2. +
Therapeutic Principles
The management of GCTs is governed by the potential for
rapid growth and for cure in essentially all patients;
This translates into a need for rapid diagnosis and staging and
expeditious application of appropriate treatment so as not to
have patients die unnecessarily or experience side effects from
treatment that would not have been required with earlier
diagnosis and proper management.
After orchiectomy, staging imaging studies, serum tumor
marker status should be performed and treatment plans should
be developed as rapidly as can be reasonably accomplished.
3. +
The probability of cure even in the presence of metastatic
disease has led to an aggressive approach with regard to the
administration of chemotherapy and the performance of
surgery after chemotherapy to resect residual masses
Chemotherapy is generally administered regardless of low
white blood cell counts or thrombocytopenia, and nephrotoxic
chemotherapy (cisplatin) is often administered even in the
presence of moderate to severe renal insufficiency.
4. +
Similarly, an aggressive surgical approach is taken to resect all
sites of residual disease after chemotherapy for NSGCT even if
this involves multiple anatomic sites.
The young age and generally good health of patients with
GCTs permits an aggressive treatment approach if needed.
5. +
Serum tumor markers strongly influence the management of
GCTs, particularly NSGCTs.
As discussed, elevated serum AFP or hCG after orchiectomy
indicates the presence of metastatic disease, and these patients
are preferentially given chemotherapy.
For patients receiving chemotherapy, increasing serum tumor
marker levels during or after therapy generally indicate refractory
or relapsed disease, respectively.
As discussed earlier, serum AFP, hCG, and LDH levels at the
initiation of chemotherapy are important prognostic factors and
influence the selection and duration of chemotherapy regimens.
6. +
Testis cancer is a relatively rare disease, and general urologist
and general oncologists do not typically treat a large volume of
patients with GCTs. In addition, the treatment algorithms are
complex and nuanced, and the data supporting certain treatments,
such as RPLND, are based on data from a relatively small number
of surgeons who have performed a large number of these
operations
Most urology residents in the United States complete their training
having performed two or fewer RPLND procedures.
Several studies reported improved survival when the treatment
was provided at high-volume institutions .
Whenever possible, patients with GCTs should be treated at high-
volume centers, and RPLND should be performed by surgeons
who are experienced with this operation.
7. +
Contrasting Seminoma and
Nonseminoma Germ Cell Tumor
For treatment purposes, the distinction between seminoma and NSGCT is very important.
Compared with NSGCT, seminoma has a more favorable natural history. In general,
seminoma tends to be less aggressive, to be diagnosed at an earlier stage, and to spread
predictably along lymphatic channels to the retroperitoneum before spreading
hematogenously to the lungs or other organs. At diagnosis, the proportion of patients with
CS I, II, and III disease is 85%, 10%, and 5% for seminoma and approximately 33%, 33%,
and 33% for NSGCT (Powles et al, 2005).
Seminoma is also associated with a lower incidence of occult metastasis among patients
with CS I (10% to 15% vs. 25% to 35% for NSGCT) and a lower risk of systemic relapse
after treatment of the retroperitoneum (1% to 4% after radiotherapy for seminoma vs. 10%
after RPLND for NSGCT), which has important implications for the use of chemotherapy.
Seminoma is less likely to have elevated serum tumor markers, and serum tumor markers
do not range as high as in NSGCT.
Also, serum tumor markers are not used in the IGCCCG risk classification of seminoma.
8. +
Compared with NSGCT, seminoma is exquisitely sensitive to
radiation therapy and platin-based chemotherapy.
Substantially lower radiation doses are required to eradicate
seminoma compared with other solid tumors
Radiation therapy is a standard treatment option for CS I, IIA, and
IIB seminoma but has no role in NSGCT, with the exception of
treatment for brain metastases.
Seminoma accounts for only 10% of advanced GCT cases despite
the fact that it accounts for 52% to 56% of all GCTs.
A poor prognosis IGCCCG risk category does not exist for
advanced seminoma, and greater than 90% of metastatic cases
are classified as good risk (compared with 56% for NSGCT)
(International Germ Cell Consensus Classification, 1997.
9. +
The risk of teratoma at metastatic sites is generally not a
consideration for advanced seminoma, which has important
implications for the management of residual masses after
chemotherapy.
However, the potential for seminoma to transform into NSGCT
elements is an important consideration in the management of
patients who fail to respond to chemotherapy or who relapse after
radiation therapy.
Of patients with metastatic seminoma who relapse after treatment,
approximately 10% to 15% have NSGCT elements at the site of
relapse.
An autopsy study showed that 30% of patients who die of
seminoma have NSGCT elements at metastatic sites
10. +
Because GCTs are almost always cured, numerous clinical trials
have been conducted in an attempt to minimize treatment and
avoid unnecessary therapies in an effort to reduce short-term and
particularly long-term side effects and toxicity.
One approach has been to limit the number of patients who
receive two interventions (“double therapy”): either surgery or
chemotherapy and not both.
However, because NSGCTs are usually mixed tumors, and
teratoma often exists at metastatic sites with other GCT elements,
“cure” often requires chemotherapy to kill the chemosensitive
components and surgery to remove teratomatous components.
11. +
Intratubular Germ Cell Neoplasia
ITGCN is diagnosed by
testicular biopsy performed for the investigation of infertility,
contralateral testis biopsy in patients with GCT, or
within the affected testis in a patient undergoing testis-sparing surgery.
The rationale for treatment of ITGCN is based on the high risk of
developing invasive GCT; 50% risk of developing an invasive GCT
within 5 years.
Treatment options include
Orchiectomy,
low-dose radiotherapy, and
close observation.
12. +
The choice of therapy should be individualized based on
the patient’s desire for future paternity,
the presence or absence of a normal contralateral testis, and
the patient’s desire to avoid testosterone replacement therapy.
Radical orchiectomy is the most definitive treatment, although low-dose
radiotherapy (≥20 Gy) is associated with similar rates of local control with
the prospect of preserving testicular endocrine function owing to the
relative radioresistance of Leydig cells compared with germinal epithelium.
However, testosterone replacement therapy is ultimately required in up to
40% of patients, and patients should be monitored after radiotherapy for
adequate testicular androgen production.
To preserve testicular endocrine function, dose reductions to less than 20
Gy have been investigated, but cases of recurrent ITGCN have been
observed
13. +
For patients with a normal contralateral testis who desire future
paternity, radical orchiectomy is preferred because scatter to the
contralateral testis from radiotherapy may impair
spermatogenesis.
For patients with abnormal semen parameters but sufficient for
assisted reproductive techniques, close surveillance with periodic
ultrasound evaluation of the testis is a reasonable strategy with
deferred therapy until successful pregnancy and/or development
of GCT.
Another option for these patients is testis exploration, sperm
harvesting, and cryopreservation for assisted reproductive
techniques and radical orchiectomy followed by testosterone
replacement therapy