Patients with stage I seminoma achieve a survival rate of about 99%, regardless of therapeutic strategy including adjuvant radiotherapy, adjuvant chemotherapy with one cycle of carboplatin, or surveillance . Good prognosis post-orchiectomy has been confirmed in several trials: Kamba et al. performed a Japanese multi-institutional retrospective observational study on 425 patients, showing 10-year OS of 100%, 100% and 99% in the surveillance, chemotherapy and radiotherapy groups, respectively. Conversely, the relapse-free survival rates at 10 years were 79%, 94% and 94%, respectively, in the same groups . The risk of relapse is highest during the first 2 years after treatment (early relapses); the annual risk rate is > 5% for surveillance and > 1% for radiotherapy or chemotherapy. However, late relapses are very uncommon and occur more frequently in the retroperitoneal space, followed by the chest or neck . They are generally detected by symptoms because they occur after the conclusion of the standard follow-up, and up to half can present with elevation of tumour markers [9, 10]. The treatment of stage I seminoma late relapse is based on the previous therapy, with good prognosis. In particular, after radiation, late relapses occur mainly outside the prior radiation field, most commonly in the pelvis, with a recurrence rate of 3–4%, and are usually responsive to cisplatin-based chemotherapy. Otherwise, late relapses after single-agent carboplatin are mostly salvaged by cisplatin chemotherapy or by radiotherapy [8, 11].
Primary tumour size greater than 4 cm and rete testis invasion represent the major prognostic factors for relapse . For example, Chung et al. showed an increase in the risk of relapse at 3 years from 2% for tumour size equal to or less than 1 cm, to 25% for tumour size of 6 cm or greater . AFP and beta-hCG represent the common biomarkers used in the follow-up of germ cell tumours, even if the increase in AFP is typical in late-relapsing of non-seminoma neoplasms, with levels greater than 100 U/L appearing to indicate poor prognosis . On the contrary, in relapses of seminoma, the level of LDH increases according to the volume of disease, especially in late relapses , as we found in our patient’s blood test. Several studies have evaluated differences between early and late relapses of germ cell tumours. Fedyanin et al. showed that patients with late relapse were usually older and had more frequent pure seminoma in primary tumours. Both groups showed similar prognostic factors at the time of relapse, even though patients with late relapse showed a larger size of disease, especially in seminoma recurrence. Regarding the outcome, subjects with late relapse achieved a lower response rate after chemotherapy, 3-year progression-free survival (PFS) and 3-year OS, and prognosis seems even worse in the case of pure seminoma . On the contrary, Mortensen et al. analysed 2000 cases of seminoma and revealed no significant differences in disease-specific or overall survival between early, late and very late groups, although increased time to relapse was negatively associated with survival . The role of the time to relapse is not clear, and the literature data are conflicting, due to the rarity of testicular disease. Regarding advanced disease, the prognosis of patients relapsing after cisplatin-based first-line treatment is variable, with 2-year survival rates ranging from 75% (very low risk) to 6% (very high risk). In these cases, salvage treatment is based on high-dose chemotherapy or conventional-dose chemotherapy, without significant differences in OS or PFS. Considering the variability in chemotherapy response, surgery should be conducted whenever possible, especially in localized relapses and in chemotherapy-refractory patients [17, 18].
Finally, our case report underlines the importance of an individualised approach to prolong duration of follow-up in patients treated for testicular cancer, considering the patient’s age and the primary risk factors (rete testis invasion and tumour size), due to the possibility of disease relapse even after many years from the initial treatment. Moreover, these patients have an increased risk for developing secondary malignant neoplasms following radiation exposure from diagnostic imaging and due to radiotherapy, which is correlated with increased risk of developing both solid tumours, leukaemia and cardiovascular diseases [19, 20].