Oncological outcomes in patients with stage I testicular seminoma and nonseminoma: pathological risk factors for relapse and feasibility of surveillance after orchiectomy

Testicular germ cell tumor is histopathologically classified into seminoma and nonseminomas, and nonseminomas are subclassified into embryonal carcinoma, choriocarcinoma, yolk sac tumor, teratoma, and mixed germ cell tumors. After an orchiectomy, the most feasible therapeutic option is determined with risk assessment based on the pathological diagnosis and clinical staging [1]. Nonseminoma is more potent to metastasize and lead to poorer prognosis compared with seminoma at same stage. Surveillance has recently been a management option in many patients with stage I seminoma, and treatment and follow-up strategy vary according to the clinicopathological characteristics in stage I nonseminoma [2, 3]. However, risk factors associated with relapse still remain controversial in both entities. This study was performed to explore pathological risk factors associated with disease relapse in men with stage I seminoma and nonseminoma, and to evaluate oncological outcomes in those managed with surveillance after orchiectomy.

Stage I testicular seminoma has been reported to relapse between 10% and 20% in previous studies [5, 6], while adjuvant radiotherapy is frequently used with a relatively encouraging outcome as relapse rates of 3–4% [7]. In our institution, the overwhelming majority of men with stage I seminoma have recently been managed with surveillance (Table 3). In the current patient series managed with surveillance, the 10-year relapse-free survival rate reached 93.4%; it is speculated that diagnostic/staging modalities such as high-performance CT might lead to an appropriate exclusion of metastases and favorable outcomes. Also, none of them died during the observation period; the prognosis of men with stage I testicular seminoma is excellent when an appropriate surveillance protocol is applied. However, their postorchiectomy management remains a matter of concern, although adverse events including treatment-associated morbidity is less in adjuvant setting radiotherapy than in radical chemotherapy for clinically recurrent disease. A few previous studies tried to define risk-stratification of testis-confined seminoma. Aparicio and associates prospectively studied 314 men with stage I seminoma managed according to risk-adapted criteria. In their trial, those with tumor diameter less than 4 cm and no rete testis involvement were managed with surveillance; 6% of these patients still experienced relapse [8]. In our study, tumor burden, tumor markers, and pT were not associated with disease relapse. Concerning pathological characteristics, however, patients with disease extension through tunica albuginea showed a poorer relapse-free survival than those without. Although the difference was not significant (P=0.09, Figure 2), 3.8% of the patients without involvement of the tunica albuginea had relapse, whereas the relapse rate reached 20% in those with tunica albuginea involvement (Table 4). A recent retrospective study reported that tunica albuginea penetration was predictive of the presence of metastasis (n=86, P=0.00001), although the study recruited men with seminoma at all stages [9]. To verify its significance in risk-stratification of stage I seminoma, a high-volume study based on cancer registry is currently underway.

It also remains controversial how patients with stage I nonseminoma should be managed. Although cause-specific death was absent in our patient series, it has been fatal in 1% to 15% in previous reports [10‐12]. Twenty-five to 30% of the patients with stage I nonseminoma managed by surveillance have been reported to experience disease relapse [7], and adjuvant chemotherapy has been the therapeutic standard for those with elevated tumor markers at diagnosis and/or highly malignant histopathology [8, 11]. Vascular invasion and predominant embryonal carcinoma are generally considered to be histopathologic risk factors [7]. In our institution, men with stage I nonseminoma with normalized tumor markers or markers showing reductions assumed based on their half-life period are principally managed with surveillance regardless of the mentioned pathological characteristics, and the present study suggested that patients with lymphovascular invasion may have higher risk for relapse. Although the difference was not significant, 40.0% of the patients showing lymphovascular invasion had disease relapse, while 18.8% of those without it experienced relapse (Figure 3, Table 6).

The present study had several limitations. It was performed in a retrospective design, and the study volume was relatively small. Also, our database did not include information about the presence of some uncommon histological components such as sarcomatous differentiation coexistent with teratoma and potentially having an impact on oncological outcomes [4, 13].

In men with stage I seminoma, surveillance after orchiectomy is a feasible option. Although further studies are warranted, the present study suggested that tunica albuginea involvement may be a risk factor associated with disease relapse in them. In men with stage I nonseminoma and normalized markers after orchiectomy, surveillance is also a feasible option, but those with lymphovascular invasion may possibly be at high risk for disease relapse.