Drs. Fiveash and Sandler are to be commended for their comprehensive
review of the current controversies surrounding the management of
stage I seminoma. As they have outlined, disease-free and overall
survival rates of these patients are excellent when treated with
modern radiotherapeutic techniques. Efficacy of radiation therapy is
no longer an issue, and current research focuses on reducing
short-and long-term morbidity.
Although recent studies of single-agent chemotherapy are encouraging,
radiation has been applied to the management of stage I seminoma
since the 1920s. The long-term complications of radiotherapy have
been examined in some detail, whereas no such data are available for
adjuvant chemotherapy. An ongoing randomized Medical Research Council
(MRC) trial is comparing adjuvant radiotherapy to adjuvant
carboplatin (Paraplatin) in stage I seminoma, but long-term morbidity
data comparable to those found in the radiotherapy literature will
not be available for decades.
Appropriate Radiation Treatment Fields
A reduction in the total dose and volume of radiation has the
potential to further reduce the already low complication rates. A
completed MRC trial that compared para-aortic and ipsilateral pelvic
radiotherapy to para-aortic radiotherapy alone, published in abstract
form, showed identical actuarial freedom from disease relapse
rates. There were, however, no failures in the pelvis among patients
who received pelvic radiotherapy, as compared with four pelvic
failures in the group given para-aortic radiotherapy alone. Longer
follow-up is needed to determine whether these differences become
statistically significant and to elucidate factors that predispose to
At UT M. D. Anderson Cancer Center, our current policy is to select
patients for para-aortic treatment alone only if they have not had
any of the following: (1) prior pelvic, inguinal, or scrotal surgery;
(2) prior orchiopexy; (3) evidence of tunica albuginea penetration;
(4) evidence of spermatic cord involvement; or (5) persistently
elevated beta-human chorionic gonadotropin levels after orchiectomy.
We agree with the authors that field reductions are important in this
relatively young patient population with fertility concerns. In our
experience, acute toxicity (nausea and vomiting) and the need for
antiemetics are decreased considerably when one uses a reduced
para-aortic field (T12-L5) without inclusion of the pelvis.
Appropriate Radiation Dose
The other issue that warrants comment is the appropriate dose of
radiation. An optimal dose to control microscopic disease has not
been universally accepted because of the limitations of retrospective
analysis and sparse modern dose-response data. Historical dose data
are available, however.
In a review of 249 patients treated at Walter Reed General Hospital
in the 1950s, Friedman described an isoeffect curve obtained by
analyzing pathologic or clinical response of primary or metastatic
tumors irradiated to specific doses. The lethal tumor dose, which
equated to a 90% local control rate at 5 years, was "600-1000 r
delivered over a period of two weeks." Friedman proposed that
although the necessary dose was quite low, the "wide margin of
[normal tissue] tolerance prompts the author to administer 2000 r to
the retroperitoneal area."
Thus, it appears that doses of 30 to 35 Gy, which are still used
today for the treatment of microscopic disease, are unnecessary.
Subclinical para-aortic disease should be well-controlled with 20 Gy
in 10 to 12 fractions.[4,5]
Summary and Future Directions
As Drs. Fiveash and Sandler point out, the trend in managing patients
with stage I seminoma should be toward reduced radiation treatment
fields and doses. This approach represents an alternative to
surveillance, with its well-defined risk of recurrence, and single
agent chemotherapy, with its potential, but undefined, long-term risks.
Although surveillance represents an attractive alternative to
adjuvant therapy, patient selection is complicated by a lack of
reliable prognostic factors for relapse. Future efforts should be
directed toward defining biomarkers that predict for occult stage II
disease. Preliminary data on DNA diploidy and immunohistochemical
expression of p53[7,8] indicate that such markers have potential in
the selection of patients for surveillance.
1. Dean AL: The treatment of teratoid tumors of the testis with
radium and the roentgen ray. J Urol 21:83-101, 1929.
2. Fossa SD, Horwich A, Russell JM, et al: Optimal field size in
adjuvant radiotherapy (XRT) of stage I seminoma: A randomized trial
(abstract). Proc Am Soc Clin Oncol 15:A595, 1996.
3. Friedman M: Tumors of the testis and their treatment, in Portmann
UV (ed): Clinical Therapeutic Radiology, pp 276-308. New York, Thomas
Nelson and Sons, 1950.
4. Giacchetti S, Raoul Y, Wibault P, et al: Treatment of stage I
testis seminoma by radiotherapy: Long-term results--A 30-year
experience. Int J Radiat Oncol Biol Phys 27:3-9, 1993.
5. Read G, Johnston RJ: Short duration radiotherapy in stage I
seminoma of the testis: Preliminary results of a prospective study.
Clin Oncol 5:364-366, 1993.
6. Mor Y, Leibovich I, Raviv G, et al: Testicular seminoma: Clinical
significance of nuclear deoxyribonucleic acid ploidy pattern as
studied by flow cytometry. J Urol 154:1041-1044, 1995.
7. Lewis DJ, Sesterhenn IA, McCarthy WF, et al: Immunohistochemical
expression of p53 tumor suppressor gene protein in adult germ cell
testis tumors: Clinical correlation in stage I disease. J Urol
8. Eid H, Van der Looij M, Institoris E, et al: Is p53 expression,
detected by immunohisto-chemistry, an important parameter of response
to treatment in testis cancer? Anticancer Res 17:2663-2670, 1997.