Revised 08 May 2013
Relapses of early stage germ cell tumours are uncommon, but even with widespread disease patients are potentially curable.
Tumour markers should be repeated and a pathological diagnosis obtained when necessary to confirm the diagnosis. Systemic relapse in patients previously treated with chemotherapy are potentially curable and should be assessed at the Cancer Agency for a multidisciplinary opinion. Usually chemotherapy will be the primary treatment for recurrent germ cell tumours, but surgery and/or radiotherapy may also be required.
Due to the complexity of the disease of these patients, referral to experienced high volume centers is strongly recommended.
The recently published IGCCCG-2 prognostic score for relapsed disease includes 7 factors (histology; presence of liver, lung or brain metastases; progression-free interval; AFP and HCG level at relapse; location of primary tumor) which differentiate 5 risk groups with significant differences in progression – and overall survival rates. This classification allows much improved prognostication of patients.
Paraaortic nodal recurrences on surveillance are managed as for N1-3 patients, as described above for clinical stage II. The majority of patients with relapse after first-line radiotherapy will have a cure rate >90% and should receive cisplatin-based chemotherapy comparable to the treatment strategy in advanced chemonaive seminoma. Conventional-dose cisplatin-based salvage chemotherapy after first-line therapy with BEP will result in long-term remissions in up to 50% of patients. Regimens of choice are four cycles of VIP, VeIP or TIP.
Systemic relapse in chemotherapy naive patients are potentially curable and are treated as for de novo M1 patients.
Salvage treatment after first-line chemotherapy for metastatic disease consists of four cycles of VIP, VeIP or TIP. Conventional-dose cisplatin-based salvage chemotherapy can achieve long-term remissions in 15-40% of patients.
A subsequent retrospective comparison of patients treated with conventional and high dose chemotherapy suggested a significant advantage of high dose chemotherapy over conventional dose chemotherapy for almost all IGCCCG-2 risk groups. A single high dose chemotherapy cycle, as consolidation after three conventional cisplatin-based cycles as second line therapy, has been demonstrated not to be superior to four conventional cisplatin-based chemotherapy cycles in patients with favourable prognostic criteria (gonadal primary; complete or marker-negative response to first-line therapy). Sequential high does chemotherapy appears to offer a benefit and is currently tested in randomized studies.
The chemotherapy approach of standard or high dose chemotherapy in relapsed patients must be discussed with the multidisciplinary team and should include consideration of the patient’s risk factors prognosis, and co-morbidities.
Residual masses after salvage chemotherapy should be resected as soon as possible after the end of chemotherapy. In case of progressive tumour markers, after salvage treatment and lack of other chemotherapeutic options, surgical resection of residual tumours should be considered if complete resection of all tumour manifestations seems feasible.
Patients with late relapse (> 2 years after first-line therapy) should be referred to the next specialized center for further management. If technically feasible, patients with late relapse and negative tumour markers should undergo immediate radical surgery to completely resect all mature teratoma or secondary non-germ cell cancer. Due to the poor results of chemotherapy in patients with late relapses, patients with small and completely resectable lesions should undergo surgery even in case of elevated tumour markers. If the lesions are not completely resectable, biopsies should be obtained for histological assessment and salvage chemotherapy should be initiated. If the patient responds to salvage chemotherapy, secondary surgery should be conducted whenever possible.