From OncoLog, October 2012, Vol. 57,
Compass: Early-Stage Testicular Cancer
Postsurgical treatment varies according to tumor stage and histology
By Sunni Hosemann
Inguinal orchiectomy is the standard initial treatment for patients who
present with a testicular mass considered suspicious. The diagnosis and
staging of testicular cancers are then made by pathological analysis,
and subsequent management decisions are guided by the tumor’s
histologic subtype and assigned stage.
Most testicular cancers (95%) are germ cell tumors—either seminomas
(40%) or non-seminomas (60%)—and this discussion is limited to those
types. Tumors are considered non-seminomas if they contain any
histological component that is not pure seminoma.
Serum tumor markers—specifically, the beta subunit of human chorionic
gonadotropin (β-hCG) and alpha fetoprotein (AFP)—also have a role in
staging and treatment decisions for testicular cancers. According to
Louis Pisters, M.D., a professor in the Department of Urology at The
University of Texas MD Anderson Cancer Center, elevated β-hCG levels
may be seen in patients with seminomas or non-seminomas, but elevated
AFP levels are seen only in patients with non-seminomas. Therefore,
tumors are categorized and treated as non-seminomas when increased AFP
is present, even if pathological analysis has not detected a
non-seminoma tumor component.
In this discussion, early-stage disease refers to stages IA and IB
(pT1–pT4, N0, M0). These stages include primary tumors that are limited
to the testis and those that involve adjacent structures (tunica
albuginea, tunica vaginalis, spermatic cord, or scrotum) with or
without evidence of lymphovascular invasion (LVI) but have not involved
regional lymph nodes or metastasized to distant sites.
The National Cancer Institute estimates that 8,590 new cases of
testicular cancer and 360 testicular cancer–related deaths will occur
this year. Testicular cancer is highly treatable and curable and is
often detected early. The survival rate for all men with testicular
cancers is 95%; for men with early-stage disease, it is over 99%. “The
cure rate for stage I disease approaches 100%, and even metastatic
disease is curable,” Dr. Pisters said. “But it is not 100%, and we
still see patients who die of both seminoma and non-seminoma.”
More than half of the testicular cancer cases in the United States are
diagnosed in men between the ages of 20 and 34 years. Testicular
cancers in older men are more commonly found to be seminomas.
Non-seminomas tend to be more aggressive.
Testicular cancers follow a very predictable pattern of spread via the
retroperitoneal lymph nodes, which are located behind all the major
organs in the abdomen and extend upward along the aorta and vena cava.
The lymphatic vessels of the testes follow the gonadal blood vessels as
they ascend through the spermatic cord and continue upward along the
aorta and vena cava to the renal hila. These lymphatic vessels’
location deep in the abdomen, their proximity to major organs, and the
distance they span have implications for both surgical and radiation
therapies. It is important to note that this pattern of spread
initially bypasses the pelvic nodes; therefore, disease in the
retroperitoneal lymph nodes would be considered regional.
Notably, the pattern of lymph drainage from the scrotum is different
from that of lymph drainage from the testes. Lymph in the scrotum first
drains to the lower extremities; thus, it is prudent to avoid enabling
the escape of cancer cells from a diseased testicle into the scrotum,
which would result in two potential pathways of spread. This is why
needle biopsies of the testicle are avoided and orchiectomy is
performed via the inguinal route rather than through the scrotum.
After orchiectomy, the question becomes: is further treatment warranted
at this time, or is active surveillance a better option?
For early-stage testicular cancers, the objective of additional
treatment is to prevent disease relapse due to subclinical or occult
metastases. Thus, postoperative treatment modalities are aimed at the
retroperitoneal lymph nodes where the cancer first spreads. Disease
recurs in 25%–30% of patients with non-seminomas and 15%–20% of
patients with seminomas. Fortunately, the cure rate is very high in
patients treated for recurrent disease, and their survival is
equivalent to that achieved with pre-emptive treatment. However,
compared with preemptive treatment, treatment for recurrent disease is
more intense and carries higher risks of long-term sequelae.
According to Dr. Pisters, risk stratification is possible for
non-seminomas using serum tumor markers and pathological
characteristics. Predictors of a high risk for relapse include evidence
of LVI or embryonal carcinoma cells’ making up more than 80% of the
tumor. Relapse occurs in about half of patients with high-risk
Postoperative treatment options
Postoperative treatment options for stage IA and IB seminomas include
active surveillance, radiation therapy, or chemotherapy. For
non-seminomas, the standard options for stage IA disease are active
surveillance or retroperitoneal lymph node dissection (RPLND). The
options for stage IB non-seminomas are active surveillance (for T2
only), RPLND, or chemotherapy.
Active surveillance is an option for patients with stage IA or IB
seminomas or stage IA non-seminomas. Surveillance is generally not
recommended for patients with stage IB non-seminomas because the
disease will recur in 50% of these patients, but it is an option for
selected patients who are compliant with follow-up. Active surveillance
consists of follow-up visits at specified intervals. Evaluations at
these visits include abdominal pelvic computed tomography, chest
radiography, and monitoring of serum tumor marker levels. Patients with
seminomas remain on active surveillance for 10 years, and those with
non-seminomas are monitored for 5 years. The time span of these clinic
visits is a limiting issue for some patients.
Radiation therapy has long been a standard option for stage IA and IB
seminomas. However, according to Karen Hoffman, M.D., an associate
professor in the Department of Radiation Oncology, the treatment
paradigm for these tumors has changed over time. Historically,
pre-emptive radiation therapy was delivered to lymph nodes in the
paraaortic and ipsilateral pelvic regions. “This produced excellent
survival rates—near 100%,” she said. Thus, for a time, it was standard
procedure to treat patients with radiation therapy after orchiectomy.
“However, it became known that the incidence of second malignant
neoplasms occurring later in life was increased in these patients and
in some cases caused premature deaths,” Dr. Hoffman said. Over time,
studies confirmed that the radiation field could be reduced to exclude
the ipsilateral pelvic nodes and that the radiation dose to para-aortic
nodes could be decreased from 30 to 20 Gy without compromising
survival. “This was important because we believe that this reduction in
field size and radiation dose reduced the risk of radiation-related
second malignancies,” Dr. Hoffman added.
Advances such as computed tomography–based planning and proton
radiation therapy have resulted in a more precisely targeted delivery
of radiation. However, some risk remains, so although radiation is
still used elsewhere, it is no longer a preferred option at MD Anderson
in patients with no known lymph node involvement. Dr. Hoffman instead
discusses the option of active surveillance with all her patients with
early-stage disease for whom it is an option.
“Currently, if I treat an early-stage seminoma patient with radiation
at all, I use proton therapy,” Dr. Hoffman said. Proton beams have a
lower entrance dose than conventional photon radiation, deliver the
therapeutic dose over a discrete area, and have no exit dose.
Therefore, proton radiation treatment of the para-aortic lymph nodes
delivers a lower dose to adjacent organs, including the pancreas and
gastrointestinal tract. “Although proton therapy has not been around
long enough to gauge its long-term effects and has not been compared
head-to-head with conventional radiation delivery, we know that it
reduces the unnecessary radiation dose to tissues outside the target
field, which should decrease longterm side effects,” she said.
RPLND is a standard option for patients with stage IA or IB
non-seminomas, in whom the surgery usually provides definitive
RPLND is usually done through a large transabdominal midline incision
and involves removing lymphatic tissue from around the great vessels.
In the past, the operation involved a full bilateral dissection and
usually resulted in nerve damage that caused loss of ejaculation and
emission capability. Today, smaller dissection fields are used to spare
these nerve bundles and retain as much function as possible.
Standard options for patients with stage IA non-seminomas are
pre-emptive RPLND or active surveillance. Some patients who opt for
active surveillance will not need further treatment, and those who
undergo RPLND when disease recurs have outcomes similar to those of
patients who undergo early surgery.
Patients with stage IB non-seminomas who require or want additional
treatment rather than surveillance must choose between RPLND and
chemotherapy. “The surgery is a large and serious operation—an
extensive abdominal surgery,” Dr. Pisters said. “Most patients prefer
For these reasons, Dr. Pisters said, RPLND has fallen out of favor as a
treatment for most of the early-stage testicular cancers discussed here
and is rarely used at MD Anderson. The exception is a small subset of
patients who have a teratoma with malignant transformation—a rare but
very aggressive histologic type for which RPLND is the only option.
Chemotherapy is a standard option for patients with stage IA or IB
seminomas or stage IB non-seminomas. According to Lance Pagliaro, M.D.,
a professor in the Department of Genitourinary Medical Oncology,
chemotherapy is a safe and effective alternative to RPLND or radiation
For seminomas, the standard adjuvant chemotherapy is carboplatin, which
has relatively mild side effects and can be administered on an
outpatient basis either as a single dose or in two doses 3 weeks apart.
A large randomized trial found equivalent rates of relapse-free
survival in patients receiving single-dose carboplatin and patients
receiving radiation therapy after orchiectomy.
“Two questions arise, however,” Dr. Pagliaro said. “The first is
whether we can improve outcomes with two cycles instead of one, and the
second is what are the effects after 10 or 20 years or longer?”
Answering these questions will require data from follow-up visits over
many years. In the meantime, noting that most recurrences are prevented
with the first dose, he considers single-dose therapy safer. In the
event of a recurrence during active surveillance or after chemotherapy,
treatment outcomes are excellent, but either radiation therapy or
intensive combination chemotherapy is required.
“I regard surveillance as the least morbid option for seminomas,” Dr.
Pagliaro said. “Most are cured without the need for further treatment.
Plus, we don’t have sufficient data about the long-term risks of some
postoperative treatments.” However, Dr. Pagliaro believes that there
are patients with early-stage seminomas for whom a single course of
carboplatin should be strongly considered. These patients include:
- Patients with tumors larger than 4 cm classified as
pT3. “These patients have a higher risk of recurrence—about 1 in 3,” he
- Patients 50 years or older, in whom seminomas are
more common. These patients have fewer concerns about fertility or
- Patients of any age who are concerned about future
access to health care. This includes men in their teens or early 20s
who are currently covered by their parents’ insurance policies and
whose future insurance coverage is uncertain.
Chemotherapy is also an option for patients with stage IB
non-seminomas. For these patients, the most important risk factors are
histological type and evidence of LVI. For patients who are considered
to be at high risk of recurrence, the chemotherapy options are one or
two cycles of bleomycin, etoposide, and cisplatin (BEP). “This is the
same chemotherapy that is used for recurrence, but less is given if
used up front,” Dr. Pagliaro said. “Although two cycles have not been
proven clearly superior to one, we know that two cycles reduces
recurrence risk from 50% with surveillance to 2%,” he said.
No study so far has compared one versus two cycles of BEP directly.
However, a large risk-adapted trial that compared chemotherapy to
surveillance after orchiectomy in patients with stage I non-seminomas
found a 90% reduction in recurrence rate with only one cycle.
Therefore, the difference in recurrence rates between patients who
receive one and two cycles of BEP could be relatively small—4% versus
2%. Dr. Pagliaro’s current view is that because most recurrences are
eliminated with one course, the benefit of less treatment outweighs the
risk of treating 100 patients with a second course to prevent two
For the average-risk patient with a stage IA non-seminoma, Dr. Pagliaro
considers active surveillance the safest choice. But for select
patients, such as those who might be less likely to tolerate
chemotherapy later or those who have concerns about compliance with
surveillance schedules, one course of BEP could be reasonable. “Most
long-term chemotherapy effects are associated with three or more
courses of therapy,” he said. “We have not seen serious treatment
effects with only one course.”
Treatment for stage I testicular cancers must be individualized, and
substantial discussions are needed to help patients weigh the various
options and choose between surveillance and postoperative treatment. In
many cases, personal circumstances and preferences weigh as heavily in
the decision as purely medical considerations. In all cases, sperm
banking should be discussed before any treatment is initiated.
The University of Texas MD Anderson Cancer Center
Karen Hoffman, M.D.
Assistant Professor, Radiation Oncology
Lance C. Pagliaro, M.D.
Professor, Genitourinary Medical Oncology
|Louis L. Pisters, M.D.
For more information, talk to your physician, visit www.mdanderson.org, or call askMDAnderson at 877-632-6789.
P, Siener R, Krege S, et al. Randomized phase III trial comparing
retroperitoneal lymph node dissection with one course of bleomycin and
etoposide plus cisplatin chemotherapy in the adjuvant treatment of
clinical stage I nonseminomatous testicular germ cell tumors: AUO trial
AH 01/94 by the German Testicular Cancer Study Group. J Clin Oncol
National Cancer Institute. Testicular Cancer.
National Comprehensive Cancer Network. Clinical Practice Guidelines in
Oncology, Head and Neck Cancer, V1.2012.
Oliver RT, Mason MD, Mead GM, et al. Radiotherapy versus single-dose
carboplatin in adjuvant treatment of stage I seminoma: a randomised
trial. Lancet 2005;366:293–300.
Tandstad T, Dahl O, Cohn-Cedermark G, et al. Risk-adapted treatment in
clinical stage I nonseminomatous germ cell testicular cancer: the
SWENOTECA management program. J Clin Oncol 2009;27:2122–2128.
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