Reviewers: Kenneth Blank, MD
Source: Journal of Clinical Oncology April 1999 Vol 17 No 4 p1146
The adjuvant treatment of stage I testicular cancer is controversial. After surgical removal of the involved testis, treatment options include radiotherapy of the para-aortic lymph nodes, radiotherapy of the para-aortic and ipsilateral iliac lymph nodes or observation. Retrospective reviews have revealed a 15% recurrence rate with observation alone that can be reduced to 1-5% with adjuvant radiotherapy. However, radiotherapy is not without side effects. Traditionally, radiotherapy was delivered to the para-aortic and ipsilateral iliac lymph nodes and side effects of peptic ulcer, oligospermia and second cancers have been reported.
Retrospective reviews have revealed that recurrence is rare in the ipsilateral iliac lymph node chains. This finding and a greater understanding of the anatomy of testicular lymph node drainage led many to speculate that radiotherapy to the ipsilateral iliac lymph nodes can be omitted without compromising cure rates and would decrease complications. To test this hypothesis, the Medical Research Council (MRC) Testicular Cancer Working Party began a randomized prospective trial comparing para-aortic radiotherapy alone to para-aortic and ipsilateral iliac lymph node irradiation. The results of this trial are reported in the April, 1999 issue of the Journal of Clinical Oncology.
Eligible patients had pure seminoma, no evidence of disease outside the testis on CT or lymphogram, no prior scrotal of inguinal surgery, no elevated alpha-fetoprotein levels and normal post-operative levels of human chorionic gonadotropin.
All eligible patients were randomly assigned to receive radiotherapy directed at the para-aortic and ipsilateral iliac lymph nodes (called a "dog leg" field) or a para-aortic field (which included the para-aortic lymph nodes only). The superior and inferior borders of the dog leg field (DL field) were the interspace between thoracic vertebrae 10 and 11 and the mid obturator foramen, respectively. The lateral margins included the ipsilateral renal hilum and the contralateral transverse processes, and followed the course of the ipsilateral iliac nodal chain in the pelvis.
The para-aortic field (PA field) had the same upper border, but the inferior border was placed at the interspace of the lumbar and sacral vertebrae. The PA field also included the ipsilateral renal hilum and contralateral transverse processes. All fields were treated with 200cGy daily fractions to a total dose of 3000cGy via anterior-posterior fields. Testicular shielding was recommended for patients receiving the DL field who wished to preserve fertility.
Patients were followed with physical exam, chest radiograph and blood tests every three months during the first year, every four month in the second year, every six months in the third year and annually thereafter. Routine computed tomography of the pelvis and abdomen was performed in the first three years.
Twenty centers randomized 478 patients between 1989 and 1993. 242 patients received DL fields and 236 PA fields. Ninety five percent and 98% of patients in the DL and PA arms, respectively, received the entire radiation dose. One patient in each arm received the wrong field. Two patients in each arm were deemed ineligible after randomization.
Acute toxicity occurred less frequently in the patients receiving PA radiotherapy. Specifically, there was significantly less leukopenia and diarrhea in patients receiving PA radiotherapy compared to patients receiving DL radiotherapy. In addition there was a trend towards reduced amounts of acute nausea and vomiting in patients receiving PA radiotherapy. Chronic toxicity was also less in the PA arm of the study. Within the first eighteen months after treatment oligospermia (low sperm counts) was more common in the DL arm. However, by three years over 90% of patients in both arms had attained normal sperm counts (>10 X 106/ml).
With a median follow-up of 4.5 years, a total of eighteen relapses had occurred - nine in each study arm. The relapse-free rate at three years was 96% in both arms. One relapse occurred within the PA radiation field and four relapses occurred in the pelvis in patients receiving PA radiotherapy. The most common site of relapse was the mediastinum occurring in seven patients. All relapsed patients except one were successfully salvaged with platin-based chemotherapy with or without further radiotherapy.
PA field radiotherapy in patients with stage I seminoma yielded similar relapse free survival rates as DL fields. DL fields were associated with higher acute toxicity and longer time to recovery of sperm counts. The authors conclude that PA radiotherapy should be the standard adjuvant treatment for stage I seminoma patients.