Clinical management

Clinical presentation

Seminoma most commonly presents as a painless testicular mass in the fourth decade of life [13]. Distant to the primary tumor, metastases may manifest particularly as a palpable mass of the abdomen or neck, gynecomastia with or without tenderness, and respiratory symptoms, such as shortness of breath or, less commonly, hemoptysis. It is a well-recognized phenomenon of testicu-lar cancer that the interval between the onset of symptoms and diagnosis is often prolonged. A combination of factors, including patient embarrassment and delays in investigation owing to such factors as treatment of presumptive epididy-mitis, postpone the correct diagnosis by 3 months on average [14,15].

Initial evaluation involves ultrasonography of the testes, a modality well suited to this purpose because of ease of access, lack of radiation, and high sensitivity and specificity for intratesticular lesions [16]. Before surgical management of the primary lesion, the serum tumor markers a-fetoprotein (AFP), human chorionic gonado-tropin (HCG), and lactate dehydrogenase (LDH) are evaluated and chest (plain radiograph or CT) and abdominal (CT) imaging is performed. Testicular biopsy is avoided on general principle, because the disruption of lymphatic integrity that may occur with scrotal violation has been associated with an absolute increase in local recurrence rates of up to 2.5% [17].

Orchidectomy

Standard surgical management of the primary tumor involves radical orchidectomy by way of an inguinal approach with high ligation of the spermatic cord at the deep inguinal ring using a nondissolvable suture as a potential future marker for retroperitoneal exploration. Partial orchidectomy remains an option in the setting of a solitary testis or bilateral testicular masses if small, to preserve testicular function [18]. The long-term fate of this approach in endocrine function and cancer control remains unknown.

Radical orchidectomy serves not only to provide local control but also to establish the pathologic nature, grade, and stage of the primary tumor. With increasing subspecialization and interhospital referral of patients for postorchidec-tomy management, the importance of central histopathologic review has recently been highlighted [19]. On pathologic review Delaney and colleagues [19] found a 4% discrepancy in tumor type, of which roughly one half were recategorized from seminomatous to nonseminomatous germ cell tumor. Additionally there was a 10% difference in the identification of lymphovascular invasion and further differences in the description of nonseminomatous tumor elements. Discrete from the increased metastatic potential of NSGCT, some centers have identified the presence of vascular invasion and rete testis invasion as risk factors for metastatic recurrence in seminoma [20]. The importance of establishing the exact nature of the tumor primary is clear in determining the most appropriate option for clinical management of the disease. This determination is most important in early-stage disease in which treatment options vary considerably based on the assignment of a particular case as a seminoma or NSGCT.

Imaging

Imaging of the primary echelon retroperitoneal lymph nodes is routinely performed with CT

scanning of the abdomen and pelvis. In seminoma patients, abdominal CT scans are normal in 70% [16]. Of those patients who have germ cell tumors and CT-detectable lymph nodes between 5 and 10 mm in maximal diameter, tumor is detected in 50%; between 10 and 20 mm this figure increases to 70% [21]. In an effort to refine the accuracy of clinical staging, other imaging modalities have been assessed. MRI offers the benefit over CT of avoiding radiation; however, metastatic evaluation is currently based on lymph node size criteria in the same way and therefore prediction of disease is similar. There is potential for improved detection of metastatic lymph node disease with MRI using paramagnetic iron oxide contrast agents; however, this awaits further investigation in the field of testicular cancer [22,23].

Positron emission tomography (PET) relies on the differential metabolism of 18fluoro-2-deoxy-D-glucose (FDG) by tumor cells to distinguish them from normal tissue. FDG is taken up more avidly by seminoma than NSGCT and it was initially expected that this would enhance clinical management [24]. The acuity of this technique is limited by false positives from inflammatory and granulo-matous tissues and false negatives for small lesions (<5-10 mm) and mature teratoma [25]. In a recent review of PET scanning in germ cell cancers, only two of nine trials reported improvement with a higher sensitivity and negative predictive value for PET over CT during staging at presentation [25]. Currently there is no clear role for PET scanning in the initial staging of seminoma.

Tumor markers

The role of tumor markers in seminoma is perhaps less pronounced than in NSGCT. AFP is not secreted by seminoma. Men who have elevated AFP regardless of tumor histology should thus be treated as an NSGCT. HCG, produced by syncytiotrophoblasts, is elevated in only 10% to 15% of cases. LDH is a nonspecific marker elevated in up to 80% of seminomas and 60% of nonseminomas when advanced, but also in many benign conditions. Specifically, AFP is useful to identify the presence of NSGCT elements when elevated and HCG may be used to follow response to treatment and for surveillance of recurrence in that fraction of patients who have disease that produces it. In contradistinction to NSGCT, tumor markers were not found to be useful for risk stratification in patients who had seminoma as described by the International Germ

Cell Cancer Collaborative Group [26]. This finding has been confirmed subsequently by several authors in the setting of low-stage seminoma. Although elevated levels of HCG have been associated with larger tumor volumes, this does not seem to translate into differences in treatment outcome [27,28]. Because of a lack of specificity and a tendency to become elevated only with more advanced disease, the relevance of LDH as a surveillance tumor marker has recently been contested [29].

Staging

With information garnered from the pathologic analysis of the orchidectomy specimen, tumor markers, examination, and imaging, a clinical stage may be assigned. Management of semi-nomatous germ cell tumors is tailored to this and the pertinent factors in decision making vary by stage. Table 1 contains the most relevant staging system for testicular germ cell tumor.

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