Radiotherapy in Seminoma: More is Not Better

In this issue, Dr. Thomas et a1.,5 describes the Princess Margaret Hospital experience in 444 patients with seminoma treated with radiotherapy from 1958 to 1976. Overall, there was an 87% five-year survival, including 87% for Stage II-A and 62% for Stage II-B. These results are as good as the results in other published series, but what is unique about this Stage II patient population is that prophylactic mediastinal irradiation was not employed. In Stage II-A disease, there were no mediastinal recurrences in 40 patients, and in Stage II-B, there were IO-46 (22%) mediastinal recurrences. However, seven of these 10 patients were cured with subsequent radiation. The authors have clearly demonstrated that prophylactic mediastinal irradiation is unnecessary to ensure optimal cure rates in Stage II disease. Furthermore, such radioprophylaxis may well be deleterious. Ytredal and Bradfield describe marrow hypoplasia and second malignancies with supraand infradiaphragmatic irradiation compared to abdominal irradiation alone.6 Also, two of 20 Stage I patients treated with prophylactic mediastinal irradiation at M. D. Anderson died from acute leukemia.4 In our experience in previously irradiated patients treated with platinum + vinblastine + bleomycin (PVB), there are major difficulties when abdominal and mediastinal irradiation were employed. There is considerably more severe and prolonged myelosuppression, and furthermore, the incidence of pulmonary fibrosis is significantly increased. These problems have also been encountered in other centers when both infraand supradiaphragmatic irradiation are employed (Peckham, M., oral communication, June, 198 1). Approximately 25% of Stage II patients with semi-. noma will fail to be cured with radiotherapy. Not only is mediastinal prophylaxis unnecessary in these patients, but it may well reduce the probability for cure with subsequent PVB chemotherapy. In 1974, combination chemotherapy with PVB was instituted at Indiana University.’ Patients with disseminated seminoma (Stage III or IV or recurrences in irradiated areas) were treated with the same program, although the vinblastine dosage was lowered 25% because of prior radiotherapy.’ We have recently published our results with PVB in 19 patients with metastatic seminoma.2 The median age was 38 (16-63), and seven (37%) had anaplastic seminoma. Four of these 19 patients had extragonadal seminoma. Only six patients did not have prior radiotherapy, and five achieved complete remission (C.R.) and remain disease-free (NED). The only failure in this group was a patient with massive hepatic metastases. The toxicity in these six patients was considerably less than that seen in the 13 patients with prior radiotherapy. Overall, 12 of 19 patients (63%) achieved a C.R.; with a minimal follow-up of two years, 11 patients (58%) are continuously NED. Similar results with PVB in disseminated seminoma have been achieved in other centers. Pinedo has reported six of eight complete remissions (Pinedo, oral communication, June, 1981) and CortesFunes three of three (Cortes-Funes oral communication, June, 1981). Thus, combining these three series, 21 of 30 (70%) complete remissions were achieved in metastatic seminoma with PVB. These results in metastatic seminoma are quite comparable to our results with the same chemotherapy in non-seminomatous tumors. We do not feel there is any present data to indicate a difference in response rate or potential curability of metastatic seminoma compared to non-seminomatous germ-cell tumors. The chemotherapy for disseminated seminoma should parallel that employed for non-seminomatous germ-cell tumors. We feel all patients with Stage III and IV (as described by Thomas et al.‘) should receive PVB as initial therapy. This is a small group of patients, as only 5-10% of all seminomas present in this manner. However, another 20-30% will present as Stage II disease, and approximately 25% of these patients will relapse after curative radiotherapy and require subsequent chemotherapy. The therapeutic results with orchiectomy and irradiation for clinical Stage I are excellent, with cure rates ranging from 95-100%. Fortunately, 60 to 75% of all