensen No relationship to disclose
Mads Agerbæk No relationship to disclose
Jakob Lauritsen No relationship to disclose
Niels Vilstrup Holm No relationship to disclose
www.jco.org
© 2015 by American Society of Clinical Oncology
Downloaded from jco.ascopubs.org on November 14, 2015. For personal use only. No other uses without permission. Copyright © 2015 American Society of Clinical Oncology. All rights reserved.
