]
Our patient was 24 years old. He did not have any
other comorbidity. He has noticed swelling in his scrotum
and was timely administered to hospital. A 3.5 cm
solid mass was reported in his left testicle with USG.
Serum Β-Hcg, AFP, and LDH levels were 437 mIU/
ml, 903 ng/mL, 362 IU/L, respectively. Left inguinal
orchiectomy was performed to the patient in August
2011. There was no complication after surgery. Admixture
of yolk sac and teratoma were reported by pathologists.
Serum &B-Hcg, AFP and LDH levels decreased
to 25.7eta; mIU/ml, 289 ng/mL, 179 IU/L, respectively, in the 1st post-operative week. Regression of tumor markers
was continued within 1½ months after the surgery.
They were at completely normal levels by the 6th postoperative
week. Systemic evaluation was made with
thoracic and abdominopelvic CT scan. There was no
sign of metastasis in the body. Although serum tumor
marker levels decreased to normal values, the normalization
time was longer than expected. Two cycles of
BEP (cisplatin 100 mg/m2, etoposid 150 mg/m2, and
bleomycin 30 U) were given to the patient in October
2011. Then, the patient followed up with testing
of tumor marker levels in every 3 months and radiologic
imaging in every 4 months. While the patient was
screening with stable disease, prominent progression of
tumor marker levels was detected in routine laboratory
tests in December 2013. Serum Β-Hcg, AFP levels were
173.5 mIU/ml and 36 ng/mL, respectively. Scrotal USG
showed 1.5 cm mass at the inferior pole of the right testicle.
Right testis sparing surgery (TSS) was performed
immediately after USG result. During surgery, 2 punch
biopsies were taken from normal testis parenchyma.
Pathology report revealed a mixed GCT with a combination
of embryonal carcinoma (65%), yolk sac (20%),
teratoma (10%), and choriocarcinoma (5%). Lymphovascular
invasion was seen. Surgical margins were intact.
Furthermore, ITGCN reported in the residual
testis parenchyma. Therefore, 20 Gy radiotherapy (RT)
(Figs. 1, 2) was given to residual testis in 10 fractions
in January 2014. Serum Β-Hcg, AFP levels were 3600
mIU/ml and 255 ng/mL, respectively, in the 1st post-operative
week. Serum Β-Hcg, AFP levels were 2400 mIU/ ml and 180 ng/mL, respectively, after the RT. PET scan
showed increased FDG uptake at the distal paraaortic
lymph node (SUVmax 7.3). Consequently, the patient
was referred to medical oncology for systemic therapy.
Afterward, 4 cycles of EP chemotherapy were applied to
the patient. EP chemotherapy was completed in March
2014. Serum Β-Hcg, AFP levels were 1.6 mIU/ml and
7.8 ng/mL, respectively, after EP chemotherapy. Regression
of involved lymph node and decreased uptake of
FDG (SUVmax 2.6) were reported in control PET scan
in May 2014. During follow-up, 3 consecutive measurements
of serum Β-Hcg levels were seen progressively
increased in June 2014 (64→122→223 mIU/ml). Accordingly,
3 cycles of TIP chemotherapy were planned.
TIP (paclitaxel 250 mg/m2, ifosfamide 1.5 g/m2, mesna
1.5 mg/m2, and cisplatin 25 mg/m2) chemotherapy was
completed in August 2014. Serum tumor marker levels
were totally normal in September 2014. There is still
no evidence of disease (NED). Survival is 110 months
and disease-free survival is 74 months now. There is
no long-term complication of treatment except testosterone
deficiency due to the Leydig cells destruction.
Fig 1: Coronal view of the radiotherapy (RT) plan. Isodose
lines red, yellow, and blue represent 107%,
95%, and 50% of the total dose, respectively.
IGRT (image-guided radiotherapy) is used to
minimize setup errors and interfraction differences.
A bolus was placed superficially to the skin
to maintain an adequate surface dose.
Fig 2: Sagittal view of the radiotherapy (RT) plan. Isodose
lines red, yellow, and blue represent 107%,
95%, and 50% of the total dose, respectively. The
penis retracted superiorly to avoid from RT field.
The 95% isodose line covers all of the remaining
testis volumes.
Radical orchiectomy is the gold standard treatment
for TC. However, TSS may be alternative to radical
orchiectomy, especially in bilateral tumors to prevent
testosterone deficiency. Although there are several publications
about TSS in the literature, there is no scientific
consensus on this topic. The common idea is being cautious
for assigning patients to TSS.[,] EAU guidelines
recommend the use of TSS to patients, which have
solitary testis, for preserving infertility and hormonal
function, which is compatible with our patient.[]
ITGCN is a precursor lesion of cancer. Heidenreich
et al. stated that ITGCN is seen at the residual
testis parenchyma in 82% of 73 patients after TSS in
their study. Existence of ITGCN ends up with TC in
50-80% of cases.[,] Therefore, RT is required in
case of ITGCN. Although RT is effective for controlling
the disease, it damages Leydig cells and causes
testosterone deficiency at the same time. In this regard,
determination of RT dose is very crucial. Leydig
cells are very sensitive to radiation. It is showed
that doses as low as 6 Gy can affect Leydig cells.[]
On the other hand, according to literature, optimal
RT dose for ITGCN is 20 Gy.[] There are several
studies in the literature comparing 20 Gy with lower
doses (14-16 Gy) in the aspects of both disease control
and hormone profile. However, decreasing the RT
dose may lead to an increasing risk of disease relapse.
[-] Consequently, hypogonadism rates after RT
are reported as 25-30% in the literature.[,] In compliance with literature findings, we applied 20 Gy
RT. Unfortunately, our patient ended up with testosterone
deficiency and required hormone substitution.
He is getting 1000 mg testosterone replacement every
3 months.
Testosterone deficiency is a consequence of both RT
and chemotherapy. Recent researches indicated that
cisplatin-based regimens cause subclinical hypogonadism
by affecting Leydig cells" function.[,] Furthermore,
another effect of radio and chemotherapy is
reported in the literature. Higher serum LH levels are
associated with a decrement in testosterone production
in the remaining irradiated testicular tissue. Furthermore,
platinium-based chemotherapeutics have a cumulative
effect on Leydig cells.[] According to this
data, testosterone deficiency was inevitable in this case
as a result of intense treatment.
Overall survival (OS) rates for bilateral synchronous
TC are lower than metachronous contralateral
TC according to SEER database. The 10-year OS rate
for patients diagnosed with metachronous contralateral
TC has been reported as 93% in SEER analysis.
[] However, there are many publications reporting
different OS time for bilateral TC patients with
different histology, stage, and risk factors in the literature.
Klatte et al. reported that all of the patients
were alive after a median follow-up of 95 months for
11 metachronous bilateral TC patients. However, only
1 of 11 patients had non-seminomatous mixed GCT
histology.[] Similarly, in the study by Hentrich et
al.,[] 32 of 33 metachronous bilateral TC patients
were reported as alive with NED after a median follow-
up of 41 months. Furthermore, in the study by
MD Anderson Cancer Center for bilateral TC, it has
been stated that only 1 of 24 patients died due to the
metastatic disease.[] In parallel with literature findings,
our patient survived for 110 months and is still
following up with NED.
Our patient evaluated as stage 1S at the time of
diagnosis, according to serum tumor marker levels
(S1). Therefore, despite return of tumor marker levels
to normal at 1.5 months after surgery, 2 cycles of BEP
were given to the patient according to recommendations
from NCCN guidelines.[,] At the time of relapse,
our patient had stage 2A disease because of N1
lymph node. Serum tumor marker levels were prominently
high after TSS. Persistent marker elevation after
surgery was a significant independent predictor of
recurrence.[] Four cycles of EP were applied to the
patient. After EP chemotherapy, markers turned down
to normal levels in March 2014. However, Β-Hcg values elevated on 3 serial measurements in June 2014. Therefore,
the patient was accepted again with the relapsed
disease and received 3 cycles of TIP chemotherapy as
the second-line regimen. TIP regimen is very useful for
relapsed GCT. Motzer et al. reported of a complete positive
response from 24 out of 30 patients with relapsed
GCT who were treated with TIP regimen.[]
Although CT is the standard modality for detecting
abdominal or retroperitoneal lymphadenopathies,
its false negative rates have been observed as high as
30-59% in the literature.[,] However, potential of
PET/CT to improve clinical staging of TCs has reported
recently.[] Besides, prospective studies of the German
multicenter PET study group revealed that PET/
CT is only slightly better than CT as a primary staging
tool for stage 1/2 non-seminomatous GCTs.[] Furthermore,
they reported that PET/CT is not better than
serum tumor markers and CT for evaluating treatment
response after chemotherapy for non-seminomatous
GCTs.[] In light of this information, we performed
CT scans for routine radiological follow-up and treatment
response evaluation of our patient. In addition,
we further combined PET/CT with CT scans for improving
the accuracy of clinical staging and treatment
response evaluation.
Management of bilateral testis tumors requires a
wide consideration of several issues all together, including
control of disease, following of serum tumor
markers, making decisions on necessity of adjuvant
treatments, timing of therapies assigned, applying of
proper RT techniques, and controlling of long-term
side effects. Our patient has been treated with the
multimodality approach under cooperation of different
departments. BTCs may have an excellent prognosis.
However, close follow-up of the disease and
multimodality approach should always be considered.
Organ sparing approach can be a useful treatment alternative
in selected patients.
