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Para-aortic irradiation for stage I testicular seminoma: results of a prospective study in 675 patients. A trial of the German testicular cancer study group (GTCSG)
R.G. Rowland / Urologic Oncology: Seminars and Original Investigations 23 (2005) 136 –142
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Results: At median follow-up of 8.5 years, the 5- and 10-year overall survival were both 93%, the 5- and 10-year cause-specific survival were both 94% and the 5- and 10-year relapse-free rates were both 85%. Patients with stage IIA and IIB disease treated with RT and stage IIB treated with chemotherapy had 5-year relapse-free rates of 91.7%, 89.7% and 83.3%, respectively. Seventeen percent of patients treated with radiotherapy and 6% of those treated with chemotherapy have relapsed. Of the RT patients the commonest sites of relapse were left supraclavicular fossa, lung/mediastinum, bone, para-aortics and liver; nine patients had a solitary site of relapse. Two patients treated with chemotherapy had recurrence in the para-aortic and iliac nodes. For RT patients, larger primary tumour size was associated with a reduction in relapse rate. Age, rete testis invasion and lymphovascular invasion were found not to be of prognostic significance. Conclusions: In stage IIA/B seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Chemotherapy is the treatment of choice for stage IIC seminoma.
Commentary The authors present a report of 126 men with stage II seminoma treated over an 18-year period. Of the 50 patients with stage IIA disease, all but one received radiation. In stage IIB patients, 30 received radiation and seven had chemotherapy. In the 39 patients with stage IIC disease, 16 were radiated and 23 were treated with chemotherapy. Patients treated with radiation had a 5-year relapse-free survival rate (RFR) of 91.7% and 89.7% for stages IIA and IIB, respectively. Stage IIC patients who were radiated had an RFR of 83.3% (six of seven). Patients with stage IIC disease had a significantly lower relapse rate after treatment with chemotherapy than they did after radiation therapy. The authors conclude that radiation therapy is highly effective for stages IIA and IIB and that chemotherapy is the treatment of choice for stage IIC patients. doi:10.1016/j.urolonc.2005.01.014 Randall G. Rowland, M.D. Para-aortic irradiation for stage I testicular seminoma: results of a prospective study in 675 patients. A trial of the German testicular cancer study group (GTCSG). Classen J, Schmidberger H, Meisner C, Winkler C, Dunst J, Souchon R, Weissbach L, Budach V, Alberti W, Bamberg M, Department of Radiation Oncology, Universitatsklinikum, Tubingen, Germany. Br J Cancer 2004;90:2305-11 A prospective nonrandomised trial was performed in order to evaluate tumour control and toxicity of low-dose adjuvant radiotherapy in stage I seminoma with treatment portals confined to the para-aortic lymph nodes. Between April 1991 and March 1994, 721 patients were enrolled for the trial by 48 centres in Germany. Patients with pure seminoma and no evidence of lymph node involvement or distant metastases received 26 Gy prophylactic limited para-aortic radiotherapy. Disease-free survival at 5 years was the primary end point. With a median follow-up of 61 months, 675 patients with follow-up investigations were evaluable for this analysis. Kaplan-Meier estimates of disease-free and disease-specific survival were 95.8% (95% CI: 94.2–97.4) and 99.6% (95% CI: 99.2–100%) at 5 years and 94.9% (95% CI: 92.5–97.4%) and 99.6% (95% CI: 99.2–100%) at 8 years, respectively. A total of 26 patients relapsed. All except two were salvaged from relapse. In all, 21 recurrences were located in infradiaphragmatic lymph nodes without any ‘in-field’ relapse. Nausea and diarrhoea grade 3 were observed in 4.0 and 1.0% of the patients, respectively. Grade 3 late effects have not been observed so far. The results of our trial lend further support to the concept of limited para-aortic irradiation as the recently defined new standard of radiotherapy in stage I seminoma. There is no obvious compromise in disease-specific or disease-free survival compared to more extensive hockey-stick portals, which were used as standard portals at the time this study was initiated.
Commentary This is a report of the routine use of para-aortic radiation for clinical stage I seminoma. The data indicate that 26 patients (3.9%) relapsed after radiation and 17 patients (2.5%) developed secondary malignancies. No patients had late grade 3 toxicity, but some grades 2 and 3 early toxicity did occur. Two patients of the 26 with relapse and four of the 17 patients with secondary malignancies died, for about a 1% mortality rate overall. This reviewer questions the advisability of this approach in patients who have T1 primary tumors, because observation trials of this patient population show only about a 3% relapse rate and virtually all of the relapsing patients are cured with chemotherapy. Perhaps radiation, whether with para-aortic or hockey-stick fields, should be reserved for those patients with a higher T stage primary tumor. doi:10.1016/j.urolonc.2005.01.013 Randall G. Rowland, M.D. Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors. Fizazi K, Culine S, Kramar A, Amato RJ, Bouzy J, Chen I, Droz J-P, Logothetis CJ, Genito-Urinary Group of the French Federation of Cancer Centers, Paris, France. J Clin Oncol 2004;22:3868-76 Purpose: The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification.
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Results: At median follow-up of 8.5 years, the 5- and 10-year overall survival were both 93%, the 5- and 10-year cause-specific survival were both 94% and the 5- and 10-year relapse-free rates were both 85%. Patients with stage IIA and IIB disease treated with RT and stage IIB treated with chemotherapy had 5-year relapse-free rates of 91.7%, 89.7% and 83.3%, respectively. Seventeen percent of patients treated with radiotherapy and 6% of those treated with chemotherapy have relapsed. Of the RT patients the commonest sites of relapse were left supraclavicular fossa, lung/mediastinum, bone, para-aortics and liver; nine patients had a solitary site of relapse. Two patients treated with chemotherapy had recurrence in the para-aortic and iliac nodes. For RT patients, larger primary tumour size was associated with a reduction in relapse rate. Age, rete testis invasion and lymphovascular invasion were found not to be of prognostic significance. Conclusions: In stage IIA/B seminoma, radiotherapy continues to provide excellent results, as the majority of patients will be cured with this treatment alone. Chemotherapy is the treatment of choice for stage IIC seminoma.
Commentary The authors present a report of 126 men with stage II seminoma treated over an 18-year period. Of the 50 patients with stage IIA disease, all but one received radiation. In stage IIB patients, 30 received radiation and seven had chemotherapy. In the 39 patients with stage IIC disease, 16 were radiated and 23 were treated with chemotherapy. Patients treated with radiation had a 5-year relapse-free survival rate (RFR) of 91.7% and 89.7% for stages IIA and IIB, respectively. Stage IIC patients who were radiated had an RFR of 83.3% (six of seven). Patients with stage IIC disease had a significantly lower relapse rate after treatment with chemotherapy than they did after radiation therapy. The authors conclude that radiation therapy is highly effective for stages IIA and IIB and that chemotherapy is the treatment of choice for stage IIC patients. doi:10.1016/j.urolonc.2005.01.014 Randall G. Rowland, M.D. Para-aortic irradiation for stage I testicular seminoma: results of a prospective study in 675 patients. A trial of the German testicular cancer study group (GTCSG). Classen J, Schmidberger H, Meisner C, Winkler C, Dunst J, Souchon R, Weissbach L, Budach V, Alberti W, Bamberg M, Department of Radiation Oncology, Universitatsklinikum, Tubingen, Germany. Br J Cancer 2004;90:2305-11 A prospective nonrandomised trial was performed in order to evaluate tumour control and toxicity of low-dose adjuvant radiotherapy in stage I seminoma with treatment portals confined to the para-aortic lymph nodes. Between April 1991 and March 1994, 721 patients were enrolled for the trial by 48 centres in Germany. Patients with pure seminoma and no evidence of lymph node involvement or distant metastases received 26 Gy prophylactic limited para-aortic radiotherapy. Disease-free survival at 5 years was the primary end point. With a median follow-up of 61 months, 675 patients with follow-up investigations were evaluable for this analysis. Kaplan-Meier estimates of disease-free and disease-specific survival were 95.8% (95% CI: 94.2–97.4) and 99.6% (95% CI: 99.2–100%) at 5 years and 94.9% (95% CI: 92.5–97.4%) and 99.6% (95% CI: 99.2–100%) at 8 years, respectively. A total of 26 patients relapsed. All except two were salvaged from relapse. In all, 21 recurrences were located in infradiaphragmatic lymph nodes without any ‘in-field’ relapse. Nausea and diarrhoea grade 3 were observed in 4.0 and 1.0% of the patients, respectively. Grade 3 late effects have not been observed so far. The results of our trial lend further support to the concept of limited para-aortic irradiation as the recently defined new standard of radiotherapy in stage I seminoma. There is no obvious compromise in disease-specific or disease-free survival compared to more extensive hockey-stick portals, which were used as standard portals at the time this study was initiated.
Commentary This is a report of the routine use of para-aortic radiation for clinical stage I seminoma. The data indicate that 26 patients (3.9%) relapsed after radiation and 17 patients (2.5%) developed secondary malignancies. No patients had late grade 3 toxicity, but some grades 2 and 3 early toxicity did occur. Two patients of the 26 with relapse and four of the 17 patients with secondary malignancies died, for about a 1% mortality rate overall. This reviewer questions the advisability of this approach in patients who have T1 primary tumors, because observation trials of this patient population show only about a 3% relapse rate and virtually all of the relapsing patients are cured with chemotherapy. Perhaps radiation, whether with para-aortic or hockey-stick fields, should be reserved for those patients with a higher T stage primary tumor. doi:10.1016/j.urolonc.2005.01.013 Randall G. Rowland, M.D. Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors. Fizazi K, Culine S, Kramar A, Amato RJ, Bouzy J, Chen I, Droz J-P, Logothetis CJ, Genito-Urinary Group of the French Federation of Cancer Centers, Paris, France. J Clin Oncol 2004;22:3868-76 Purpose: The prognostic relevance of the rate of decline of serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) during the first 3 weeks of chemotherapy for nonseminomatous germ cell tumors (NSGCT) was studied in the context of the International Germ Cell Cancer Collaborative Group (IGCCCG) classification.