Late relapse of testicular germ cell neoplasms: a descriptive analysis of 122 cases

The problem of late relapse of testicular germ cell tumor (GCT) is poorly understood. No more than approximately 300 cases have been reported to date. It appears that late relapse (L/R) of GCT involves a more aggressive biology than virginal GCT. In the present study we increased the understanding of L/R by analyzing these events in a large patient sample.

Late relapse was defined as recurrence of disease more than 2 years after completion of primary treatment. A total of 122 patients (50 with pure seminoma and 72 with nonseminoma) were retrospectively studied. Several parameters were analyzed including age, clinical stage, treatment at primary presentation, occurrence of prior early relapse, interval to L/R, tumor markers, site of relapse, and mode and outcome of L/R treatment. Possible effects of various clinical parameters on treatment results were studied by multivariate statistical analysis.

Median age at first presentation was 34 years and 26.5 years in patients with seminoma and nonseminoma, respectively. The intervals to L/R were 42 months (range 25 to 276) in seminoma and 64.5 months (range 28 to 216) in nonseminoma. A total of 75% of nonseminomas but only 20% of seminomas had disseminated disease at first presentation, while 51 patients with nonseminoma had initially received chemotherapy. alpha-Fetoprotein was increased in 45 patients (of 59 eligible) with nonseminoma at L/R, human chorionic gonadotropin in 12 cases. alpha-Fetoprotein levels greater than 100 U/l indicated poor prognosis. Topographically relapses were mainly confined to lymph nodes of the abdomen, chest and neck. Of 72 patients with nonseminoma cure failed in 37 in contrast to only 6 patients with seminoma (of 48 eligible). Inclusion of surgery increased the chance of cure (RR 4.0, 95% confidence interval 0.9-18.5).

Late relapses of GCT are biologically and clinically distinct from virginal GCT. These events occur in nonseminoma and seminoma, but clinical features are quite different in the 2 groups. Increase of alpha-fetoprotein is typical in late relapsing nonseminoma and levels of more than 100 U/l appear to indicate poor prognosis. Anatomically L/R presents as lymphadenopathy of abdomen, chest or neck. Treatment should include surgery in nonseminoma. Seminomas and otherwise chemotherapy naive cases might respond to chemotherapy only. Particular risk groups for late relapse are nonseminoma with prior early relapse, patients receiving chemotherapy for disseminated disease at first presentation and those with pure teratoma. These latter subgroups should be followed with annual health examinations for at least 10 years.