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547
Bilateral Testicular Tumors
Management and Outcome in 21 Patients
Christopher L. Coogan, M.D.
Richard S. Foster, M.D.
Garrick R. Simmons, M.D.
Piero G. Tognoni, M.D.
Bruce J. Roth, M.D.
John P. Donohue, M.D.
Department of Urology and Department of Medicine, Section of Hematology/Oncology, Indiana
University Medical Center, Indianapolis, Indiana.
BACKGROUND. The authors examined the clinical course of patients with bilateral
testicular tumors to determine whether the outcome after treatment was different
from patients with unilateral tumors.
METHODS. Using a computerized data base of 2088 patients with testicular carcinoma at Indiana University, 21 patients (1%) were identified with bilateral testicular carcinoma. A retrospective review of hospital and clinic charts was performed.
Sixteen patients with metachronous and 5 patients with synchronous testicular
tumors were identified.
RESULTS. Treatment was based on clinical stage and was similar to therapy given
for unilateral disease. The mean age at presentation of the first testicular tumor
was 28.4 years (range, 16 – 47 years). Approximately 50% of the second primary
tumors presented . 5 years after the contralateral tumor. At a mean follow-up of
49.9 months (range, 1–276 months), 18 patients were without evidence of disease,
2 were alive with disease, and 1 patient had died of disease.
CONCLUSIONS. The treatment of patients with bilateral germ cell tumors is based
on the pathology and clinical stage and should not be different from the traditional
management of unilateral testicular carcinoma. Patients with unilateral testicular
carcinoma should be informed of the necessity of long term follow-up because
contralateral testicular carcinoma may occur as long as 25 years later. Cancer 1998;
83:547–52. © 1998 American Cancer Society.
KEYWORDS: bilateral, testicular carcinoma metachronous, synchronous.
T
Presented in part at the North Central Section of
the American Urological Association Meeting,
Monterey, California, September 26, 1997.
Dr. Coogan’s current address: Department of Urology, Rush-Presbyterian-St. Luke’s Medical Center,
Chicago, Illinois.
Address for reprints: Richard S. Foster, M.D., Department of Urology, 550 N. University Blvd., Indianapolis, IN 46202.
Received October 10, 1997; revision received February 4, 1998; accepted February 10, 1998.
© 1998 American Cancer Society
esticular carcinoma is the most common solid malignancy in men
ages 15–35 years.1,2 The incidence of testicular carcinoma is 4.5
per 100,000 and is increasing.3 In 1970, the mortality rate for testicular
carcinoma was approximately 90% compared with , 10% in 1990.1
Patients who develop testicular carcinoma in one testis are 500 –1000
times more likely to develop testicular carcinoma in the contralateral
testis.4,5 The incidence of bilateral testicular carcinoma varies between 0.5–7%.4 –10
Prior therapy for testicular carcinoma potentially could affect treatment decisions for subsequent contralateral tumors by increasing the
morbidity of such therapy. Similarly, therapy for the initial tumor (retroperitoneal lymph node dissection [RPLND]) potentially could affect
the behavior of a subsequent tumor (altered lymphatic drainage). The
objectives of this study were to determine: 1) Is therapy for a second
primary tumor different than therapy for the initial tumor? and 2) Is the
chance for cure or morbidity of therapy different?
MATERIALS AND METHODS
Using a computerized data base of 2088 patients with testicular
carcinoma at Indiana University, 21 patients (1%) were found to have
548
CANCER August 1, 1998 / Volume 83 / Number 3
TABLE 1
Bilateral Testicular Tumors: Presentation, Management, and Outcome in 21 Patients
Patient
(age)
(yrs)
Site/pathology
1st testis tumor
Clinical
stage
Treatment
(pathology)
[courses]
Interval to the
2nd primary
(mos)
1 (28)
L-seminoma
A
XRT
70
2 (32)
R-seminoma
A
XRT
66
3 (32)
R-seminoma
A
XRT
4 (34)
L-seminoma
B
5 (27)
L-seminoma
6 (27)
Treatment
(pathology)
[courses]
Pathology
2nd testis
Clinical
stage
Embryonal
seminoma
syncytiotropho
blasts
Embryonal
C
BEP[3] PC
RPLND
(Teratoma)
NED (10)
B
NED (29)
44
Embryonal
teratoma
C
XRT
75
B
A
XRT
21
R-seminoma
A
XRT
29
Embryonal
yolk sac
seminoma
Embryonal
teratoma,
Seminoma
Embryonal
seminoma
7 (50)
R-seminoma
A
XRT
216
PNET,
Embryonal
teratoma
A
8 (20)
L-seminoma
A
XRT
24
Embryonal
teratoma
C
9 (29)
L-yolk sac
embryonal
teratoma
L-embryonal
seminoma
A
71
Seminoma
A
13
Seminoma
B
BEP PC
RPLND➩
Seminoma
VIP[2]➩AuBMT
AWD (6)
R-embryonal
cell
carcinoma
B
RPLND (No
pathologic
change)
RPLND
(One
focus of
seminoma)➩
Surveillance
RPLND (No
pathologic
change)
RPLND
(Embryonal)
BEP[2]
BEP[4] PC
RPLND
(Teratoma)
RPLND
(embryonal)
BEP[4]
RPLND (No
pathologic
change)
BEP[4] PC
RPLND
(Yolk sac)
VIP[6],
paclitaxel,
doxorubicin
RPLND
(PNET,
embryonal)➩
Surveillance
BEP[4] PC
RPLND
(Necrosis)
XRT
180
Seminoma
A
XRT
NED (1)
10 (29)
11 (26)
A
A
C
Outcome
(mos)
NED (6)
NED (78)
NED (79)
AWD (54)
NED (5)
NED (5)
NED (10)
(continued)
bilateral testicular carcinoma. A retrospective review
of hospital charts and phone calls to follow-up physicians was performed in these 21 patients. The orchiectomy pathology, clinical and pathologic stage, treatments, morbidity, and outcome were evaluated.
RESULTS
The mean age of the patients at presentation of the
first testicular tumor was 28.4 years (range, 16 –50
years). This was similar to the mean age of all patients
in the Indiana data base (28.8 years). The patients’
presentation, treatment, and outcome are presented
in Table 1. No patient had a history of cryptorchidism.
No patient had any first-degree relatives with a history
of testicular carcinoma. A summary of the outcome in
the metachronous and synchronous group is presented in Table 2. Sixteen patients were found to have
metachronous tumors at an average interval of 65.1
months (range, 5–216 months) between diagnosis. Approximately 50% of the second primary tumors occurred . 5 years after the initial testicular tumor. Five
patients presented with synchronous tumors.
Bilateral Testicular Tumors/Coogan et al.
549
TABLE 1 (continued)
Bilateral Testicular Tumors: Presentation, Management, and Outcome in 21 Patients
Patient
(age)
(yrs)
Site/pathology
1st testis tumor
Clinical
stage
Treatment
(pathology)
[courses]
Interval to the
2nd primary
(mos)
12 (22)
R-teratoma
C
BEP[3], VIP[2]
XRT
13 (22)
L-embryonal
teratoma
A
14 (23)
R-embryonal
sarcoma
A
15 (28)
L-seminoma
A
16 (20)
L-embryonal
A
17 (47)
Synchronous
R-seminoma
L-seminoma
Synchronous
R-seminoma
L-seminoma
Synchronous
R-seminoma
L-seminoma
Synchronous
R-seminoma
L-embryonal
Synchronous
R-teratoma
L-teratoma
18 (32)
19 (36)
20 (16)
21 (18)
Pathology
2nd testis
Clinical
stage
Treatment
(pathology) [courses]
5
Atrophy with
tumor necrosis
C
Surveillance➩
Recurrence➩
Stage C➩
BEP[3]➩
PC RPLND
(Teratoma)
RPLND
(Embryonal,
seminoma)➩
Methotrexate,
chlorambucil,
actinomycin
D ➩ XRT
XRT
14
Yolk sac
choriocarcinoma
Syncytiotrophoblasts
A
Vincristine
Cyclophosphamide
Actinomycin D
AuBMT PCRPLND (PNET)
Surveillance
68
Embryonal
seminoma
C
Bleomycin,
Vincristine,
Doxorubicin,
Uinblastine PC
RPLND (Necrosis)
NED (276)
122
Embryonal yolk
sac
A
NED (29)
24
Embryonal
A
B
RPLND
(Seminoma)
➩BEP[2]
BEP[4]
Surveillance➩
➚Tumor
markers➩ BEP[3]
Surveillance
A
XRT
NED (22)
A
XRT
NED (9)
B
BEP[3]
NED (113)
C
BEP[4] PC
RPLND
(Teratoma)
NED (168)
Outcome (mos)
DOD (52)
NED (60)
NED (12)
NED (20)
L: left; XRT: radiation therapy; BEP: bleomycin, etoposide, and cisplatin; PC RPLND: postchemotherapy retroperitoneal lymph node dissection; NED: no evidence of disease; R: right; VIP: etoposide, ifosfamide, and
cisplatin; PNET: primitive neuroectodermal tumor; AuBMT: autologous bone marrow transplantation; DOD: dead of disease.
Metachronous Tumors
In the 16 patients with metachronous tumors, 13 initially presented with clinical Stage A disease, 2 presented with clinical Stage B disease, and 1 presented
with clinical Stage C disease (Tables 1 and 2). Clinical
staging at the time of presentation of the second testicular primary tumor revealed seven patients had
clinical Stage A disease, three had clinical Stage B
disease, and six patients had clinical Stage C disease.
Nine patients initially presented with seminoma
whereas seven presented with a nonseminomatous
germ cell tumor in the metachronous group. Seven
patients presented with clinical Stage A disease at the
time of diagnosis of their second primary tumor. Two
patients underwent RPLND, two patients received radiotherapy for seminoma, and three patients were
placed in a surveillance protocol (one subsequently
failed and required chemotherapy). Three patients
presented with clinical Stage B disease. Two underwent RPLND (one patient with active disease) and one
underwent chemotherapy followed by postchemotherapy RPLND (PC-RPLND). All six patients who pre-
550
CANCER August 1, 1998 / Volume 83 / Number 3
TABLE 2
Bilateral Testicular Tumors Disease Status
No.
Age at 1st
primary
(range) (yrs)
Interval
(range) (yrs)
Metachronous
16
28.0 (20–50)
55.0 (5–276)
Synchronous
All
5
21
32.0 (16–47)
28.0 (16–50)
Disease status
(median follow-up)
(mos)
NED: 13 (12)
AWD: 2 (30)
DOD: 1 (52)
NED: 5 (22)
NED: 18 (25)
AWD: 2 (30)
DOD: 1 (52)
NED: no evidence of disease; AWD: alive with disease; DOD: dead of disease.
sented with clinical Stage C disease received chemotherapy followed by PC-RPLND. Two patients had
active disease (both received chemotherapy postoperatively), two patients had teratoma in the resected
specimen, and two patients had necrosis only in the
resected specimen (Table 1). At a mean follow up of
44.5 months (range, 1–276 months), 13 had no evidence of disease (NED), 2 were alive with disease
(AWD), and 1 was dead of disease (DOD).
Synchronous Tumors
Five patients presented with synchronous testicular
carcinoma (Tables 1 and 2). Two presented with clinical Stage A disease, two presented with clinical Stage
B disease, and one presented with clinical Stage C
disease. Four patients had identical pathology in both
testes (three-seminomas and one-teratoma) and one
had different pathology in each testis (seminoma and
embryonal). The treatment and outcome can be seen
in Tables 1 and 2. At a mean follow-up of 66.4 months
(range, 9 –168 months), all patients were classified
NED.
DISCUSSION
Approximately 0.5–7% of patients with testicular carcinoma will develop a contralateral testicular tumor.4 –10 The incidence of testicular carcinoma is increasing5 and the improved survival in patients with
testicular carcinoma may lead to an increased incidence of bilateral tumors.11 In the current report, 1%
of our patients were found to have a second primary
testicular tumor. The true incidence of bilateral testicular carcinoma is difficult to determine. The majority
of patients in our computer bank are referred and
often highly selected patients. However, it is important to note that patients with disease in one testicle
are at a 500 –1000-fold increased risk of contralateral
testicular carcinoma compared with the general pop-
ulation, suggesting either a genetic predisposition or
exposure to an environmental toxin.4,12,13
Testicular carcinoma is associated with cryptorchidism, atrophy, possibly trauma, and hormonal
or genetic factors.14 Certain subgroups may be at an
increased risk of developing carcinoma in situ (CIS) on
the contralateral side. Risk factors include: 1) cryptorchidism, 2) testicular atrophy, 3) low sperm count,
4) elevated follicle stimulating hormone levels, and 5)
age at diagnosis of the first primary tumor , 30
years.15,16 Although no patient in this study had a
history of cryptorchidism, the incidence of cryptorchidism in patients with bilateral testicular carcinoma can be as high as 22%.5 The incidence of CIS in
the contralateral testis in patients with testicular carcinoma ranges between 4.4 – 6.6%.9,16 It currently is
standard practice in Denmark to perform a biopsy of
the contralateral testis in patients with testicular carcinoma in one testis. Patients who are found to have
CIS receive prophylactic radiotherapy to prevent tumor occurrence in the contralateral testis. Radiotherapy virtually eliminates the possibility of a contralateral tumor and preserves hormonal production in the
testis, but eliminates any future fertility potential.9
Approximately 80 – 85% of bilateral testicular tumors occur metachronously, whereas 15–20% occur
synchronously.17,18 Synchronous testicular tumors
nearly are always of a similar pathology.5,7 In the current study, five patients presented with synchronous
testicular tumors. Two patients presented with clinical
Stage A disease, two patients presented with clinical
Stage B disease, and one patient presented with clinical Stage C disease. Although the number of cases is
small, patients with synchronous tumors may present
at a higher stage disease compared with those with
unilateral testicular carcinoma. However, the outcome
remains excellent. All patients were NED after radiotherapy or chemotherapy and PC-RPLND at a mean
follow-up of 66 months (range, 9 –168 months). Patients with synchronous testicular tumors should be
treated based on their clinical stage and pathology. In
our small cohort, survival was 100% and all patients
have been continuously NED.
Metachronous tumors occurred at a mean of 65.1
months after the first primary tumor. Although 13 of
16 patients (81%) presented with clinical Stage A disease at diagnosis of their first primary tumor, only 7 of
16 (44%) presented with clinical Stage A disease at the
diagnosis of the second primary tumor. Delay in diagnosis is possible in patients with a second testicular
primary tumor for several reasons. The consequence
of losing both testicles is far greater than losing one
testicle, which may lead to patient denial. Testicular
self-examination may be difficult because there is no
Bilateral Testicular Tumors/Coogan et al.
contralateral testis for comparison. Patients often are
only followed for 5 years, yet 50% of second primary
tumors will occur . 5 years later. Some authors have
speculated that systemic chemotherapy may have a
prophylactic effect on the development of a second
testicular primary tumor,12 but this has been refuted
by others.19 Recently, van Basten et al. noted a 3%
incidence of contralateral testicular tumors and a
markedly reduced (1.8% vs. 5%) incidence of bilateral
tumors in men treated with cisplatin-based chemotherapy.20
Dieckmann et al. found that approximately 50% of
metachronous tumors in their study had a similar
pathology.5 Seminoma accounted for 80% of the cases
with a similar pathology, whereas 20% were nonseminomas.5 No patient in our study presented with metachronous seminoma. This may represent a selection
bias based on the referral patterns at Indiana University. Only 3 of 16 patients (19%) presented with a
similar histology of their second primary tumor. Of the
nine patients who presented with seminoma in their
first primary tumor, all presented with nonseminoma
in their second primary tumor. Again, this may be a
referral bias rather than true incidence.
Treatment of bilateral testicular carcinoma is
based on the pathology and clinical stage. Of the seven
patients with clinical Stage A disease at presentation
of a second primary tumor, two patients (nonseminoma) underwent RPLND, two received radiation
therapy (seminoma), and three (nonseminomatous)
were placed in a surveillance protocol. One surveillance patient required subsequent chemotherapy for
elevated tumor markers. All were NED at a mean follow-up of 28 months. Patients with advanced disease
(n 5 9) were treated with chemotherapy and/or PCRPLND (Table 1). The decision regarding use of
RPLND must be based on prior therapy, pathology of
the testis, clinical stage, and patient preference. No
patients in this study underwent bilateral primary
RPLND for metachronous tumors. The technical aspects of RPLND after radiotherapy are dependent on
the field and dose of radiation, time from last treatment, and template necessary for treatment. Nervesparing techniques are not necessary because patients
are anorchid. However, a recent study advocated partial orchiectomy in patients with a second primary
tumor in highly selected patients.21 However, this approach must be considered investigational.
Survival in our patients with bilateral testicular
carcinoma does not appear to be worse than in patients with unilateral testicular carcinoma. In the current study, at last follow-up 18 patients were NED, 2
were AWD, and 1 was DOD. The one patient who was
DOD presented with clinical Stage C disease and had
551
a primitive neuroendocrine tumor at PC-RPLND, a
poor prognostic indicator. Survival is excellent in patients who receive proper staging and therapy and
does not appear to differ from survival in patients with
unilateral testicular carcinoma.19,22–25
The incidence of testicular carcinoma appears to
be increasing.5 Second testicular primary tumors have
been reported to be found up to 25 years later.12 The
majority of second primary tumors are found by testicular self-examination, emphasizing the need for
long term testicular self-examination.12 Patients
should be counseled on the necessity and proper technique of testicular self-examination. Treatment options for the second primary tumor should be based
on clinical stage, pathology of the testis, and prior
therapy. Management of the second primary tumor
should not be different from traditional management
of testicular carcinoma. Survival remains excellent in
patients with bilateral testicular carcinoma and most
likely is not different on a stage for stage basis compared with patients with a single primary tumor. Follow-up and surveillance for a second primary tumor
should be lifelong because contralateral testicular carcinoma may occur up to 25 years later.
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