Seminomas are generally less aggressive than nonseminomatous germ cell tumors . Among men with clinical stage I testicular germ cell tumors that are managed with surveillance following inguinal orchiectomy, the relapse rate is about 17 % for pure seminomas compared to 25–30 % for nonseminomatous tumors [2]. This difference has also been reported in the setting of metastatic disease. In the outcomes analysis performed by the International Germ Cell Cancer Consensus Group in 1997, men with germ cell tumors with metastases to the liver, bone, or other nonpulmonary organs had a 5-year survival of 72 % if the tumor was pure seminomas compared to 48 % if the cancer was a nonseminomatous tumor [3]. Among seminomas, spermatocytic seminomas are a very rare subtype with a distinct histopathological, genetic, and clinical profile as discussed in previous chapters [4]. Spermatocytic seminomas are generally seen in older men and do not have metastatic potential unless sarcomatous transformation is seen. Orchiectomy alone without chemotherapy, radiation therapy, or additional surgery is thus appropriate treatment for men with these tumors.

Pure seminomas do have metastatic potential and management paradigms reflect this . Among men with stage I disease, risk stratification can be performed based on the size of the tumor and the presence or absence of invasion of the rete testis. An international pooled analysis of 638 men reported that the risk of relapse was 32 % for men with tumors larger than 4 cm and rete testis invasion, 16 % for men with one of these risk factors, and 12 % for those with neither [5]. The low risk of relapse has been prospectively confirmed in studies by the Spanish Germ Cell Cancer Cooperative Group. For instance, among 153 low-risk and intermediate-risk clinical stage I patients managed with surveillance following orchiectomy, the 3-year disease-free survival rate was 93.5 % among patients with no risk factors, 83.7 % among men with tumors larger than 4 cm, and 78.3 % for those with rete testis invasion; in this study, high-risk men whose tumors were bigger than 4 cm and also invaded the rete testis were treated with carboplatin chemotherapy [6]. The presence or absence of lymphovascular invasion is also associated with risk of relapse in univariable analysis, but not when controlling for tumor size and rete testis invasion. Because the risk of relapse is only about 30 % even for high-risk patients and the risk of dying of the cancer is less than one percent, many experts prefer surveillance for all clinical stage I seminoma patients, while others favor a risk-adapted approach so that only high-risk patients are treated either with carboplatin chemotherapy or with radiation therapy .

Embryonal carcinoma (EC) has long been recognized as a more aggressive cancer with a higher rate of relapse for stage I and stage II disease. Many studies over the past 25 years have reported that among men with stage I testis cancer, EC is associated with a higher risk of relapse if the patient is managed either with postorchiectomy surveillance or with retroperitoneal lymph node dissection (RPLND) . Although the first major studies to relate this reported that the presence of EC was associated with a higher risk of relapse in stage I patients, subsequent analyses reported an association between the risk of relapse and the proportion or volume of the tumor that consisted of EC. Men who have both lymphovascular invasion (LVI) and preponderance of EC have been reported to be at particularly high risk of having occult metastatic disease.

One challenge in interpreting these findings is the fact that different studies have used different endpoints. Surveillance studies that have used relapse as an endpoint have reported only a modest association between EC and that endpoint. In contrast, much stronger associations have been reported between tumors consisting predominantly of EC, on the one hand, and a finding of lymph node involvement by the tumor in patients undergoing an RPLND. For instance, a study of 223 men undergoing postorchiectomy surveillance for clinical stage I nonseminomatous testicular germ cell tumors reported that the risk of relapse at 3-year follow-up was only 33 % among men with a predominance of EC, but this group could be divided into high- and low-risk subgroups: 55 % risk of relapse if there was both LVI and a predominance of EC and only a 16 % risk of relapse if there was a predominance of EC but no LVI [7] . In contrast, surgical series have reported much higher rates of retroperitoneal lymph node positivity in patients with a predominance of EC, although with varying definitions of predominance. In these series, the association of EC and LVI limited the contribution of EC as an independent variable. In one series of 149 men with clinical stage I nonseminomatous tumors undergoing RPLND, of 48 men with more than 80 % EC, 42 also had LVI, and among 77 with less than 45 % EC, 71 did not have LVI. Of the six who were LVI positive but had less than 45 % EC, 3 (50 %) had pathological stage II disease, so the absence of EC predominance only predicted a low risk of relapse if LVI was absent. Of those with 46–79 % EC, seven of nine without LVI were pathological stage I, while 15 of 15 with LVI were pathological stage II. It was only when more than 80 % of the tumor was EC that it became predictive of a majority of men without LVI (four out of six) having pathological stage II disease [8].

Indiana University reported that a predominance of EC (defined as the presence of more EC than any other histology) was more clinically relevant. Among 226 patients undergoing RPLND with pathological stage I disease, the subsequent relapse rate was about 20 % if either LVI or EC predominance was present and 29 % if both were present compared to a relapse risk of less than 7 % if neither risk factor was present. Similarly, among 292 patients with clinical stage I disease undergoing RPLND, the risk of pathological stage II disease was 39 % if LVI was present, 32 % if EC was predominant, and 47 % if both risk factors were present. However, the difference in risk for one versus two risk factors was not statistically significant in either of these two analyses [9]. Memorial Sloan Kettering Cancer Center reported their findings in patients with clinical stage I pure EC, which showed that 19 of 26 men (73 %) had retroperitoneal nodal metastases, including 13 of 18 (72 %) with LVI and six of eight (75 %) without LVI [10] .

The significance of these findings remains unclear. Relevant clinical questions are whether a predominance of EC should be used to decide how to manage patients with clinical stage I or pathological stage II patients. Because the rates of nodal metastases and relapse following RPLND are both higher in patients with EC predominance, should these patients be managed instead with primary chemotherapy rather than nodal dissection or surveillance? For instance, if half or more of patients with pure EC or both LVI and EC predominance will have lymph node metastases discovered at RPLND and most such patients will elect to undergo two cycles of adjuvant chemotherapy, would it be preferable to simply give them one or two cycles of primary chemotherapy in lieu of RPLND? And if such patients have a 50 % or higher risk of relapse if placed on surveillance, might such men prefer to be treated now with a relatively brief course of chemotherapy and minimize the likelihood of needing additional treatment in the future rather than live with a high likelihood of having to put their lives on hold at some unpredictable point in the subsequent few years in order to undergo a longer course of chemotherapy in the event of a relapse? In current practice, most recent studies have based such risk stratification on the presence or absence of LVI and have not included EC. So at this time, EC is not generally taken into account when making treatment decisions for patients with testicular cancer but does have some prognostic implications with regard to risk of relapse and nodal metastases among men with clinical stage I disease .

Men with pure teratomas of the testis have a lower risk of metastatic disease and relapse compared to other germ cell tumors, but such tumors are rare. Investigators in southwestern France reported that among 1000 cases of testis cancer, only 17 were pure teratoma, eight of whom had clinical stage I disease, while nine had metastatic disease present at diagnosis. All patients were alive and without evidence of the cancer at a mean follow-up of 10 years [11] .