Contrast enhanced (oral and intravenous) CT of the chest, abdomen and pelvis is required as an initial staging investigation [5, 6]. For the evaluation of the lungs and mediastinum, chest CT scan is much more sensitive than a plain chest X-ray [7, 8]. However, it should be noted that pulmonary/pleural nodules of <1 cm can represent a false positive finding in CT scans [8]. Furthermore, CT scans of the abdomen and pelvis might give false-negative results in up to 30 % of cases due to difficulties in the interpretation of lymph nodes based on morphology and size alone [5]. Therefore, the differentiation between clinical stages I and IIA by CT might be unreliable. A detailed description of the location, number and size of lymph nodes should be provided in the radiology report. Magnetic resonance imaging (MRI) scans of the abdomen and pelvis do not provide additional information and should be restricted to those patients in whom intravenous contrast media is contraindicated [9]. Based on available data, PET has not conclusively demonstrated to improve sensitivity over CT staging alone [10, 11]. Even in high-risk stage I patients PET scan was not sensitive enough to predict early metastatic disease in a statistically significant proportion of patients. PET scans are therefore not recommended outside the clinical trials as a part of routine initial staging procedures.

Clinical staging of a patient with a testicular germ cell tumour is done according to the TNM classification (Table 28.2) [12]. In order to verify clinical stage I disease markers need to be followed until normalization after orchidectomy. Those patients who do not have marker normalization after orchidectomy obviously have metastatic disease. Patients with metastatic disease are categorised according to the classification devised by the International Germ Cell Cancer Collaborative Group (IGCCCG) [13] which includes histology, location of primary tumour, location of metastases and pre-chemotherapy levels of AFP, HCG and LDH as prognostic markers to categorise patients into ‘good’, ‘intermediate’ and ‘poor’ prognosis groups (Table 28.3). The individual treatment strategy is based on both the TNM classification and the IGCCCG-prognostic factor-based classification.

The testicular tumors have a specific mode of spread, with the metastases occurring through lymphatic and vascular routes. Local spread is limited by the tunica albuginea of the testis. The lymphatic spread is a common form of metastasis in all histological types. Haematogenous spread occurs to the lungs, liver and brain. As testes develop in the retroperitoneum in the abdomen, their lymph drains to paraaortic and other lymph nodes in the infrarenal region. The lymphatics from the epididymis drain into testicular lymphatics. These lymphatics join lymphatics from the tunica albuginea in rete testis and proceed to the spermatic cord [14]. The lymphatics initially accompany testicular vessels. After crossing the ureter they spread out to join retroperitoneal lymph nodes anterior to the lumbar vessels [15, 16]. The right testicular vein drains into the anterior aspect of the inferior vena cava and the left testicular vein drains into left renal vein.

Right-sided tumors metastasize to the infrarenal aortocaval, precaval, right paracaval, and retrocaval lymph nodes. Left-sided tumors spread to the left paraaortic and preaortic lymph nodes. The echelon lymph nodes are lateral to the paracaval and paraaortic lymph nodes in the region between the first and third lumbar vertebra on the iliopsoas muscle, which can get involved particularly in cases with relapse [17]. When the anatomy of the inguinoscrotal region is disturbed by surgical procedures like orchidopexy or scrotal exploration, there is likely to be a direct spread to the iliac or inguinal lymph nodes, which normally drain scrotal skin.

The role of surgery in pure seminomas is limited mostly to the radical orchidectomy. Post-orchidectomy management for stage I disease involves surveillance, with treatment reserved for patients who have relapse, or adjuvant treatment with either radiotherapy or chemotherapy [36] and this aspect of management is described later. Retroperitoneal lymph node dissection is not recommended.

Primary RPLND is not an option stage I seminoma even after relapse and for stage II seminomas; RPLND has been replaced largely by chemotherapy and/or radiotherapy [37]. In a retrospective study comparing radiotherapy and RPLND in stage I and II seminoma, Warszawski et al [38] observed in their 161 subjects treated between 1975 and 1991 (98 patients received radiotherapy and 63 patients underwent RPLND) a higher relapse rates after RPLND (9.5 % Vs. 2.0 %).

Post-chemo RPLND (PC-RPLND) in seminomas: The original recommendation was to resect tumours >3 cm diameter. However viable seminoma is found in less than 20 % of patients after chemotherapy. Also pure seminoma is a different entity compared to NSGCT. There is a higher degree of desmoplastic reaction than NSGCT and there is relatively higher grade of poor tissue planes. Most often the excision of residual masses cannot be completed in a safe manner with nearly 40 % of patients requiring additional operative procedures [39]. Overall RPLND does not seem to have any therapeutic benefit even when undertaken as a technically challenging procedure.

Lymphovascular infiltration (vascular invasion, VI) by the primary tumour is one of the most important prognostic indicators for occult metastases and must be assessed in all patients [40–44]. Without adjuvant treatment 48 % of the patients with VI would develop metastases while only 14–22 % of those without metastasis relapse. Based on these data, VI alone does not represent a valuable prognostic risk factor for a risk-adapted approach as it is likely to result in an unnecessary overtreatment rate of about 50 %. The proliferation rate and the percentage of embryonal carcinoma (EC) present in relation to the total tumour volume are further prognostic indicators [42, 43]. The combination of absence of VI and a percentage of EC <45 % correctly identified 91.5 % of all patients with true pathological stage I disease [42]. On the other hand, the presence of VI and a percentage of EC >80 % correctly predicted pathological stage IIA/B disease in 88 % of the patients. Based on these data, the German Testicular Cancer Study Group performed a prospective study in which 200 patients with clinical stage I NSGCT were assigned to RPLND and risk factors were assessed prospectively [43]. The combination of absence of VI, percentage of EC <50 % and a MIB-1 proliferating index <20 % correctly identified pathological stage II disease with 86.5 % accuracy. If none of the prognostic risk factors were present, the risk of occult retroperitoneal disease was 16 % and patients were classified as low risk. The risk of lymph node metastases was 65 % if at least VI and percentage EC >50 % were present and the patients were classified high risk. In another small prospective evaluation, Perotti et al [44] tested a prediction model in which patients with a percentage of EC >80 % and/or the presence of VI were assigned to a high risk of occult metastatic disease. The authors correctly predicted final pathological stage II disease in 67 % when only one prognostic factor was present.

The combination of imaging studies, histopathological evaluation and immunhistochemical techniques is likely to improve the prediction of the final pathological stage of the disease. Localization and size of lymph nodes in conjunction with a low volume of embryonal carcinoma, absence of vascular invasion and a low MIB-1 proliferation rate might give important information with regard to the probability of lymph node metastases. In a retrospective analysis of 91 clinical stage 1 NSGCT patients using a combined approach with quantitative immunohistochemical, histopathologic, and radiologic assessment who underwent nerve-sparing RPLND, Liebovitch et al [45] found 40 out of 41 patients were correctly classified as low risk tumours for metastases. They concluded Patients with lymph nodes <1 cm diameter which are located in the primary landing zone, a low volume of embryonal carcinoma harbour a risk of <10 % of occult retroperitoneal lymph node metastases and might be best managed by active surveillance.

If the correct treatment were to be executed, the cure rate for patients with CS I NSGCT should be 99 % regardless of the treatment chosen. Basically, three treatment options, which have similar cure rates but significantly differing in frequency and type of treatment-associated toxicities, might be offered to these patients: (i) active surveillance; (ii)primary chemotherapy with 1–2 cycles PEB and (iii) Nerve-sparing RPLND. When choosing a risk–adapted approach in clinical stage I NSGCT, the clinician has to reflect that all the patients are expected to be long-term survivors and there that long-term side effects of treatment would be minimal or non existent. It is therefore the aim of ongoing clinical research to minimize the modalities of treatment and their toxicities without compromising therapeutic efficacy. The European Germ Cell Cancer Consensus Group Conference (EGCCCG) recommends low risk patients that they should be primarily offered active surveillance [4], whereas systemic chemotherapy with 2 cycles PEB represents the treatment of choice for high risk patients.

Active surveillance encompasses a treatment strategy with the aim of detecting retroperitoneal or systemic relapses and to treat only those patients with documented metastatic disease thereby decreasing the risk of unnecessary overtreatment. During the initial post-treatment phases of follow-up, regular clinical examinations, monitoring of serum tumour markers and imaging investigations are carried out. The frequency and type of examinations are dependent on the estimated risk of relapse and the time that has elapsed since completion of therapy and should be modified according to these risks. However, only limited information about the optimal follow-up strategy exists.

When recommending active surveillance for low risk or in certain scenarios also for stage I high risk NSGCT, two major important aspects have to be considered: (1) risk of secondary malignancies due to the repetitive radiation exposure of the imaging studies and (2) more intensive treatment in case of relapse (3 cycles PEB ± postchemotherapy RPLND) as compared to primary active therapy (1 cycle PEB).

In patients who were on active surveillance for CS I with a low risk NSGCT, the relapse rate was 27–30 % on a long-term follow up of ≥20 years [41, 46, 47]. Relapses occur in the retroperitoneum in 54–78 % of patients, in the lungs in 13–31 %, but are rarely seen in more than one visceral organ. With this approach 78–86 % of patients do not need any further treatment after orchiectomy [41, 43, 46–48]. If a patient under surveillance relapses, the administration of chemotherapy will result in a cure rate close to 100 %. When the surveillance is not suitable, adjuvant chemotherapy with two cycles of BEP is recommended. Nerve sparing retroperitoneal lymph node dissection (RPLND) is a feasible option at high-volume centers [43]. A randomized phase III trial of one cycle BEP versus RPLND in 382 unstratified patients with clinical stage I disease (plus adjuvant chemotherapy for those who were to be pathological stage II after RPLND) suggested a significantly reduced recurrence rate using adjuvant BEP as compared to surgery (1.1 % versus 7.5 %, respectively [43].

Patients with a low risk of relapse (no VI) for follow up should be managed by surveillance according to the EGCCCG recommendation. This requires at least 5 CT scans performed at 0, 3, 12, 18 and 24 months [4]. This follow-up protocol with extensive imaging studies, however, might lead to a high radiation exposure with significant long-term consequences for the patients.

In a recent study, Tarin et al. [49] estimated the risk of secondary cancer associated with CT imaging related radiation during the surveillance of stage I NSGCT patients. In their analysis they evaluated surveillance protocols recommending about 16 CT scans over a 5-year period and they took into consideration a 64-slice CT scanner obtaining images of the abdomen and pelvis with and without inclusion of the chest. For calculation of organ specific radiation doses a standardized, phantom male patient was employed using the Monte Carlo simulation techniques. With a 5-year surveillance protocol the lifetime cancer risk ranged from 1 in 52 (1.9 %) for an 18-year old to 1 in 63 (1.2 %) for a 40-year old patient. If chest CTs were also obtained the risk increases to 1 in 39 (2.6 %) and 1 in 58 (1.6 %), respectively. The relative risk of a secondary malignancy with surveillance compared to a single scan after RPLND is approximately 15.2.

Various studies have been designed to reduce the number of CT scans during the surveillance strategy. Atsü et al [50] analysed the outcome of 140 CS I NSGCT who were followed with only 2 CT scans at postoperative months 6 and 12 with no CT scans thereafter. All patients underwent serial measurements of the serum tumour markers, abdominal ultrasonography and chest X-rays at variable frequency depending on the time intervals between orchidectomy and follow-up. Relapses developed in 32 (24 %) patients and they were detected within a median of 5 (2–23) months. 28 relapses developed during the first year and only 4 relapses occurred during the second year of surveillance. All patients were salvaged by systemic chemotherapy combined with postchemotherapy RPLND in 7 cases. In their study, the presence of any EC in the orchiectomy specimen resulted in a 3.7-fold increase of the relapse risk. In order to reduce the number of CT scans during follow-up, the prospective randomized Medical Research Council Trial (MRC, UK) TE08 was initiated which compared the diagnostic efficacy of 2 versus 5 CT scans during the first 2 years of follow-up to detect the number of patients who relapse with intermediate and poor prognosis disease at relapse [51]. 247 patients and 167 patients were randomized to the two-scan and the five-scan group, respectively. Besides CT scans all patients underwent follow-up assessments at various time intervals: clinical examination, evaluation of serum tumour markers AFP, ß-hCG and LDH as well as chest X-ray With a median follow-up of 40 months, 37 (15 %) relapses had developed in the two-scan and 33 (20 %) relapses occurred in the five-scan group. None of the patients had a poor prognosis disease at the time of relapse, but 2 (0.8 %) patients and 1 (0.6 %) patient had intermediate prognosis disease. There were, however, some other statistically significant differences between the two groups with regard to the indicators of relapse. The proportion of patients in whom elevated tumour markers were the first indicators of relapsing disease was 21.6 and 6.1 % in the two-scan and the five-scan group, respectively. Interestingly, 16 patients had normal markers at time of their orchidectomy but elevated markers at time of relapse underlining the importance of serum tumour markers measurements in every patient with CS I NSGCT who undergoes active surveillance. In the two arms combined a total of 11 patients developed lung metastases with 7 of them being tumour marker negative. The following conclusions can be drawn from this large prospective randomized trial: (a) fewer CT scans reduce the radiation exposure and costs without harming the patient, (b) regular measurements of tumour markers ß-hCG, AFP and LDH together with chest X-ray and two abdominal CT scans are necessary for a surveillance program, and (c) it is unclear if this approach of reduced imaging studies can be applied for high risk patients since only 10 % of the recruited NSGCT demonstrated vascular invasion with a relapse rate of 32 %.