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GERM CELL TUMORS: LOOKING TO THE FUTURE
Germ Cell Tumors: Looking to the Future
George J. Bosl, MD
OVERVIEW
Our knowledge about the management of men with germ cell tumors (GCTs) and its tumor biology continues to evolve. Vascular disease,
metabolic syndrome, second malignant neoplasms, and hypogonadism occur after treatment for GCTs and the latency pattern resembles
that seen in patients treated for Hodgkin lymphoma. Patients receiving treatment for GCTs should be informed not only of the near-term
toxicity (experienced during or shortly after administration), but also the delayed and late effects of chemotherapy and the need for
lifelong surveillance for all late outcomes, including late relapse. Recent data suggest that the treatment outcome of patients with
intermediate-risk, poor-risk, and relapsed GCTs can be improved through multicenter trials that include the general oncology community.
Finally, GCTs are a malignancy of primordial germ cells. Programmed differentiation is clinically evident in vivo and probably
related to chemotherapy resistance. This biology has much clinical relevance, some of which is already in use.
In 2015, more than 90% of men with newly diagnosed
GCTs will be cured. The chemotherapy backbone of
etoposide/cisplatin (EP) with or without bleomycin (BEP)
cures patients with even far advanced newly diagnosed
metastatic disease. A sizable proportion of patients who
relapse or progress after initial chemotherapy are cured
with standard and high-dose regimens. 1 Since chemotherapy
cures nearly all patients with low-volume disease, surveillance
has become a standard of care for patients with
clinical stage (CS) I seminoma and CS I-A nonseminomatous
GCT (NSGCT), few of whom relapse after orchiectomy.
Adjuvant chemotherapy with one or two chemotherapy
cycles has been adopted by some for CS I-B disease and is
often recommended for patients who have pathologic
stage IIB disease at primary retroperitoneal lymph node
dissection. 1,2
However, physicians and patients should not be misled.
Attention to detail may be more important in the management
of patients with GCTs than in any other curable malignancy
since a large proportion of patients is observed without
treatment after orchiectomy and easily lost to follow-up. The
number of survivors is increasing, with close to 250,000 survivors
of GCTs comprising approximately 4% of all male
cancer survivors, more than lung cancer. 3 Despite the low
death rate, the number of lost life years is greater for patients
with GCTs than for any other cancer in adults. 4
Complacency, fostered by the high cure rate, obscures the
effect of rare fatal events resulting from improper diagnosis,
loss to follow-up, late chemotherapy side effects, the
need for improved therapy for intermediate-, poor-risk, or
relapsed disease, and the poor understanding of GCT biology.
What should oncologists be looking for in the next
10 years?
MANAGEMENT OF SURVIVORS
“An individual is considered a cancer survivor from the time
of diagnosis to the balance of his or her life” (Offıce of Cancer
Survivorship) and survivorship deals “…with the full spectrum
of survivorship issues related to living with, through,
and beyond the cancer diagnosis” (National Coalition of
Cancer Survivors). 5,6 Hence, men with GCT should be followed
long after being rendered free of disease. Indeed, the
oncologist may be the only physician that these young patients
have. Although persistent peripheral neuropathy, ototoxicity,
and hypogonadism are observed, cardiovascular
disease and second malignant neoplasms are the most important
late effects since they can be life threatening.
Cardiovascular Disease
Both acute and late toxicities exist for men with GCTs. Venous
and arterial vascular events may occur during cisplatinbased
chemotherapy (and rarely carboplatin), including
myocardial infarction, stroke, peripheral arterial thrombosis,
and pulmonary emboli. 7,8,9 Delayed vascular toxicity presenting
as Raynaud’s phenomenon occurs in 6% to 7% of patients
receiving bleomycin as part of chemotherapy for
GCT. 10,11,12 Cardiac and rare cerebrovascular morbidity and
mortality may occur 10 to 20 years (or more) after the completion
of chemotherapy. 13,14,15 Although the mechanism is
not understood, insulin resistance, increased abdominal visceral
fat, and hyperlipidemia may appear shortly after che-
From the Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Disclosures of potential conflicts of interest are found at the end of this article.
Corresponding author: George J. Bosl, MD, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email: boslg@mskcc.org.
© 2015 by American Society of Clinical Oncology.
asco.org/edbook | 2015 ASCO EDUCATIONAL BOOK
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