Updated: June 2005

APF negative, moderate elevations of LDH or bHCG acceptable.

N0 M0 (clinical stage I)

Despite normal CT scans, a 20% risk of clinical occult metastatic disease in locoregional lymph nodes with subsequent disease progression remains, if no adjuvant treatment is applied after orchiectomy. Nevertheless, the cure rate in CS I seminoma patients is almost 100% and can be achieved by three strategies: adjuvant radiation treatment, surveillance strategy with administration of irradiation or chemotherapy in case of relapse, or adjuvant chemotherapy with single agent carboplatin.

Adjuvant radiotherapy of the para-aortic or para-aortic plus pelvic region is currently the most frequently used adjuvant treatment resulting in a relapse rate of 3-4%. Almost all of these recurrences are located outside the irradiated area, mostly in the pelvis (1.7%) or close to the border of the radiation fields. Total radiation dose is 20-25 Gy.

Surveillance strategy may be used as an alternative to adjuvant irradiation, but initial assessment at a cancer center is strongly recommended. The potential advantage of surveillance is that patients are spared acute and late radiation toxicity and possibly an associated increased risk of secondary malignancies. Surveillance is labour-intensive and requires long-term follow-up in highly motivated patients. Patients not available or unwilling to undergo prolonged and close follow-up are not candidates for a surveillance strategy. Reported relapse rate on surveillance are approximately 20%. Almost all relapses should be salvageable with further therapy.

Studies of surveillance have identified tumour size (4 cm vs. >4 cm, hazard ratio 2.0) and rete testis invasion (hazard ratio 1.7) as important predictors of relapse in multivariate analysis. Other factors which may increase relapse rates include younger age (<34 years), lymphatic or vascular invasion, and undifferentiated histology.

Adjuvant chemotherapy with single agent Carboplatin is an alternative to radiation therapy or surveillance for stage I seminoma. A large phase III trial comparing one cycle of adjuvant carboplatin with adjuvant radiation demonstrated an equal efficacy of Carboplatin to adjuvant radiation. Relapses in the Carboplatin arm, however, occurred mainly in the retroperitoneum. In a second prospective study patients were stratified for treatment according to their histopathological risk factors (as outlined above). Patients without histopathological risk factor were put on surveillance, whereas patients with one or both risk factors were treated with two cycles of Carboplatin. Relapse rates were similar in both arms (appr. 3-4%). However, these studies still have a rather short follow-up and therefore a close follow-up as for patients on surveillance is recommended for these patients until long term data are available. Consultation with a specialized center regarding the optimal treatment strategy in an individual patient is strongly recommended.

References:

1. Jones WG, Fossa SD, Mead GM, et al. A randomised trial of two radiotherapy schedules in the adjuvant treatment of stage I seminoma (MRC TE 18). Eur J Cancer 2001;37: Suppl. 6:S157.abstract #572.
2. Fossa A, Jones WG, Stenning S, Collaborateurs ftT. Quality of life (QL) after radiotherapy (RT) for stage I seminoma : results from a randomized trial of two RT schedules (MRC TE18). Proc Am Soc Clin Oncol 2002; 21: abstract # 750.
3. Warde P, Specht L, Horwich A, Oliver T, Panzarella T, Gospodarowicz M, von der Maase H.; Prognostic factors for relapse in stage I seminoma managed by surveillance: a pooled analysis. J Clin Oncol. 2002, 20: 4448-4452.
4. Oliver RT, Mason M, Von der Masse H, Stenning SP, Kirk S, Rustin GJ, Mead GM, Ell, PPL: A randomised comparison of single agent carboplatin with radiotherapy in the adjuvant treatment of stage I seminoma of the testis, following orchidectomy: MRC TE19/EORTC 30982. Proc Am Soc Clin Oncol 2004, 22: abstract 4517
5. J. Aparicio, J. R. Germa, X. Garcia Del Muro, P. Maroto, J. A. Arranz, A. Saenz, A. Barnadas, J. Dorca, E. Alba Risk-adapted management of stage I seminoma: The second Spanish Germ Cell Cancer Group (GG) study. Proc Am Soc Clin Oncol 2004; 22: 4518

N1-3 M0 (Clincal stage II A/B/C)

Relapse-free survival for patients with stage II A / B seminoma is approximately 95% and 90% at 6 years, respectively. Post inguinal orchidectomy, radiation treatment to the para-aortic and ipsilateral pelvic area is the standard treatment option for stage II A/B. Where fertility is an issue, the remaining testicle is shielded in conjunction with sperm banking.

Chemotherapy with three cycles of standard-dose cisplatin, etoposide and bleomycin (BEP), or four cycles of etopside, cisplatin (EP, in case of contraindication for bleomycin) represent an alternative treatment for patients not willing to undergo radiotherapy, in particular for patients with larger retroperitoneal disease (N2-3).

Advanced Seminoma - N3 >10 cm or M1 (Clinical stage IIC or III; "good" or "intermediate" prognosis acc. To the IGCCCG classification)

These patients will be treated with chemotherapy according to the IGCCCG classification and may require subsequent resection of residual masses. A multi-disciplinary assessment is preferred before instigating therapy. These patients should have their evaluation and therapy expedited (visceral metastases from seminoma is rare).

Post treatment residual masses

Post-chemotherapy, as well as post-radiotherapy, residual masses in seminoma patients should not necessarily be resected, irrespective of their size, but should be closely followed by imaging investigations and tumour marker determinations. If close observation is not possible, residuals larger than 3 cm can be resected. PET scanning appears to be a promising tool in defining patients with residual lesions who need additional therapy, and such patients should be discussed at the weekly multidisciplinary GU Tumour Case Conference.

References:

1. Herr HW, Sheinfeld J, Puc HS et al. Surgery for a post-chemotherapy residual mass in seminoma. J Urol 1997; 157: 860-862.
2. Puc HS, Heelan R, Mazumdar M et al. Management of residual mass in advanced seminoma: results and recommendations from the Memorial Sloan-Kettering Cancer Center. J Clin Oncol 1996; 14: 454-460.
3. Albers P, Weissbach L, Krege S et al. Predictions of necrosis after chemotherapy of advanced germ cell tumors: results of a prospective multicenter trial of the German Testicular Cancer Study Group. J Urol 2004; 171: 1835-1838.
4. Mosharafa AA, Foster RS, Leibovich BC et al. Is post-chemotherapy resection of seminomatous elements associated with higher acute morbidity? Journal of Urology 2003; 169: 2126-2128.
5. Duchesne GM, Stenning SP, Aass N et al. Radiotherapy after chemotherapy for metastatic seminoma--a diminishing role. MRC Testicular Tumour Working Party. Eur J Cancer 1997; 33: 829-835.
6. De Santis M, Becherer A, Bokemeyer C et al. 2-18fluoro-deoxy-D-glucose Positron Emission Tomography Is a Reliable Predictor for Viable Tumor in Postchemotherapy Seminoma: An Update of the Prospective Multicentric SEMPET Trial. J Clin Oncol 2004; 22: 1034-1039.