Updated: June 2005

T1-3 N0 M0 S0 (clinical stage I)

The cure rate of patients with non-seminoma clinical stage I is 99%. Vascular invasion (VI) of the primary tumour is the most important prognostic indicator for relapse. Patients with VI have a risk of 48% to develop metastatic disease, whereas only 14–22% of patients without VI will relapse. The evidence and percentage of embryonal carcinoma of the total tumour volume is the second most relevant prognostic factor, with an increase in risk correlating to the proportion of embryonal carcinoma within the primary tumour.

Treatment Options:

Three treatment options exist for clinical stage I patients:

1) surveillance, which is the preferred treatment option irrespective of the risk status
2) & 3) only in patients unwilling or unable to undergo surveillance, adjuvant chemotherapy or retroperitoneal lymphdenectomy (RPLND) are alternate options.

1. Surveillance (preferred treatment option)
   • All staging is unequivocally normal;
   • patient is considered reliable and available for close follow up including serial CT scans of the retroperitoneum; and
   • surveillance is acceptable to the referring urologist, the patient and the BC Cancer Agency oncologist.
2. Retroperitoneal lymph node dissection (nerve-sparing)
   • This option to preserve the contralateral sympathetic nerves is a surgical technique which allows ejaculation in most patients. But, where intraoperative lymphadenopathy is encountered, a full bilateral block dissection should be performed. Relapses after RPLND occur mainly in the lungs (approximately 10%).
3. Adjuvant chemotherapy with two cycles of BEP may be considered in selected high risk patients unwilling or unable to undergo surveillance or RPLND, although this approach has never been tested in a prospective randomized study. These patients should therefore be discussed at the multidisciplinary conference. With this approach, the risk of relapse is reduced to approximately 4-5%. Referral to an experienced centre is advised.

T0-4 N1-2 M0 S0 (clinical stage II and "good prognosis" according to the IGCCCG classification)

The cure rate for CS IIA and IIB non-seminoma is close to 98%.

Treatment should be selected to provide the best chance of cure with a single modality, as this will minimize morbidity. Early referral for assessment is preferred.

1. Primary chemotherapy according to the IGCCCG classification is recommended for a retroperitoneal mass or an abnormal/ equivocal scan and persistent elevation of tumour markers. Residual post-chemotherapy masses should be resected
2. For patients with minor (<3 cm) lymphadenopathy and negative markers two therapeutic options can be considered: First, radical bilateral retroperitoneal lymph node dissection with postoperative adjuvant chemotherapy where complete pathological examination of removed tissue shows tumour >2 cm or >5 nodes or extranodal extension; otherwise close follow-up for early detection of relapse and institution of chemotherapy salvage. Second, observation for patients willing to undergo close observation with repeat CT scans. Referral to an experienced center is advised

References:

1. Vergouwe Y, Steyerberg EW, Eijkemans MJ, et al: Predictors of occult metastasis in clinical stage I nonseminoma: a systematic review.[see comment]. Journal of Clinical Oncology 21:4092-9, 2003
2. Albers P, Siener R, Kliesch S, et al: Risk factors for relapse in clinical stage I nonseminomatous testicular germ cell tumors: results of the German Testicular Cancer Study Group Trial. Journal of Clinical Oncology 21:1505-12, 2003
3. Donohue JP, Foster RS, Rowland RG, et al: Nerve-sparing retroperitoneal lymphadenectomy with preservation of ejaculation. J Urol. 144:287-291, 1990
4. Donohue JP, Thornhill JA, Foster RS, et al: The role of retroperitoneal lymphadenectomy in clinical stage B testis cancer: the Indiana University experience (1965 to 1989). J Urol 153:85-89, 1995
5. Weissbach L, Bussar MR, Flechtner H, et al: RPLND or primary chemotherapy in clinical stage IIA/B nonseminomatous germ cell tumors? Results of a prospective multicenter trial including quality of life assessment. Eur Urol 37:582-594, 2000
6. Pont J, Holtl W, Kosak D, et al: Risk-adapted treatment choice in stage I nonseminomatous testicular germ cell cancer by regarding vascular invasion in the primary tumor: a prospective trial. Journal of Clinical Oncology 8:16-20, 1990
7. Amato RJ, Ro JY, Ayala AG, et al: Risk-adapted treatment for patients with clinical stage I nonseminomatous germ cell tumor of the testis. Urology 63:144-8; discussion 148-9, 2004

Any T any N1-3 M0 S2,3; T any N any M1 S0-3 (Clinical stage III or "good", "intermediate" or "poor" prognosis according to the IGCCCG classification)

Induction chemotherapy followed by resection of residual masses is the standard approach for these patients. Because of the complexity and specialized nature of this treatment, referral to the BC Cancer Agency for opinion is strongly recommended.

For patients with "good prognosis" disease according to IGCCCG criteria, standard treatment is three cycles BEP. In case of contraindications against bleomycin, four cycles of cisplatin and etoposide (EP) can be given. Four cycles of BEP are the standard treatment for patients with intermediate prognosis. For patients with "poor prognosis" standard treatment consists of four cycles of BEP. Four cycles of etoposide, ifosfamide and cisplatin (VIP) are equally effective compared to BEP, but cause more acute myelotoxicity without offering additional benefits. VIP should however be considered in patients with contraindications for bleomycin or patients who are at high risk for bleomycin induced toxicity (age > 40 years; poor renal function; wide-spread metastastic disease; high cumulative bleomycin dose). VIP should also be considered for patients with pulmonary metastases in whom a secondary post-chemotherapy resection of lung metastases is expected.

In patients with a residual mass >1 cm and normalization of tumour markers, the residual masses have to be resected. Histological findings in subsequent surgery for residual masses after first line chemotherapy will reveal necrosis in about 35%, mature teratoma in 50% and vital cancer in 15%. The incidence of vital cancer may be even higher after salvage chemotherapy. If technically feasible, all residual masses should be resected. In patients with residual masses at multiples sites, an individual decision should be made regarding number and extension of resections. If malignancy is evident in the resected specimen, two further cycles of intensive chemotherapy may be required.

Patients with brain metastases at initial presentation are still potentially curable and should be treated with chemotherapy. Such patients require a multidisciplinary approach including: neurosurgery, radiation oncology and medical oncology. For asymptomatic brain metastases, the benefit of initial cranial irradiation is unclear. Patients in whom brain metastases are discovered after an otherwise complete systemic chemotherapy, or persist after an otherwise complete systemic response to chemotherapy, should have resectable lesions removed and proceed with cranial irradiation thereafter. Patients who relapse or progress with systemic disease including brain metastases after previous chemotherapy have a poor prognosis. Treatment should include palliative cranial irradiation.

To maintain the highest chances for curability, "poor-prognosis" patients should be transferred to a specialized centre without any delay to benefit from optimal interdisciplinary management and supportive care.

Reference:

1. O'Sullivan JM, Huddart RA, Norman AR, et al: Predicting the risk of bleomycin lung toxicity in patients with germ-cell tumours. Annals of Oncology 14:91-6, 2003