Radiotherapy for stages I and IIA/B testicular seminoma.

Bamberg M, Schmidberger H, Meisner C, Classen J, Souchon R, Weinknecht S, Schorcht J, Walter F, Engenhart-Cabillic R, Schulz U, Born H, Flink M

Department of Radiotherapy, University of Tuebingen, Germany.

Radiotherapy is generally accepted as a standard treatment for early-stage testicular seminoma. Relapse rates of 2% to 5% in clinical stage I and 10% to 20% in stage IIA/B (according to the Royal Marsden classification) can be achieved. Disease-specific survival reaches 100%. With such excellent cure rates, treatment-related side effects gain particular importance. Therefore, a prospective multicenter trial was initiated for radiotherapy of testicular seminoma with limited treatment portals and low total doses of irradiation. In clinical stage I, 483 patients were treated with 26 Gy to the para-aortic region only. In stage IIA, 42 patients and, in stage IIB, 18 patients received irradiation to the para-aortic and high iliac lymph nodes with 30 and 36 Gy, respectively. With a median time to follow-up of 55 months for stage I and 55.5 months for stage IIA/B, there were 18 (3.7%) and 4 (6.7%) cases of relapse in both treatment groups. Disease-specific survival was 99.6% in stage I and 100% in stage IIA/B. Acute toxicity was dominated by moderate gastro-intestinal side effects. No major late toxicity has been observed to date. Limited volume pure para-aortic treatment for stage I and para-aortic/high iliac irradiation for stage IIA/B with 26, 30 and 36 Gy, respectively, yields excellent cure rates with only moderate acute toxicity and is therefore recommended as standard treatment.

Int J Radiat Oncol Biol Phys 1998 Sep 1;42(2):313-7

Postoperative radiotherapy for Stage I/II seminoma: results for 212 patients.

Bauman GS, Venkatesan VM, Ago CT, Radwan JS, Dar AR, Winquist EW

Department of Radiation, London Regional Cancer Centre, Ontario, Canada.

Between 1950 and 1995, 212 patients seen at the London Regional Cancer Centre received adjuvant radiotherapy following orchiectomy for Stage I (169) and II (43) seminoma. Median follow-up for the group was 7.5 years. RESULTS: Progression free, cause specific, and overall survival were 95%, 98%, and 95% at 5 years, and 94%, 98%, and 94% at 10 years respectively. An increased risk of failure was noted among patients with bulky Stage II disease. No other prognostic factors for relapse were identified. Late toxicity was uncommon with only 12/212 (6%) developing any late GI toxicity potentially attributable to radiotherapy. The incidence of second malignancies (excluding second testicular tumors) was 6/212 (actuarial:1%, 1%, 6% at 5,10,15 years respectively). There was a trend toward increased acute complications for patients treated with larger volumes of radiation. Post-operative radiotherapy remains a safe and efficacious adjuvant treatment for Stage I and early Stage II seminoma.

Clin Oncol (R Coll Radiol) 1998;10(4):237-41

The management and clinical course of testicular seminoma: 15 years' experience at a single institution.

Coleman JM, Coleman RE, Turner AR, Radstone CR, Champion AE

Weston Park Hospital NHS Trust, Sheffield, UK.

Testicular seminoma is one of the most curable solid neoplasms, with 5-year survival rates in excess of 90%. However, controversy persists around its optimum management, particularly for Stage I disease. The outcome of 314 patients with testicular seminoma who were treated at a single institution is reported. A comparison of adjuvant radiotherapy and surveillance for Stage I is presented, and the possible prognostic influence of an elevated serum beta-human chorionic gonadotrophin (beta hCG) is assessed. The 5-year disease-free survival for all stages of presentation was 95.5%. There were more relapses in Stage I patients undergoing surveillance (14/94, 15%) than postorchidectomy radiotherapy (6/144, 4%; P = < 0.05). However, survival was identical irrespective of treatment policy, with no disease-related deaths in either group of Stage I patients. There were eight tumour-related deaths from advanced disease and 14 deaths from non-tumour causes. Three were due to cardiorespiratory disease, four to an unrelated second malignancy, two from infection and one from suicide; in four patients, the cause was unknown. Preoperative beta hCG was elevated in 29 (18%) of Stage I patients and in 24 (62%) of those presenting with Stage II disease. Patients were more likely to have advanced disease (> or = Stage II) if beta hCG was elevated (P < 0.001). Neither disease-free nor overall survival were influenced by the preoperative level of beta hCG. Surveillance appears to be a safe alternative to postorchidectomy radiotherapy for Stage I disease, provided the patient is prepared for intensive long term follow-up. An increased risk of relapse, but not of tumour death, can be expected and unnecessary treatments avoided.

Strahlenther Onkol 1996 Apr;172(4):186-92

Results of radiotherapy for 230 patients with stage I-II seminomas.

Hultenschmidt B, Budach V, Genters K, Sack H

Department of Radiooncology, University of Essen.

From 1978 to 1992, 230 male patients with the diagnosis of pure seminoma of the testis were treated by postoperative radiotherapy at the University of Essen. According to the Royal Marsden Staging System, 188 patients were presenting with stage I disease, 24 with stage IIA, 13 with stage IIB and 5 with stage IIC disease. All patients received irradiation to the paraaortic lymph nodes (median dose: 36 Gy). In 154 patients the ipsilateral iliac lymph nodes were additionally irradiated with or without inguinal lymph nodes and in 66 patients the contralateral pelvic nodes were included. Since 1987, the total dose was reduced to 26 Gy for microscopic disease. A mediastinal irradiation (median dose: 30 Gy) was performed in 22 patients. Eight patients with stage IIB and IIC disease were additionally treated with chemotherapy. RESULTS: Overall actuarial survival (Kaplan-Meier method) for all patients was 97.8% at 5 years and 96.5% at 10 years. Ten-year survival corrected for intercurrent mortality (n = 8) was 100%. In 5 patients recurrent disease (n = 5) was observed, in 6 patients seminoma occurred in the contralateral testis. For stage I seminoma the disease-free survival was 96.8%. For the whole group of stage II seminoma the DFS was 88.1%, for stage IIA 91.7% and for stage IIB 76.9%. In stage IIC no recurrences occurred. In general, the radiation therapy was well tolerated with minor side effects only. CONCLUSIONS: Postoperative radiotherapy for seminoma stage I, IIA and IIB alone offers excellent control and survival rates with tolerable side effects.

J Clin Oncol 1999 Apr;17(4):1146

Optimal planning target volume for stage I testicular seminoma: A Medical Research Council randomized trial. Medical Research Council Testicular Tumor Working Group.

Fossa SD, Horwich A, Russell JM, Roberts JT, Cullen MH, Hodson NJ, Jones WG, Yosef H, Duchesne GM, Owen JR, Grosch EJ, Chetiyawardana AD, Reed NS, Widmer B, Stenning SP

Norwegian Radium Hospital, Oslo, Norway. s.d.fossa@klinmed.u10.no

PURPOSE: To compare relapse rates and toxicity associated with para-aortic (PA) strip or PA and ipsilateral iliac lymph node irradiation (dogleg [DL] field) (30 Gy/15 fractions/3 weeks) for stage I testicular seminoma. PATIENTS AND METHODS: Between July 1989 and May 1993, 478 men with testicular seminoma stage I (T1 to T3; no ipsilateral inguinoscrotal operation before orchiectomy) were randomized (PA, 236 patients; DL, 242 patients). RESULTS: Median follow-up time is 4.5 years. Eighteen relapses, nine in each treatment group, have occurred 4 to 35 months after radiotherapy; among these, four were pelvic relapses, all occurring after PA radiotherapy. However, the 95% confidence interval (CI) for the difference in pelvic relapse rates excludes differences of more than 4%. The 3-year relapse-free survival was 96% (95% CI, 94% to 99%) after PA radiotherapy and 96.6% (95% CI, 94% to 99%) after DL (difference, 0.6%; 95% confidence limits, -3.4%, +4.6%). One patient (PA field) has died from seminoma. Survival at 3 years was 99.3% for PA and 100% for DL radiotherapy. Acute toxicity (nausea, vomiting, leukopenia) was less frequent and less pronounced in patients in the PA arm. Within the first 18 months of follow-up, the sperm counts were significantly higher after PA than after DL irradiation. CONCLUSION: In patients with testicular seminoma stage I (T1 to T3) and with undisturbed lymphatic drainage, adjuvant radiotherapy confined to the PA lymph nodes is associated with reduced hematologic, gastrointestinal, and gonadal toxicity, but with a higher risk of pelvic recurrence, compared with DL radiotherapy. The recurrence rate is low with either treatment. PA radiotherapy is recommended as standard treatment in these patients.

Semin Oncol 1998 Apr;25(2):160-73

Early stage and advanced seminoma: role of radiation therapy, surgery, and chemotherapy.

Gospodarwicz MK, Sturgeon JF, Jewett MA

Department of Radiation Oncology, Princess Margaret Hospital and University of Toronto, Ontario, Canada.

Testicular seminoma is an uncommon tumor that accounts for approximately 50% of all germ cell testicular tumors. The vast majority of patients present with early-stage disease and almost all patients are cured of their disease. Management is based on disease extent with patients with stage I seminoma having numerous treatment options, varying from surveillance to adjuvant retroperitoneal radiation therapy and prophylactic adjuvant single-agent chemotherapy. Only 20% of patients present with more advanced disease; the majority of those have stage II disease with retroperitoneal lymph node involvement. The standard management is retroperitoneal radiation therapy with chemotherapy being used for patients with bulky disease. Systemic chemotherapy with cisplatin alone or etoposide and cisplatin is the standard approach to advanced and metastatic disease with cure rates approaching 85% to 90%.

Int J Urol 1998 Jul;5(4):357-60

Long-term results of adjuvant irradiation or surveillance in stage I testicular seminoma.

Miki T, Nonomura N, Saiki S, Kotake T

Department of Urology, Osaka University Medical School, Suita, Japan.

Twenty-seven patients who underwent prophylactic radiation therapy (RT group) and 41 patients followed only by surveillance (S group) after high orchiectomy were evaluated. Their follow-up consisted of frequent clinical examinations, abdominal CT scans, chest x-rays and serum tumor markers. RESULTS: In the RT group, with a median follow-up period of 15 years, 1 patient (3.6%) had a recurrence in the lung at 4 months after orchiectomy and died, but the remaining 26 are alive with no evidence of disease (NED). In the S group, with a median follow-up period of 7.3 years, 5 (12.2%) relapsed in the retroperitoneal lymph nodes, but all are alive with NED following chemotherapy. The remaining 36 are all alive without recurrence (follow-up period, 38 to 132 months). Although the relapse rate in the S group was relatively higher than in the RT group, there was no significant difference between the 2 groups. CONCLUSION: If a frequent follow-up protocol is administered and followed by the patient, surveillance alone may be a recommended management for stage I testicular seminoma.

Arch Esp Urol 2000 Jul-Aug;53(6):505-16

[Radiotherapy for the treatment of testicular seminomas].

Sancho Pardo G, Gomez de Segura G

Servicio de Oncologia Radioterapica, Hospital de la Santa Cruz y San Pablo, Barcelona, Espana.

OBJECTIVE: Conventional treatment of testicular seminoma has been orchiectomy followed by adjuvant lymph node irradiation. Over the last 10 years the role of postoperative elective radiotherapy has been questioned. This paper reviews the role of radiotherapy in the treatment of seminoma of the testis. METHODS: The literature is reviewed with special reference to the results achieved in the treatment of testicular seminoma with and without radiotherapy. The advantages and disadvantages of postoperative radiotherapy, the techniques and dose administered are discussed. RESULTS/CONCLUSIONS: The results obtained with radiotherapy postorchidectomy in stage I seminoma of the testis are excellent, with a disease free survival of 95%-100%. The use of more limited fields of irradiation and lower dose has reduced the radiation-induced toxicity. Currently, many centers have opted for clinical surveillance after orchiectomy. Their experience have permitted identification of the risk factors and there have been attempts to identify the group of patients that benefit from adjuvant therapy. The low incidence of stage II tumors has not permitted performing randomized studies to determine the benefits of adjuvant therapy and its comparison with chemotherapy. Consolidation radiotherapy for bulky stage II and stage III and IV tumors continues to be a controversy, although its potential value in carefully selected patients is recognized.

Int J Radiat Oncol Biol Phys 1998 Jan 15;40(2):455-9

Para-aortic irradiation only appears to be adequate treatment for patients with Stage I seminoma of the testis.

Sultanem K, Souhami L, Benk V, Bahary JP, Roman T, Shenouda G, Freeman C

Department of Oncology, McGill University, Montreal, Quebec, Canada.

PURPOSE: Results of treatment of patients with Stage I seminoma with orchiectomy and radiotherapy are excellent. Even without adjuvant radiotherapy, the relapse rate is only 15-20%; most of the patients fail in the retroperitoneum, with rare failures observed in the pelvis (0.5-2%). In 1991, we began a prospective study evaluating para-aortic lymph node radiation as the only adjuvant treatment for such patients. This paper reports our preliminary results. MATERIALS & METHODS: Between March 1991 and January 1996, 35 patients with histologically proven Stage I seminoma were entered in the study. Median age was 37.9 years (range: 27-65 years). A radical inguinal orchiectomy was performed in all patients. Staging workup consisted of a chest X-ray; B-HCG, alpha-fetoprotein, and CT scan of the abdomen and pelvis in all patients. Lymphangiogram was done in 23 (66%) of 35 patients for further evaluation of the retroperitoneal lymph nodes. Radiotherapy consisted of treatment to the para-aortic region only. Parallel opposed fields extending from the top of T11 to the bottom of L5 were used. The median field size was 8.7 x 21.8 cm (range: 7-11 x 18-26 cm). The median total dose, prescribed at midpoint, was 25 Gy given in 15 daily fractions of 1.66 Gy. Follow-up was performed every 3 months for the first year, every 4-5 months for the second and third years, and every 6 months thereafter. Chest X-ray, tumor markers, and CT scan of the pelvis were performed routinely as part of the follow-up investigation. RESULTS: At a median follow-up of 39.7 months (range: 16-74 months), 34 (97.1%) of 35 patients are alive with no evidence of disease for an overall actuarial survival rate of 97.1% at 5 years and a cause-specific actuarial survival rate of 100%. Treatment morbidity was limited to Grade I-II acute side effects in 18 (51.4%) of 35 patients. No late side effects were seen. CONCLUSION: From our preliminary results, adjuvant radiation treatment limited to the para-aortic lymph node region, without ipsilateral pelvic irradiation, appears to be adequate treatment for Stage I seminoma. Such an approach in our patients resulted in minimal toxicity and excellent disease-free survival.

Long-term outcome of postorchiectomy radiation therapy for stage I and II testicular seminoma.

Akimoto T, Anticancer Res. 1997 Sep-Oct;17(5B):3781-5.

Department of Radiology and Radiation Oncology, Gunma University School of Medicine, Japan. takimoto@sb.gunma-u.ac.jp

To evaluate the treatment-related late sequelae including gonadal function and second malignancy 94 patients with stage I and II testicular seminoma treated with postorchiectomy radiation therapy were analyzed retrospectively. The 10-year cause specific, disease free and actuarial survival rates were 100, 98.5 and 96.1% for stage II and 91.7, 83.3 and 91.7% for stage II, respectively. The most common late sequelae of gastrointestinal tract was peptic ulcer, developing in 16% of all patients with a median interval of 12 months, but severity was mild except one who needed subtotal gastrectomy. Second malignancies developed in 9 patients (9.5%) with a median interval of 13 years, but calculated O/E ratio excluding 2 patients with secondary germ cell tumor of contralateral testis was 2.3 and did not reach a significant level statistically. Concerning gonadal function assessed from the number of the children, 79% of the patients who wanted to have children after the treatment were successful in fathering children. No fatal complications were observed.

Radiotherapy for stages I and II testicular seminoma: results and morbidity in 238 patients.

Vallis KA, Br J Radiol. 1995 Apr;68(808):400-5.

Department of Clinical Oncology, Western General Hospital, Edinburgh, UK.

We have undertaken a retrospective analysis of 238 patients with Stages I and II seminoma of the testis treated with radiotherapy in Edinburgh between 1974 and 1989. There were five deaths from seminoma. Cause-specific survival for the whole group at 2 and 5 years was 99.2% and 98.1%, respectively. Cause-specific survival at 2 and 5 years by stage (Royal Marsden staging classification) was: Stage I, 99.5% and 98.7% and Stage II, 98.1% and 96.1%. Fourteen (5.9%) patients relapsed (one after treatment for his second testicular seminoma). Eight were given successful salvage treatment, five died of seminoma and one died of intercurrent disease. 13 (5.5%) patients developed World Health Organisation (WHO) grade 3 gastrointestinal or haematological toxicity and two developed grade 4 gastrointestinal toxicity as a result of abdominal radiotherapy. 22 patients (9.2%) developed problems ascribed to late morbidity of abdominal radiotherapy including 18 with peptic ulcer disease. Contralateral testicular tumours occurred in seven (2.9%) patients and five (2.1%) patients developed malignancies at other sites.

Long-term evaluation of postorchiectomy radiotherapy for stage II seminoma.

Whipple GL, Am J Clin Oncol. 1997 Apr;20(2):196-201.

Radiation Oncology Department, SUNY Health Science Center, Syracuse, New York 13210, U.S.A.

PURPOSE: To determine survival, long-term tumor control, and the effects of irradiation for stage II seminoma. MATERIALS AND METHODS: Forty-five patients with stage II testicular seminoma were treated between 1966 and 1989. There were 31 patients with stage IIA disease and 14 with stage IIB disease. All patients underwent orchiectomy followed by iliac and paraaortic irradiation (median dose: 30 Gy), with 37 patients receiving prophylactic mediastinal and supraclavicular irradiation (median dose: 30 Gy). Follow-up ranged from 6 months to 20.6 years, with a median of 9.4 years. RESULTS: Uncorrected survival was 98% at 5 years, 84% at 10 years, and 79% at 15 years. Survival corrected for intercurrent disease was 98% at 5, 10, and 15 years. Five patients developed recurrences with four successfully salvaged by chemotherapy and/or irradiation. There were no serious acute toxicities, and no late complications have developed from infradiaphragmatic irradiation. Supradiaphragmatic irradiation was associated with an increased risk of coronary artery disease compared to the age-matched general population. CONCLUSION: Radiotherapy remains an effective treatment for stage II testicular seminoma, with a 98% adjusted survival rate at 15 years, without serious acute toxicity. Supradiaphragmatic irradiation should not be used in stage IIB patients for whom salvage chemotherapy is an option.