Version May 2024
INTRODUCTION — Testicular germ cell tumors (GCTs) can consist of one histologic pattern or represent a mix of multiple histologic types. Testicular GCTs are divided into two groups: pure seminoma and nonseminomatous GCTs (NSGCTs) [1,2]. Patients with stage I seminoma have an excellent prognosis following radical inguinal orchiectomy. Therefore, treatment can be tailored to individual patient preferences.
The treatment approach for patients with stage I seminoma is reviewed here. The epidemiology, clinical manifestations, diagnosis, and staging of testicular GCTs, and the approach to patients with stage II and stage III seminoma are presented separately.
●(See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors".)
●(See "Treatment of stage II seminoma".)
●(See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
DIAGNOSIS AND INITIAL TREATMENT — The diagnosis of a testicular malignancy is generally established at radical orchiectomy, which also serves as the initial treatment. For patients with stage I seminoma, this procedure is the definitive management and is generally followed by surveillance (algorithm 1). (See 'Postsurgical management' below.)
Classification as stage I seminoma requires:
●Histologic diagnosis of pure seminoma (without any evidence of nonseminomatous elements) on final pathologic analysis of the orchiectomy specimen.
●No pretreatment elevation of alpha-fetoprotein (AFP).
●No evidence of lymph node involvement or distant metastases based on staging imaging (contrast-enhanced computed tomography [CT] or contrast-enhanced magnetic resonance imaging [MRI]) of the abdomen and pelvis, and chest imaging (radiograph or CT). Patients with evidence of more advanced disease on imaging are classified as having stage II seminoma or advanced germ cell tumor. (See "Treatment of stage II seminoma" and "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
●Normal tumor marker studies following orchiectomy. However, patients with stage IS seminoma (ie, those with residual elevation of serum beta-human chorionic gonadotropin [beta-hCG]) after orchiectomy require additional investigation by repeating the elevated tumor marker and obtaining a contrast-enhanced CT of the chest, abdomen, and pelvis to evaluate for disease. However, unlike patients with nonseminomas, these patients are not all necessarily treated as having advanced disease. Patients with progressively rising beta-hCG levels, even in the absence of disease on imaging studies, should generally be treated with chemotherapy for disseminated disease, whereas those with stable, minimally elevated beta-hCG levels may be observed or treated with radiation therapy. (See "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
Patients with seminoma do not require surgical staging of the retroperitoneal nodes. Hence, they are classified as "clinical" stage I seminoma using American Joint Committee on Cancer (AJCC) terminology (table 1A-B). Patients with findings of lymphadenopathy by imaging (based on the AJCC staging for clinical regional lymph nodes), and patients who undergo a retroperitoneal node dissection for clinical stage I seminoma and are diagnosed with pathologically involved nodes do not have stage I seminoma; instead, they have more advanced disease and are treated accordingly. (See "Treatment of stage II seminoma" and "Initial risk-stratified treatment for advanced testicular germ cell tumors".)
POSTSURGICAL MANAGEMENT — Approximately 85 percent of patients with stage I seminoma are cured with orchiectomy. Given the likelihood of cure following orchiectomy, we concur with guidelines from the National Comprehensive Cancer Network (NCCN) and recommend surveillance rather than adjuvant therapy [3]. (See 'Surveillance' below.)
For patients who are not willing and able to undergo all the follow-up testing that is involved with surveillance, and for those patients who desire a more aggressive treatment course in order to reduce their risk of relapse, reasonable alternative options to surveillance include:
●Adjuvant single-agent carboplatin (see 'Adjuvant chemotherapy' below)
●Adjuvant radiation therapy (RT) (see 'Adjuvant radiation therapy' below)
Surveillance
Approach to surveillance and rationale — For most patients with stage I testicular seminoma, we suggest surveillance only rather than adjuvant treatment (algorithm 1). Surveillance is appropriate for patients who are willing and able to adhere to the follow-up schedule. Surveillance has low relapse rates, achieves the same long-term cure rate as adjuvant therapy, and allows most patients to avoid the side effects and late toxicity of chemotherapy and RT. For those patients who relapse during surveillance, treatment is curative for almost all of them. Overall survival with surveillance is as excellent as that following adjuvant chemotherapy or RT (greater than 95 percent). However, surveillance has not been compared with adjuvant treatment in a randomized clinical trial [1,4]. As a result, some patients may elect for adjuvant treatment to minimize their chances of relapse. (See 'Alternatives to surveillance (adjuvant therapy)' below.)
For patients undergoing surveillance, follow-up protocols include a history, physical exam, and serial radiologic imaging of the abdomen and pelvis with either CT or MRI to ensure early detection of any recurrence. Surveillance with serum tumor markers is optional. Further details on the specific surveillance protocol for stage I seminoma treated with orchiectomy and supporting evidence are discussed separately. (See "Posttreatment follow-up for testicular germ cell tumors", section on 'Stage I seminoma' and 'Imaging studies' below and 'Tumor markers' below.)
The main benefit of surveillance is to avoid unnecessary treatment and the associated treatment-related adverse effects among the patients who will not relapse following orchiectomy [1]. Patients contemplating surveillance should be informed that their chance of survival with this approach is excellent, and the risk of death from seminoma is approximately 1 percent or less regardless of whether they choose surveillance or adjuvant therapy. Although studies have not shown a clear impact of nonadherence with surveillance on survival outcomes, patients should be advised to strictly adhere to the surveillance schedule. Patients whose relapses are detected early would have more treatment options, including those with less long-term toxicity [5,6].
The effectiveness of surveillance has been consistently demonstrated in observational studies, with relapse rates ranging between 12 and 19 percent and overall survival of 95 percent or greater [1,7-13]. As examples:
●In one study, the following outcomes were reported in a cohort of 1954 males with stage I seminoma undergoing surveillance who were followed for a median of 15 years [8]:
•For the 369 patients who relapsed (19 percent), the median time to relapse was 14 months. Relapses occurred more frequently during the first two years (over 70 percent) and were less common after year 5 (7 percent).
•In almost all patients, relapsed disease was associated with a good prognosis. The disease-specific survival at 15 years was 99.3 percent.
●In another study that included 1344 males with stage I seminoma managed with surveillance, 173 (13 percent) relapsed at a median of 14 months, but only eight (<1 percent of entire cohort) relapsed beyond three years [9]. Only two of the relapses (1 percent) were intermediate risk at relapse. There were no deaths from disease and only one treatment-related death.
In a partially overlapping database study of 766 patients managed with surveillance, the incidence of late relapse (defined as more than two years after orchiectomy) was 4 percent [10]. In this subset, the pattern of relapse and the subsequent favorable response to treatment were similar to that for early relapse.
Imaging studies — A number of different surveillance imaging recommendations are used for patients with clinical stage I seminoma. Our practice is to perform either contrast-enhanced CT or contrast-enhanced MRI of the abdomen and pelvis at regular intervals during surveillance. Specific protocols for surveillance of stage I seminoma treated with orchiectomy, including frequency of abdominopelvic imaging, are discussed separately. (See "Posttreatment follow-up for testicular germ cell tumors", section on 'Stage I seminoma'.)
MRI is a reasonable alternative to CT imaging for those who wish to avoid radiation exposure or intravenous CT contrast. For most patients, we prefer to use the same imaging modality (eg, either CT or MRI) throughout surveillance to facilitate comparison with prior scans. However, some patients may choose to initiate surveillance with CT imaging and subsequently switch to MRI to reduce radiation exposure. Chest radiograph is performed if clinically indicated, with chest CT reserved for patients who have clinical signs or symptoms concerning for pulmonary metastatic disease or other clinical indications for a chest CT.
In a phase III trial (TE24 Trial of Imaging and Schedule in Seminomas Testis [TRISST]) of patients with stage I seminoma, surveillance with MRI was noninferior to CT in detecting relapsed disease, suggesting that MRI is a reasonable alternative to CT in this setting [11]. This study also compared less frequent imaging (three imaging studies over three years) with more frequent imaging (seven imaging studies over five years). We do not use the less frequent imaging schedule because it was associated with a higher incidence of stage IIC or greater disease at relapse (absolute increase of 2.5 percent) in this study. Nevertheless, survival outcomes were excellent for all patients diagnosed with and treated for relapsed disease.
In this 2x2 randomized controlled trial, 669 male patients with stage I seminoma who received no postorchiectomy adjuvant therapy were randomly assigned to one of four surveillance plans using either CT imaging (with either three studies over 36 months or seven studies over 60 months) or MRI (using the same two schedules) [11]. At a median follow-up of six years, the relapse rate was 12 percent (82 patients), with a majority occurring within three years of initiating surveillance (all but five patients). The six-year incidence of more advanced (≥ stage IIC) relapsed disease was 1.5 percent (10 patients). Fewer patients on MRI surveillance (two patients; 0.6 percent) had advanced disease at relapse compared with those on CT surveillance (eight patients; 2.6 percent); this trend toward MRI superiority met the prespecified criteria for noninferiority.
Additionally, there were fewer relapses with advanced disease while using more frequent surveillance imaging with seven studies (one patient, 0.3 percent) compared with less frequent imaging with three studies (nine patients, 2.8 percent). Among those with relapsed disease who received salvage therapy, 76 of 82 patients (93 percent) were alive and without evidence of disease recurrence, and the overall survival (OS) rate was 99 percent.
Tumor markers — Surveillance with serum tumor markers is optional. Some experts do not follow serum tumor markers for stage I seminoma because they are rarely increased in the absence of radiologic evidence of disease [12,14]. Other experts follow serum tumor markers because they are easy to obtain and can detect relapsed disease earlier in a minority of patients. (See "Serum tumor markers in testicular germ cell tumors" and "Posttreatment follow-up for testicular germ cell tumors", section on 'Guidelines for follow-up'.)
The clinical utility of serum tumor markers was evaluated in one observational study of 527 males with stage I seminoma managed by surveillance [12]. At a median of 72 months, relapse occurred in 75 males (14 percent). Only 11 of these males (15 percent) had an elevated marker at the time of relapse. Elevated tumor markers were detected prior to the documentation of clinical or radiologic progression in only one patient (1.3 percent).
Although most relapses for stage I seminoma are diagnosed on imaging, serum tumor markers alone can still detect relapses. For patients where surveillance imaging scans are performed less frequently, serum tumor markers are particularly useful to obtain during the interval between scans. In a randomized phase III trial (TRISST) evaluating various surveillance strategies for stage I seminoma, relapsed disease was seen in 82 patients. Among this group, serum tumor markers alone detected first relapses more commonly among patients who were imaged less frequently (5 of 46 patients; 11 percent) than those imaged more frequently (3 of 36 patients; 8 percent) [11].
Alternatives to surveillance (adjuvant therapy) — Some patients may be unwilling or unable to adhere to surveillance schedules, while others may desire adjuvant therapy over surveillance to reduce the risk of disease relapse. Patients who choose to undergo adjuvant treatment should be informed that it reduces their risk of recurrence, but it does not improve OS. OS is also excellent with surveillance alone following orchiectomy. (See 'Surveillance' above.)
For patients who are willing to accept the risks of treatment without an OS advantage, adjuvant treatment options include single-agent carboplatin or RT (algorithm 1). (See 'Adjuvant chemotherapy' below and 'Adjuvant radiation therapy' below.)
Semen cryopreservation should be offered to all patients diagnosed with testicular cancer prior to instituting postorchiectomy therapy if they wish to preserve fertility. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors", section on 'Cryopreservation of sperm'.)
Adjuvant chemotherapy — For patients who are unwilling or unable to adhere to surveillance or those who strongly desire to reduce relapse risk and willingly accept the risks of late treatment-related toxicity, we suggest adjuvant therapy with single-agent carboplatin rather than RT. In a randomized trial, relapse-free rates were similar for adjuvant single-agent carboplatin and adjuvant RT. While there are limited data on the long-term toxicities of carboplatin, adjuvant RT is associated with certain late toxicities, such as cardiovascular disease. (See 'Adjuvant radiation therapy' below.)
Patients who select adjuvant carboplatin may receive either one or two cycles of treatment, but the optimal number of cycles is not established. Some UpToDate contributors offer two cycles rather than one cycle which is associated with reduced risk of relapse. However, other contributors prefer one cycle of carboplatin since OS is similar to two cycles of carboplatin, and there are limited data on the long-term toxicities of carboplatin. When selecting the number of cycles of carboplatin to administer, clinicians should discuss the risks and benefits of each approach with their patients.
●Efficacy – Adjuvant carboplatin has been investigated in clinical trials of patients with stage I seminoma treated with orchiectomy. Single-agent carboplatin was used rather than a cisplatin-based combination since it is effective and less toxic. In a phase III trial conducted by the European Organisation for Research and Treatment of Cancer (EORTC), 1477 patients with stage I seminoma were randomly assigned to adjuvant therapy with either a single course of carboplatin (dosed at an area under the concentration x time curve [AUC] of 7) or RT [15,16]. At a median follow-up of 6.5 years, relapse-free rates were similar with carboplatin and RT (94.7 and 96.0 percent, respectively) [16]. There were no deaths due to seminoma in the carboplatin arm and one death due to seminoma in the RT arm.
Retrospective analyses have looked at the relapse rate with either one or two cycles of carboplatin [17-24]. In these studies, the relapse rate is consistently higher among patients who received one cycle of carboplatin (approximately 3 to 9 percent) compared with those who received two cycles (0 to 3 percent). However, OS is similar for both treatments.
Prognostic data are available for patients wish to know their chances of relapse after adjuvant carboplatin. In a retrospective series of 185 males from 31 centers who were treated for relapsed stage I seminoma following one or two cycles of adjuvant carboplatin, the five-year disease-free survival and OS rates were 82 and 98 percent, respectively [25]. In general, overall survival after adjuvant carboplatin is as high as that seen with surveillance or radiation therapy. However, tumors that relapse after adjuvant carboplatin are more likely to also be resistant to further cisplatin-based therapy.
●Risks and toxicities – The most common acute side effects of carboplatin are hematologic (anemia, thrombocytopenia), nausea, and vomiting. There are limited data on late treatment-related toxicities with single-agent carboplatin in patients with testicular seminoma [26,27]. Observational studies in patients with stage I seminoma suggest that adjuvant carboplatin is associated with a lower risk of cardiovascular disease compared with adjuvant RT [27]. However, in patients with ovarian cancer, carboplatin therapy (albeit at higher cumulative doses than those used for stage I seminoma) is associated with an increased risk of leukemia [28]. Further details on the treatment-related toxicity in testicular cancer are discussed separately. (See "Treatment-related toxicity in testicular germ cell tumors" and "Approach to the care of long-term testicular cancer survivors", section on 'Side effects of treatment'.)
For patients with stage I seminoma, some studies suggest that adjuvant carboplatin may simply delay, rather than prevent, the development of a contralateral testicular germ cell tumor. One observational study with long-term follow-up (median of nine years) suggested an increased incidence of contralateral testicular cancers among patients with stage I seminoma who were treated with adjuvant carboplatin compared with the general population [26]. By contrast, in a randomized phase III trial of 1477 patients with stage I testicular seminoma, adjuvant carboplatin was associated with a reduced rate of a subsequent contralateral germ cell tumor compared with adjuvant RT (2 versus 15 relapses, HR 0.22, 95% CI, 0.05-0.95), but this study had shorter follow-up (median of 6.5 years) [16].
Adjuvant radiation therapy — Adjuvant RT is an appropriate alternative for patients who decline adjuvant chemotherapy. Adjuvant RT prevents relapse in approximately 96 percent or more of patients with clinical stage I seminoma [7,29]. Although adjuvant RT is associated with an increased risk of long-term toxicities (such as cardiovascular disease and second malignancies [30,31]), this risk has decreased over time, presumably due to reductions in contemporary treatment fields and the doses delivered [32]. (See "Treatment-related toxicity in testicular germ cell tumors".)
The favorable outcome in patients with clinical stage I seminoma who received adjuvant RT is illustrated by a combined analysis of 1893 patients treated between 1989 and 2001 in one of three randomized phase III trials [29]. Although relapses were seen in 4 percent of patients, there were only four deaths from seminoma, and the remaining patients were successfully treated with chemotherapy at the time of recurrence.
The acute side effects associated with RT include fatigue, gastrointestinal effects, and myelosuppression, which is usually mild. Other infrequent toxicities include skin tanning in the treatment area, and impaired fertility, which can be mitigated with use of a testicular shield during treatment. Late treatment-related toxicities are discussed separately. (See "Treatment-related toxicity in testicular germ cell tumors".)
Technique — In patients with clinical stage I seminoma who choose adjuvant RT, patients should undergo simulation in the supine position [33]. A clamshell shield should be used to preserve spermatogenesis and testosterone production in the remaining testis to reduce the dose of RT it is exposed to. A clamshell should be used even in patients who have undergone sperm banking. Tattoos should be placed at the level of the isocenter anteriorly and laterally.
Treatment field — Because the paraaortic lymph nodes are the initial nodal group to be involved in the majority of patients who experience tumor spread, paraaortic strip RT protocols were introduced in an effort to decrease treatment-related morbidity (image 1). The original radiotherapy fields used included bilateral paraaortic nodes and pelvic lymph nodes (a "hockey-stick" or "dog-leg" field) (image 2).
The MRC Testicular Tumor Working Group TE10 trial randomly assigned 478 males with stage I seminoma to paraaortic strip or paraaortic plus ipsilateral iliac lymph node RT following inguinal orchiectomy [34]. The short-term side effects of RT were decreased, and the incidence of azoospermia was significantly decreased using para-aortic strip RT compared with a more extensive RT field (11 versus 35 percent). With a median follow-up of 4.5 years, there were nine relapses in each group (4 percent). There was only one death due to seminoma in the trial. Additionally, modeling data suggest that the use of para-aortic fields compared with "dog-leg" or "hockey-stick" fields may reduce the secondary cancer risk by 45 percent [35].
Classically, the upper border of the para-aortic field was at the top of T11. By lowering the upper border of the para-aortic field to the top of T12, there is reduced dose to the kidney, stomach, and bowel, thereby limiting potential second malignancies. In one prospective study of 80 patients with stage I seminoma, the use of this cranially reduced para-aortic treatment field resulted in no relapses at median follow-up of approximately seven years [36].
CT-based treatment planning should be based on vascular anatomy [33]. Field sizes should no longer be constructed solely on bony anatomy, as studies have shown that relying on bony anatomy alone can lead to marginal misses.
Adjuvant mediastinal RT is not necessary to minimize the risk of relapse, and it leads to an unacceptably high long-term risk of cardiopulmonary disease [37].
Dose — Due to the radiosensitivity of seminoma, a low therapeutic dose is required to effectively treat seminoma, with a recommended dose of 20 Gy in 10 fractions [38,39]. A scrotal shield should be used, even with paraaortic strip radiation, to minimize radiation to the remaining testicle [40].
The effect of dose was studied in the MRC TE18 trial, in which 625 males with seminoma were randomly assigned to 20 Gy in 10 fractions or 30 Gy in 15 fractions [38]. With a median follow-up of five years, the disease-free survival rates were 98 and 97 percent for the 30 and 20 Gy groups, respectively [38]. While males receiving the higher dose had significantly more lethargy (20 versus 5 percent) and inability to work (46 versus 28 percent) at four weeks, these differences disappeared by 12 weeks. However, six new primary cancers were diagnosed, all in males treated with 30 Gy. Nine new germ cell primary cancers were diagnosed, six in the 20 Gy group, and three in the 30 Gy group.
Recurrent disease — Recurrent disease typically is detected by imaging studies. When a recurrence is limited to the retroperitoneal lymph nodes, this is typically treated like stage II seminoma. (See "Treatment of stage II seminoma".)
If more extensive disease is present, treatment is based on risk stratification. (See "Initial risk-stratified treatment for advanced 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".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Testicular cancer (The Basics)")
●Beyond the Basics (see "Patient education: Testicular cancer (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Prognosis – The overall prognosis of patients with stage I testicular seminoma is excellent following orchiectomy. (See 'Introduction' above.)
●Surveillance – For most patients with stage I testicular seminoma who are treated with orchiectomy, we suggest surveillance only rather than adjuvant treatment (algorithm 1) (Grade 2C) given low relapse rates, excellent long-term overall survival (>95 percent), and avoidance of unnecessary toxicity with this approach. However, this strategy 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. (See 'Surveillance' above.)
•Surveillance protocol – The specific surveillance protocol for patients with stage I testicular seminoma treated with orchiectomy are discussed separately. (See "Posttreatment follow-up for testicular germ cell tumors", section on 'Stage I seminoma'.)
●Alternatives to surveillance (adjuvant therapy)
•Adjuvant carboplatin – 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, we suggest adjuvant therapy with single-agent carboplatin rather than radiation therapy (RT) (Grade 2C). (See 'Adjuvant chemotherapy' above.)
-Patients who select adjuvant carboplatin may receive either one or two cycles of treatment, but the optimal number of cycles is not established. Some UpToDate contributors prefer two cycles of carboplatin which is associated with a reduced risk of relapse. Other contributors offer one cycle of carboplatin since overall survival (OS) is similar and there are limited data for the long-term toxicities of carboplatin. Clinicians should discuss the risks and benefits of each approach with their patients.
•Adjuvant RT – Adjuvant RT is an appropriate alternative for patients who decline adjuvant chemotherapy. (See 'Adjuvant radiation therapy' above.)
ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Clair J Beard, MD, and William K Oh, MD, who contributed to earlier versions of this topic review.
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