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Wood et al.

Table 2b. The International Germ Cell Cancer Collaborative 2004 had a median time to relapse of 18 months, with the
Group
latest relapse occurring at 6 years. Follow-up efforts should
Prognostic therefore concentrate on the first 2 years after radiotherapy.
Histology Clinical factors
category The traditional management of stage I seminoma patients
NSGCT Good Testes/retroperitoneal primary and after orchiectomy has consisted of radiotherapy to the paraaor-
no non-pulmonary visceral tic and pelvic (retroperitoneal) lymph nodes. The low inci-
metastases and good markers: dence of pelvic lymph node involvement in stage I semino-
AFP < 1000 ng/ml and
HCG < 5000 IU/l and ma led to the investigation of adjuvant radiotherapy directed
LDH < 1.5 × ULN* to the paraaortic lymph nodes alone. The advantages of
such an approach include decreased scatter to the remain-
Intermediate Testes/retroperitoneal primary and no
non-pulmonary visceral metastases ing testicle and a reduction in the integral radiation dose
and intermediate markers: that the patient receives, presumably decreasing the risk of
AFP ≥ 1000 ng/mL and ≤ 10,000 ng/mL or second malignancy. The Medical Research Council Testicular
HCG ≥ 5000 IU/l and ≤ 50,000 ng/mL or Study Group randomized 478 patients to traditional paraaor-
LDH ≥ 1.5 × ULN and ≤ 10 × ULN 29
tic and pelvic radiation or paraaortic irradiation alone.
Poor Mediastinal primary or non- Patients treated with paraaortic radiotherapy alone had a
pulmonary visceral metastases or 4% relapse rate compared to a 3.4% relapse rate in patients
poor markers with any of: treated to the paraaortic and pelvic lymph nodes. All patients
AFP > 10,000 ng/mL or
HCG > 50,000 IU/l or who received paraaortic and pelvic radiotherapy relapsed
LDH > 10 × ULN in supra-diaphragmatic sites, but 1.6% of patients treated
to the paraaortic lymph nodes alone group failed with dis-
Seminoma Good Any primary site and
no non-pulmonary visceral ease in the pelvis. This trial demonstrated that treating the
metastases and paraaortic nodes alone gives excellent results, but when
normal AFP, any HCG, any LDH used a small risk of pelvic failure remains. Therefore, if this
Intermediate Any primary site and treatment approach is adopted, regular imaging with CT of
non-pulmonary visceral metastases the pelvic lymph nodes must be performed to ensure that if
and normal AFP, any HCG, any LDH
pelvic relapse occurs, it is detected at an early stage. Data
NSGCT = nonseminoma germ cell tumour; AFP = alpha-fetoprotein; HCG = human from the Christie Hospital in Manchester, United Kingdom,
chorionic gonadotrophin; LDH = lactate dehydrogenase; ULN = upper limit of normal.
where no routine evaluation of the pelvis is carried out after
paraaortic radiation alone, has shown that the median size
MRI in follow-up with a second randomization to either 3 of the pelvic lymph nodes at time of detection of relapse is
scans or 7 scans in total. This study has been endorsed by 5 cm (range 2.5 to 9 cm). 30 The advantage of paraaortic
the National Cancer Institute of Canada-Clinical Trials Group radiotherapy alone is therefore not clear, particularly in com-
(NCIC-CTG) genitourinary Group. parison to surveillance.
Data from the MD Anderson and the Royal Marsden hos-
Adjuvant radiotherapy pitals suggest that long-term survivors of testicular semino-
ma treated postorchiectomy with radiotherapy are at sig-
Adjuvant retroperitoneal radiotherapy has been the stan- nificant excess risk of death as a result of cardiac disease. 31,32
dard treatment of stage I seminoma for more than 60 years. In the MD Anderson series of 453 patients treated between
The overall survival rate in most series in the modern era 1951 and 1999, the standardized cardiac mortality ratio
ranges between 92 and 99% at 10 years, with few if any for patients greater than 15 years after radiotherapy (infra-
deaths from seminoma. In large single or multi-institution- diaphragmatic radiotherapy, no mediastinal radiotherapy)
al series, the relapse rate has varied from 0.5% to 5% (Table was 1.80 (95% CI 1.01– 2.98). 32 Huddart and colleagues
4). 19,23-27 The most common sites of relapse following adju- reported a similar increase in cardiac events in a cohort of
vant radiotherapy are the mediastinum, lungs and the left 992 patients treated at the Royal Marsden Hospital with a
supraclavicular fossa. A small proportion of patients, usu- risk-ratio of 2.4 (95% CI 1.04 –5.45) in those treated with
ally with predisposing factors, relapse in the inguinal nodes. infra-diaphragmatic radiotherapy as compared to those man-
Chemotherapy is the treatment of choice for supra- aged by surveillance. 31
diaphragmatic relapse and gives close to a 100% cure rate. An increased risk of second cancers after radiation ther-
Inguinal relapse can often be treated successfully with radio- apy for stage I seminoma has been documented in a num-
therapy to the involved area. 28 ber of studies, and since this increased risk is expressed
Most relapses occur within 2 years of radiotherapy. In more than 10 to 15 years following radiation therapy, it is
the PMH series, 283 patients treated between 1981 and often not apparent in series with shorter follow-up. 33,34 The

E22 CUAJ • April 2010 • Volume 4, Issue 2