|Year : 2019 | Volume
| Issue : 8 | Page : 87-90
Adjuvant radiotherapy for Stage I seminoma: A Single-institutional experience
Gul Kanyilmaz1, Irem Saricanbaz2, Huseyin Bora3, Eray Karahacioglu3, Eda Yirmibesoglu Erkal4
1 Department of Radiation Oncology, Necmettin Erbakan University Meram Medicine School, Konya, Turkey
2 Department of Radiation Oncology, Ankara Numune Education and Research Hospital, Ankara, Turkey
3 Department of Radiation Oncology, Gazi University Faculty of Medicine, Ankara, Turkey
4 Department of Radiation Oncology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey
|Date of Web Publication||22-Mar-2019|
Dr. Gul Kanyilmaz
Department of Radiation Oncology, Necmettin Erbakan University Meram Medicine School, Akyokus Mevkii, Konya
Source of Support: None, Conflict of Interest: None
Objectives: There is no consensus regarding the management of Stage 1 seminomas following inguinal orchiectomy. In this study, we evaluated the treatment results and treatment-related toxicity for patients with Stage 1 seminomas treated with adjuvant radiotherapy (RT) at a single institution.
Methods: Sixty-five patients who underwent adjuvant RT following orchiectomy for Stage 1 seminomas between January 1996 and December 2007 were retrospectively reviewed. The age, tumor location, histopathological type, stage, tumor size, RT field, and radiation dose were recorded for all patients.
Results: The patients' ages ranged from 17 to 61 years (median, 37 years). Sixty-three patients (97%) were diagnosed with classical seminoma and the remaining two patients (3%) had spermatocytic seminoma. After orchiectomy, 37 patients (57%) received para-aortic RT and 28 patients (43%) received dog-leg field RT. RT was applied with 1.8–2 Gy/day fractionation and the median RT dose was 26 Gy (range, 20–38). Follow-up ranged from 0.3 to 18 years (median, 9.5 years). Local control had been achieved in all patients and all of them were alive with no evidence of disease. Fifty-one patients (77%) had at least 5 years of follow-up and 27 patients (41%) had at least 10 years of follow-up. Overall survival at 10 years was 100%.
Conclusion: Although retrospective in nature, this single-institutional study provides useful information about the outcomes and toxicities associated with adjuvant RT in patients with Stage 1 seminomas reporting excellent disease control and survival rates at the expense of acceptable toxicity.
Keywords: Dose and field, late complication, radiotherapy, secondary malignancy, testicular seminoma
|How to cite this article:|
Kanyilmaz G, Saricanbaz I, Bora H, Karahacioglu E, Erkal EY. Adjuvant radiotherapy for Stage I seminoma: A Single-institutional experience. J Can Res Ther 2019;15, Suppl S1:87-90
|How to cite this URL:|
Kanyilmaz G, Saricanbaz I, Bora H, Karahacioglu E, Erkal EY. Adjuvant radiotherapy for Stage I seminoma: A Single-institutional experience. J Can Res Ther [serial online] 2019 [cited 2020 Nov 28];15:87-90. Available from: https://www.cancerjournal.net/text.asp?2019/15/8/87/243502
| > Introduction|| |
Testicular seminomas are the most common germ cell tumors in men aged 15–40 years. Approximately 60% of these tumors are seminomas and most of them present as Stage 1 disease. There is no consensus regarding the management of Stage 1 seminomas following inguinal orchiectomy.,, Radiotherapy (RT) to the regional lymph nodes, short-course platinum-based chemotherapy, and active surveillance are viable options following orchiectomy.,, Regardless of the adjuvant management option, most patients are cured of their disease, with a 5-year overall survival rate and a 5-year disease-specific survival rate of 99%–100%., This success, however, is balanced by the emergence of considerable long-term side effects that include second primary malignancies, cardiovascular diseases, nephrotoxicity, hypogonadism, decreased fertility, and psychosocial problems. For this reason, the morbidities associated with the preferred management option are important in terms of decision-making.
There are no randomized trials directly comparing the above-mentioned management options in terms of survival and toxicity. In contrast to the claims in support of active surveillance based on the high success rates of salvage treatment in the form of RT or chemotherapy in case of recurrences, others favor upfront RT or chemotherapy based on economical and psychological concerns at the time of recurrences. In this study, we aimed to present the treatment results and treatment-related toxicity for patients with Stage 1 seminomas treated with adjuvant RT in a single institution.
| > Methods|| |
The study design was approved by the Institutional Review Board of our university.
Sixty-five patients who underwent adjuvant RT following orchiectomy for Stage 1 seminomas between January 1996 and December 2007 were retrospectively reviewed. All patients were staged according to, then available, the American Joint Committee on Cancer staging system. The age, tumor location, histopathological type, stage, tumor size, RT field, and radiation dose were recorded for all patients.
RT was delivered using a linear accelerator with 10 MV photons, using opposed anteroposterior and posteroanterior fields. For patients who received treatment to the para-aortic lymph nodes only, the RT fields extended from the superior border of T11 vertebral body to the inferior border of the L5 vertebral body. For patients who received treatment to the para-aortic lymph nodes and the ipsilateral pelvic lymph nodes, the inferior border was placed at the top of the obturator foramen. For left-sided tumors, the ipsilateral border was extended to include the left renal hilar lymph nodes.
Following RT, patients were followed up every 3 months for 2 years, every 6 months for 3–5 years, and annually thereafter. At each follow-up, a physical examination was performed, and blood tests (including the alpha-fetoprotein [AFP] and beta-human chorionic gonadotropin [β-HCG]), chest X-rays, and abdominal and pelvic computed tomography (CT) were obtained. Treatment-related toxicity was evaluated using the Radiation Therapy Oncology Group toxicity criteria.
Statistical analysis was performed using SPSS for Windows 17.0 (SPSS Inc., Chicago, IL, USA). Survival analysis was performed using Kaplan–Meier method. Overall survival was described as the time from diagnosis to the date of the patient's death or loss to follow-up.
| > Results|| |
The patients' ages ranged from 17 to 61 years (median, 37 years). The presenting symptoms for all the patients were scrotal masses and swelling. Thirty-seven (57%) patients presented with right-sided seminomas, whereas 28 patients (43%) had left-sided disease. Increased β-HCG levels were found in four patients (6%) and increased AFP levels were found in one patient (1%). All the patients underwent inguinal orchiectomy. Sixty-three patients (97%) were diagnosed with classical seminoma and the remaining two patients (3%) had spermatocytic seminoma. All the patients were classified as having Stage 1 disease. Tumor diameter ranged from 3 to 100 mm (median, 40 mm). All patients received RT postoperatively. The time between orchiectomy and RT ranged from 1 to 6 months (median, 3 months). After orchiectomy, 37 patients (57%) received para-aortic RT and 28 patients (43%) received dog-leg field RT. RT was applied with 1.8–2 Gy/day fractionation and the median RT dose was 26 Gy (range, 20–38).
Follow-up ranged from 0.3 to 18 years (median, 9.5 years). Local control had been achieved in all patients and all of them were alive with no evidence of disease. Fifty-one patients (77%) had at least 5 years of follow-up and 27 patients (41%) had at least 10 years of follow-up. Overall survival at 10 years was 100%.
Grade 3–4 acute toxicity was not observed. Grade 1–2 acute gastrointestinal (GIS) toxicity was observed in 8 patients (12%) who received para-aortic RT and in 7 patients (11%) who received dog-leg field RT. Grade 1–2 late GIS toxicity occurred in three patients (8%) who received para-aortic RT and one patient (3%) who received dog-leg field RT. There was no statistically significant difference between the two groups concerning acute GIS toxicity of patients. During the follow-up period, the secondary malignancies were not detected. One patient, who had received 26 Gy to the para-aortic lymph nodes, developed prostate cancer at 16 years of follow-up.
| > Discussion|| |
The standard treatment for Stage 1 seminomas is radical inguinal orchiectomy. Orchiectomy is both diagnostic and therapeutic for the disease. Postoperative RT has long been considered as a standard adjuvant treatment approach, providing excellent long-term survival.,,, Although highly effective, adjuvant RT puts all patients at risk for treatment-related toxicity (particularly second malignancies). However, acute and late toxicities resulting from RT have been significantly reduced over the past 20 years due to the reduction of radiation field sizes and total radiation doses, still maintaining a high cure rate. The concept of radiation field size has changed from treating the lymph nodes both in the mediastinum and below the diaphragm to treating only the lymph nodes below the diaphragm. Moreover, the treatment fields shrinked from the “dog-leg” field to the para-aortic field which includes only the aortic lymph nodes. RT doses have also been reduced from 40 to 50 Gy to 20 to 26 Gy. Many authors suggest that the reduction of radiation field sizes and the reduction of total radiation dose would help to lower the risk of second malignancies within the radiation field and the contralateral testis.,,, In the current study, 60% of patients have received a total dose ≤ 26 Gy and 56% of patients have received para-aortic RT with no second malignancies observed during the follow-up period directly associated with RT.
There have recently been attempts of pioneering novel strategies that would minimize acute and late toxicities associated with RT. Proton beam therapy offers the potential of decreasing toxicity by capitalizing on unique physical dose deposition characteristics to avoid normal tissue that reduces the risk of GIS toxicity and second malignancies. Simone et al. have shown that for patients with Stage 1 seminomas, proton beam therapy reduces the predicted second malignancies as compared to photon therapy. Intensity-modulated RT (IMRT) uses an increased number of fields and monitor units, which cause a higher whole-body exposure to leakage radiation. Therefore, there are some concerns about the second malignancies which may be increased by IMRT compared with conventional treatment techniques. Therefore, IMRT is not recommended for the treatment of seminomas.
Adjuvant chemotherapy is an alternative treatment option for patients with Stage 1 seminomas. Researchers in support of postoperative platinum-based chemotherapy claim the effects of carboplatin to be equivalent to that of RT., However, similar to RT, high-dose carboplatin and standard-dose cisplatin have been associated with second malignancies in addition to cardiovascular effect., Whether one dose of carboplatin (area under curve = 7) might lead to the similarly frequent late toxicity compared to historical platinum therapies remains unknown.
Active surveillance is another recommended treatment option for patients with Stage 1 seminomas that would allow the prevention of acute and late toxicities associated with chemotherapy or RT. The main concern regarding active surveillance is compliance of patient for follow-up visits. Alomary et al. have shown that 21% of patients on surveillance were lost to follow-up after a median of 5.5 years. For patients with Stage 1 seminomas, at least 5% of relapses would occur after 5 years, suggesting that noncompliant patients could present with more advanced disease, would need more intensive treatment, and could experience worse outcomes. Furthermore, strict follow-up examinations would require sufficient financial resources and adequate health-care facilities for regular diagnostic testing., Another concern involving active surveillance is the recurrence rates in related patients. The probability of recurrence has been estimated at 15%–20%, mostly to be observed in patients possessing adverse risk factors such as increased tumor size (>4 cm) and rete testis invasion.,
During the decision-making process for adjuvant treatments, the relapse site should also be considered. Similar to active surveillance, relapses following chemotherapy frequently occur in the retroperitoneal sites, thus necessitating abdominal and pelvic CT scans at regular intervals. The doses of radiation received upon CT imaging might be regarded as noteworthy and recent studies assert that such doses could increase the risk of second malignancies. Thus, the rationale for the alternative treatment regimens should be reevaluated based on the toxicity regarding follow-up testing.
| > Conclusion|| |
Although retrospective in nature, this single-institutional study provides useful information about the outcomes and toxicities associated with adjuvant RT in patients with Stage 1 seminomas, reporting excellent disease control and survival rates at the expense of acceptable toxicity.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30.
Boujelbene N, Cosinschi A, Boujelbene N, Khanfir K, Bhagwati S, Herrmann E, et al.
Pure seminoma: A review and update. Radiat Oncol 2011;6:90.
Aparicio J, Díaz R. Management options for stage I seminoma. Expert Rev Anticancer Ther 2010;10:1077-85.
Horwich A, Dearnaley DP. Treatment of seminoma. Semin Oncol 1992;19:171-80.
Madej G. Chemioterapia Dorosłych i Dzieci. Warszawa: PZWL; 1992.
Martin J, Chung P, Warde P. Treatment options, prognostic factors and selection of treatment in stage I seminoma. Onkologie 2006;29:592-8.
Chung P, Warde P. Stage I seminoma: Adjuvant treatment is effective but is it necessary? J Natl Cancer Inst 2011;103:194-6.
Tandstad T, Smaaland R, Solberg A, Bremnes RM, Langberg CW, Laurell A, et al.
Management of seminomatous testicular cancer: A binational prospective population-based study from the Swedish Norwegian testicular cancer study group. J Clin Oncol 2011;29:719-25.
Travis LB, Beard C, Allan JM, Dahl AA, Feldman DR, Oldenburg J, et al.
Testicular cancer survivorship: Research strategies and recommendations. J Natl Cancer Inst 2010;102:1114-30.
Pectasides D, Pectasides E, Constantinidou A, Aravantinos G. Stage I testicular seminoma: Management and controversies. Crit Rev Oncol Hematol 2009;71:22-8.
Alomary I, Samant R, Gallant V. Treatment of stage I seminoma: A 15-year review. Urol Oncol 2006;24:180-3.
Oliver RT, Mead GM, Rustin GJ, Joffe JK, Aass N, Coleman R, et al.
Randomized trial of carboplatin versus radiotherapy for stage I seminoma: Mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214). J Clin Oncol 2011;29:957-62.
Mead GM, Fossa SD, Oliver RT, Joffe JK, Huddart RA, Roberts JT, et al.
Randomized trials in 2466 patients with stage I seminoma: Patterns of relapse and follow-up. J Natl Cancer Inst 2011;103:241-9.
Fosså SD, Aass N, Kaalhus O. Radiotherapy for testicular seminoma stage I: Treatment results and long-term post-irradiation morbidity in 365 patients. Int J Radiat Oncol Biol Phys 1989;16:383-8.
Fosså SD, Horwich A, Russell JM, Roberts JT, Cullen MH, Hodson NJ, et al.
Optimal planning target volume for stage I testicular seminoma: A Medical research council randomized trial. Medical research council testicular tumor working group. J Clin Oncol 1999;17:1146.
van den Belt-Dusebout AW, de Wit R, Gietema JA, Horenblas S, Louwman MW, Ribot JG, et al.
Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol 2007;25:4370-8.
Zwahlen DR, Martin JM, Millar JL, Schneider U. Effect of radiotherapy volume and dose on secondary cancer risk in stage I testicular seminoma. Int J Radiat Oncol Biol Phys 2008;70:853-8.
Niazi TM, Souhami L, Sultanem K, Duclos M, Shenouda G, Freeman C, et al.
Long-term results of para-aortic irradiation for patients with stage I seminoma of the testis. Int J Radiat Oncol Biol Phys 2005;61:741-4.
Simone CB 2nd
, Kramer K, O'Meara WP, Bekelman JE, Belard A, McDonough J, et al.
Predicted rates of secondary malignancies from proton versus photon radiation therapy for stage I seminoma. Int J Radiat Oncol Biol Phys 2012;82:242-9.
Hall EJ, Wuu CS. Radiation-induced second cancers: The impact of 3D-CRT and IMRT. Int J Radiat Oncol Biol Phys 2003;56:83-8.
Travis LB, Fosså SD, Schonfeld SJ, McMaster ML, Lynch CF, Storm H, et al.
Second cancers among 40,576 testicular cancer patients: Focus on long-term survivors. J Natl Cancer Inst 2005;97:1354-65.
Bosl GJ, Vogelzang NJ, Goldman A, Fraley EE, Lange PH, Levitt SH, et al.
Impact of delay in diagnosis on clinical stage of testicular cancer. Lancet 1981;2:970-3.
Brenner DJ, Hall EJ. Computed tomography – an increasing source of radiation exposure. N Engl J Med 2007;357:2277-84.