Treatment of stage I nonseminomatous germ cell tumors

INTRODUCTION — 

Germ cell tumors (GCTs) account for most testicular cancers. The most common histologic subtypes of GCTs are nonseminomatous and seminomatous (ie, seminomas) tumors. Stage I nonseminomatous germ cell tumor (NSGCT) is a highly curable malignancy.

The treatment of stage I NSGCT following orchiectomy will be presented here. The clinical presentation, diagnosis, and staging of testicular cancer and the treatment of stage II NSGCT is presented separately.

●(See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors".)

●(See "Treatment of stage II nonseminomatous germ cell tumors".)

GENERAL PRINCIPLES — 

With only rare exceptions (eg, those who present with widely disseminated disease requiring emergent treatment), male patients with testicular cancer undergo a radical inguinal orchiectomy for diagnosis and initial treatment. If imaging studies show no evidence of regional or distant metastases and serum tumor markers are normal after orchiectomy, patients are defined as having clinical stage IA or IB nonseminomatous germ cell tumor (NSGCT) (table 1 and table 2). (See "Radical inguinal orchiectomy for testicular germ cell tumors", section on 'Surgical treatment of the testis' and "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors", section on 'CT scan'.)

Patients with stage IS NSGCT are those with disease limited to the testicle but who have persistently elevated tumor markers following orchiectomy (table 1 and table 2). For such patients with no evidence of disease on imaging studies and whose markers are declining after orchiectomy (even if the decline is slower than the expected half-life), we observe the patient and follow the tumor markers to nadir. Most patients with stage IS NSGCT turn out to have stage IA or IB NSGCT, and this approach avoids premature initiation of chemotherapy and overtreatment. However, patients with persistently elevated and rising tumor markers postorchiectomy likely have disseminated disease and should be treated with chemotherapy using the same approach as those with advanced or metastatic disease [1]. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)

This review focuses on the treatment of stage IA and stage IB NSGCT. Stage I NSGCT is a highly curable malignancy. The goals of therapy are to reduce the risk of relapse and minimize treatment-related toxicity. Most patients with clinical stage I NSGCT are cured with orchiectomy alone and do not require further treatment (75 percent). However, it is difficult to identify which patients with stage I NSGCT are at highest risk for recurrence and thus have the most to gain from adjuvant treatment. While treatment immediately following orchiectomy can reduce the risk of relapse, it represents overtreatment for most patients and can result in both short- and long-term complications. In addition, although the risk of recurrence is approximately 25 percent for patients undergoing surveillance, treatment at the time of recurrence is almost always curative [2-4]. Long-term disease-specific survival exceeds 99 percent regardless of whether patients undergo surveillance, chemotherapy, or retroperitoneal lymph node dissection (RPLND). (See "Approach to the care of long-term testicular cancer survivors".)

RISK STRATIFICATION — 

Numerous attempts have been made to identify patients with clinical stage I nonseminomatous germ cell tumors (NSGCTs) at high risk for relapse and thus most likely to benefit from adjuvant treatment following orchiectomy. The most widely used risk factors for recurrence in patients undergoing surveillance following orchiectomy for clinical stage I disease include the following [5-10]:

●Lymphovascular invasion (LVI).

●Predominance of an embryonal carcinoma (EC) component in the primary tumor – Predominance is histologically defined when EC comprises a greater proportion of the tumor than any other individual germ cell tumor component.

●Pathologic tumor stage T3 or T4 (table 1).

These risk factors can stratify patients with testicular NSGCT by risk of relapse:

●Low risk – Tumors with none of these risk factors are associated with relapse rates ranging from 10 to 14 percent [2,3,11].

●High risk – Tumors with one or more of these risk factors have a higher risk of relapse.

•Tumors with a predominance of EC alone (no LVI) are associated with relapse rates between 20 and 40 percent, although the data on this are mixed [2,3,12,13]. For tumors demonstrating LVI alone (no EC), relapse rates range between 40 and 55 percent [2,3,11]. Tumors with both a predominance of EC and LVI are associated with relapse rates of over 50 percent [2,14-16].

•There are limited data for relapse rates in patients with T3 or T4 disease due to the rarity of these tumors and their exclusion from most surveillance series [17,18].

Studies that have evaluated the risk for relapse associated with EC and/or LVI include the following:

●In one observational series of 223 patients, the relapse rate was approximately 20 percent in those whose tumor had a predominance of EC without LVI, 40 percent in those with LVI but no EC predominance, and 55 percent in those with both risk factors compared with 10 percent in those with neither risk factor [2].

●By contrast, another series reported that patients with pure EC (ie, tumor that is comprised entirely of EC) with or without LVI had a relapse rate of 45 percent [3].

●Several studies reported that patients with LVI and no EC at all had relapse rates of 20 percent or less [14,19,20].

●Other research indicates that the risk of micrometastatic disease increases as the proportion of EC increases [15,16].

Interpreting studies of the prognostic significance of EC is complicated by the fact that different studies have used different measures to pathologically characterize EC, including whether EC is present or absent, whether it is predominant (variously defined as more than 40 percent, more than 50 percent, or representing a greater proportion of the tumor than any other individual germ cell tumor type), or whether it is pure [13]. These issues have made it more challenging to clarify its significance as an independent prognostic risk factor. At least three studies suggest that the mere presence of EC is a significant risk factor for relapse, and a meta-analysis suggests that both the presence and predominance of EC are significant prognostic risk factors [13,14,19-21]. Regardless, EC is a weaker predictor of relapse than LVI [13].

As an example, one systematic review and meta-analysis of 24 studies evaluating LVI and EC as risk factors for relapse in patients with clinical stage I NSGCT demonstrated that LVI was a strong risk factor and that both the presence and predominance of EC had prognostic value for occult metastatic disease [13]. This study defined occult metastatic disease as either lymph node metastases discovered during primary retroperitoneal lymph node dissection (RPLND) or relapse during surveillance. In the pooled analysis, the presence of LVI was associated with a higher rate of occult metastases versus the absence of LVI (48 versus 17 percent, odds ratio [OR] 4.33, 95% CI 3.55-5.3). Both presence and predominance of EC were also associated with higher rates of occult metastases (33 versus 16 percent, OR 2.49, 95% CI 1.64-3.77 for presence versus absence of EC; 40 versus 20 percent, OR 2.62, 95% CI 1.93-3.56 for tumors with EC involvement greater than 50 percent versus less than 50 percent).

TREATMENT APPROACH — 

Surveillance, adjuvant chemotherapy, and retroperitoneal lymph node dissection (RPLND) are therapeutic options for patients with clinical stage I nonseminomatous germ cell tumors (NSGCTs) (algorithm 1). Each approach is associated with a 99 percent rate of long-term disease-specific survival. Importantly, for patients who are interested in fertility preservation, sperm banking should be performed prior to treatment with RPLND or chemotherapy.

The approach to management depends upon various factors, including:

●The likelihood of relapse (based on the presence of low- versus high-risk disease characteristics)

●The relative importance of the risk of relapse and of the different toxicities for an individual patient

●The ability of a patient to adhere to posttreatment surveillance

Low-risk disease — For most patients with low-risk disease who are treated with orchiectomy, we suggest surveillance rather than adjuvant treatment (algorithm 1) given excellent long-term overall survival and the avoidance of unnecessary toxicity with this approach. Surveillance is appropriate for patients who are willing and able to adhere to the follow-up schedule. The specific surveillance protocol for stage I testicular NSGCT is discussed separately. (See "Posttreatment follow-up for testicular germ cell tumors", section on 'Stage I NSGCT (surveillance)'.)

However, surveillance has not been compared with adjuvant treatment in a randomized trial, and some patients may elect for adjuvant treatment to minimize their chances of relapse. For patients who are unwilling or unable to adhere to surveillance or those who strongly desire to reduce relapse risk and willingly accept the risk of late treatment-related toxicity, one cycle of adjuvant bleomycin, etoposide, and cisplatin (BEP) (table 3) is an appropriate alternative. RPLND is also an appropriate alternative for those with access to an experienced urologist, especially if the tumor is predominantly teratoma.

Surveillance — Patients who undergo surveillance after orchiectomy have an excellent prognosis, with disease-free survival of 97 percent or more and overall survival of 99 percent [2,3,9,11,22]. In addition, surveillance avoids the complications and toxicity of chemotherapy. Most patients who relapse do so with good-risk disease, which is treatable with curative intent [11,14]. Data supporting the role of surveillance in stage I NSGCT after orchiectomy are as follows:

●Surveillance was evaluated in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) Management Program [9]. Between 1998 and 2005, 745 patients in Sweden and Norway were treated prospectively for clinical stage I NSGCTs. Surveillance was recommended for patients without lymphovascular invasion (LVI; n = 491), although they were allowed to choose adjuvant chemotherapy. At a median follow-up of 4.7 years:

•The relapse rate was higher among patients who underwent surveillance rather than BEP (table 3) chemotherapy (12 versus 1.3 percent with one cycle of BEP or 0 percent with two cycles of BEP).

•The overall mortality rate was only 1 percent, and none of these deaths was due to progressive testicular cancer.

•The results from SWENOTECA in patients with high-risk disease are discussed separately. (See 'Surveillance' below.)

●Similar results were reported from the British Columbia Cancer Agency and the Oregon Testis Cancer Program [2]. Among the 77 patients with low-risk disease, the relapse rate during surveillance was 10 percent. No deaths from testicular cancer were reported.

●An international pooled analysis of 1139 patients with clinical stage I testicular NSGCTs reported that among the 935 with low-risk disease, 132 (14 percent) relapsed [11]:

•Among the patients who relapsed, 88, 10, and 2 percent were classified as having good-risk disease, intermediate-risk disease, and poor-risk disease, respectively. (See "Diagnosis and treatment of relapsed and refractory testicular germ cell tumors", section on 'Management'.)

•Among low-risk patients (ie, no evidence of LVI), the median time to relapse was eight months. Most relapses (89 percent) occurred within two years.

•Of the 812 patients who were disease-free at three years, only eight (1 percent) subsequently relapsed. Late relapse was not associated with adverse outcome.

•Five patients in the entire cohort (0.5 percent) died of their cancer or from treatment, and one was alive with disease at the time of the report. The disease-specific survival exceeded 99 percent.

●In an observational cohort study of almost 1300 patients with clinical stage I NSGCT who were treated with orchiectomy followed by surveillance, the relapse rate for the entire cohort at five years was 30.6 percent; the median time to relapse was five months [14]. Despite this, the mortality rate was <0.5 percent; only six patients died of testicular cancer. Of 356 patients treated with chemotherapy at the time of relapse, 98 underwent postchemotherapy resection of residual masses, indicating that 8 percent of the nearly 1300 patients undergoing surveillance ended up receiving multimodality treatment (ie, chemotherapy followed by surgery).

Adjuvant chemotherapy — Although surveillance is appropriate for most patients with low-risk disease, not all patients will be comfortable with surveillance due to concerns about relapse risk. In observational studies, although the relapse rate ranges from 7 to 31 percent, most relapses are favorable risk disease and treatable with curative intent [2,3,9,14,22]. For patients who express a preference for treatment after orchiectomy to reduce relapse risk and understand and accept the risks of late toxicity, adjuvant chemotherapy with one cycle of BEP is a reasonable management strategy [23]. (See 'Adjuvant chemotherapy' below.)

Retroperitoneal lymph node dissection — For patients who have access to a urologic surgeon with extensive experience performing RPLND, surgery is also a reasonable option and reduces the need for surveillance computed tomography (CT) scans; however, most urologists do not have such experience. In our view, patients whose disease is comprised predominantly of teratoma are ideal candidates for RPLND. This approach is extrapolated from data in high-risk stage I NSGCT. (See 'Retroperitoneal lymph node dissection' below.)

For patients with teratoma with somatic malignant transformation, RPLND is the preferred treatment option, and we do not offer surveillance or primary chemotherapy for such patients. (See 'Risk stratification' above and "Surveillance for stage I testicular germ cell tumors following orchiectomy".)

High-risk disease — For patients with high-risk disease, adjuvant chemotherapy, surveillance, and RPLND, if an appropriately experienced urologic surgeon is available, are reasonable options. Because all three options are associated with a disease-specific survival of 99 percent or more, there is no single best option for all patients [24]. Selection of therapy is based upon patient preference and the available expertise. For those rare patients with teratoma with somatic malignant transformation, RPLND is the preferred treatment option and we do not offer either surveillance or primary chemotherapy for such patients.

One factor that must be taken into account if placing high-risk patients on surveillance is the psychologic stress of worrying about relapse and the potential psychologic trauma to the patient if relapse occurs and his life must be put on hold on short notice and at an unpredictable time. One appeal of adjuvant chemotherapy after orchiectomy is the near certainty it provides that the disease has been cured, particularly in this high-risk group.

Therefore, the decision of which modality to use should be based on patient preference:

●For patients with high-risk NSGCTs, surveillance is a highly effective strategy for long-term survival, although it leaves the patient with a substantial risk of recurrence (which would require treatment) at some point in the subsequent two to three years. (See "Surveillance for stage I testicular germ cell tumors following orchiectomy", section on 'Surveillance protocols'.)

Roughly half of patients with high-risk disease will relapse, and approximately one-fourth of those (ie, one-eighth of high-risk patients undergoing surveillance) will require additional treatment (eg, RPLND in addition to three or four cycles of chemotherapy). In light of these statistics, some patients may reasonably choose to proceed with chemotherapy after orchiectomy in order to nearly eliminate the risk of needing such aggressive treatment in the future. (See 'Adjuvant chemotherapy' below.)

●For some patients, the potential life disruption associated with recurrent disease and the psychologic trauma of relapse (with the subsequent need to undergo 9 to 12 weeks of chemotherapy) are unacceptable. In such cases, chemotherapy at the time of initial presentation is a reasonable option.

●For other patients who wish to lower their risk of relapse, RPLND represents another option, provided the technical expertise is available. In our view, patients whose disease is predominantly comprised of teratoma are ideal candidates for this approach. (See "Retroperitoneal lymph node dissection for early-stage testicular germ cell tumors".)

Surveillance — For patients with high-risk disease, several studies have shown that although surveillance is associated with a higher rate of relapse, overall survival is excellent [2,3,11,25]. Data are as follows:

●The safety of surveillance was reported from the British Columbia Cancer Agency and the Oregon Testis Cancer Program, which included 209 patients with high-risk clinical stage I NSGCT (60 with LVI, 109 with embryonal carcinoma [EC]-predominant tumors, and 40 with both) [2]. After a median follow-up of over four years:

•Disease-specific survival was 100 percent, and only one patient had evidence of cancer at the time of the report.

•The relapse rate was 50 percent among patients with LVI (30 of 60 relapsed) and 55 percent for patients with LVI and EC-predominant tumors. By contrast, it was <20 percent for patients with EC-predominant tumors but no evidence of LVI.

Despite the high rate of relapse, all but one patient had good-risk disease at relapse, and only 17 (8 percent) required postchemotherapy resection of residual masses. No patients required second-line chemotherapy.

●A separate study from Princess Margaret Hospital in Toronto reported similar outcomes among 125 patients with high-risk clinical stage I NSGCT [3].

•Among patients with clinical stage I NSGCT with LVI (n = 92), the relapse rate was 54 percent.

•Among patients with tumors that were pure EC without LVI (n = 33), the relapse rate was 45 percent.

Survival data were not reported separately for high-risk and low-risk patients. In the total study of 371 patients, 104 patients relapsed, three of whom died and two of whom were alive with evidence of disease, including one who refused treatment for relapse. While the five-year disease-specific survival was 99 percent for the entire cohort, the mortality rate was 3 percent following relapse, and 2 percent were alive with disease.

●An international pooled analysis of 183 patients with high-risk stage I NSGCT due to LVI reported a relapse rate of 44 percent [11]. At the time of the report, none had died from his cancer. One patient died of other causes, and one was alive with disease.

Adjuvant chemotherapy

Rationale — For patients with high-risk stage I NSGCT, adjuvant chemotherapy is an option that reduces the recurrence risk relative to surveillance but has similar overall survival outcomes. Patients who elect for adjuvant chemotherapy are typically treated with one cycle of BEP. (See 'One versus two cycles of BEP' below.)

●The use of adjuvant chemotherapy was evaluated by the German Testicular Cancer Study Group (GTCSG), which randomly assigned 382 patients with clinical stage I NSGCT to treatment with either one cycle of BEP or RPLND [26]. With a median follow-up of 4.7 years, there were two relapses and no cancer-related deaths among the 191 patients treated with BEP. Four developed febrile neutropenia. The study reported:

•A significantly lower rate of recurrence with BEP compared with RPLND (2 versus 15 events)

•An improvement in the two-year recurrence-free survival rate with BEP (99 versus 92 percent, hazard ratio [HR] 7.9, 95% CI 1.8-34.5)

•Cancer-specific survival was 100 percent in both arms

●Data comparing adjuvant chemotherapy with surveillance also come from the SWENOTECA Management Program. Patients with LVI present (n = 227) were recommended to proceed with one cycle of BEP (although they could choose surveillance or two cycles of BEP) (table 3) [9]. The relapse rate was higher among patients managed with surveillance compared with one or two cycles of BEP adjuvant chemotherapy (42 versus 3 and 0 percent, respectively). There were no relapses among the 70 patients who chose to receive two cycles of BEP [9]. Still, the mortality rate in the entire cohort was 1 percent (n = 8 deaths), none of which was from progressive disease. A follow-up publication on this study when it had accrued more patients reported that among 258 patients with LVI who received a single cycle of BEP, the relapse rate remained 3.2 percent and five-year disease-specific survival was 100 percent [27].

●In a multi-center single-arm trial (United Kingdom 111), 236 patients with clinical stage I NSGCT received a single cycle of BEP and were followed for a median of 49 months [18]. With a median follow-up of 49 months, four patients had a malignant recurrence (1.3 percent), and three had a recurrent teratoma (1.2 percent), for a combined recurrence rate of approximately 3 percent. Following salvage treatment with a combination of chemotherapy and surgery, three of the four patients with malignant recurrence were alive and had no evidence of disease, while the fourth died of refractory cancer. The three patients who relapsed with teratoma were all rendered disease free with RPLND. Two-year relapse-free and overall survival rates were 97 and 99 percent, respectively.

●The benefit of adjuvant chemotherapy is also supported by a review of the data from observational studies performed by the authors of this topic [10,28-36]. Among 655 patients who received adjuvant chemotherapy for clinical stage I disease, there were only 16 relapses (2.4 percent), which occurred at a median follow-up ranging from 31 to 113 months. In addition, there were only seven cancer-related deaths identified (1 percent).

One versus two cycles of BEP — All patients with high-risk stage IA or IB NSGCT who opt for chemotherapy should receive BEP (table 3). We suggest a single cycle of BEP rather than two cycles because disease-specific survival is over 99 percent with either approach and BEP chemotherapy is associated with dose-dependent long-term toxicity. For the rare group of patients with T3 or T4 tumors, there are limited data to suggest the optimal number of cycles of BEP (one versus two).

Limiting the amount of platinum-based chemotherapy has reduced concerns of acute and delayed side effects of treatment (including a lowered risk of bleomycin-induced pulmonary toxicity). There is also evidence that limiting the exposure to chemotherapy reduces the risk that patients will become infertile [28,29,37]. (See "Treatment-related toxicity in testicular germ cell tumors" and "Approach to the care of long-term testicular cancer survivors" and 'Risk stratification' above.)

There are no data from randomized controlled trials to determine whether one or two cycles should be administered. Data suggest a lower rate of relapse with two cycles of BEP (up to 2.9 percent) versus those treated with a single cycle of BEP (up to 6.5 percent). However, this difference may have been due to chance. Moreover, it is not clear that the small absolute benefit, if real, justifies the potential late toxicities of an additional cycle of chemotherapy. Long-term overall survival in this population is excellent regardless of the number of cycles given. (See "Approach to the care of long-term testicular cancer survivors", section on 'Side effects of treatment'.)

The following studies illustrate the relapse rates seen with one and two cycles of BEP:

●The United Kingdom 111 study of over 230 patients with clinical stage IB disease treated with one cycle of BEP reported that two-year disease-free and overall survival rates were 97 and 99 percent, respectively.

●Similarly, the German Testicular Cancer Study Group trial reported a two-year disease-free survival rate of 99.5 percent with one cycle of BEP.

●Another study of primary chemotherapy for patients with stage I NSGCT (considered to have an estimated relapse risk of at least 30 percent) reported a 6.5 percent relapse rate (3 of 46 patients) with a single cycle of BEP versus a rate of 2.9 percent (3 of 102 patients) with two cycles [31].

●The SWENOTECA group reported that among patients with LVI, a single cycle of BEP was associated with a relapse rate of 3.2 percent (8 of 258 patients) compared with a rate of 0 percent among 70 patients treated with two cycles [9,27].

●Among eight studies that included a total of 622 patients with high-risk disease, the relapse rate following two cycles of BEP was 1.6 percent (n = 10) [9,17,29,31,33,38-40].

Retroperitoneal lymph node dissection — RPLND is a reasonable alternative to chemotherapy, particularly for patients with a teratoma-predominant tumor and for those patients who are not comfortable with surveillance or want to reduce the risk of requiring chemotherapy. However, RPLND should only be performed if the technical expertise is available (ie, surgeons who perform at least 24 procedures annually, in our opinion) [5]. When performed by experienced surgeons, RPLND is safe, with essentially no mortality and an extremely low rate of ejaculatory dysfunction or other long-term morbidity. In addition, the use of RPLND substantially reduces the number of patients who ultimately receive chemotherapy. (See "Retroperitoneal lymph node dissection for early-stage testicular germ cell tumors".)

Unfortunately, very few centers have specialized surgeons sufficiently trained and experienced to perform a high-quality RPLND, and the effectiveness and safety of RPLND in less experienced hands may be compromised [2]. In addition, patients should be aware that adjuvant chemotherapy may still be required after RPLND. Among patients managed with RPLND, approximately 20 percent are likely to have a higher stage at final pathology and thus have an indication for adjuvant cisplatin-based chemotherapy. Further details are discussed separately. (See "Treatment of stage II nonseminomatous germ cell tumors", section on 'Pathologic stage II NSGCT'.)

In a phase III trial from the German Testicular Cancer Group, one cycle of BEP was compared to RPLND in patients with stage I NSGCT treated with orchiectomy [26]. In this study, 9 of the 15 patients (60 percent) who relapsed after RPLND had local recurrences, either in the retroperitoneum (n = 7) or scrotum (n = 2), the latter representing a highly unusual occurrence [26]. This high rate of local relapse may reflect a lack of experience in performing an RPLND, underscoring the importance of the experience, knowledge, and skill of the surgeon. Referral to a center of excellence is warranted for patients undergoing RPLND. (See "Retroperitoneal lymph node dissection for early-stage testicular germ cell tumors".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Testicular cancer".)

SUMMARY AND RECOMMENDATIONS

●General principles – Germ cell tumors (GCTs) account for most testicular cancers. Stage I nonseminomatous germ cell tumor (NSGCT) is a highly curable malignancy. The goals of therapy are to reduce the risk of relapse and minimize treatment-related toxicity. (See 'General principles' above.)

●Risk stratification – The most widely evaluated histologic risk factors for recurrence in males undergoing surveillance following orchiectomy for clinical stage I NSGCT include the presence of lymphovascular invasion (LVI), the predominance of embryonal carcinoma (EC), and tumor stage above T2 (table 1). (See 'Risk stratification' above.)

•Males are at low risk if they have none of these risk factors.

•Males are at high risk if they have any of these risk factors. Males with both LVI and a predominance of EC are at highest risk of relapse.

●Low-risk disease – For most patients with low-risk disease who are treated with orchiectomy, we suggest surveillance rather than adjuvant treatment (algorithm 1) (Grade 2C), given excellent long-term overall survival and the avoidance of unnecessary toxicity with this approach. The specific surveillance protocol for stage I testicular NSGCT is discussed separately. (See 'Low-risk disease' above and 'Surveillance' above and "Posttreatment follow-up for testicular germ cell tumors", section on 'Stage I NSGCT (surveillance)'.)

However, surveillance has not been compared with adjuvant treatment in a randomized trial, and some patients may elect for adjuvant treatment to minimize their chances of relapse. For patients who are unwilling or unable to adhere to surveillance or those who strongly desire to reduce relapse risk and willingly accept the risk of late treatment-related toxicity, one cycle of adjuvant bleomycin, etoposide, and cisplatin (BEP) (table 3) is an acceptable alternative. (See 'Adjuvant chemotherapy' above.)

Retroperitoneal lymph node dissection (RPLND) is also an appropriate alternative for those with access to an experienced urologist, especially if the tumor is predominantly teratoma. (See 'Retroperitoneal lymph node dissection' above.)

●High-risk disease – For patients with high-risk disease who are treated with orchiectomy, options include adjuvant chemotherapy with BEP chemotherapy (table 3), active surveillance, or RPLND (algorithm 1). As all these treatment options result in excellent disease-specific survival, selection of therapy is based upon patient preference and the available expertise. (See 'High-risk disease' above.)

•In patients who opt for chemotherapy, we suggest one cycle of BEP rather than two cycles (Grade 2C). Disease-specific survival is high with either approach, and BEP chemotherapy is associated with dose-dependent long-term toxicity. (See 'One versus two cycles of BEP' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Philip W Kantoff, MD, who contributed to an earlier version of this topic review.