- Email: [email protected]
B testicular seminoma
Int. J. Radiation Oncology Biol. Phys., Vol. 56, No. 3, pp. 746 –748, 2003 Copyright © 2003 Elsevier Inc. Printed in the USA. All rights reserved 0360-3016/03/$–see front matter
doi:10.1016/S0360-3016(03)00011-7
CLINICAL INVESTIGATION
Testis
APPROPRIATE RADIATION VOLUME FOR STAGE IIA/B TESTICULAR SEMINOMA PETER W. M. CHUNG, M.B.,* PADRAIG R. WARDE, M.B.,* TONY PANZARELLA, M.SC.,† ANDREW J. S. BAYLEY, M.D.,* CHARLES N. CATTON, M.D.,* MICHAEL F. MILOSEVIC, M.D.,* MICHAEL A. S. JEWETT, M.D.,‡ JEREMY F. G. STURGEON, M.B.,§ MALCOLM MOORE, M.D.,§ AND MARY K. GOSPODAROWICZ, M.D.* Departments of *Radiation Oncology, †Biostatistics, ‡Surgical (Urology) Oncology, and §Medical Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada Purpose: Prophylactic left supraclavicular fossa irradiation has been suggested to reduce relapse rates in patients treated for Stage IIA/B testicular seminoma. To address this issue, we reviewed patterns of failure and treatment outcome in patients treated with radiation therapy at our institution. Methods and Materials: Between 1981 and 1999, 79 men with Stage II seminoma (IIA, 49; IIB, 30) were treated with radiation therapy (RT) to the para-aortic and ipsilateral (ⴞ contralateral) pelvic lymph nodes (dose: 25–35 Gy). Results: With a median follow-up of 8.5 years, the 5-year relapse-free rate was 91% (standard error: 3%), and 2 patients have died of seminoma, giving a 5-year cause-specific survival of 97%. A total of 7 patients have relapsed with 2 isolated to the left supraclavicular fossa. Five of 7 patients have been successfully salvaged. Conclusions: Prophylactic left supraclavicular fossa irradiation might have prevented relapse in 2 of 79 patients in Stage IIA/B seminoma. However, 97% of patients would have received unnecessary left neck RT, so we continue to recommend, as standard treatment, infradiaphragmatic RT only. © 2003 Elsevier Inc. Seminoma, Stage II, Radiation therapy.
and ⬍5 cm) testicular seminoma received primary radiation therapy after inguinal orchidectomy. Evaluation postorchidectomy included full clinical history and examination, chest X-ray, CT scan of the abdomen and pelvis (some patients also had lymphangiogram in the early 1980s), and measurement of tumor markers (␣fetoprotein and beta human chorionic gonadotrophin). Pathology review at our institution was undertaken before treatment to confirm the diagnosis of seminoma. All patients were treated with megavoltage radiation (1.25–18 MV) using parallel-opposed fields with appropriate shielding. The treatment volume included the paraaortic nodes (superior extent T9 –T11 vertebral level), together with the ipsilateral (⫾ contralateral) iliac nodes (inferior extent obturator foramen) encompassing known disease. A dose of 25 Gy in 20 daily fractions followed by a boost of 10 Gy in 5 to 8 daily fractions to the involved para-aortic nodes was delivered. All patients completed treatment and received the planned dose. No prophylactic supradiaphragmatic radiation was given to any patient.
INTRODUCTION For men with testicular seminoma, radiation therapy (RT) has been a standard treatment modality for most of the last century. The current standard of treatment is infradiaphragmatic RT to the para-aortic and iliac lymph nodes for Stage IIA and IIB (1997 UICC TNM classification) disease and chemotherapy for Stage IIC patients (lymph nodes ⬎5 cm). Prophylactic mediastinal irradiation was abandoned because of treatmentassociated toxicity (1, 2) and increased difficulties in delivering salvage chemotherapy at subsequent relapse (3, 4). Zagars and Pollack suggested that prophylactic irradiation of the left supraclavicular fossa (LSCF) might have a role in reducing relapse rates and in improving results of treatment (5). To address this issue, we reviewed and analyzed patterns of failure in all cases of Stage IIA/B seminoma treated with primary RT at our institution since 1981. METHODS AND MATERIALS Between 1981 and 1999, 79 men (median age: 35 years, range: 22– 68 years) with Stage IIA (abdominal lymph nodes ⬍2 cm) and IIB (abdominal nodes ⬎2 cm Reprint requests to: Dr. Padraig Warde, Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9 Canada. Tel: (416) 946-2122; Fax: (416) 946-4586; E-mail: padraig.
[email protected] Received Oct 17, 2002, and in revised form Dec 27, 2002. Accepted for publication Jan 3, 2003. 746
Radiation volume for Stage II seminoma
● P. W. M. CHUNG et al.
747
Fig. 1. Relapse-free rate for Stage IIA/B patients.
Statistical methods Survival and relapse-free rates were calculated from the date of diagnosis using the Kaplan-Meier method. Time zero was taken as the time of orchidectomy. The sample size was determined by the number of available cases during the period of the study, not by a priori considerations of statistical power. RESULTS At median follow-up of 8.5 years (range: 1.1–20.7 years), 2 patients had died of seminoma. The 5-year relapse-free rate was 91% (standard error: 3%) (Fig. 1). In total, 7 have relapsed (Table 1), 4 within 12 months, another 2 within 24 months, and the final 1 within 36 months of orchidectomy. Of the Stage IIA patients who recurred, 1 had isolated LSCF relapse, 1 had relapse in the soft tissue around the left scapula, the third had bony disease with a paraspinal mass, and the other had bony and pulmonary metastases. In the Stage IIB patients, 1 had solitary LSCF, 1 had LSCF and Table 1. Relapse sites by stage of disease Stage
Total no. patients
No. relapsing
2A
49
4
2B
30
3
Site Left supraclavicular Soft tissue left scapula Bone ⫹ para-spinal soft tissue Bone ⫹ lung Para-aortics Left supraclavicular Left supraclavicular ⫹ left axilla
axillary, and the other had para-aortic recurrence. The latter contained embryonal carcinoma at postchemotherapy retroperitoneal lymphadenectomy for a nonregressing mass. Salvage treatment Chemotherapy was the main modality used at first relapse in 6 of 7 patients. Five patients remained disease free; one patient, who refused further treatment after two courses of chemotherapy, died of disease. The other patient had supradiaphragmatic RT as primary salvage; he was treated in the early 1980s, had subsequent bony relapse, and received chemotherapy, but died of disease 1.6 years after first treatment.
DISCUSSION Our current analysis for patients with Stage IIA/B testicular seminoma at Princess Margaret Hospital shows that the overall outcome remains excellent. These results are comparable to those in other published series of patients treated with para-aortic and iliac RT only, followed by salvage chemotherapy for relapse (6 – 8). Recently, Zagars and Pollack recommended that prophylactic LSCF irradiation to reduce relapse at this site would have a significant effect on relapse rates and thus should be used as standard treatment (5). This recommendation is based on Stage II patients treated with primary RT over 39 years (1960 –1999). Three cohorts comprising a total of 73 men were treated over this period. In the first cohort, 36 men treated before 1984 received infradiaphragmatic and prophylactic mediastinal irradiation (LSCF included). From
748
I. J. Radiation Oncology
● Biology ● Physics
1984 to 1992, a second cohort of 17 patients received infradiaphragmatic RT only. The final cohort of 20 patients received infradiaphragmatic RT plus prophylactic LSCF RT (1993–1999). Relapse rates for these cohorts were 6% (2/ 36), 19% (5/17), and 5% (1/20), respectively. In the patients who received infradiaphragmatic RT only, the commonest site of relapse was the LSCF alone (3 of 5 that relapsed). Thus, prophylactic LSCF RT was initiated to prevent relapse at this site. The 20 patients treated subsequently with prophylactic LSCF RT had no relapses at this site, and only 1 patient relapsed in the mediastinum. Thus the policy of LSCF RT would seem to be sensible given the results in this series. However, it should be noted that the policy is based on 3 patients relapsing in a cohort of 17. In our series, relapse occurred in 9% of patients overall, and 5-year cause-specific survival was 97%; this is in keeping with other recently published series treated with infradiaphragmatic RT only, which showed relapses of 5% to 10% with cause-specific survival of 96% to 100% (6 – 8). Solitary LSCF relapse was not a prominent feature in any of these series (⬍5%). At most, prophylactic LSCF would have prevented relapse in 2 of 79 patients in our series, but there are no patient or tumor characteristics that identify those men that will relapse at this site only. For Stage IIA patients, 1 of 49 (2%) may have benefited from LSCF irradiation. In Stage IIB, 1 of 30 patients (3%) may have had
Volume 56, Number 3, 2003
relapse prevented. Even taking into account the other patient who had simultaneous LSCF and left axillary relapse (2 separate distinct masses, where prophylactic RT to LSCF alone may not have prevented relapse in the axilla), 7% would have benefited. We would not make a separate recommendation for treatment between Stage IIA and IIB patients based on these numbers. Because salvage chemotherapy is highly effective, it is difficult to justify a policy of routine LSCF RT, no matter how little toxicity is associated with treatment, because the therapeutic gain is likely to be minimal for the vast majority of patients. A different approach has been used with the aim of reducing relapses in Stage IIA/B seminoma (9). This combines single-agent carboplatin to eradicate micrometastatic deposits with infradiaphragmatic RT to treat macroscopic disease in a sequential manner. This is interesting, but the crude relapse rate was 6%, and the cause-specific survival was 97% and requires further investigation to ensure associated toxicity is low with the therapeutic gain over RT alone significantly large, before it could be adopted as standard treatment. In summary, we continue to recommend only infradiaphragmatic RT in Stage IIA/B seminoma; the addition of elective LSCF RT would overtreat the vast majority of patients, who are likely never to recur.
REFERENCES 1. Hanks GE, Peters T, Owen J. Seminoma of the testis: Longterm beneficial and deleterious effects of radiation. Int J Radiat Oncol Biol Phys 1992;24:913–919. 2. Lederman GS, Sheldon TA, Chaffey JT, et al. Cardiac disease after mediastinal irradiation for seminoma. Cancer 1987;60: 772–776. 3. Einhorn LH, Williams SD. Chemotherapy of disseminated seminoma. Cancer Clin Trials 1980;3:307–313. 4. Peckham MJ, Horwich A, Hendry WF. Advanced seminoma: Treatment with cisplatinum-based combination chemotherapy or carboplatin (JM 8). Br J Cancer 1985;52:7–13. 5. Zagars GK, Pollack A. Radiotherapy for stage II testicular seminoma. Int J Radiat Oncol Biol Phys 2001;51:643–649.
6. Bamberg M, Schmidberger H, Meisner C, et al. Radiotherapy for stage I and IIA/B testicular seminoma. Int J Cancer 1999; 83:823–827. 7. Bauman GS, Venkatesan VM, Ago CT, et al. Postoperative radiotherapy for stage I/II seminoma: Results for 212 patients. Int J Radiat Oncol Biol Phys 1998;42:313–317. 8. Vallis KA, Howard GC, Duncan W, et al. Radiotherapy for stages I and II testicular seminoma: Results and morbidity in 238 patients. Br J Radiol 1995;68:400–405. 9. Patterson H, Norman AR, Mitra SS, et al. Combination carboplatin and radiotherapy for the management of stage II testicular seminoma: Comparison with radiotherapy treatment alone. Radiother Oncol 2001;59:5–11.
doi:10.1016/S0360-3016(03)00011-7
CLINICAL INVESTIGATION
Testis
APPROPRIATE RADIATION VOLUME FOR STAGE IIA/B TESTICULAR SEMINOMA PETER W. M. CHUNG, M.B.,* PADRAIG R. WARDE, M.B.,* TONY PANZARELLA, M.SC.,† ANDREW J. S. BAYLEY, M.D.,* CHARLES N. CATTON, M.D.,* MICHAEL F. MILOSEVIC, M.D.,* MICHAEL A. S. JEWETT, M.D.,‡ JEREMY F. G. STURGEON, M.B.,§ MALCOLM MOORE, M.D.,§ AND MARY K. GOSPODAROWICZ, M.D.* Departments of *Radiation Oncology, †Biostatistics, ‡Surgical (Urology) Oncology, and §Medical Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada Purpose: Prophylactic left supraclavicular fossa irradiation has been suggested to reduce relapse rates in patients treated for Stage IIA/B testicular seminoma. To address this issue, we reviewed patterns of failure and treatment outcome in patients treated with radiation therapy at our institution. Methods and Materials: Between 1981 and 1999, 79 men with Stage II seminoma (IIA, 49; IIB, 30) were treated with radiation therapy (RT) to the para-aortic and ipsilateral (ⴞ contralateral) pelvic lymph nodes (dose: 25–35 Gy). Results: With a median follow-up of 8.5 years, the 5-year relapse-free rate was 91% (standard error: 3%), and 2 patients have died of seminoma, giving a 5-year cause-specific survival of 97%. A total of 7 patients have relapsed with 2 isolated to the left supraclavicular fossa. Five of 7 patients have been successfully salvaged. Conclusions: Prophylactic left supraclavicular fossa irradiation might have prevented relapse in 2 of 79 patients in Stage IIA/B seminoma. However, 97% of patients would have received unnecessary left neck RT, so we continue to recommend, as standard treatment, infradiaphragmatic RT only. © 2003 Elsevier Inc. Seminoma, Stage II, Radiation therapy.
and ⬍5 cm) testicular seminoma received primary radiation therapy after inguinal orchidectomy. Evaluation postorchidectomy included full clinical history and examination, chest X-ray, CT scan of the abdomen and pelvis (some patients also had lymphangiogram in the early 1980s), and measurement of tumor markers (␣fetoprotein and beta human chorionic gonadotrophin). Pathology review at our institution was undertaken before treatment to confirm the diagnosis of seminoma. All patients were treated with megavoltage radiation (1.25–18 MV) using parallel-opposed fields with appropriate shielding. The treatment volume included the paraaortic nodes (superior extent T9 –T11 vertebral level), together with the ipsilateral (⫾ contralateral) iliac nodes (inferior extent obturator foramen) encompassing known disease. A dose of 25 Gy in 20 daily fractions followed by a boost of 10 Gy in 5 to 8 daily fractions to the involved para-aortic nodes was delivered. All patients completed treatment and received the planned dose. No prophylactic supradiaphragmatic radiation was given to any patient.
INTRODUCTION For men with testicular seminoma, radiation therapy (RT) has been a standard treatment modality for most of the last century. The current standard of treatment is infradiaphragmatic RT to the para-aortic and iliac lymph nodes for Stage IIA and IIB (1997 UICC TNM classification) disease and chemotherapy for Stage IIC patients (lymph nodes ⬎5 cm). Prophylactic mediastinal irradiation was abandoned because of treatmentassociated toxicity (1, 2) and increased difficulties in delivering salvage chemotherapy at subsequent relapse (3, 4). Zagars and Pollack suggested that prophylactic irradiation of the left supraclavicular fossa (LSCF) might have a role in reducing relapse rates and in improving results of treatment (5). To address this issue, we reviewed and analyzed patterns of failure in all cases of Stage IIA/B seminoma treated with primary RT at our institution since 1981. METHODS AND MATERIALS Between 1981 and 1999, 79 men (median age: 35 years, range: 22– 68 years) with Stage IIA (abdominal lymph nodes ⬍2 cm) and IIB (abdominal nodes ⬎2 cm Reprint requests to: Dr. Padraig Warde, Department of Radiation Oncology, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, Ontario, M5G 2M9 Canada. Tel: (416) 946-2122; Fax: (416) 946-4586; E-mail: padraig.
[email protected] Received Oct 17, 2002, and in revised form Dec 27, 2002. Accepted for publication Jan 3, 2003. 746
Radiation volume for Stage II seminoma
● P. W. M. CHUNG et al.
747
Fig. 1. Relapse-free rate for Stage IIA/B patients.
Statistical methods Survival and relapse-free rates were calculated from the date of diagnosis using the Kaplan-Meier method. Time zero was taken as the time of orchidectomy. The sample size was determined by the number of available cases during the period of the study, not by a priori considerations of statistical power. RESULTS At median follow-up of 8.5 years (range: 1.1–20.7 years), 2 patients had died of seminoma. The 5-year relapse-free rate was 91% (standard error: 3%) (Fig. 1). In total, 7 have relapsed (Table 1), 4 within 12 months, another 2 within 24 months, and the final 1 within 36 months of orchidectomy. Of the Stage IIA patients who recurred, 1 had isolated LSCF relapse, 1 had relapse in the soft tissue around the left scapula, the third had bony disease with a paraspinal mass, and the other had bony and pulmonary metastases. In the Stage IIB patients, 1 had solitary LSCF, 1 had LSCF and Table 1. Relapse sites by stage of disease Stage
Total no. patients
No. relapsing
2A
49
4
2B
30
3
Site Left supraclavicular Soft tissue left scapula Bone ⫹ para-spinal soft tissue Bone ⫹ lung Para-aortics Left supraclavicular Left supraclavicular ⫹ left axilla
axillary, and the other had para-aortic recurrence. The latter contained embryonal carcinoma at postchemotherapy retroperitoneal lymphadenectomy for a nonregressing mass. Salvage treatment Chemotherapy was the main modality used at first relapse in 6 of 7 patients. Five patients remained disease free; one patient, who refused further treatment after two courses of chemotherapy, died of disease. The other patient had supradiaphragmatic RT as primary salvage; he was treated in the early 1980s, had subsequent bony relapse, and received chemotherapy, but died of disease 1.6 years after first treatment.
DISCUSSION Our current analysis for patients with Stage IIA/B testicular seminoma at Princess Margaret Hospital shows that the overall outcome remains excellent. These results are comparable to those in other published series of patients treated with para-aortic and iliac RT only, followed by salvage chemotherapy for relapse (6 – 8). Recently, Zagars and Pollack recommended that prophylactic LSCF irradiation to reduce relapse at this site would have a significant effect on relapse rates and thus should be used as standard treatment (5). This recommendation is based on Stage II patients treated with primary RT over 39 years (1960 –1999). Three cohorts comprising a total of 73 men were treated over this period. In the first cohort, 36 men treated before 1984 received infradiaphragmatic and prophylactic mediastinal irradiation (LSCF included). From
748
I. J. Radiation Oncology
● Biology ● Physics
1984 to 1992, a second cohort of 17 patients received infradiaphragmatic RT only. The final cohort of 20 patients received infradiaphragmatic RT plus prophylactic LSCF RT (1993–1999). Relapse rates for these cohorts were 6% (2/ 36), 19% (5/17), and 5% (1/20), respectively. In the patients who received infradiaphragmatic RT only, the commonest site of relapse was the LSCF alone (3 of 5 that relapsed). Thus, prophylactic LSCF RT was initiated to prevent relapse at this site. The 20 patients treated subsequently with prophylactic LSCF RT had no relapses at this site, and only 1 patient relapsed in the mediastinum. Thus the policy of LSCF RT would seem to be sensible given the results in this series. However, it should be noted that the policy is based on 3 patients relapsing in a cohort of 17. In our series, relapse occurred in 9% of patients overall, and 5-year cause-specific survival was 97%; this is in keeping with other recently published series treated with infradiaphragmatic RT only, which showed relapses of 5% to 10% with cause-specific survival of 96% to 100% (6 – 8). Solitary LSCF relapse was not a prominent feature in any of these series (⬍5%). At most, prophylactic LSCF would have prevented relapse in 2 of 79 patients in our series, but there are no patient or tumor characteristics that identify those men that will relapse at this site only. For Stage IIA patients, 1 of 49 (2%) may have benefited from LSCF irradiation. In Stage IIB, 1 of 30 patients (3%) may have had
Volume 56, Number 3, 2003
relapse prevented. Even taking into account the other patient who had simultaneous LSCF and left axillary relapse (2 separate distinct masses, where prophylactic RT to LSCF alone may not have prevented relapse in the axilla), 7% would have benefited. We would not make a separate recommendation for treatment between Stage IIA and IIB patients based on these numbers. Because salvage chemotherapy is highly effective, it is difficult to justify a policy of routine LSCF RT, no matter how little toxicity is associated with treatment, because the therapeutic gain is likely to be minimal for the vast majority of patients. A different approach has been used with the aim of reducing relapses in Stage IIA/B seminoma (9). This combines single-agent carboplatin to eradicate micrometastatic deposits with infradiaphragmatic RT to treat macroscopic disease in a sequential manner. This is interesting, but the crude relapse rate was 6%, and the cause-specific survival was 97% and requires further investigation to ensure associated toxicity is low with the therapeutic gain over RT alone significantly large, before it could be adopted as standard treatment. In summary, we continue to recommend only infradiaphragmatic RT in Stage IIA/B seminoma; the addition of elective LSCF RT would overtreat the vast majority of patients, who are likely never to recur.
REFERENCES 1. Hanks GE, Peters T, Owen J. Seminoma of the testis: Longterm beneficial and deleterious effects of radiation. Int J Radiat Oncol Biol Phys 1992;24:913–919. 2. Lederman GS, Sheldon TA, Chaffey JT, et al. Cardiac disease after mediastinal irradiation for seminoma. Cancer 1987;60: 772–776. 3. Einhorn LH, Williams SD. Chemotherapy of disseminated seminoma. Cancer Clin Trials 1980;3:307–313. 4. Peckham MJ, Horwich A, Hendry WF. Advanced seminoma: Treatment with cisplatinum-based combination chemotherapy or carboplatin (JM 8). Br J Cancer 1985;52:7–13. 5. Zagars GK, Pollack A. Radiotherapy for stage II testicular seminoma. Int J Radiat Oncol Biol Phys 2001;51:643–649.
6. Bamberg M, Schmidberger H, Meisner C, et al. Radiotherapy for stage I and IIA/B testicular seminoma. Int J Cancer 1999; 83:823–827. 7. Bauman GS, Venkatesan VM, Ago CT, et al. Postoperative radiotherapy for stage I/II seminoma: Results for 212 patients. Int J Radiat Oncol Biol Phys 1998;42:313–317. 8. Vallis KA, Howard GC, Duncan W, et al. Radiotherapy for stages I and II testicular seminoma: Results and morbidity in 238 patients. Br J Radiol 1995;68:400–405. 9. Patterson H, Norman AR, Mitra SS, et al. Combination carboplatin and radiotherapy for the management of stage II testicular seminoma: Comparison with radiotherapy treatment alone. Radiother Oncol 2001;59:5–11.