Beruflich Dokumente
Kultur Dokumente
Seminoma
By Jacqueline Vuky, Satish K. Tickoo, Joel Sheinfeld, Jennifer Bacik, Alison Amsterdam, Madhu Mazumdar, Victor Reuter,
Dean F. Bajorin, George J. Bosl, and Robert J. Motzer
Purpose: We describe the response to conventional
or high-dose salvage chemotherapy in patients with
advanced seminoma who experience disease progression after receiving first-line platinum-based treatment.
Patients and Methods: Twenty-seven patients with
progressive, advanced, pure seminoma were treated
with salvage chemotherapy. Fifteen patients were
treated with conventional-dose cisplatin-and-ifosfamide combination chemotherapy. Twelve patients
were treated with high-dose chemotherapy followed
by autologous stem-cell rescue.
Results: Fifteen patients (56%) achieved a complete
response (CR), nine achieved CR with a conventionaldose cisplatin and ifosfamide program, and six experienced CR after high-dose chemotherapy. Fourteen patients (52%) are alive and disease-free, with 13 (48%)
continuously disease-free at a median follow-up of 72
months. Twelve (57%) of 21 patients whose pretreatment tumors were studied morphologically were found
to have seminoma with atypia. Eight patients underwent resection after salvage chemotherapy; six with
histologic findings of necrotic debris/fibrosis alone are
alive and disease-free at last follow-up. Both patients
with viable seminoma found at surgery died of disease.
Conclusion: Most patients with advanced seminoma
are cured with standard first-line programs of cisplatin
and etoposide with or without bleomycin. A small minority of patients with pure seminoma have resistant
tumors and require salvage chemotherapy. In this setting, approximately 50% of patients with recurrent
pure seminoma achieve durable CR with conventional
or high-dose salvage chemotherapy. Identification of
biologic markers to predict clinical outcome and an
enhanced understanding of the basic biologic features
of seminoma may lead to improvements in the management of this disease.
J Clin Oncol 20:297-301. 2001 by American
Society of Clinical Oncology.
INCE THE INTRODUCTION of cisplatin-based combination chemotherapy, 70% to 80% of patients with
metastatic testicular germ cell cancers (GCT) are cured.1 In
this regard, pure seminoma histology is recognized as
particularly chemotherapy sensitive and is associated with a
high chance of cure, using standard chemotherapy programs
of cisplatin and etoposide with or without bleomycin.2
When patients with pure seminoma are stratified according
to internationally accepted risk criteria, 90% of patients are
classified as good risk, and more than 85% are cured with
cisplatin-based combination chemotherapy.2,3
A minority of patients with advanced pure seminoma,
however, do not achieve a complete response (CR) with
initial chemotherapy or will relapse after a CR and require
salvage therapy.3 In this setting, patients are treated on programs that have been largely used in nonseminoma, because
their histology is more likely to be refractory to standard
chemotherapy programs. Effective second-line chemotherapy
in patients with resistant GCT using ifosfamide and cisplatin
with either etoposide or vinblastine results in a CR of 50%,
with durable complete remission in approximately 25% of
patients.4,5 In patients who are not cured by ifosfamide-based
and cisplatin-based salvage chemotherapy, high-dose chemotherapy (HDCT) with autologous stem-cell rescue can cure
15% to 25% of patients.6,7 However, published series of both
regimens to date have been composed almost entirely of
patients with nonseminoma histology.
The small number of patients who require salvage chemotherapy has limited the study of optimal management of
pure seminoma in the salvage setting.8 We describe the
experience at our center in the management of 27 patients
with resistant seminoma. Treatment outcomes and surgical
resection after salvage chemotherapy are discussed.
Patients
Twenty-seven patients with metastatic pure seminoma who required
salvage chemotherapy were identified from July 1987 to December
1999 on a clinical trial approved by the institutional review board at
297
298
VUKY ET AL
Table 1.
No. of
Patients
15
13
2
12
9
3
Pathology Review
Twenty-one (78%) of 27 patients had histopathologic material
available for adequate review for presence of seminoma with atypia
versus usual seminoma by a pathologist (S.K.T.).11 All samples
reviewed were obtained before the initiation of salvage chemotherapy.
Fine needle-aspiration (cytologic) specimens were not included in the
analysis as a result of the difficulty with specimen interpretation in
regard to this distinction. Patients were defined as having atypia when
moderate to marked nuclear pleomorphism, nuclear overlapping, lack
or paucity of tumor lymphocytic infiltration, and/or absence of cytoplasmic clarity were observed.11 Tumors found to contain more than
50% of such features were considered seminomas with atypia, and all
others were categorized as classical seminomas.
Twelve (57%) of 21 patients with tumors studied morphologically
were found to have the presence of seminoma with atypia. Seven of
these patients had pathologic material reviewed from testis, and five,
from retroperitoneal lymph node. Eleven were obtained before the
patient received any chemotherapy, and one was obtained after chemotherapy but before entry onto this study.
RESULTS
Patient Characteristics
Patient characteristics are shown in Table 2. Primary site
was testis in 26 (96%) and extragonadal (retroperitoneum)
in one patient. Initial response to first-line therapy was CR
in eight patients (30%) and IR in 19 (70%). Six patients
(22%) had prior radiation therapy. Twenty-three patients
(85%) had been treated with one prior cisplatin-based or
carboplatin-based regimen, and four patients (15%) had
received two prior regimens. Twelve (44%) and 17 (65%)
had abnormally elevated serum concentrations of HCG and
LDH, respectively, before salvage chemotherapy.
Response and Survival Analysis
CR to salvage chemotherapy was achieved in 15 (56%) of
27 patients; none of these patients required resection of
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299
Patient Characteristics
Characteristic
No.
Patients
Age, years
Median
Range
Site of metastatic disease before salvage
treatment
Retroperitoneum
Lung
Mediastinum
Bone
Liver
Other
Sites of metastatic disease
1
2
3
Abnormal value prechemotherapy markers
HCG (normal, 2.2 mIU/mL), mIU/mL
Median
Range
LDH (normal, 200 U/L), U/L
Median
Range
Prior cisplatin or carboplatin chemotherapy
1 regimen
2 regimens
First-line chemotherapy regimen
Etoposide and cisplatin
Bleomycin, etoposide, and cisplatin
Etoposide and carboplatin
Other cisplatin-based
Prior response to first-line chemotherapy regimen
CR
IR
27
35
23-62
19
7
6
4
2
6
70
26
22
15
7
22
12
12
3
44
44
11
18.7
2.6-7,736
494
212-2,180
23
4
85
15
14
7
2
4
52
26
7
15
8
19
30
70
Table 3.
Total
No. of Patients
Alive at Last
Follow-Up
No.
27
Response to salvage therapy
CR
Combination cisplatin ifosfamide
High-dose chemotherapy
IR
Combination cisplatin IR
ifosfamide
High-dose chemotherapy
15
9
6
12
6
6
14
93
8
6
8
0
1
Fig 1.
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Copyright 2002 American Society of Clinical Oncology. All rights reserved.
300
VUKY ET AL
Table 4.
Survival Status
No. (N 27)
14
1
12
13
52
4
44
48
Overall status
Alive, disease-free
Alive with disease
Dead
Continuously disease-free
Table 5.
Patient No.
Surgical Procedure
2
3
6
7
8
Pathology Resected
Residual
Status
Follow-Up
(months)
Fibrosis
Alive
52
Necrosis
Necrosis
Alive
Alive
21
72
Fibrosis
Alive
87
Seminoma
Dead
Seminoma
Necrosis
Necrosis
Dead
Alive
Alive
13
9
12
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301
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Copyright 2002 American Society of Clinical Oncology. All rights reserved.